Geographically-targeted COVID-19 vaccination is more equitable than age-based thresholds alone -
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+COVID-19 mortality increases dramatically with age and is also substantially higher among Black, Indigenous, and People of Color (BIPOC) populations in the United States. These two facts introduce tradeoffs because BIPOC populations are younger than white populations. In analyses of California and Minnesota–demographically divergent states–we show that COVID vaccination schedules based solely on age benefit the older white populations at the expense of younger BIPOC populations with higher risk of death from COVID-19. We find that strategies that prioritize high-risk geographic areas for vaccination at all ages better target mortality risk than age-based strategies alone, although they do not always perform as well as direct prioritization of high-risk racial/ethnic groups.
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Characteristics of Long Covid: findings from a social media survey -
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+Many people are not recovering for months after being infected with SARS-CoV-2. Long Covid has emerged as a major public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life in people who were not admitted to hospital during the first two weeks of the illness. We co-produced a survey with people living with Long Covid. We collected the data through an online survey using convenience non-probability sampling, with the survey posted both specifically on Long Covid support groups and generally on social media. The criteria for inclusion were adults with lab-confirmed (PCR or antibody) or suspected COVID-19 managed in the community (non-hospitalised) in the first two weeks of illness. We used agglomerative hierarchical clustering to identify specific symptom clusters, and their demographic and functional correlates. We analysed data from 2550 participants with a median duration of illness of 7.7 months (interquartile range (IQR) 7.4-8.0). The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cough, fever, and chills were common initial symptoms that became less prevalent later in the illness, whereas cognitive dysfunction and palpitations became more prevalent later in the illness. 26.5% reported lab-confirmation of infection. The biggest difference in ongoing symptoms between those who reported testing positive and those who did not was loss of smell/taste. Ongoing symptoms affected at least 3 organ systems in 83.5% of participants. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 66.4% reported taking time off sick (median of 60 days, IQR 20, 129). 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n=2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n=305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n=2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n=283, 11.2%) exhibited more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup. This is an exploratory survey of Long Covid characteristics. Whilst it is important to acknowledge that it is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions (to include those not lab-confirmed in the first pandemic wave).
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SARS-CoV-2 spike protein gene variants with N501T and G142D mutation dominated infections in minks in the US -
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+Large number of minks were infected with SARS-CoV-2 virus containing the spike protein Y453F mutation in Europe, causing zoonosis concerns. To evaluate the genetic characteristics of the US and Canadian mink-derived SARS-CoV-2 sequences, we analyzed all animal-derived (977), all Canadian (19,529) and US (173,277) SARS-CoV-2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the US mink-derived SARS-CoV-2 sequences. These variants were not found in mink-derived SARS-CoV-2 spike protein gene sequences from other countries. The Y453F mutation was not identified in the US and Canadian mink-derive sequences. The N501T mutation occurred two months earlier in the human than in the minks in the US, and the novel N501T-G142D variant and N501T-G142D-F486L variant were found in human prior to minks. The result of this study indicates that the novel variants may have evolved during human infection and then transmitted to mink populations in the US.
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Comparison of SARS-CoV-2 VOC 202012/01 (UK variant) and D614G variant transmission by different routes in Syrian hamsters -
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+Many SARS-CoV-2 variants of concern has been reported recently which were linked to increased transmission. In our earlier study on virus shedding using VOC 202012/01(UK variant) and D614G variant in hamster model, we observed significantly higher viral RNA shedding through nasal wash in case of UK variant. Hence we compared the transmission of both the UK and D614G variant by various routes in Syrian hamsters to understand whether the high viral RNA shedding could enhance the transmission efficiency of the variant. The current study demonstrated comparable transmission efficiency of both UK and D614G variants of SARS-CoV-2 in Syrian hamsters.
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Occurrence of COVID-19 symptoms during SARS-CoV-2 infection defines waning of humoral immunity -
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+Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.
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Immunoinformatic approach to design a vaccine against SARS-COV-2 membrane glycoprotein -
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+SARS-COV-2 is a pandemic virus causing COVID-19 disease which affects lungs and upper respiratory tract leading to progressive increase in the death rate worldwide. Currently, there are more than 123 million cases and over 2.71 million confirmed death caused by this virus. In this study, by utilizing an immunoinformatic approach, multiepitope-based vaccine is designed from the membrane protein which plays a vital role in the virion assembly of the novel-CoV. A total of 19 MHC class- I binders with HLA-A and HLA-B alleles have been selected with NetMHC pan EL 4.0 method from IEDB MHC-I prediction server. Four epitopes candidates from M-protein were selected based on the antigenicity, stability, immunogenicity, Ramachandran plot and scores with 100 % was taken for docking analysis with alleles HLA-A (PDB ID: 1B0R) and HLA-B (PDB ID: 3C9N) using ClusPro server. Among the four epitopes, the epitope FVLAAVYRI has the least binding energy and forms electrostatic, hydrogen and hydrophobic interactions with HLA-A (-932.8 Kcal/mol) and HLA-B (-860.7 Kcal/mol) which induce the T-cell response. Each HLA-A and HLA-B complex in the system environment achieves stable backbone configuration between 45-100 ns of MD simulation. This study reports a potent antigenic and immunogenic profile of FVLAAVYRI epitope from M-protein and further in vitro and in vivo validation is needed for its adaptive use as vaccine against COVID-19.
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D155Y Substitution of SARS-CoV-2 ORF3a Weakens Binding with Caveolin-1: An in silico Study -
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+The clinical manifestation of the recent pandemic COVID-19, caused by novel SARS-CoV-2, varies from mild to severe respiratory illness. Although environmental, demographic and co-morbidity factors have an impact on the severity of the disease, the contribution of mutations in each of the viral genes towards the degree of severity needs to be elucidated for designing better therapeutic approach against COVID-19. Here, we studied the effect of two substitutions D155Y and S171L, of ORF3a protein, found in COVID-19 patients. Using computational simulations we discovered that the substitutions at 155th and 171st positions changed the amino acids involved in salt bridge formation, hydrogen-bond occupancy, interactome clusters, and the stability of the protein. Protein-protein docking using HADDOCK analysis revealed that out of the two observed substitutions, only the substitution of D155Y, weakened the binding affinity of ORF3a with caveolin-1. The increased fluctuation in the simulated ORF3a-caveolin-1 complex suggested a change in the virulence property of SARS-CoV-2.
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Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets -
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+A subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike IgG enhanced platelet-mediated thrombosis on von Willebrand Factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on Fc{gamma}RIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases syk and btk respectively or by the P2Y12 antagonist cangrelor.
