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+ + + ++Background: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic. However, limited information is available from countries in sub-Saharan Africa (SSA). Evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are also scarce in these countries. The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. Methods: The PeriCOVID study is a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. A nasopharyngeal swab was taken from mothers at enrolment for RT-PCR confirmation of SARS-CoV-2 infection, and maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. The primary outcome was seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. Placental transfer of antibodies was described using the geometric mean ratio (GMR). We also estimated the proportion of asymptomatic or subclinical COVID-19 infections in pregnant women using serological testing, and collected adverse pregnancy and infancy outcomes (e.g. still-birth, prematurity, maternal or infant death). Results: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron) , in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes. Discussion: This study describes the increasing prevalence of SARS CoV-2 antibodies in pregnant woman in Uganda and Malawi across waves of SARS-CoV-2 infection. Our study adds to existing evidence that suggests under-reporting of infection if based solely on cases with clinical disease, or a positive RT-PCR for SARS-CoV-2, as most of the women in our study had asymptomatic infections and did not seek medical care. This has implications for screening in subsequent outbreaks and pandemics where protection of pregnant women and effect of infection in pregnancy on the infant are unknown. +
++Background The coronavirus disease 2019 (COVID-19) pandemic has put a strain on the healthcare system, and sudden changes in disease status during home treatment have become a serious issue. Therefore, prediction of disease severity and allocation of sufficient medical resources, including high-flow nasal cannula (HFNC), to patients in need are important. We aimed to determine risk factors for the need of HFNC use in COVID-19. Methods This was a single-center retrospective observational cohort study including all eligible hospitalized adult patients aged ≥18 years diagnosed with COVID-19 between April 14, 2020 and August 5, 2021 who were treated in the study hospital. The primary outcome was critical respiratory illness meeting one of the following criteria: oxygenation flow rate ≥ 10 L/min, high-flow oxygenation, noninvasive ventilation, invasive ventilation, and death. Nineteen potential predictive variables, including patient characteristics at hospital admission, were screened using least absolute shrinkage and selection operator and logistic regression to construct a predictive risk score. Accuracy of the risk score was determined using area under the receiver operating characteristic curve. Results The study cohort included 148 patients. The rate of critical respiratory illness was 22.9% (all patients needed high-flow device support). Among the 19 potential variables, percutaneous oxygen saturation (SpO2) <92% (odds ratio [OR] 7.50, 95% confidence interval [CI] 2.806–20.82) and IL-6 (OR 1.021, 95% CI 1.010–1.033) were included in developing the risk score, which was termed interleukin (IL)-6-based COVID-19 severity (IBC-S) score. Conclusions The IBC-S score, an easy-to-use risk score based on parameters available at the time of hospital admission, predicted critical respiratory failure in patients with COVID-19. In primary care settings, the IBC-S score based on interleukin-6 and SpO2 might aid in determining patients who should be transported to a tertiary medical institution or an isolation facility. +
++To design effective vaccines and other immune interventions against a pathogen, it is necessary to know which aspect of immunity associates with protection. We investigated whether neutralizing antibodies associate with infection clearance in long-term SARS-CoV-2 infection during HIV-mediated immunosuppression. We monitored neutralizing antibody activity against SARS-CoV-2 in five participants with advanced HIV disease and delayed control of HIV viremia. These participants had persistent SARS-CoV-2 infection ranging from 110 to 289 days which was associated with low or undetectable neutralizing antibody responses. SARS-CoV-2 clearance was associated with the emergence of neutralizing antibodies and occurred in two participants before suppression of HIV viremia, but after some CD4 T cell reconstitution. Vaccination only further increased neutralizing antibody levels in the advanced HIV disease participants who achieved HIV suppression pre-vaccination. During the prolonged SARS-CoV-2 infection we observed widespread evolution which was particularly pronounced in one Delta variant infection. This resulted in high-level escape from Delta-elicited neutralizing antibodies and a virus antigenically distinct from both ancestral SARS-CoV-2 and Omicron XBB in hamster experimental infections. The results offer new evidence that neutralizing antibodies associate with SARS-CoV-2 protection and argue that successful management of HIV may be necessary to curtail long-term infection and evolution of co-infecting pathogens. +
++Background: B-cell hypo-responsiveness has been associated with intestinal parasitic co-infection. The effect of parasite co-infection on antibody response to SARS-CoV-2 is unknown. Here, we aimed to determine antibody response to SARS-CoV-2 among COVID-19 patients co-infected with intestinal parasites and those without parasite co-infection. Methods: In this prospective cohort study, a total of 589 samples were serially collected from 72 RT-PCR-confirmed patients. Anti-SARS-CoV-2 nucleocapsid protein (NP) antibody titers were measured longitudinally during hospitalization. SARS-CoV-2 infection was confirmed by RT-PCR on samples obtained from nasopharyngeal swabs, while direct microscopic examination, modified Ritchie concentration, and Kato-Katz methods were used to identify parasites and ova from fresh stool samples. Data were analyzed using STATA version 14. Results: Of the 72 COVID-19 patients, 39 (54.2%) were co-infected with intestinal parasites while 33 (45.8%) had no parasitic co-infection. Overall, the median cut-off index (COI) for anti-NP antibody titer among COVID-19 patients co-infected with parasites was 6.91 (IQR: 0.55-40.7) compared to 7.51 (IQR: 0.21-59.21) in those without parasites (p=0.764). In addition, 174/261 [66.7% (95% CI: 60.68-72.16)] and 231/328 [70.4% (95% CI: 65.23-75.14)] specimens from COVID-19 patients with parasite co-infection and without parasites, respectively, had anti-SARS-CoV-2 antibody above the cut-off COI value (p=0.328). The positivity rate for anti-SARS-CoV-2 NP < 14 days after symptom onset was 66.3% (95% CI: 60.21-71.85) and 70.0% (95% CI: 64.72-74.74) for those not infected and co-infected with parasites, respectively (p=0.343). In addition, 31/72 (41.9%) of the patients who were negative at the time of enrollment were seroconverted. The trend in anti-NP antibodies among seroconverted individuals with and without parasites is also similar. Conclusions: Co-infection with parasitic infection has very little effect on the anti-SARS-CoV-2 antibody immune response. Further studies on the profile of neutralizing antibodies in parasite-endemic areas are warranted to ascertain vaccine efficacy. +
++The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 810 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes. +
++Background: Immune-suppressed solid organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. The highly infectious SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear. Methods: We characterized Spike-specific T cell responses to ancestral SARS-CoV-2, Omicron BA.4/5 and XBB.1.5 peptides in a prospective study of kidney, lung and liver transplant recipients (n = 42) throughout a three- or four-dose ancestral Spike mRNA vaccination schedule. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4+ and CD8+ T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137 and/or CD107a. Results: Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to Omicron BA.4/5 and XBB.1.5 were significantly lower in magnitude compared to ancestral strain responses. Antigen-specific CD4+ T cell frequencies correlated with anti-receptor-binding domain (RBD) antibody titres, with post-second dose T cell responses predicting subsequent antibody responses. Patients receiving prednisone, lung transplant recipients and older adults displayed weaker responses. Conclusions: Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but responses to these variants are diminished. Antigen-specific T cells can predict future antibody responses and identify vaccine responses in seronegative individuals. Our data support monitoring both humoral and cellular immunity in SOTRs to track effectiveness of COVID-19 vaccines against emerging variants. +
++Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known. Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for cardiometabolic diagnoses by 18 months after birth, compared with unexposed offspring born during the COVID-19 pandemic. Design. This retrospective cohort study included the live offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020 - December 31, 2021) at 8 hospitals within 2 health systems in Massachusetts. Exposure. SARS-CoV-2 positivity on polymerase chain reaction (PCR) test during pregnancy. Main Outcome Measures. Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to cardiometabolic disorders. Offspring weight-for-age, length-for-age, and body mass index (BMI)-for-age z-scores at birth, 6 months, 12 months, and 18 months of age. Results. The full study cohort includes 29,510 live born offspring (1,599 exposed and 27,911 unexposed offspring). 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis by 18 months of age (crude OR 1.47 [95% CI: 1.10-1.94], p=0.007; adjusted OR 1.37 [1.01-1.83]; p=0.04). These diagnoses were preceded by significantly greater mean BMI-for-age z-scores in exposed versus unexposed offspring at 6 months (mean z-score difference 0.19, 95% CI: 0.10, 0.29, p<0.001), and a greater proportion of offspring at risk of, or meeting criteria for, overweight/obesity (16.5% vs. 12.2%, p=0.006). Conclusions. Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months and greater BMI-for-age at 6 months. +
++We administered BNT162b2 as a third dose to 314 adults ≥30 years of age who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1, 6 and 12 months, and found stable levels of antibody responses to the ancestral strain and Omicron BA.2 at 6-12 months after receipt of the BNT162b2 third dose, with increased antibody levels in individuals who also received a fourth vaccine dose or reported a SARS-CoV-2 infection during follow-up. +