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Sea Defense Strategy Strengthening Through Improving The Readiness of Indonesian Naval Vessel Crew (Study: The Health Office of 1st Fleet Command) E -
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+One of the sea defense strategies in the scope of deterrence is by presenting the Indonesian Navy force in the sea. This demands the readiness of the Indonesian Naval Vessel includes the platform material readiness and its personnel. The Indonesian Naval Vessel unit is generally different from the land unit makes it difficult the crew and need the health manipulation to avoid health problems or diseases that can interfere with their performance. Research errors regarding the implementation of the Indonesian Naval Vessel crew/soldier medical checks at the 1st Fleet Command Health office for readiness in order to support the defense task, the factors that influence and what is the effort supposed to do. The aim of the study was to analyze the implementation of the Indonesian Naval Vessel crew checks at the 1st Fleet Command Health Office what factors influenced and the best strategies implemented to obtain optimal results of the implementation of the Indonesian Naval Vessel crew soldier medical checks. This study uses a qualitative method. The analysis uses the theory of policy implementation from George Edward III. Data were obtained from informants related to the implementation of medical checks for Indonesian Naval Vessel crew in 1st Fleet Command which were then analyzed using qualitative. The results showed that the implementation of medical checks for Indonesian Naval Vessel crew was not optimal. Efforts are being made to coordinate at the planning stage, it is necessary to make a policy that requires Indonesian Naval Vessel crew to carry out medical checks without exception and provide Covid-19 vaccinations. So that soldiers can serve optimally.
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Evaluating the impacts of tiered restrictions introduced in England, during October and December 2020 on COVID-19 cases: A synthetic control study. -
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+Background In 2020, a second wave of COVID-19 cases unevenly affected places in England leading to the introduction of a tiered system of controls with different geographical areas subject to different levels of restrictions. Whilst previous research has examined the impact of national lockdowns on transmission, there has been limited research examining the marginal effect of differences in localised restrictions or how these effects vary between socioeconomic contexts. We therefore examined how Tier 3 restrictions in England implemented between October-December 2020, which included additional restrictions on the hospitality sector and people meeting outdoors affected COVID-19 case rates, compared to Tier 2 restrictions, and how these effects varied by level of deprivation. Methods We used data on weekly reported COVID-19 cases for 7201 neighbourhoods in England and adjusted these for changing case-detection rates to provide an estimate of weekly SARS-CoV-2 infections in each neighbourhood. We identified those areas that entered Tier 3 restrictions at two time points in October and December, and constructed a synthetic control group of similar places that had entered Tier 2 restrictions, using calibration weights to match them on a wide range of covariates that may influence transmission. We then compared the change in weekly infections between those entering Tier 3 to the synthetic control group to estimate the proportional reduction of cases resulting from Tier 3 restrictions compared to Tier 2 restrictions, over a 4-week period. We further used interaction analysis to estimate whether this effect differed based on the level of socioeconomic deprivation in each neighbourhood and whether effects were modified by the prevalence of a new more infectious variant of SARS-CoV-2 (B.1.1.7) in each area. Results The introduction of Tier 3 restrictions in October and December was associated with a 14% (95% CI 10% to 19%) and 20% (95% CI 13% to 29%) reduction in infections respectively, compared to the rates expected if only Tier 2 restrictions had been in place in those areas. We found that effects were similar across levels of deprivation and limited evidence that Tier 3 restrictions had a greater effect in areas where the new more infectious variant was more prevalent. Interpretation Additional restrictions on hospitality and meeting outdoors introduced in Tier 3 areas in England had a moderate effect on transmission and these restrictions did not appear to increase inequalities, having a similar impact across areas with differing levels of socioeconomic deprivation. Where transmission risks vary between geographical areas a tiered approach of local restrictions on outdoor mixing and hospitality can contribute to control of SARS-CoV-2 and is unlikely to increases inequalities in transmission.
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COVID-19 symptom frequency comparison: non-hospitalised positively and negatively tested persons with flu-like symptoms in Austria -
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+Background. The majority of clinical studies reporting on COVID-19 symptom frequencies focus on patients already hospitalized. Thus, reported symptom frequencies may not be applicable to the general population. Here we report COVID-19 symptom frequencies for the general population in a major European city. Methods. During a scientific collaboration between the Vienna Social Fund (FSW, Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the AI-biotech company Symptoma we recorded symptom frequencies gathered by the COVID-19 chatbot of the city government of Vienna and corresponding SARS-CoV-2 nucleic acid amplification test (NAAT) results. Chatbot users answered 13 yes/no questions about symptoms and provided information about age and sex. Subsequently a medically trained professional came to their address to take a sample and NAAT results were obtained. Findings. Between November 2 and January 5, a total of 3011 persons experiencing flu-like symptoms had completed the chatbot-session and were subsequently tested by a NAAT. NAATs were performed by at home visitations of medical professionals. NAAT analysis was positive in 816 persons (27.1%). We compared the symptom frequencies between COVID-19 positive and negative users, and between male and female users. The symptoms (sorted by frequency) of users with positive NAATs were malaise (81.1%), fatigue (72.9%), headache (64.1%), cough (57.7%), fever (50.7%), sore throat (40.7%), rhinorrhea (31.0%), sneezing (28.4%), dysgeusia (27.1%), hyposmia (26.5%), dyspnea (11.4%) and diarrhea (10.9%) while 34.9% reported a close contact with a COVID-19 case. Among these the frequencies of cough, fever, hyposmia, dysgeusia, malaise, headache, close contact with COVID-19 case and fatigue were significantly (P < 0.01) increased in COVID-19 positive persons while the frequencies of dyspnea, diarrhea and sore throat were significantly (P < 0.01) decreased in COVID-19 positive persons. There was no significant difference for rhinorrhea and sneezing.
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Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility -
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+We explore the energetic frustration patterns associated with the binding between the SARS-CoV-2 spike protein and the ACE2 receptor protein in a broad selection of animals. Using energy landscape theory and the concept of energy frustration–theoretical tools originally developed to study protein folding–we are able to identify interactions among residues of the spike protein and ACE2 that result in COVID-19 resistance. This allows us to identify whether or not a particular animal is susceptible to COVID-19 from the protein sequence of ACE2 alone. Our analysis predicts a number of experimental observations regarding COVID-19 susceptibility, demonstrating that this feature can be explained, at least partially, on the basis of theoretical means.