++People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March – October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n=12), secondary immunosuppression (N=8) and those with primary or acquired immunodeficiency (i.e. HIV; N=7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups. +
++Purpose: Retail workers are an understudied occupational group that may have been at increased risk of contracting SARS-CoV-2 during the COVID-19 pandemic. Therefore, we set up a longitudinal cohort of participants working in this sector to better document the incidence of SARS-CoV-2 infection and the immune response to infection and/or vaccination in this group. Participants: A total of 304 participants were recruited between April 20, 2021 and October 22, 2021. They were invited to attend three visits (each separated by ~12 weeks) during which they provided blood samples and information on participant characteristics, COVID-19 symptoms, and vaccination. An extension phase of two additional visits was carried out between March 15th, 2022 and October 3rd, 2022 to document the impact of the Omicron variant among the 198 participants who were still eligible for recruitment. Participants were aged 18 to 75 and worked in grocery stores, hardware stores, bars or restaurants within the Quebec City metropolitan area (Canada). Findings to date: This article describes participants9 demographic, socioeconomic, behavioral, clinical and occupational characteristics, and their COVID-19 symptoms (where applicable). It also describes SARS-CoV-2 vaccination status and any SARS-CoV-2 diagnostic test (i.e., PCR or rapid antigen) performed from the beginning of the pandemic until the last visit. Future plans: The incidence of SARS-CoV-2 infections will be assessed. The immune response (innate and acquired) to SARS-CoV-2 infection or vaccination will be studied using a variety of techniques, including reference and experimental enzyme-linked immunosorbent assays, microneutralization assays with live viruses, experimental pseudoneutralization with an angiotensin-converting enzyme 2-spike assay, peripheral blood mononuclear cells and neutrophil stimulation, and a proliferation assay based on carboxyfluorescein diacetate succinimidyl ester. +
++Objective: To determine the clinical and laboratory characteristics, as well as evaluating the factors associated with mortality in patients with COVID-19 infection and acute kidney injury (AKI) hospitalized in the Intensive Care Unit (ICU) of the Hospital Nacional Arzobispo Loayza. Materials and Methods: Retrospective cohort study, with convenience sampling during the period from April 2020 to March 2021, through the review of medical records data. Inclusion criteria were; patients ≥ 18 years old, with a diagnosis of COVID-19 infection, who were admitted to ICU with normal renal function and developed AKI during their stay in ICU. Exclusion criteria were; patients who developed AKI prior to ICU admission, patients with chronic kidney disease with and without dialysis. Results: A total of 177 medical records that met the inclusion and exclusion criteria were evaluated. The mean age was 57.2+/-13.2 years, 145 (81.4%) were male; comorbidities were: obesity 112(63.3%), arterial hypertension 55 (31.1%) and diabetes mellitus 30(16.9%); the most frequent cause of AKI was hypoperfusion (93%). 83 participants (46.8%) received dialytic support in the intermittent hemodialysis modality. In-hospital mortality was 151 (85.3%) and was higher in the group with stage 3 AKI: 109 (72.2%). The increase in ferritin level (OR: 10.04 (95%CI 4.4-38.46), p<0.001) and APACHE score (OR: 1.75 (95%CI 1.4-2.12), p<0.001), as well as the decrease in PaO2/FiO2 level (OR: 0.85 (95%CI 0.59-0.92), p<0.041, were related to mortality. Conclusions: AKI in ICU patients with COVID-19 infection has a high mortality and the related factors were the increase in APACHE II score and ferritin level, as well as the decrease in PaO2/FiO2 level. Keywords: Acute kidney injury, COVID-19, Intensive care units (MeSH) +
++Background: Decisions to impose temporary travel measures are less common as the global epidemiology of COVID-19 evolves. Risk-based travel measures may avoid the need for a complete travel ban, however evaluations of their effects are lacking. Here we investigated the public health effects of a temporary traffic light system introduced in the United Kingdom (UK) in 2021, imposing red-amber-green (RAG) status based on risk assessment. Methods: We analysed data on international flight passengers arriving into Scotland, COVID-19 testing surveillance, and SARS-CoV-2 whole genome sequences to quantify effects of the traffic light system on (i) international travel frequency, (ii) travel-related SARS-CoV-2 case importations, (iii) national SARS-CoV-2 case incidence, and (iv) importation of novel SARS-CoV-2 variants. Results: International flight passengers arriving into Scotland had increased by 754% during the traffic light period. Amber list countries were the most frequently visited and ranked highly for SARS-CoV-2 importations and contribution to national case incidence. Rates of international travel and associated SARS-CoV-2 cases varied significantly across age, health board, and deprivation groups. Multivariable logistic regression revealed SARS-CoV-2 cases detections were less likely among travellers than non-travellers, although increasing from green-to-amber and amber-to-red lists. When examined according to travel destination, SARS-CoV-2 importation risks did not strictly follow RAG designations, and red lists did not prevent establishment of novel SARS-CoV-2 variants. Conclusions: Our findings suggest that country-specific post-arrival screening undertaken in Scotland did not prohibit the public health impact of COVID-19 in Scotland. Travel rates likely contributed to patterns of high SARS-CoV-2 case importation and population impact. +
++Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic. +
+Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: COVID-19
Intervention: Drug: Obeldesivir
Sponsor: Gilead Sciences
Not yet recruiting
EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition: Post-COVID-19 Syndrome
Intervention: Behavioral: rehacom
Sponsor: Cairo University
Enrolling by invitation
Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A COVID-19 Preventive Vaccine in Healthy Volunteers - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI; Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
Sponsor: Cellid Co., Ltd.
Not yet recruiting
Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions: Vaccination Hesitancy; COVID-19
Interventions: Behavioral: Behavioural science-informed text messages; Behavioral: Control
Sponsors: The Behavioural Insights Team; Public Health England; Department of Health and Social Care; NHS England and NHS Improvement
Completed
Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: Ivermectin; Drug: Placebo
Sponsor: Insud Pharma
Terminated
Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition: Post-COVID-19 Syndrome
Intervention: Drug: Methylprednisolone
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy
Intervention: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
Sponsors: Duke University; American Society of Hematology
Not yet recruiting
A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions: SARS CoV 2 Infection; Influenza, Human
Interventions: Biological: BIMERVAX; Biological: SIIV
Sponsor: Hipra Scientific, S.L.U
Not yet recruiting
Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions: Mental Health; COVID-19; Misinformation
Interventions: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging
Sponsors: Harvard Medical School (HMS and HSDM); Partners in Health
Active, not recruiting
A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Biological: BNT162b2 (Omi XBB.1.5)
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Pulmonary Artery Pressure in COVID-19 Survivors - Condition: Pulmonary Hypertension Secondary
Intervention: Diagnostic Test: right heart catheterization (RHC).
Sponsor: Mansoura University Hospital
Enrolling by invitation
Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions: Cardiovascular Health; Physical Function
Intervention: Behavioral: Golden Circle
Sponsor: University of Illinois at Urbana-Champaign
Completed
Supported Employment COVID-19 Rapid Testing for PWID - Condition: Health Behavior
Intervention: Behavioral: Supported Employment
Sponsor: University of Oregon
Not yet recruiting
Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 - Condition: Coronavirus Infections
Interventions: Drug: tixagevimab/cilgavimab 150+150 mg; Drug: tixagevimab/cilgavimab 300+300 mg; Drug: regdanvimab
Sponsors: City Clinical Hospital No.52 of Moscow Healthcare Department; Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Active, not recruiting
Study of LAU-7b for the Treatment of Long COVID in Adults - Condition: Long COVID
Interventions: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles
Sponsor: Laurent Pharmaceuticals Inc.
Not yet recruiting
Peptide foldamer-based inhibitors of the SARS-CoV-2 S protein-human ACE2 interaction - The entry of the SARS-CoV-2 virus into a human host cell begins with the interaction between the viral spike protein (S protein) and human angiotensin-converting enzyme 2 (hACE2). Therefore, a possible strategy for the treatment of this infection is based on inhibiting the interaction of the two abovementioned proteins. Compounds that bind to the SARS-CoV-2 S protein at the interface with the alpha-1/alpha-2 helices of ACE2 PD Subdomain I are of particular interest. We present a stepwise…
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis - Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and…
Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-modifying Therapies - Respiratory virus infections initiate and transmit from the upper respiratory tract (URT). Coronaviruses, including OC43, are a major cause of respiratory infection and disease. Failure to mount an effective anti-viral immune response in the nasal mucosa increases the risk of severe disease and person to person transmission highlighting the need for URT infection models to support development of nasal treatments that improve coronavirus anti-viral immunity. We aimed to determine if OC43…
The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community - SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in…
Management of chronic myelogenous leukemia with COVID-19 and hepatitis B - The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and…
Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance - CONCLUSIONS: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.
Neutralizing antibody and T-cell responses against SARS-CoV-2 variants by heterologous CoronaVac/ChAdOx-1 vaccination in elderly subjects with chronic obstructive pulmonary disease - CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen.