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Factors associated with COVID-19 vaccine receipt at two integrated healthcare systems in New York City: A Cross sectional study of healthcare workers -
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+Objectives To examine factors associated with COVID-19 vaccine receipt among healthcare workers, including healthcare worker job type, race, and gender, as well as the role of vaccine confidence in decisions to vaccinate, and to better understand specific concerns related to COVID-19 vaccination among healthcare workers. Design Cross-sectional anonymous survey among front-line, support service, and administrative healthcare workers. Setting Two large integrated healthcare systems (one private and one public) in New York City during the initial rollout of the COVID-19 vaccine among healthcare workers. Participants 1,933 healthcare workers, including nurses, physicians, allied health professionals, environmental services staff, researchers, and administrative staff. Main Outcome Measures The primary outcome was COVID-19 vaccine receipt during the initial rollout of the vaccine among healthcare workers. Results Among 1,933 healthcare workers who had been offered the vaccine, 81% had received the vaccine at the time of the survey. Receipt was lower among Black (58%) compared with White (91%) healthcare workers; and lower among Hispanic (69%) compared with non-Hispanic (84%) healthcare workers. Among healthcare workers with concerns about COVID-19 vaccine safety, 65% received the vaccine. Among healthcare workers who agreed with the statement that the vaccine is important to protect family members, 86% were vaccinated. Of those who disagreed, 25% received the vaccine. Across all participants, 27% expressed concern about being experimented on with the COVID-19 vaccine. In a multivariable analysis, concern about being experimented on with the COVID-19 vaccine, concerns about COVID-19 vaccine safety, lack of influenza vaccine receipt, disagreeing that COVID-19 vaccination is important to protect family members, and Black race were independently associated with COVID-19 vaccine non-receipt. Over 70% of all healthcare workers responded that they had been approached for vaccine advice multiple times by family, community members, and patients. Conclusions Our data demonstrated high overall receipt among healthcare workers. Even among healthcare workers with concerns about COVID-19 vaccine safety, side effects, or being experimented on, over 50% received the vaccine. Attitudes around the importance of COVID-19 vaccination to protect others played a large role in healthcare workers9 decisions to vaccinate. We observed striking inequities in COVID-19 vaccine receipt, particularly affecting Black and Hispanic workers. Further research is urgently needed in developing strategies with healthcare workers to address issues related to vaccine equity and uptake in the context of systemic racism and barriers to care. This is particularly important given the influence healthcare workers have in vaccine decision-making conversations in their communities.
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Is the vitamin D status of patients with COVID-19 associated with reduced mortality? -
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+A systematic review with meta–analysis was performed to assess a possible association between plasma vitamin D levels and mortality in patients with COVID–19. PubMed, EMBASE, and Cochrane Library databases were searched. Studies involving COVID-19 patients that reported an association between plasma vitamin D levels and COVID–19 mortality published until February 5, 2020, were included. The risk ratio (RR) and confidence interval (CI) were pooled using a fixed–effects or random-effects model. A total of 11 studies that measured plasma vitamin D levels at admission were included in the meta–analysis, ten cohorts and one case-controls. Low plasma vitamin D levels (25(OH)D) in patients with COVID-19 were not associated with mortality (RR=1.35, 95%CI 0.84–1.86). Subgroup analysis by vitamin D cut–off (<20 or 25 ng/ml and <10 or 12 ng/ml) showed were not associated with mortality. When the RR in mortality analysis was calculated included four studies that did not perform adjusted analysis for confounding factors, the result was 1.43 (95% CI 1.18–1.69), suggesting that confounders may have led many observational studies to incorrectly estimate the association between vitamin D status and mortality in COVID–19 patients. Deficient vitamin D levels were not associated with a higher mortality rate in patients with COVID–19. Randomized clinical trials are needed to assess this association.
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Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil -
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+The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. Novel SARS-CoV-2 lineages P.1 and P.2, first identified respectively in Manaus and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed a whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraiba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) aiming to identify SARS-CoV-2 mutations that could be involved in the surge of COVID19 cases in Brazil. Here, we showed a widespread dispersion of P.1 and P.2 across Brazilian regions. Except for Manaus, P.2 was the predominant lineage identified country-wise. P.2 lineage was estimated to have originated in February, 2020 and has diverged into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December. P.1 origin was inferred to have happened in August 2020. We also confirmed the presence of the variant under investigation (VUI) NP13L recently described in the southernmost region of Brazil to have spread across the Northeastern states. P.1, P.2 and NP13L are descended from the ancient B.1.1.28 strain, although during the first phase of the pandemic in Brazil presence of B.1.1.33 strain was also reported. Here, for the first time, we investigate the possible occurrence of a new variant of concern descending from B.1.1.33 that also carries the E484K mutation. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to early identify novel variants of concern and to monitor for vaccine effectiveness.
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Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition: Covid19 Interventions: Drug: Xuanfei Baidu Granules; Other: Placebo Sponsor: Darcy Spicer Recruiting
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SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition: Covid19 Intervention: Diagnostic Test: Anti-SARS-CoV2 Serology Sponsor: Université de Reims Champagne-Ardenne Completed
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Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19 - Condition: Covid19 Interventions: Drug: Emricasan; Other: Placebo Sponsor: Histogen Recruiting
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Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma - Condition: Covid19 Interventions: Other: Convalescent Plasma with antibody against SARS-CoV-2.; Other: Standard treatment for COVID-19 Sponsors: Hospital Son Llatzer; Fundació d’investigació Sanitària de les Illes Balears Recruiting
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ANTIcoagulation in Severe COVID-19 Patients - Condition: Severe COVID-19 Pneumonia Interventions: Drug: Tinzaparin, Low dose prophylactic anticoagulation; Drug: Tinzaparin, High dose prophylactic anticoagulation; Drug: Tinzaparin,Therapeutic anticoagulation Sponsor: Assistance Publique - Hôpitaux de Paris Not yet recruiting
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Neuromodulation in COVID-19 Patients - Condition: COVID-19 Interventions: Device: Transcranial direct-current stimulation; Device: Sham Transcranial direct-current stimulation Sponsors: D’Or Institute for Research and Education; Rio de Janeiro State Research Supporting Foundation (FAPERJ); Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Not yet recruiting
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Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition: COVID-19 Interventions: Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56; Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56; Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56; Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56; Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56; Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56; Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56; Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56 Sponsors: Jiangsu Province Centers for Disease Control and Prevention; Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd Recruiting
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Clinical Decision Support System Based on Non-invasive Tele-monitoring of COVID-19 Patients - Condition: COVID-19 Intervention: Device: Clinical decision support system based on non-invasive multimodal monitoring Sponsors: Increase-Tech; Hospital Clínico Universitario de Valladolid; University of Valladolid; Sanidad de Castilla y León Active, not recruiting
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Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19 - Condition: Covid19 Interventions: Biological: KDS-1000; Other: Placebo Sponsor: Kiadis Pharma Not yet recruiting
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STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19 - Condition: Covid19 Interventions: Drug: Brensocatib; Drug: Placebo Sponsors: University of Dundee; NHS Tayside; Insmed Incorporated Completed
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Post COVID-19 Syndrome and the Gut-lung Axis - Condition: Covid19 Interventions: Dietary Supplement: Omni-Biotic Pro Vi 5; Dietary Supplement: Placebo Sponsors: Medical University of Graz; CBmed Ges.m.b.H. Not yet recruiting
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Covid-19 Vaccination in Adolescents - Condition: Covid19 Interventions: Biological: Tozinameran; Biological: Oxford-AstraZeneca COVID-19 vaccine; Biological: CoronaVac Sponsor: The University of Hong Kong Not yet recruiting