Cysteamine-mediated blockade of the glycine cleavage system modulates epithelial cell inflammatory and innate immune responses to viral infection - Transient blockade of glycine decarboxylase (GLDC) can restrict de novo pyrimidine synthesis, which is a well-described strategy for enhancing the host interferon response to viral infection and a target pathway for some licenced anti-inflammatory therapies. The aminothiol, cysteamine, is produced endogenously during the metabolism of coenzyme A, and is currently being investigated in a clinical trial as an intervention in community acquired pneumonia resulting from viral (influenza and…
Bioengineered Neutrophil Extinguisher Targets Cascade Immune Pathways of Macrophages for Alleviating Cytokine Storm in Pneumonia - Cytokine storm is a common complication of COVID-19 pneumonia and has been proven to contribute to high mortality rates. However, current treatment approaches exhibit limited potential to balance immune response and overproduction of inflammatory cytokines, leading to poor therapeutic outcomes. Herein, a smart bioengineered neutrophil, Extinguisher, composed of live neutrophils encapsulating the liposome formulation of NF-κB suppressor MLN4924 and STING inhibitor H-151 (Lip@MH), is developed for…
Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys - Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming the bioactive triphosphate 2-NTP. 2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for 1 have prompted interest in oral approaches to generate 2-NTP. Here, we describe the discovery of a 5’-isobutyryl ester prodrug of 2 (GS-5245, Obeldesivir, 3) that has low cellular…
Novel mono- and multivalent N-acetylneuraminic acid glycoclusters as potential broad-spectrum entry inhibitors for influenza and coronavirus infection - N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density-dependent fashion. Compared with inhibition by Neu5Ac,…
Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides - The COVID-19 pandemic has caused significant global impact, resulting in long-term health effects for many individuals. As more patients recover, there is a growing need to identify effective management strategies for ongoing health concerns, such as post-COVID-19 syndrome, characterized by persistent symptoms or complications beyond several weeks or months from the onset of symptoms. In this review, we explore the potential of dietary polysaccharides as a promising approach to managing…
Alkyne as a Latent Warhead to Covalently Target SARS-CoV-2 Main Protease - There is an urgent need for improved therapy to better control the ongoing COVID-19 pandemic. The main protease M^(pro) plays a pivotal role in SARS-CoV-2 replications, thereby representing an attractive target for antiviral development. We seek to identify novel electrophilic warheads for efficient, covalent inhibition of M^(pro). By comparing the efficacy of a panel of warheads installed on a common scaffold against M^(pro), we discovered that the terminal alkyne could covalently modify…
Discovery and Mechanism Study of SARS-CoV-2 3C-like Protease Inhibitors with a New Reactive Group - 3CL^(pro) is an attractive target for the treatment of COVID-19. Using the scaffold hopping strategy, we identified a potent inhibitor of 3CL^(pro) (3a) that contains a thiocyanate moiety as a novel warhead that can form a covalent bond with Cys145 of the protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed the mechanism of covalent formation between 3a and the protein in its catalytic pocket. Moreover, several analogues of compound 3a were designed and synthesized….
Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum - Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and…
The Invisible Fire on Maui - For those on the Hawaiian island whose jobs depend on tourism, a period of mourning and recovery has also brought fear for their livelihoods. - link
Robo-Taxis Are Legal Now - In San Francisco, it’s getting easier to hail a ride from no one. - link
The Spectre of Andrew Cuomo Continues to Haunt New York - The former governor is out of office, fixated on getting even, and looming over state politics. - link
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+You can learn a lot from utopias, even though you (probably) don’t live in one. +
++When we think about the future, our minds turn almost effortlessly to bad things. Maybe it’s the climate problem, or the AI apocalypse, or political chaos — the list goes on and on. +
++Dystopianism has always been an easy game to play, and there’s something useful about imagining how badly things might go if we don’t deal with our issues now. +
++If imagining the worst-case scenario is a useful exercise, then imagining the best-case scenario must also be useful — and for the same reasons. +
++So why does this seem so much harder to do? +
++A new book by Kristen Ghodsee called Everyday Utopia offers some interesting answers. It’s a sweeping look at various communal experiments over the last two centuries and it makes the case that utopian thinking is both necessary and pragmatic. Beyond that, it’s a critique of our present society and the lack of care and connection that defines so much of it. +
++I invited Ghodsee onto The Gray Area to talk about what she learned from all these experiments and how we might apply those lessons today. Below is an excerpt of our conversation, edited for length and clarity. +
++As always, there’s much more in the full podcast, so listen and follow The Gray Area on Apple Podcasts, Google Podcasts, Spotify, Stitcher, or wherever you find podcasts. New episodes drop every Monday and Thursday. +
++A book about alternative ways of living is obviously animated in some way by a critique of the present order. How would you sum up that critique? +
++This is very much a post-pandemic book. It was initially animated by a lot of the isolation and loneliness and general discombobulation that people felt during the pandemic and what we realized about our family structures. The hegemonic model in the United States is monogamous pairing, generally heterosexual, where we provide exclusive bi-parental care to our own biological offspring in a single-family home surrounded by hoards of our own privately owned stuff. That’s our model and for many people it made the pandemic even more difficult. +
++Almost immediately, people who had families rushed out to form pandemic pods. They tried mutual aid experiments and they did everything they possibly could to create communities of support, which shows you that the way that we live normally is somewhat problematic. +
++The real arc of the book is to go through every piece of that formula. So the nuclear family, the exclusive bi-parental care, the way we raise our children in these isolated single-family homes away from other children, our relationship to property and the physical built environment within which we dwell, within which we warehouse ourselves when we are raising our families — all of these different pieces of the way we organize our private lives are fairly recent inventions. And they are conventions that are eminently changeable. +
++When we look out across the historical record and when we look cross-culturally, we can see that there have been multiple ways of organizing our family lives, depending on different external factors. Human beings are uniquely creative, flexible, and adaptable. And our family forms and our mating practices are also uniquely creative, flexible, and adaptable. +
++So the critique here is that too many of us today are fixed in our idea of what a family is supposed to look like. How we form families, how we insert those families into dwellings, and the ways in which those families interact with other families. All of those things are preconditioned by a certain set of cultural norms that are very anachronistic for the world that we are going to be living in in the 21st century. +
++It’s about a change in our attitude towards the natural environment. We are coming from an era where people believed that the earth’s resources were abundant. And we are now having to come to grips with the idea that the earth’s resources are not abundant and that unlimited economic growth is not necessarily desirable. +
++One of the things that makes the sort of experiments you’re describing in the book feel like such distant possibilities is that they’re revolutionary in the most concrete, intimate way. Because we’re talking about transforming not just our social and political lives, but our private lives, our family lives. And this is something you say a lot of people fail to appreciate. Why do you think that is? Why are so many people so eager to critique our economic system, but much less interested in what might be amiss in our private lives? +
++I think that people do feel that their private lives are under much closer scrutiny. You can talk about economic systems, you can talk about politics, and it’s not necessarily about you and the people that you love and the people that you’re sharing your resources with. +
++There’s this way in which our private life is this place of incredible expectation around unconditional love, care, and support. And I really want to stop and recognize that. I’m not saying that family is bad. I’m actually saying that family is really good and that we should just expand our definition of what family is. +
++Especially for communities of color and for immigrant communities, the family is an incredibly safe space where you get support and you get unconditional love. But there’s this very primal fear that people have, that if you start to change anything about these relationships and the way that they get maintained and sustained over time, then the whole thing could fall apart and we will all end up being unloved and alone. We are so afraid, on a very visceral level, of being unloved and alone. And given that the family is this place where, in a very cruel, hostile environment, we often get company and support and emotional care, it’s really hard for us to shake that up in our personal lives. What I argue in the book is we’ll actually be more loved and in a greater level of community if we expand our notion of what family life is. +
++The other part of this argument is the much more radical part. I think that our family form as it is currently instantiated for most people, particularly in the United States, is that our form of the family upholds a particular kind of political and economic system. With high levels of inequality, where the nuclear family and this exclusive bi-parental care in our own privately owned homes with our stuff actually facilitates the intergenerational transfer of wealth and privilege largely from fathers to their legitimate sons. This model was a particular adaptation to plow agriculture where you didn’t want to divide agricultural estates and then you get the institution of primogeniture or ultimogeniture, where either the first son or the last son inherits everything so you don’t have to divide the estates. +
++There are really interesting evolutionary and anthropological reasons, as well as historical reasons, why we have the particular family form that we do. But the key thing is that the way we do family really underpins a particular political and economic way of being in the world. And so if you critique the family, if you try to challenge the family in any way, you’re already challenging the economic and political and social system. +
++I suppose one of the conservative reactions to this is to say that, on the one hand, you’re right, the way we live now is a historical aberration. This is not how humans have lived for most of our history. The world could have turned out very differently. And yet this is where we are. This is how our society evolved, and our institutions and even our psyches in lots of ways have adapted to it. And that’s not something you can easily overturn, or at least not too quickly. Does this sort of objection give you any pause at all? +
++The simple answer is no. But I’d also say that I respect the hesitation there. I understand where it’s coming from. I am sympathetic to this fear that if you upset the status quo the whole thing might fall apart. But I go back to the evolutionary anthropology of the family and the fact that it’s becoming increasingly clear that our mating practices are separable from our child rearing practices in the contemporary way that we imagine the family. +
++We think of the bi-parental model of exclusive care for biological children as the appropriate container for childbearing, right? So there’s a romantic couple (usually it’s a romantic couple), and that romantic couple pairs off and has kids and raises those kids exclusively without much support from outside of that bi-parental unit. +
++But that’s not really how human beings evolved to raise children. We are pair bonders. There’s very good evidence that we tend to form pairs, we tend to have strong attachments. That doesn’t necessarily mean they’re heterosexual, that doesn’t even necessarily mean that they’re monogamous, but we do tend to be pair bonders. +
++We even see in cenobitic monastic communities when you have groups of monks or nuns who are taking in children, often orphans, and they’re raising those children collectively. Even there you find that pair bonds form, though they’re not couples in a romantic sense. But that doesn’t necessarily mean that the pair or the pair bond is the appropriate container for child rearing. +
++Any argument that human beings are naturally one way or the other, or that we’ve evolved in a particular way because of a particular set of environmental or climatic or political circumstances, that’s not true. We are so flexible, and that’s true for both parts of this, for the child rearing part of it and for the mating practices part of it. +
++We are fixed in a particular model right now, but if certain external factors were to change — or if we wanted to change certain external factors — we could change our family lives, the way we’re organizing our love and care and support, because we live in a society right now with high levels of loneliness and isolation and with a real care deficit. +
++I think we need to think creatively the way we did during the pandemic about reorganizing our domestic lives to make them more capacious and more supportive and more loving in the absence of any sort of state efforts to do things like expand universal child care or provide support for the elderly and so on and so forth. +
++There’s a whole chapter in the book about raising kids in common. Plato famously makes the case for this in The Republic and he says it’s the only way to ensure that citizens remain truly committed to the good of the society. Maybe he’s right about that, I don’t know. But I’m a parent and I can definitely say that there’s no way in hell I would ever want to do this, and I don’t know any parents who would. I guess the question is, what are the benefits to that radical arrangement and what we can learn from that and how can we adapt it to the world we’re in now? +
++I think this is a great question. You have this utopian extreme put forward by Plato, where child care is common and parents don’t even know their children and children don’t know their parents. That’s the absolute extreme. But I walk it back to something that people can understand. +
++I’m talking about letting your kids spend more time with their grandparents. Let your kids spend more time with other loving adults in your community. They might be your neighbors, they might be your college friends. They might be your colleagues at work. In a lot of religious traditions, there are these things called godparents; the idea is that a couple has a parental backup plan in case you and your partner dies. But it’s really a case where religious traditions are trying to instantiate a relationship with other adults in their children’s lives, so that they’re surrounded by a loving community of adults. +
++I’m a mom. I understand what you’re saying, especially when your kids are young and vulnerable and you’re overprotective of them, and the world is this big, bad, scary place and you want to make sure that they get all the love and attention and resources that they need to thrive. And let’s face it, for a lot of us, other children are competitors, not only for resources, but for our attention. Anybody who grew up in a really big family will know this. But if you think about the evolutionary anthropology of the family, we’ve always been these cooperative breeders. Older siblings have always played a role in raising young children because unlike other non-human primates, we have our children very close together and they’re so dependent on us and we’ve always relied on broader networks. +
++I don’t say in the book that you should go join a commune and give up your parental rights or something like that. But I do point out that there are some states in the US which now allow for what’s called de facto parenting. So if you’re a divorced couple, and let’s say there’s a stepparent, a stepmother, or a stepfather who’s providing parental care, in many states that person cannot become a legal guardian unless the biological parent gives up their parental rights. So some states are saying, why shouldn’t children have three parents? Why not four parents in LGBTQ+ communities where you might have a surrogate mother and an egg donor and maybe two sperm donors? Or in the case of mitochondrial replacement therapy, which is where you have an egg from one woman, and then the mitochondria of that egg is from a second woman, and then you have a sperm donor. You literally have a child that is biologically related to three adults, three parents. +
++But our society doesn’t really know what to do with a non-bi-parental model of care. And so there are legal interventions we could make. There are social interventions that we could make. We could really take godparenting seriously and think hard about identifying other adults that can be a presence in our children’s lives as they grow up. I don’t think anybody would say that that’s a bad thing. +
++It is not psychologically healthy for us to be so isolated and to have all of our love and care from just two people, and I think this became really apparent to people during the pandemic. And now that we are coming out of that, I want people to think, “Hey, maybe those pandemic pods were a great idea! Maybe we should keep them around in some form as a supplement to our parenting efforts.” +
++One thing we definitely agree on is it’s worth remembering how easily things that seem permanent or fixed can change almost overnight. Often it’s because those changes are forced, like during the pandemic where suddenly the state just starts giving out a form of universal basic income, and parents are forming these pandemic pods where they’re sharing child care and homeschooling responsibilities. That doesn’t prove these are things we should do, but it does prove that we can do them — and there’s a lesson there. +
++Yeah, and it’s really worth emphasizing because I think there are two critiques of the book. One that I’ve heard and that I want to address head-on is that I’m saying that all the different examples that I give in the book are somehow models for us to emulate. And that’s not at all what I’m saying. What I’m saying is that they can each teach us different things about how people in the past have organized and reorganized their domestic lives in certain ways for certain reasons, and that we could learn from those things. +
++The second thing is that by talking about the ways that utopian communities have organized their private lives differently, that I’m advocating for some kind of state intervention. And in fact, the whole point of this book is to ask what we can do in the absence of state intervention. I’m not talking about socialism here. I’m saying that if we’re not talking about top-down transformations from the state, what are the sorts of things people can do in their own lives within their own communities? +
++To hear the rest of the conversation, click here, and be sure to follow The Gray Area on Apple Podcasts, Google Podcasts, Spotify, Stitcher, or wherever you listen to podcasts. +
+How stores sucked the fun out of an American pastime +
++Whether it was spritzing on perfumes in a department store or fantasizing about a more organized home in the seemingly endless aisles of Bed Bath & Beyond, shopping was once a far more pleasurable experience than it is today. It was both a social and languid activity, an opportunity to connect with a friend or explore our materialistic desires in contented solitude. Retail therapy, we called it. +
++Now going to the store, whether it’s a Macy’s in a suburban mall or the neighborhood CVS — basically, all but the most luxury of retailers — is a battle that leaves consumers feeling defeated. +
++Shoppers’ complaints abound. Vox spoke with customers across the country who bemoaned a dearth of employees in stores of all stripes. Equally aggravating: empty shelves, or only a register or two open at any given time. +
++Hayley Leibson avoids in-store shopping whenever possible. But the 29-year-old wasn’t able to avoid it after she had a baby and needed formula, she says. While the worst of the baby formula shortage has ebbed, sometimes Leibson still needs to visit a few stores in the Bay Area to find it. A couple of months ago, the Target she frequents started locking up formula, and there seemed to be fewer employees around to help her get it, with “much more emphasis on trying to funnel people to self-checkout,” she says. She sees lines of people waiting for the product they want to be unlocked. To shop in a store these days, she laments, “You have to budget a lot of time.” +
++A Target spokesperson declined to comment on whether it locked up baby formula, writing in an emailed statement, “On a limited basis, we employ theft-deterrent merchandising strategies, such as locking cases, for categories that are prone to theft.” +
++Understaffing, inventory problems, and heavy-handed theft prevention measures are hardly new to the retail industry, but the problems have become more commonplace in the last few years, when the dial of frustration and discomfort turned higher. Yet the through line of why shopping from beyond the comfort of your home feels so miserable now has less to do with the pandemic’s disruption and everything to do with retailers unable — or unwilling — to invest in stores, including the labor that makes a shopping trip go smoothly or not. +
++Despite what companies may want you to think, nearly every issue you encounter while shopping is a result of bad working conditions for retail employees. +
++The early department stores that popped up in the late 1800s and early 1900s were an elegant, even opulent innovation that centralized consumers’ shopping needs; their beautifully decorated windows drew in passersby, and the stores themselves were massive and filled with a vast range of goods, with knowledgeable, attentive staff ready to aid customers. These retail spaces not only had sales floors, but also gardens, tea rooms, and full-service restaurants. +