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COVID-19 Self-Testing Through Rapid Network Distribution - Condition: Covid19 Interventions: Behavioral: COVID-19 self-test; Behavioral: COVID-19 test referral Sponsors: University of Pennsylvania; Public Health Management Corporation Not yet recruiting
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Risk of Contamination by COVID-19 During Oral Care With Aerosolization - Condition: Contamination by COVID 19 During Oral Care Intervention: Procedure: Oral care with/without aerosolization Sponsors: Assistance Publique - Hôpitaux de Paris; Institut National de la Santé Et de la Recherche Médicale, France Not yet recruiting
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Text-based Reminders to Promote COVID-19 Vaccinations - Condition: Covid19, Vaccines Interventions: Behavioral: Self-benefit; Behavioral: Prosocial-benefit; Behavioral: Early access; Behavioral: Fresh start Sponsors: University of California, Los Angeles; Carnegie Mellon University Enrolling by invitation
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From PubMed
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Dual inhibition of CB(1) R and iNOS as a potential novel approach to the pharmacological management of acute and long COVID-19 - COVID-19 (SARS-CoV-2) causes multiple inflammatory complications, resulting not only in severe lung inflammation but also in harm to other organs. While current focus is on the management of acute COVID-19, there is growing concern about long term effects of COVID-19 (Long Covid), such as fibroproliferative changes in lung, heart and kidney. Therefore, identifying therapeutic modalities is needed not only for the management of acute COVID-19 but also for preventing Long Covid, which could…
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The Renin-Angiotensin System, Hypertension, and SARS-CoV-2 Infection: a Review - PURPOSE OF REVIEW: This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other…
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Possible Therapeutic Use of Natural Compounds Against COVID-19 - The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases. Following uptake, SARS-CoV-2 replicates in autophagosome-like structures in the cytosol following its escape from endolysosomes. Accordingly, the greater endolysosome pathway…
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D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-alpha/NF-kappaB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis - At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly…
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Plant Products as Inhibitors of Coronavirus 3CL Protease - Background: The ongoing COVID-19 pandemic has created an alarming situation due to extensive loss of human lives and economy, posing enormous threat to global health security. Till date, no antiviral drug or vaccine against SARS-CoV-2 has reached the market, although a number of clinical trials are under way. The viral 3-chymotrypsin-like cysteine protease (3CL^(pro)), playing pivotal roles in coronavirus replication and polyprotein processing, is essential for its life cycle. In fact, 3CL^(pro)…
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In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2 - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a newly-discovered coronavirus and responsible for the spread of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infected millions of people in the world and immediately became a pandemic in March 2020. SARS-CoV-2 belongs to the beta-coronavirus genus of the large family of Coronaviridae. It is now known that its surface spike glycoprotein binds to the angiotensin-converting enzyme-2 (ACE2), which is expressed on the lung epithelial…
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SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition - Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces…
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Generation of SARS-CoV-2 reporter replicon for high-throughput antiviral screening and testing - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and antiviral discovery are hampered by the lack of a cell-based virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a noninfectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny…
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A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase - The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several…
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Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment - CONCLUSIONS: Our study established Drosophila as a model for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the potential of Selinexor for inhibiting Orf6 toxicity using an in vivo animal model system.
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Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor - CONCLUSIONS: Our study revealed Orf6 as a highly pathogenic protein from the SARS-CoV-2 genome, identified its key host interacting proteins, and Selinexor as a drug candidate for directly targeting Orf6 host protein interaction that leads to cytotoxicity.
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An overview of some potential immunotherapeutic options against COVID-19 - After the advent of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in the late 2019, the resulting severe and pernicious syndrome (COVID-19) immediately was deployed all around the world. To date, despite relentless efforts to control the disease by drug repurposing, there is no approved specific therapy for COVID-19. Given the role of innate and acquired immune components in the control and elimination of viral infections and inflammatory mutilations during SARS-CoV2…
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Sarbecovirus ORF6 proteins hamper induction of interferon signaling - The presence of an ORF6 gene distinguishes sarbecoviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 from other betacoronaviruses. Here we show that ORF6 inhibits induction of innate immune signaling, including upregulation of type I interferon (IFN) upon viral infection as well as type I and III IFN signaling. Intriguingly, ORF6 proteins from SARS-CoV-2 lineages are more efficient antagonists of innate immunity than their orthologs from SARS-CoV lineages….
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In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase - Since the outbreak emerged in November 2019, no effective drug has yet been found against SARS-CoV-2. Repositioning studies of existing drug molecules or candidates are gaining in overcoming COVID-19. Antiviral drugs such as remdesivir, favipiravir, ribavirin, and galidesivir act by inhibiting the vital RNA polymerase of SARS-CoV-2. The importance of in silico studies in repurposing drug research is gradually increasing during the COVID-19 process. The present study found that especially…
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High-dose ACEi might be harmful in COVID-19 patients with serious respiratory distress syndrome by leading to excessive bradykinin receptor activation - PURPOSE: We aimed to critically review the available information on the potential contribution of excessive kallikrein-kinin systems (KKSs) activation to severe respiratory inflammation in SARS-CoV-2 infection, and the likely consequence of ACE inhibition in seriously affected patients.
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From Patent Search
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5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link
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USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link
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Peptides and their use in diagnosis of SARS-CoV-2 infection - - link
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A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link
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IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link
Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen -
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Ein Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen, umfassend: ein Bildschirmgerät, das einen Umfang hat; eine UV-Entkeimungslampe, die sich am Umfang des Bildschirmgeräts befindet; eine Stromquelle, die elektrisch mit der UV-Entkeimungslampe verbunden ist; eine Steuerschaltung, die elektrisch mit der UV-Entkeimungslampe verbunden ist; und eine Befestigungsvorrichtung, durch die die UV-Entkeimungslampe am Umfang des Bildschirmgeräts befestigbar ist, wobei die Befestigungsvorrichtung einen Sitzkörper, eine erste Klemmplatte und eine zweite Klemmplatte aufweist, wobei der Sitzkörper mit der UV-Entkeimungslampe versehen ist, wobei die erste Klemmplatte und die zweite Klemmplatte beabstandet am Sitzkörper gleitbar angeordnet sind, wodurch ein Klemmabstand zwischen der ersten Klemmplatte und der zweiten Klemmplatte besteht, wobei ein elastisches Element zwischen der zweiten Klemmplatte und dem Sitzkörper angeordnet ist, um die zweite Klemmplatte dazu zu zwingen, sich der ersten Klemmplatte zu nähern.
Schublade mit antiepidemischer Wirkung, mit einem Schrank (1); mindestens einer Schublade (2), die in dem Schrank (1) angeordnet ist, wobei jede Schublade (2) einen Schubladenraum (25) aufweist; einer UV-Sterilisationsvorrichtung (3), die an der Schublade (2) angeordnet ist; einer Stromquelle (4), die elektrisch mit der UV-Sterilisationsvorrichtung (3) verbunden ist; einer Steuerschaltung (5), die elektrisch mit der Stromquelle (4) und der UV-Sterilisationsvorrichtung (3) verbunden ist; und einem Sensor (6), der elektrisch mit der Steuerschaltung (5) verbunden ist.
Gerät zur Unterstützung und Verstärkung natürlicher Lüftung -
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Lüftungssystem für einen mit öffnbaren Fenstern (16) ausgestatteten Gebäuderaum, gekennzeichnet dadurch, dass es ein Gehäuse (18) und einen Ventilator (20) aufweist, wobei durch das Gehäuse eine vom Ventilator erzeugte Luftströmung strömen kann, wobei das Gehäuse dafür eine Einströmöffnung (24) für Luft und eine Ausströmöffnung (22) für Luft enthält, wobei eine der beiden Öffnungen der Form eines Öffnungsspalts (26) zwischen einem Fensterflügel (12) und einem Blendrahmen (14) des Fensters (16) angepasst ist.