++“Shopping really was a delightful thing, a special thing that you got to do,” says market researcher Pamela Danziger, whose work focuses on the behaviors of affluent consumers in particular. Bloomingdale’s, the famed New York department store founded in 1861, “was one of the first on the forefront of experiential retail,” creating a beautiful, comforting in-store environment and fostering an aspirational desire to consume, says Danziger. +
++Retail jobs in department stores were coveted, too; they were much safer than factory jobs, came with benefits and vacation days, and conferred a degree of job security. They provided a novel path of economic opportunity for white women in particular, though such desirable employment opportunities were denied to Black Americans. +
++The department store set the trend for pleasurable shopping experiences, which trickled down to other retailers, from drug stores to big-box retail. As retail jobs grew much less stable and lucrative, however, the joy of shopping also began to wane. +
++Most consumers still shop in physical stores, at least for certain items. It’s one thing to buy clothes online — Amazon recently became the top clothing retailer in the US — but less common to buy groceries on the internet. While Covid-19 boosted consumers’ reliance on e-commerce, the gains haven’t lasted. According to the Census Bureau, e-commerce made up only 15 percent of total retail sales in the first quarter of 2023. Brick-and-mortar stores have been closing for years, long before the pandemic. Still, retail foot traffic is indeed down, and a kind of chicken-or-egg effect is taking place. +
++Fewer shoppers mean retailers have been stocking fewer items in-store, instead having inventory delivered to brick-and-mortar locations when a customer places an order for pick-up. That only reinforces the experience of the modern store as an under-stocked desert, making people even less likely to want to shop in person, and stores less inclined to spend their tightened budgets on staffing stores adequately or improving them. None of this bodes well for the future of retail: The investment bank UBS estimates that between 40,000 and 50,000 retail stores will close in the next five years. +
++“The upshot over time is that you lose market share,” says Neil Saunders, a managing director of retail at the analytics and consulting firm GlobalData. “The business that you run becomes smaller and smaller, customer satisfaction goes down, sales go down. And eventually you enter a vicious cycle.” +
++Early department store owners “were real merchants,” Danziger says. “What we’ve got today are executives sitting in their corner offices who haven’t met a shopper in years.” Physical stores will always exist, she adds. “But we’re continuing to see erosion in terms of the number of visits, erosion in terms of time spent there.” +
++That last bit is crucial: It’s not just the number of visits a consumer makes that retailers care about. How long someone spends in the store, called “dwell time,” matters, too. The longer someone is in a store, the more money they’re likely to spend. +
++Dwell time understandably hinges on how pleasant the store experience is. Are there knowledgeable staff members available if a customer needs help? Are the items they want in stock? How easy are in-store returns? If customers are itching to get out of there as fast as possible, that’s bad for sales. A 2019 survey by First Insight, a consumer analytics firm, found that the majority of respondents spent more money when shopping in physical stores than online. Since the pandemic, however, consumers have been making more frequent but shorter visits to grocery and superstore chains, according to a report last year from Placer.ai, a location analytics firm that has been tracking retail foot-traffic trends. Today, shopping in stores has narrowed into a task with a clear start and end: Find an item, buy it, exit. +
++Susan Reda, vice president of education at the National Retail Federation (NRF), an industry trade association, doesn’t believe that consumers are now less willing to shop in person. “I do think they’re going back into stores, and that when they get there, they expect a good experience.” Despite negative shifts in foot traffic, research shows that people seeking out brick-and-mortar shopping do so in part because of the experience of being in the store. +
++In an attempt to lure crowds back, some stores are leaning into experiential offerings, emphasizing the beauty or the engagement that a physical space can offer shoppers. Reda cited the opening of a redesigned Tiffany & Co. store on New York’s Fifth Avenue, the famed luxury shopping destination. It’s one thing for high-end brands like Tiffany to pour money into their stores — that’s what they’ve always done — while the deterioration of more mundane retail experiences is an entirely separate matter. Target, for example, is also absolutely concerned with improving the in-store experience, according to Saunders. “Target has invested billions into its stores to refurbish them, to make them more shoppable,” he says. A less brand-conscious chain like Walgreens? Not so much. +
++Like Leibson, New Yorker Angelica Wilson has noticed the many everyday household items locked behind plastic cases at her local drugstore, where it is supposed to be convenient to grab a few items and go. Given how understaffed the stores also seem, the entire experience is far more of a hassle — and simply more unpleasant — than it once was or ought to be. Wilson finds herself using the in-store pickup option more often, just to minimize the time she has to spend in the aisles. +
++Stores locking up merchandise is a last resort, Reda says, and in the NRF’s view, an exception rather than a trend. But Walmart, CVS, Walgreens, and Rite Aid, which together make up the vast majority of pharmacy sales in the US, all lock up some items. “I don’t think retailers move to do that until there’s absolutely no other solution,” she says. +
++In some cities, the issue of theft has reached a breaking point, with the NRF pointing to Los Angeles, New York, Houston, Miami, San Francisco, and Oakland as the worst areas for organized retail theft last year. Recently, the owner of the Westfield San Francisco Centre mall announced it was giving up control of the property after several of the mall’s retailers closed, citing crime as a primary reason. San Francisco’s Cotopaxi location briefly closed, and its CEO blamed organized theft rings that he said had become unmanageable and a threat to its employees. (The store reopened three weeks later.) It’s worth being skeptical of just how widespread the problem of so-called organized retail theft is; the average rate of “shrink” — the industry’s term for lost inventory — was 1.4 percent in 2021, lower than 2020’s 1.6 percent, according to the NRF’s own figures. So why are so many things locked up? +
++It’s proof that retailers are struggling to address issues without affecting the in-store experience. “I’m not sure that they’ve got the balance right,” Saunders says. “Locking things up has a negative impact on sales.” +
++Even a once-respected retailer with a long heritage can fall hard if its leadership doesn’t bother investing in stores — just look at Sears or, Saunders argues, Macy’s, which he refers to as “the most atrocious retailer in the country,” noting the outdated styles of the stores and their state of disarray, as well as other effects of cutting in-store staff and customer service employees. +
++“They do absolutely nothing to entice the customer to buy.” +
++The decline of the in-store retail experience — both in terms of its quality and the number of stores that exist — has transformed what it means to work in retail, and how pleasant customers find the in-store shopping experience is inextricable from how retail employees are faring. It’s directly affected by how well-paid they are, how well-trained they are, and how well-staffed their stores are. This link often goes unmentioned; the discontent of customers and the woes of employees are viewed on parallel tracks instead of as mirrors. +
++Working retail has long been physically and mentally arduous. The pandemic revealed how dangerous the work can also be: In the US, almost seven in 10 people who died in the first year of the pandemic were of low socioeconomic position — the majority of whom worked in blue collar, retail, or service jobs. Over 7.3 million retail workers quit last year; one consulting firm reported a 75 percent turnover rate last year for hourly in-store positions, while a 2023 US News ranking of 190 jobs put retail salespeople at the very bottom. +
++Understaffing is a chronic issue in the retail industry. Cutting hours for existing staff, too, is hardly a new strategy to keep costs down in retail — Covid has, once again, merely put more pressure on that lever as workers were pushed past their breaking point. +
++And then there’s the treatment of retail employees by shoppers themselves: The subreddit r/retailhell offers infinite accounts of customers who harangue, bully, and even assault workers. One person who worked at a big-box retailer but did not want to be named for fear of professional repercussions told Vox that retail had been a “nightmare job” for them — that customers “did nothing but torture” employees. +
++Though there’s a current worker shortage in the industry, the long-term forecast is that there will be fewer stores and fewer retail jobs. For example, the post-lockdown recovery in the nation’s retail playground, New York, has lagged far behind that of other industries: There are 11.1 percent fewer jobs in the sector than there were in February 2020, according to a report by the Center for an Urban Future. +
++The labor shortage has temporarily allowed workers to demand better pay and working conditions, and empowered them to unionize. It’s also meant ugly, protracted battles as companies deploy an arsenal of union-busting tactics, whether it’s cutting pay or closing store locations that have signaled an intention to organize. Some retailers are even doubling down on replacing human workers with cheaper machines such as digital kiosks and self-checkout counters. The lack of staff that shoppers are noticing in stores is in part by design, and it predates the pandemic. +
++To be sure, one way to tackle the high turnover and labor shortage of retail — and address customers’ growing complaints about the state of in-store shopping broadly — is paying workers more. Major retailers like Walmart and Target have advertised a higher starting range of pay, but real wages for retail — that is, wages after accounting for inflation — have only seen a 0.5 percent bump since 2019. More money also isn’t a magical salve for all the other dangers that come with a retail job today. How high a wage is acceptable to contract a deadly virus? Or to fend off angry customers, enforce local public health mandates or store policies on masking, or act as security guards on top of other in-store duties? Or even be punished when you do intervene to stop theft? +
++Steve Rowland is a former retail store manager of 27 years who now hosts a weekly podcast called The Retail Warzone; each episode features stories sent in by retail workers or other issues that concern the industry. +
++“I was a store manager for a very long time, that had to do these things that I didn’t really agree with, that caused unnecessary hardship on a lot of people in the industry,” Rowland says. “A lot of the retail workers are really just overlooked. So it’s my mission to shine a light on it and try to help some consumers actually understand what’s going on behind the scenes.” +
++One of the most memorable stories that Rowland covered is that of Kroger employee Evan Seyfried, who died by suicide in 2021. His family has filed a wrongful death lawsuit against Kroger, claiming that “torturous conditions” at work had led to his death. +