The Presidential Press Conference in the Biden Era Is as Awful as Ever - Under Trump, we had to listen. But now? There must be a better way. - link
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The Return of Mass Shootings - Will there be a way forward this time? - link
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Two Georgia Churches Grapple With the Shootings in Atlanta - Members of a Korean Baptist congregation reflected on the persistence of racism. The church where the gunman belonged insisted that he alone was responsible. - link
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The Movement to Exclude Trans Girls from Sports - The opposition is cast as one between cis-girl athletes on the one hand and a vast liberal conspiracy on the other. - link
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The Historians Under Attack for Exploring Poland’s Role in the Holocaust - To exonerate the nation of the murders of three million Jews, the Polish government will go as far as to prosecute scholars for defamation. - link
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From Vox
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9 questions about the humanitarian crisis on the border, answered -
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+Asylum seekers from Honduras walk toward a US Border Patrol checkpoint near Mission, Texas, on March 23. | John Moore/Getty Images
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+Unaccompanied migrant children are coming in record numbers — but it’s not the kind of crisis you might think it is.
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+The southern border is presenting President Joe Biden with a major humanitarian, political, and logistical challenge.
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+The left is criticizing the administration’s inhumane treatment of record numbers of unaccompanied migrant children arriving from Central America as thousands are being kept in jail-like facilities — the same “cages” that drew condemnation in 2019 under then-President Donald Trump. The right is falsely claiming that Biden inherited a secure border from his predecessor and that his policies have led to a national security crisis.
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+Meanwhile, media coverage of the border has been hyperbolic, depicting a “surge” of migrants overwhelming the US border. Five of the nine reporters at Biden’s press conference on Thursday asked questions about immigration.
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+If this sounds familiar, it’s because the same humanitarian crisis has been playing out since at least 2014, when the US saw a dramatic shift in the kinds of migrants who were arriving at the southern border. Formerly mostly single Mexican adults, the migrants now include a growing number of families and children from Central America’s “Northern Triangle”: Guatemala, Honduras, and El Salvador.
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+ Chip Somodevilla/Getty Images
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+President Biden and Vice President Harris meet with Health and Human Services Secretary Xavier Becerra, Homeland Security Secretary Alejandro Mayorkas, and other immigration advisers on March 24.
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+As a solution, the Biden administration is racing to open more beds in shelters designed to care for children while telling migrants thinking about making the perilous journey north, “Don’t come.” Biden has appointed Vice President Kamala Harris to oversee the response.
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+“We’re building back up the capacity that should have been maintained and built upon that Trump dismantled,” Biden said during a press conference Thursday.
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+But while increasing capacity to welcome these unaccompanied children will help assuage the immediate humanitarian crisis at the border, how to prevent migrants from coming at all is a much more difficult problem. Migration at the southern border has for years been driven by longstanding instability in Central America that has only intensified amid the pandemic and has forced many to leave their home countries.
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What is going on at the US-Mexico border?
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+The Biden administration is struggling to accommodate an increasing number of unaccompanied children arriving on the border. About 70 percent of them are teenagers, but hundreds are under the age of 12.
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+As of March 24, more than 5,100 such children, a record number, were in US Customs and Border Protection custody, staying in unsuitable, jail-like facilities, often for longer than the 72-hour legal limit.
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+Another 11,900 children were in custody of the Department of Health and Human Services. Those children are staying either in permanent shelters — state-licensed facilities that are better equipped to administer care but have had to slash capacity amid the pandemic — or in temporary influx facilities that have comparatively little oversight. So far, the Biden administration has opened or is in the processing of opening six of these temporary facilities in Texas and California and is trying to expand space in others.
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+The Biden administration has been racing to transfer children in CBP custody to these HHS facilities. It is also working to release children more quickly to sponsors, including family members or foster families, in the US. But it hasn’t been able to keep pace with the number of new arrivals.
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+ John Moore/Getty Images
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+A temporary Customs and Border Protection processing center in Donna, Texas. The administration has barred media access to these kinds of facilities, with the exception of one in Carrizo Springs, Texas.
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+The increase in arrivals among unaccompanied children is happening even though, for the most part, the border remains closed. Last March, at the outset of the pandemic, Trump invoked Title 42, a section of the Public Health Safety Act that allows the US government to temporarily block noncitizens from entering the US “when doing so is required in the interest of public health.” Since then, more than 514,000 migrants have been expelled, including more than 13,000 children.
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+Biden has chosen to keep the policy in place. He has carved out some exceptions: In addition to unaccompanied children, the administration has started processing 28,000 people who were sent back to Mexico to await their immigration court hearings in the US under a Trump-era program known as the Migrant Protection Protocols, or the “Remain in Mexico” program.
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+The administration has also been admitting many families to the US because a change in Mexican law has limited the country’s capacity to detain those with young children. A CBP official told reporters on Friday that agents are encountering about 2,300 parents and children daily and 1,900 are being allowed to stay in the US.
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Who are the migrants arriving on the US-Mexico border?
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+For decades, single adult men from Mexico made up the majority of those attempting to cross the US-Mexico border. But in 2014, the US started seeing many more families and unaccompanied children making the journey — a trend that has continued.
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+They are primarily coming from the Northern Triangle countries of Guatemala, Honduras, and El Salvador, which for years have been suffering from gang-related violence, government corruption, frequent extortion, and some of the highest rates of poverty and violent crime in the world.
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+The pandemic-related economic downturn and a pair of hurricanes late last year that devastated Honduras and Guatemala in particular have only exacerbated those more longstanding problems. Many people are hoping to apply for asylum or other humanitarian protections, and the US is obligated by federal law and international human rights agreements to give them that chance.
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+The majority of unaccompanied children arriving on the border also have family in the US, so they’re aiming to reunite with their relatives.
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+ John Moore/Getty Images
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+A child’s abandoned shoe lies near a river close to the US-Mexico border on March 24.
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+In addition, thousands of asylum seekers have been waiting in Mexico for months or years due to Trump-era policies that kept them out, including Title 42 and the Migrant Protection Protocols. More than 71,000 asylum seekers were also stranded in Mexico under the Migrant Protection Protocols.
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+While the Biden administration has started processing people with active cases, many people whose cases were closed are also still waiting in Mexico in the hope that they will eventually be processed. (Biden administration officials have signaled that they eventually intend to identify those people and admit them to the US for a chance to seek protection.)
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Are we really seeing more migrants?
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+CBP encountered more than 100,000 migrants at the southern border in February, including more than 9,000 unaccompanied children and nearly 19,000 families, though only a fraction of them have been admitted to the US due to Title 42, the public health restrictions on border crossings. Those numbers are expected to be even higher by the end of March.