++“We have a society that will boycott over the smallest thing. Why don’t you boycott the fact that employers treat their employees as a controllable expense — having less staff in stores, less people to serve the customer, less people to make the customer experience what they expect it to be?” Rowland asks. +
++The dissonance between cutting costs — a perennial directive of a profit-seeking business — and providing the kind of store where people want to shop is only growing. And consumer dissatisfaction with this newly austere shopping experience means more stress for retail workers. +
++Big retail companies should lead the charge to enact and enforce policies protecting their staff from customer abuse and violence, argues Rowland. If a huge corporation like Walmart — one of the biggest employers in the US — had “ironclad” policies protecting its workers, “that company is going to be the one people want to work for.” +
++For the shopper, there’s also a conundrum. Who do you speak to when you have a problem with a store being understaffed or understocked? Asking to speak to the manager can feel like Karen behavior, while complaining to a company’s corporate offices can lead to a handful of store workers being punished for policies and strategies that they have no involvement in setting. Retail workers underscore the value of recognizing cause and effect, and how top-line business decisions trickle down to affect the everyday experience of picking up a few things from the mall. +
++“The average consumer has the argument that if you raise wages, those costs are going to be passed on to the consumer,” says Rowland. “The thing that they should be complaining about is when they raise wages, they cut staff in stores. That’s where the cost is getting passed down to the consumer — that person being there to help them.” +
+Exploring the wider range of meditation is no longer reserved for the monasteries. The new science of meditation is just getting started. +
++Meditation has taken two divergent paths through the Western mind. For many, it’s a few quick, calming breaths, perhaps timed with a smartphone app, in search of a stress tonic that can soften anxiety’s edges. Along a less-traveled route, meditation remains what it long was: a deeply transformative pursuit, a devoted metamorphosis of the mind toward increasingly enlightened states. +
++But this bifurcated view of meditation as a relaxing practice for the masses and a life-changing practice for the committed few is deeply misleading. A spectrum runs between them, harboring experiences that are far more interesting and powerful than what the growing mindfulness industry advertises, and more accessible to average people than what tropes of arcane states like enlightenment suggest. +
++Given that wealthy countries like the US aren’t exactly riding trend lines toward new peaks of mental health (depression rates in American adults are at an all-time high, while young people appear in the grips of a mental health crisis), scalable ways of not just mindfully soothing, but completely re-creating psychological experiences for the better should set off sirens of general, scientific, and funding intrigue. +
++For the past two decades, the growing science of meditation has roughly followed the same split that ignores this middle path. Most research studies basic mindfulness as a health intervention in novice meditators, where modestly positive results have led to comparisons like exercise for the mind, or mental flossing. On the other end, researchers will occasionally strap EEG electrodes to the scalp of Tibetan monks, offering a glimpse inside the unusual brain activity of an advanced meditator. +
++A new band of researchers, however, is finding that you don’t need 10,000 hours in a monastery before meditation can upend your entire psychology — and yet, the current body of meditation research has had surprisingly little to say about this middle ground between stress relief and enlightenment. +
++As the number of meditating Americans has more than tripled in recent years, an onslaught of apps, books, and seminars helped mold the public image of meditation around the simpler and more sellable idea of mindfulness as a form of stress reduction. That image is paying off: The broader mindfulness industry was valued at $97.6 million in 2021 and is projected to triple in value by 2031. Critics call it “McMindfulness,” a capitalist perversion of meditation that deals with stress by focusing inward on the breath, rather than outward on the social structures that cause so much of that stress. Regardless of how you package it, “mindfulness programs only scratch the surface of meditation,” Matthew Sacchet, a neuroscientist, professor of psychiatry, and director of Harvard’s Meditation Research Program, told me. +
++Sacchet is part of a recent turn in meditation research that is putting the fuller, stranger range of meditative experiences under the scrutiny of laboratory conditions. Rather than evaluating meditation in the same way that we do therapy or drug trials, new theories from cognitive science (like predictive processing) along with new tools — such as machine learning models that read more deeply into neural activity than humans can alone — are shifting the science of meditation in the direction of grasping after the nature of the mind and the ways we might transform it for the better. +
++“There was this initial focus on meditation as attention and emotional regulation practices,” said Ruben Laukkonen, an assistant professor at Southern Cross University. “But over time, there’s been a recognition that in contemplative traditions, that’s not really the goal. These are side effects. When you talk to people who really take this stuff seriously, you find that there’s these layers of experience that unfold that are much deeper.” +
++Research labs and private companies are already developing technologies they hope can democratize access to meditation’s deep-end experiences. From psychedelics to brain stimulation, the hunt is on for ways to cut the time it usually takes to begin experiencing more profound effects. “Ultimately, our mission is to understand advanced meditation to scale advanced meditation, and we believe that this will have profound impact on individual well-being and the collective health of society,” said Sacchet. +
++Scaling access to the benefits of advanced meditation could offer something a little stronger (or a lot stronger, depending on how the tech fares) to the more than 100 million users who turn to mindfulness apps like Calm or Headspace in search of a psychological balm. In a world hell-bent on hacks for everything from emails to nutrition, why not consciousness, too? If deeper states of meditation can go beyond calming the mind and transform its fundamental habits in ways that dissolve stress and raise well-being, then making the process faster and more user-friendly could pay major dividends. +
++But concerns abound. Even if profoundly altered states of consciousness are amenable to hacking (an unsettled debate), there’s hardly any evidence that today’s generation of tools is up to the task. Worse, if it is, what if accelerating the process of pulling up and shifting around the roots of consciousness just short-circuits millions of minds? And yet, without serious shortcuts, how many people will realistically devote a meaningful chunk of their daily lives to sitting quietly, doing nothing? +
++On one hand, the Western study of consciousness has been hamstrung since Galileo cleaved sensory experience from the scientific method, and I can think of few things more worthy of deep research. Just as studying the extremes of particle physics (say, smashing atoms of gold together to create temperatures in excess of 7.2 trillion degrees Fahrenheit) can reveal generalizable principles about all matter, the extremes of conscious experience are probably a good place to look for a better understanding of all minds. We have a lot more to learn about how to raise well-being, which, at its core, is a property of consciousness. +
++As far as defiling ancient practices with shiny new technologies or the perils of swapping gurus for algorithms, these are the fascinating, messy, indeed dangerous, and perhaps extraordinarily wonderful examples of how the dharma — the Buddha’s teachings — is adapting to a new environment. We should support this process as wisely as we can, not turn away. And how could we? The future of our minds may depend on it. +
++What we now call contemplative science is the interdisciplinary study of how practices like meditation, prayer, and psychedelic use affect the mind, brain, and body. Its American roots go back to at least the 1960s, when the inflow of Buddhist ideas enchanted a generation of, as the Beat poet Allen Ginsberg put it, “angelheaded hipsters burning for the ancient heavenly connection to the starry dynamo in the machinery of night.” But it wasn’t just poets and hipsters; the likes of scientists and lawyers also started meditating. +
++Back then, there were no mindfulness apps or corporate “Zen booths” offering meditation as a reprieve to stressed-out workers. The point of meditation, as taught by transplanted Asian teachers of the time like Japan’s D. T. Suzuki and Tibet’s Chogyam Trungpa Rinpoche, was a deep transformation of consciousness — the full force of awakening. Suzuki described Zen, which derives from the Sanskrit word for meditation, as “the art of seeing into the nature of one’s own being … it points the way from bondage to freedom.” +
++The idea of meditation as a means of awakening flared up and then began fading out along with the counterculture itself. The hippies’ rejection of the soulless, sexless mainstream failed to build an alternative that could last, leaving their gusto for higher levels of consciousness adrift, sailing out to the cultural fringes. In the light of modern science, the quest for higher vibrations has come to appear essentially unserious — a New Age trope. But one of those scientists-turned-meditators, Jon Kabat-Zinn, had a vision for how to bring it back into the mainstream. +
+ ++The son of a biomedical scientist and a painter, Kabat-Zinn earned a PhD in molecular biology in 1971. Having already established a daily meditation practice in 1966, he spent his early years at the University of Massachusetts Medical School stewing over what his “karmic assignment,” or life’s work, should be. Then, during a two-week meditation retreat in the woods west of Boston, he saw it in a 10-second vision, “an instantaneous seeing of vivid, almost inevitable connections and their implications,” as he put it. Simply: “Why not make meditation so commonsensical that anyone would be drawn to it?” +
++Shortly after, in 1979, he founded the Stress Reduction Clinic at the medical school, which eventually became the eight-week course known as Mindfulness-Based Stress Reduction (MBSR), and served as the format for the mindfulness boom to come. In this interpretation, mindfulness is a simple instruction: pay attention to the present moment, on purpose, without judgment. Secular and testable, MBSR offered a form of meditation fit for accountants and clinical trials, rather than hippies and communes. +
++Kabat-Zinn authored a few studies on MBSR in the 1980s, but it wasn’t until the early 2000s that mindfulness research really took off. At the 2005 Society for Neuroscience annual meeting, the Dalai Lama told a crowd of 14,000 conference participants (some of whom were upset by the presence of a religious leader at a scientific affair — one online petition to withdraw his invitation received nearly 800 signatures) that Buddhism and cognitive science share deep similarities. “I believe a close cooperation between these two investigative traditions can truly contribute toward expanding the human understanding of the complex world of inner subjective experience that we call the mind,” he said. +