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+Single adults still account for the vast majority of people who are arriving (about 71 percent), but the number of unaccompanied children arriving on the border is unprecedented. There are more than 17,000 currently in government custody and an average of 466 arriving daily as of March 24. By comparison, CBP apprehended 11,475 unaccompanied children during the month of May 2019, the last time that migration levels spiked. (It doesn’t make sense to compare to 2020 levels because movement dramatically dropped off at the outset of the pandemic, particularly after Title 42 was implemented.)
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+Though Biden administration officials have warned that the US could encounter more migrants on the southern border than they have in 20 years, experts have cautioned against calling the current flow of migrants a “surge” for several reasons.
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+Migration levels tend to fluctuate based on the season. The number of migrants arriving on the border has historically increased in the warmer months between about February and June when the journey is less treacherous than it would be in the hot summer sun.
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+What we’re observing on the border is in part a “predictable seasonal shift,” as Tom K. Wong, an associate professor at the University of California San Diego, and his co-authors write in the Washington Post.
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+“When the numbers drop again in June and July, policymakers may be tempted to claim that their deterrence policies succeeded. But that will just be the usual seasonal drop,” they write.
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+There was also an almost 50 percent drop in migration at the border following the implementation of the pandemic-era border restrictions last March, rather than a typical seasonal increase. It’s likely that those restrictions “delayed prospective migrants rather than deterred them — and they’re arriving now,” they add.
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+ John Moore/Getty Images
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+US Border Patrol agents take asylum seekers into custody in McAllen, Texas, on March 23.
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+There’s also reason to believe the number of migrants encountered by border patrol overall is inflated. Title 42 created perverse incentives for single adults to attempt to cross the border multiple times. Before the pandemic, they might have been dissuaded from trying again for fear of facing criminal prosecution for illegal entry and disqualifying themselves from legal migration pathways, such as asylum. But under the pandemic-era process, they are merely fingerprinted, processed, and dropped off in Mexico without consequence.
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+CBP estimates that the resulting recidivism rate, the number of people who try to cross, get caught, and try again, is roughly 40 percent. (By comparison, the recidivism rate was about 7 percent in fiscal year 2019.)
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+David Bier, an immigration policy analyst at the CATO Institute, modeled the extent to which the number of crossings has been inflated by Title 42:
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+The Border Looks Identical to 2019 Without Repeat Crossers. I estimated rates of “newly arriving” border crossers using partial CBP data to illustrate what we’ve known all along: Title 42 expulsions (and earlier MPP) inflate crossings dramatically https://t.co/P4zUe06Axzpic.twitter.com/suS8Jw001k
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+The number of families arriving on the border still appears to be tracking below 2019 levels, when more than 84,000 were apprehended in a single month.
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Why are they coming?
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+On top of the factors pushing people out of their home countries, four years of Trump’s policies have created pent-up demand. Migrants correctly perceive that Biden is seeking to take a more humane approach than his predecessor and see an opportunity to seek refuge in the US where they did not before.
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+Many of these people are fleeing dangerous or unlivable conditions and felt they had no choice but to leave their home countries.
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+Smugglers have sought to capitalize on that desperation by spreading misinformation about the Biden administration’s plans to process asylum seekers. Immigrant advocates on the border have reported hearing rumors spreading that migrants staying in certain camps will be processed or that the border would open at midnight.
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+Title 42 has also created an incentive for families to choose to separate. Parents have sent their children to the border alone, knowing that they would be accepted by US authorities, while they await a chance to cross either in Mexico or their home countries. That has been the case since last fall, when a court forced the Trump administration to begin accepting unaccompanied children. The Biden administration opted to continue doing so, acknowledging its humanitarian obligations.
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+Reuters reported that smugglers have consequently been arranging trips from Central America just for children, encouraging families to pay thousands of dollars to send them alone by bus, car, boat, or plane.
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What happens to migrants once they arrive at the border?
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+Single adults and families presenting themselves at a port of entry or apprehended while attempting to cross the border without authorization are currently being expelled under Title 42.
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+When border agents encounter children, the process is different. They are taken to jail-like CBP holding facilities, but they are subject to legal protections that prohibit the federal government from keeping them there for longer than 72 hours before they must be transferred to the HHS shelter system.
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+At times over the past seven years when resources at the border have become overwhelmed by arrivals of families and unaccompanied children, however, children have been kept in those facilities beyond the legal limit. That is why the Obama administration, the Trump administration, and now the Biden administration have been accused of keeping “kids in cages.”
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+In recent weeks, there have been reports of children in the facilities sleeping on gym mats with nothing but mylar blankets to keep them warm and not being permitted to go outside or take a shower for days at a time. The Biden administration has so far prevented the media from touring the facilities, which would offer better insight into the conditions.
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+BuzzFeed reported that, as of Wednesday, more than 3,000 children in the facilities had been there longer than the legal limit.
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+The conditions inside HHS facilities are better, but there have been reports of abuses in both permanent and temporary shelters for migrant children over the years, even predating Trump.
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+ John Moore/Getty Images
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+Asylum seekers listen to instructions at an outdoor US Border Patrol processing center under the Anzalduas International Bridge near Mission, Texas, on March 23.
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+In one of the most egregious cases, migrant children were administered powerful psychotropic drugs at one shelter south of Houston, Texas, in 2018. A for-profit emergency influx center in Homestead, Florida, that once held up to 3,200 children also came under fire in 2019 following reports of sexual abuse, overcrowding, and negligent hiring practices.
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+Though the White House has been restricting access to both CBP and HHS facilities, NBC News toured one of the temporary HHS facilities that the Biden administration is currently using in Carrizo Spring, Texas, on Wednesday. More than 100 of the children in that facility tested positive for Covid-19 during the intake process and were isolating. It has a dining hall, dormitories, and an area to meet with legal representation and is decorated with colorful paintings.
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+However, it’s located in a remote location, about a two-hour drive from San Antonio, the nearest major city. That makes it difficult for government watchdogs to conduct independent oversight and ensure that the children are being treated humanely and in compliance with legal requirements and are not subject to prolonged periods of confinement.
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+The administration is making it easier for children to be released from those facilities to sponsors. It terminated a 2018 agreement with HHS under which sponsors were subject to more stringent vetting, which involved getting their fingerprints taken and additional paperwork. That information was shared with child welfare and immigration authorities, leaving the sponsors potentially vulnerable to deportation if they did not have legal status.
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+The administration is also facilitating cooperation between border patrol, HHS, and FEMA to ensure that children are transferred to shelters and released more quickly. And it is rushing to increase the number of available HHS shelters and expand bed space in existing facilities while complying with Centers for Disease Control and Prevention guidelines on Covid-19.
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Is what’s happening on the border a crisis?
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+Some argue it is — but not necessarily in the way the word is usually used.
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+Republicans have sought to frame the situation at the border as a national security crisis, with House Minority Leader Kevin McCarthy claiming during a recent visit to the border that recent migrants are “not just people from Mexico or Honduras or El Salvador. They’re now finding people from Yemen, Iran, Turkey. People on the terrorist watch list they are catching, and they’re rushing in all at once.”