++Shortly after, scientists picked up on the already existing construct of MBSR, publications on mindfulness began erupting, and the field of contemplative science sprang to life. +
++“For 20 years, there were a lot of single-arm trials [without controls like placebo groups or randomization] showing MBSR, in its various forms, can actually help improve health outcomes,” said David Vago, a founding neuroscientist at the International Society for Contemplative Research. +
++Now, as the research matures into controlled studies and meta-analyses, meditation is losing a bit of its luster. It’s beginning to look more like just another decently effective medical intervention. A 2021 systematic review of 44 meta-analyses found that mindfulness was mostly on par with cognitive behavioral therapy or antidepressants in terms of treatment effects (mindfulness was superior in a few categories, however, including treating depression and substance abuse). +
++That’s still good news, but it’s hard to see how something that works about as well as Prozac or a therapist offers the “seeds of a necessary global renaissance in the making,” as Kabat-Zinn has written, let alone the end of suffering, as the Buddha taught. +
++“So we’re left with this big question,” Vago said. “Is the goal of meditation to reduce our perceived stress or symptoms of anxiety? Are those the true goals of the practice? I would say not. But that’s how the medical model has been used to test the efficacy of meditation.” +
++Everyone I spoke to agreed that there’s more to meditation than just another somewhat effective health intervention. But discovering what more, exactly, will require a different set of questions and tools than what delivered the current generation of mindfulness research. And the past few years have seen a proliferation of precisely that. +
++Just as the mindfulness era began with the establishment of a university center, a contemplative science focused on psychological transformation is growing its own institutions. +
++Sacchet is expanding the Meditation Research Program into a larger operation — the Center for the Science of Meditation — that aims to conduct gold-standard research on the deep end of meditation experiences. “These types of experiences are often described as transformative,” Sacchet explained, “that is, as laying the foundations for new ways of being, which may include updated understandings of meaning in life, and increased capacities for joy, happiness, and general well-being.” +
++Laukkonen, who focuses on the cognitive neuroscience of meditation, said that ”we have new theoretical frameworks that can capture contemplative effects. That’s a huge shift because it’s really hard to appreciate states that don’t fit into your theoretical paradigm.” Adding to the new theories are new scientific tools and gizmos. “The analytical techniques are getting more sophisticated, which allows you to ask questions that you couldn’t ask before. All these things feed into each other.” +
++He described how ongoing research is using machine learning models to decode and measure meditative “depth” or the “expertise” of one’s practice, opening a new frontier of understanding. Rather than simply studying the outcomes of mindfulness practice, they’re peering into the real-time processes. +
++In a 2021 paper, Laukkonen and his colleague Heleen Slagter suggested that one way to think about the depth of meditation is the degree to which the mind is engaged in abstractions or conceptual thought. They describe meditation as a process of deconstructing engrained habits of mind “until all conceptual processing falls away, unveiling a state of pure awareness.” +
++On that basis, by training machine learning models on brain activity across a variety of tasks that involve conceptual thinking, Laukkonen hypothesizes that we could teach the algorithms to recognize the neural signatures of conceptual thought in general. Then, we could use those models to measure the degree of conceptual thought present in any brain state, such as during meditation. The rough idea is: the less conceptual thinking (or abstraction), the deeper the meditation. “That’s where the field is moving toward, trying to identify mechanisms or biomarkers for change and progress. We’re starting to map that out,” Vago said. +
+ ++Alongside new theories and technologies, ancient claims of unbelievable meditative states are being observed under the scrutiny of scientists in controlled settings for the first time. A few thousand years ago, the Mahāvedalla Sutta (a scripture of Theravada Buddhism) described one such state that advanced meditators could enter at will — nirodha samāpatti, or cessation attainment. Think of cessation, also scripturally described as the “non-occurrence of consciousness,” like voluntarily inducing the effects of general anesthesia. Consciousness switches off without a trace, while the basic homeostatic operations of the body — temperature, heartbeat, breathing — remain online. +
++The scripture says meditators can predetermine a length of time to “go under” merely by setting an intended duration, like an internally fashioned alarm clock. That duration is said to be able to stretch up to seven days, provided their body can last that long. After setting the intention, they settle into meditation, and the light of consciousness switches off. When it returns, meditators were said to emerge crisp and refreshed, with elevated senses of clarity and vitality (decidedly unlike the woozy return from anesthesia). +
++Laukkonen, Sacchet, and their colleagues met someone who claimed they could enter cessation on command and was willing to do so in a lab. While they’re still processing the data, a preliminary publication of their findings suggests nirodha samāpatti — at least for 90-minute stretches — may not be as outlandish as it sounds. +
++In a recent but separate pilot study conducted by Sacchet, he found that right before an advanced meditator has micro-cessations — referred to in the ancient texts as “nirodha” without the samāpatti — the alpha band of brain activity (the major rhythm of brain activity in typical, waking adults) begins winding down. It’s at its lowest immediately following the nirodha, which only lasts maybe a second or two. Then alpha activity begins climbing again, returning to normal levels in less than a minute. +
++The preliminary data on the full nirodha samāpatti found the same pattern. Leading up to cessation, alpha activity began dropping. It bottomed out during cessation and rose again afterward. While these patterns aren’t enough to confirm the full account of cessation, they do look like a plausible neural correlate for temporarily extinguishing consciousness. +
++Being able to train one’s mind to manually switch off consciousness for some predetermined period does not weave seamlessly into conventional understandings of human psychology. Maybe, like bears, there is some evolutionary value in short periods of mental hibernation. Or maybe, buried in the deeper folds of consciousness, there are capabilities unrelated to survival that can help improve well-being anyway. +
++If the ordinary egoic sense of consciousness evolved for environments where a constant hum of fight or flight mentality helped keep us alive, advanced meditation may offer a way of reprogramming some of these inherited tendencies that no longer serve us in our comparatively new evolutionary environments, like discarding clothes that no longer fit. The same goes for psychedelics. +
++“My hope is that ultimately, this work will contribute to bringing advanced meditation out of the monastery,” Sacchet said, describing its “incredible promise for moving beyond addressing mental health issues, toward helping people thrive.” +
++To do that, meditation probably needs to reach more than a sliver of humanity, which could be a problem: Many people do not like to meditate. One infamous study found that many participants would rather administer electric shocks to themselves than sit quietly doing nothing for 15 minutes. And 15 minutes is on the low end of meditation periods, even for basic mindfulness. Although unusual states can arise at any point in one’s practice, it’s common for those endeavoring toward the deep end to spend an hour a day or more in meditation. Some devote entire lifetimes. Multiple, even, if you’re into reincarnation. Who’s got time for that? +
++But if American culture is obsessed with anything, it’s optimization. Can we get the same or more outputs from fewer inputs? Can we automate any part of the process? Research labs and venture capitalists alike are already exploring whether the more transformative fruits of contemplative practice may be had quicker, easier, and more efficiently than through decades of patient meditation. +
++One label for this optimization effort is “spirit tech,” a mixed bag consisting mainly of brain stimulation, neurofeedback, and psychedelics. This isn’t new, precisely — mantras, monasteries, and robes are forms of spirit tech that have been used for generations. But today’s emerging options seem closer than ever to making a meaningful dent in the barriers that have kept the masses from experiencing advanced meditative states for themselves. +
+ ++One of the spirit tech frontiers is transcranial ultrasound stimulation, a method Jay Sanguinetti, an assistant professor, and Shinzen Young, a celebrated meditation teacher, are working on as co-directors of the SEMA Lab (Science Enhanced Mindful Awareness) at the University of Arizona. In prior research, they showed that targeted bursts of ultrasound can alter brain connectivity. Now, they’re exploring whether sonicating — the fun word for targeting ultrasound waves — a brain into configurations known to correlate with deeper states of meditation can accelerate the process. +
++Standing at the precipice of democratizing access to sudden bursts of deep meditation experiences is exciting. The less glamorous risks that might come with a shortcut to the depths of contemplative practice, not as much. While very rare, these can range from anxiety spikes to psychotic breaks. Young told a meditation student about “falling into the Pit of the Void,” one of the ways Buddhist tradition describes how intense experiences can go wrong. Until the professor of psychiatry Willoughby Britton’s research on adverse meditation experiences, or “dark nights of the soul” (later rebranded as the varieties of contemplative experience study), there was little clinical support for those suffering from negative meditation experiences. +
++Even now, Daniel Ingram, a former emergency room physician and author of Mastering the Core Teachings of the Buddha, cautioned, “there’s basically a long, slow trainwreck happening between people getting into these experiences and the clinical mainstream just not understanding them.” +
++Notably, in a promotional video for their research, Young narrates: “If you’ll pardon my French, we are scared shitless of this technology.” And yet, as in the world of AI, they’re building it anyway. The hope is that they’re able to do so in a more prudent manner than others — profit-seeking companies, especially — who are eager to rush their brain-zapping technology to market before carefully assessing the risks. +
++Vago told me that support systems help to navigate these experiences. Once you zap — or sonicate — someone into a brain state associated with deep-end meditation, enlightenment doesn’t simply lock into place. He said that “psychedelics and brain stimulation technology will get us there fast, but you have to know what to do with it. If you don’t have the proper setup, and you didn’t do any meditation to stabilize the mind, you could have adverse effects that leave you feeling dissociated and lonely. It takes scaffolding.” +
++There are also questions of efficacy. Even if you can quickly techno-boost someone into a sudden burst of enlightenment-like states, are they really experiencing the same thing as someone who patiently meditated for years to get there? Should meditators seek to enter some predefined brain state by any means possible, or does the path you take make a difference? +
++“If you get people into these states, then you give them the impression that that is the goal state. Then they come into their meditation practice with a complete misunderstanding of what the purpose is according to any of the classical instructions, and they spend their meditation trying to get into a state, which prevents all of the interesting and useful transformations from happening. So it’s a paradox,” as Laukkonen put it. +
++In his view (held by many others I spoke with), contemplative traditions do not describe meditation as a practice for getting into funky states of mind; these are side effects. Instead, meditation is about deep transformations in the ordinary ways that consciousness operates, developing altered traits rather than merely altered states, as others in the field have put it. Still, maybe certain altered states are more conducive to finding and stabilizing altered traits than others. +
++Contemplative traditions have embraced paradox as a central element of their teachings. Optimizing around a paradox, however, is tricky business. You might wind up reinforcing the very construct of the self that meditation aims to deconstruct. Laukkonen still approved of research into spirit tech from a basic scientific perspective. But, he added: “It’s really about freedom and liberation. And what is liberating about chasing different states of consciousness, and not enjoying the one that you have?” +
++Whether the widening field of contemplative science will drum up an American desire for freedom and liberation, who knows? “What people want,” said Ingram, “is a long, happy, good life most of the time. The problem is that we don’t actually know what leads to that.” We’ve done large, multigenerational studies on heart disease, and deep, epidemiological inquiries into diet and nutrition. But major spiritual experiences that leave people forever transformed, that pull up suffering from its roots in deep psychological habits? We don’t have much peer-reviewed research on those. +
++As contemplative scientists are now diving in, Ingram hopes that public health officials will follow. Alongside deeper scientific knowledge that could help scale interest in advanced meditation, supporting those already having these experiences requires better clinical support. Ingram, Sacchet, and Vago are all members of the Emergent Phenomenology Research Consortium (EPRC), a network of scholars and practitioners aiming to foster deeper dialogue between clinical care, public health, and the deep end of human experience. Their vision is deeply bureaucratic, that unholy road into the heart of modern institutions. They want new diagnostic codes, updated medical textbooks, more informed public health guidelines, and insurance reimbursement procedures. +
++More broadly, Ingram emphasized that spreading the knowledge contemplative scientists may glean from studying advanced meditation will require better packaging. We have ideas like biological taxonomies and genetics that provide a shared basis for cross-cultural understanding and exploration of universally relevant fields. “We need that for the deep end of spiritual experience,” he said. “What works as well in Riyadh, as Rome, as Rio, as rural Alabama? What’s the functional, scalable essence?” +
++It’s possible that what matters most in the murky terrain of advanced meditation will forever elude scientific measurement, mass uptake, and bureaucratic integration, at least to some degree. But the growing field of contemplative science is poking around to see where the boundaries may lie. As the best spiritual teachers all emphasize, rather than taking anyone’s word for it, we should find out for ourselves. +
+ +FIDE World Cup | Chess great Kasparov congratulates Praggnanandhaa; lauds mother for ‘special kind of support’ - Praggnanandhaa created history by advancing to the final of the FIDE World Cup; the final matches will begin on August 22
Spanish football boss apologises for kissing World Cup star - Rubiales grabbed his crotch in a victory gesture — seemingly oblivious to 16-year-old Princess Infanta Sofía standing nearby
Morning Digest | All eyes on Modi’s possible meet with Xi in South Africa; Praggnanandhaa heads to World Cup Chess finals, and more - Here is a select list of stories to start the day
Fifa Women’s World Cup 2023: A tale of Spanish resurgence and overwhelming emotion - Spain’s success dwindled after the men won the 2010 World Cup, until now, with signs of glory showing again. The 2023 edition had the incredible highs and heartbreaking lows — with fans showing up in unprecedented numbers to back the women, and institutional sexism rearing its ugly head once again
The playfields of Madras and Chennai: opportunities galore for sports and games for all - In the early 1900s, it was Buchi Babu Naidu, an aristocratic Madras resident who decided to kit Indians up for the game
BJP likely to wait for the Congress list before finalising candidates - An agency has been engaged to conduct surveys about the party’s standing, probable candidates, with reports being sent to Central leadership only, sources said
Prime Minister Modi arrives in South Africa to attend 15th BRICS summit - Mr. Modi is visiting the African country from August 22 to 24 at the invitation of South African President Cyril Ramaphosa. South Africa is hosting the first in-person summit of BRICS
Sloth bear trapped in the Nilgiris, relocated -
Madras in motion - The Hindu traces the evolution of Chennai city through various transportation systems
Supreme Court questions petitioners’ submission that Indian Constitution has no application to Jammu and Kashmir after 1957 - Senior advocate Dinesh Dwivedi, for a petitioner, said the Indian Constitution ceased to apply to J&K, and the State Constitution became the governing document
Greece wildfires: Eighteen bodies found in Greek forest - Initial reports suggest those who died in a forested area of Dadia may have been migrants.
Two Ukrainian drones downed over Moscow region, says Russia - Authorities say two other drones were intercepted over Bryansk, near the Ukrainian border.
Wagner chief Prigozhin seen in first video address since coup attempt - The mercenary boss appears in his first video address since the mutiny - allegedly in Africa.
Lost luggage showing signs of recovery after hitting 10-year high - New airline data indicates the number of lost, delayed or damaged bags is returning to pre-pandemic levels.
Could decriminalisation solve Scotland’s drug problem? - Can lessons be learned from Portugal, which relaxed its drugs laws more than 20 years ago?
After Russia’s failure, India is next in line to attempt a Moon landing - No country besides China has successfully landed on the Moon since 1976. - link
Political polarization toned down through anonymous online chats - Republicans seem to depolarize more than Democrats. - link
Scientists find evidence that Vlad the Impaler shed bloody tears - Letter from 1475 contains proteins suggesting he suffered from hemolacria, respiratory problems. - link
Chris Kemp unplugged—Astra’s CEO dishes on the space company’s struggles - “I’m a public company, I can’t make this shit up.” - link
BA.2.86 shows just how risky slacking off on COVID monitoring is - The variant has grabbed attention, but with such limited data, the risk is unclear. - link
A sign on a restaurant window says “If you order it and we don’t have it, you instantly win one million dollars” -
++A man walking by notices the sign and walks in the restaurant and sits down at the table with a smirk on his face. The waiter asks what he will be having and the man says “I will have white rhinoceros stew please.” The waiter comes out with a boiling hot bowl of exactly what the man ordered. The man is taken by surprise, but he eats the stew and pays for his very expensive meal. He leaves angrily. +
++The next day he comes back and sits at the table with a smirk on his face again. He tells the waiter “today I will have bullet ants stuffed with dolphin meat.” The waiter leaves and quickly comes back after a few minutes with exactly what the man ordered. The man surprised again eats his meal angrily, pays and leaves. +
++The next day he comes back and sits at the table and tells the waiter “today I will have a lactating mermaid breast sandwich” a few minutes go by and the waiter comes out holding two massive duffle bags with the one million dollars. The man overcome with excitement says “I knew it! You dont have mermaid breast!” +
++The waiter tells him politely “we actually have it sir, it’s just that we ran out of bread” +
+ submitted by /u/AsscreamSundae69
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A blonde heard that milk baths would make her more beautiful, so she left a note for her milkman to leave 15 gallons of milk. When the milkman read the note, he felt there must be a mistake. He thought she probably meant 1.5 gallons, so he knocked on the door to clarify the point. -
++The blonde came to the door and the milkman said, “I found your Note to leave 15 gallons of milk. Did you mean 1.5 gallons?” The blonde said, “I want 15 gallons of milk. I’m going to fill my bathtub up with milk and take a milk bath”. The milkman asked, “Do you want it pasteurized?” The blonde said, “No, just up to my boobs.” +
+ submitted by /u/YZXFILE
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A man who lost his hat decided the easiest way to replace it was to steal it. -
++So he goes to the local church in search of a hat. A sermon about the ten commandments was going on as he made his way to the cloakroom. He stopped, thought for a moment, and changed his mind. +
++Upon seeing the pastor, the man walks up to him and says, “Father, I must say, your sermon saved me from doing something wrong. I came here with sin in my heart, but your sermon showed me the error of my ways.” Upon hearing this, the pastor congratulates him and asks him what specifically made him change his mind, to which the man replies, “You see, I lost my hat and came here to steal one from the cloakroom. But when you got to the ‘Thou shalt not commit adultery’ part, I suddenly remembered where I left my hat.” +
+ submitted by /u/CrystalSplicer
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Gen Z names are so stupid. For instance, a young man introduced himself to me as Jathan….. Not Jason. Not Nathan… Jathan. -
++Anyway, I’m not good with remembering names so I try to incorporate them into the conversation to help me to remember. So I said to him +
++“It’s very nice to meet you Jathan.” +
++“That is a very unique name, Jathan.” +
++“Are you from around here Jathan?” +
++To which he replied +
++“Wow, are you therious right now?” +
+ submitted by /u/PluckPubes
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Let’s hear your best lawyer joke. I’ll go first. -
++Why do lawyers wear neckties? +
++To hold the foreskin back. +
+ submitted by /u/idahowoodworker
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