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+CBP told CNN, meanwhile, that “encounters of known and suspected terrorists at our borders are very uncommon.” No one has been been killed or injured in attacks on US soil by terrorists who crossed the southern border without authorization and, since 1975, only nine people convicted of planning a terrorist attack entered the US illegally, including some on ships and airplanes.
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+Rather, the migrants arriving on the southern border are ones who have fled humanitarian crises in their home countries and who have encountered a system in the US that is ill-suited to offer them protection. Their arrival has strained existing resources on the border — but unlike the Trump administration, the Biden administration is taking steps to build up the necessary infrastructure to process them humanely.
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+“As more migrants arrive at our southern border, particularly vulnerable unaccompanied children, it’s clear we’re encountering a humanitarian crisis,” Elizabeth Neumann, a Trump-era counterterrorism official at the Department of Homeland Security, said during a press call earlier this week. “But I don’t believe that this is a national security crisis.”
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+The same crisis occurred in 2014, when more than 237,000 Central Americans, including over 60,000 unaccompanied children, showed up at the southern border. And it happened again in 2019, when CBP encountered 144,000 migrants over the course of just a single month and almost 1 million over the course of the year.
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+It’s clear that the current situation is not an aberration, but a reoccurring problem to which the federal government has not adapted.
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How is Biden’s border policy different from Trump’s?
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+Trump sought to keep migrants out and prevent them from being released into the US at any cost — including separating more than 5,000 families who arrived on the border starting in the spring of 2018.
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+Biden has promised a more humane approach to the border. He has sought to reunify families that were separated, halted the construction of Trump’s border wall, and ended the Remain in Mexico program. His officials have also acknowledged that CBP facilities are no place for a child, and they are working urgently on ensuring that children are kept in facilities that are suitable and to release them to sponsors more quickly.
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+But he has kept in place Title 42, the pandemic border restrictions. Like Trump, Biden is also pursuing a regional strategy to mitigate migration.
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+Trump sought to outsource the task of deporting asylum seekers to Mexico, brokering “Asylum Cooperative Agreements” with Guatemala, Honduras, and El Salvador that required migrants to apply for protections in those countries before doing so in the US. (Those countries, however, were not capable of offering protection given that they have high levels of crime and instability and are not used to dealing with an influx of people seeking refuge.)
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+In a similar vein, a senior Biden administration official said last week that the US is looking to “share responsibility for protecting vulnerable migrants” by resettling migrants in the US and other countries in order to avoid “caravans” arriving at the border.
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+The administration has already restarted the Central American Minors program, which allows children in danger to apply to come to the US from their home countries instead of having to come to the US-Mexico border to do so. Trump had ended the program after taking office, leaving around 3,000 children stranded who had already been approved for travel.
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+It is looking to establish similar procedures by which people can apply for protection from their home countries. But it’s not clear to what extent such programs would deter people from making the journey north.
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+The Biden administration has also been coordinating with the Mexican government on migration issues, as well as vaccine distribution: The US recently announced that it is planning to share 2.5 million doses of the AstraZeneca vaccine, which has not yet been authorized by American regulators, with Mexico. On the same day, Mexico announced that it is closing its border with Guatemala and Belize to non-essential travel. It has also announced that the US-Mexico border would remain closed through at least April 21. (The White House has maintained those conversations are unrelated.)
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+Biden said during a press conference Thursday that the US is also in ongoing negotiations with Mexico so that the country can absorb more migrants. “They should all be going back,” he said. “The only people we are not going to let sit there on the other side of the Rio Grande with no help are children.”
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How much of this is the result of Biden’s policies?
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+Republicans have been eager to call this a “Biden border crisis.” Migration levels were already rising in the months before he took office, but because Trump was expelling nearly all migrants arriving on the border, they were largely invisible:
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+Here are some basic facts being left out.
- The current spike in apprehensions began last year. - 72% of all people apprehended at the border are still being expelled. - Unaccompanied kids haven’t been expelled since November. - Family apprehensions are <50% of 2019 levels. pic.twitter.com/Fa4Cm5g85V
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+— Aaron Reichlin-Melnick (@ReichlinMelnick) March 21, 2021
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+Trump’s policies, which promised to deter migrants from attempting to cross the southern border, were ultimately unsuccessful, instead creating pent-up demand that is only beginning to become evident now. And the Trump administration did nothing to improve conditions in the Northern Triangle that were driving people to flee, even revoking some $4 billion in aid.
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+“This new surge we are dealing with now started in the past administration but it is our responsibility” to deal with it, Biden said Wednesday.
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+Republicans have criticized Biden for not being strong enough in telling migrants they’re not welcome. But his administration has been clear that the border is “not open” and that they should not come in an “irregular fashion.” As political pressure has ramped up, he has been even more strict, telling migrants in a recent interview with ABC “don’t come,” “don’t leave your town or city or community,” and that they would soon be able to “apply for asylum in place.”
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+The White House has been amplifying that messaging with more than 17,000 radio ads in Brazil, El Salvador, Guatemala, and Honduras since January 21, playing in Spanish, Portuguese, and six indigenous languages and reaching an estimated 15 million people. There have also been ad campaigns on Facebook, Instagram, and Twitter:
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+— U.S. Embassy Haiti (@USEmbassyHaiti) March 24, 2021
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+But these are desperate people who have been waiting for an opportunity to migrate for a long time, so it’s not clear whether that kind of messaging actually resonates.
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+“No matter how many ads you run, no matter how terribly you treat people seeking protection, people will still come,” Omar C. Jadwat, director of the ACLU’s immigrants rights project, tweeted.
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What does the situation at the border mean for immigration policy going forward?
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+The challenges that the administration is facing on the border are affecting conversations around immigration reform in Congress, as well as the Biden administration’s long-term plans for how to mitigate migration from Central America.
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+Sen. Dick Durbin (D-IL), who has long been at the forefront of immigration issues in Congress, recently told reporters that he did not see a way to pass a Biden-backed comprehensive immigration reform bill known as the US Citizenship Act of 2021 and its promise of a pathway to citizenship for the roughly 11 million undocumented immigrants living in the US.
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+“I don’t see a means of reaching it,” he said. “I think we are much more likely to deal with discrete elements [of immigration reform].”
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+ Eric Thayer/Bloomberg via Getty Images
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+Makeshift housing camps for migrants seeking asylum hearings in Tijuana, Mexico. President Biden says he plans to visit the US-Mexico border “at some point” for a firsthand look at conditions.
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+Instead, he has been trying to drum up support for the DREAM Act, which would offer a path to citizenship to more than a million undocumented immigrants who came to the US as children provided that they meet certain requirements. He recently said he’s close to getting the 10 Republican votes needed for the bill to proceed in the Senate.
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+The House also recently passed two bills that would address aspects of immigration reform on a piecemeal basis. The Dream and Promise Act would offer a path to citizenship to these so-called “DREAMers” as well as people with temporary humanitarian protections, but given that it is largely a statement of Democratic priorities and does not make trade-offs on border security, it’s likely to be dead on arrival in the Senate.
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+The other bill, the Farm Workforce Modernization Act, would legalize roughly 1.2 million farmworkers. It passed with the support of 30 Republicans, and Rep. Zoe Lofgren, who was one of the leads on the bill in the House, said there has been interest in the bill among Republican Senators.
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+In the meantime, the Biden administration has laid out a long-term plan to tackle migration from Central America — an effort that Vice President Kamala Harris will oversee.
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+In addition to cooperating with neighboring countries on migration mitigation efforts, Department of Homeland Security Secretary Alejandro Mayorkas said that the administration is working on a new regulation that would speed up asylum adjudications such that the process would take months, rather than years, while “ensuring procedural safeguards and enhancing access to counsel.” It’s not clear what mechanisms the administration will use to do so, but it’s the kind of reform that immigrant advocates have been calling for — so long as it does not infringe on asylum seekers’ due process rights.
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Celebrating Ramona Quimby’s enduring appeal, in honor of Beverly Cleary -
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+Ramona Quimby is one of the most beloved kid book characters of all time. | HarperCollins
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+Beverly Cleary has died at 104. Her Ramona Quimby books gave us one of the sharpest characters in American kid lit.
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+“Don’t pester, Ramona,” said Mrs. Quimby. “I’ll get you there in plenty of time.”
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+“I’m not pestering,” protested Ramona, who never meant to pester. She was not a slowpoke grownup. She was a girl who could not wait. Life was so interesting that she had to find out what happened next.
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+
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+Ramona Quimby was not meant to be a main character, not at first. She first appeared as a minor character in the Henry Huggins books by beloved children’s author Beverly Cleary. But when Cleary passed away on Thursday at age 104,Ramona was left as her most iconic creation.
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+“It occurred to me that all the children appeared to be only children,” recalled Cleary. It was 1950 andCleary was a school librarian, writing her first book, at the urging of a little boy who marched up to her and demanded, “Where are the books about kids like us?”
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+Henry Huggins and the many books that followed were meant to be an antidote to the sugary, sentimental children’s stories that were fashionable in the 1950s; Cleary was writing about real children. And real children do sometimes have siblings, of course — so Cleary invented Ramona, the pesky younger sister of Henry’s friend and neighbor Beezus.
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+But Ramona, that unstoppable ball of energy and excitement, was not willing to idle on the sidelines as a minor character. She demanded her own stories.
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+First came 1955’s Beezus and Ramona, the story of poor, long-suffering elder sister Beezus, who just wants to sit quietly and embroider potholders. Instead, she is forced to run interference on Ramona, trying and mostly failing to keep her from baking her dolls with her birthday cake (so she could practice being the witch in Hansel and Gretel) or taking a single bite out of every apple in the house (because the first bite always tastes the best).
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+It’s a similar dynamic to the one that had worked so well in the Henry Huggins books, where the main character wants life to be calm and orderly (Henry, Beezus), but winds up saddled with a disruptive, unruly sidekick who trails chaos in their wake (Henry’s dog Ribsy, Ramona). Eventually that dynamic grows unsatisfying, because you’re left with a purely reactive main character and a side character who’s a lot better at driving a story.
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+Ramona Quimby is part of the pantheon of unruly kid-lit heroines
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+So with 1968’s Ramona the Pest, Ramona steps into the spotlight for the first time. She becomes a protagonist in her own right, joining the pantheon of the unruly, disruptive, tomboyish heroines of kid lit: Laura Ingalls, Harriet the Spy, Jo March, and other untidy girls who function as walking wrecking balls to the status quo.
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+From Beezus and Ramona to 1999’s Ramona’s World (the last of the Ramona books), Ramona crashes through ceilings, throws her shoes at scary dogs, smashes eggs in her hair, paints her nose black with mascara, and squeezes an entire tube of toothpaste into the bathroom sink. She never acts out of malice — Ramona is sometimes angry but never cruel — but rather out of sheer curiosity and enthusiasm for life.
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+Part of the pleasure of reading about Ramona comes from the deep satisfaction she gets from all of her pranks. It never occurred to me as a child to want to squeeze out an entire tube of toothpaste (I was a Beezus), but when Ramona eyes the tube and thinks, “How smooth and shiny it looked with only one little dent where someone had squeezed it once,” and at last gives into temptation, I understand the appeal on a deep and visceral level.
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+As Ramona squeezes, “the paste coiled and swirled and mounded in the washbasin. Ramona decorated the mound with toothpaste roses as if it were a toothpaste birthday cake.” Who wouldn’t want to get creative with toothpaste after reading that?
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+The coziness of Ramona’s world gives her room to act out
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+Of course, while unruly kid-lit heroines can be appealingly disruptive, they never cross the line into being outright threatening. Instead, they’re always nested in warm, nurturing domesticity. Laura Ingalls has her variety of Little Houses, Harriet the Spy has her cozy routine with Ole Golly on the Upper East Side, Jo March has Orchard House and Marmee — and Ramona Quimby has the house on Klickitat Street.
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+Ramona fairly wallows in the security of her home and her family. It’s just as satisfying for her to revel in a pair of fresh new pajamas as it is to make toothpaste roses: “Oh, how soft and warm and cozy they felt, like the fur of a baby rabbit,” she thinks as she puts them on. Besides pajamas, there are burgers to be eaten, “soft and juicy,” and always consumed “close together in a booth [that] made Ramona feel snug and cozy.” There are beds with “clean white sheets,” and there are hugs with her mother, who always has “a good smell of clean clothes and perfumed soap.” Ramona’s pranks can be exciting and messy and noisy in part because her home and family are there to provide a dependable, clean, and calm backdrop.
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+The Quimbys’ financial troubles are the dark underbelly of the Ramona books
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+But as profoundly cozy as the house on Klickitat Street is, the Quimbys have their troubles. Lurking in the background of Ramona’s clear-eyed account of her family life is what could, if told from her parents’ point of view, be a domestic tragedy. Ramona’s father, who dropped out of school after Beezus was born, spends most of the seven Ramona books shuttling in and out of jobs he hates. He briefly returns to school to become an art teacher — but then Mrs. Quimby gets pregnant again and he returns to work he can’t stand.
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+Meanwhile, Mrs. Quimby yo-yos back and forth between staying at home with her children and working part time, and depending on the book she is either tired and stressed from tending two small children and working an office job or bored out of her skull from being stuck at home. By the time we reach Ramona’s World, she’s back at home and listlessly joining a book club in an attempt to “exercise her brain.”
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+Ramona’s slowly growing awareness of her parents’ unhappiness creates the emotional underbelly of the books: She is not entirely clear on why, exactly, her parents keep coming home tired and grumpy and ordering her to clean her room, but the fact of it hurts her deeply. It also adds emotional stakes to the comfortable domesticity of her world, which prevents it from getting cloying.
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+If the Quimbys’ financial problems put their family in danger, it also makes them even more fiercely protective. And as the books develop, Ramona takes on more and more responsibility for keeping everyone happy, going from resentfully trying not to antagonize Beezus in her first few books to proudly looking after her own little sister in Ramona’s World. The warmth and coziness of the Quimby family is an oasis of calm against the uncertainty of the rest of the adult Quimbys’ lives — and it gives Ramona the freedom she needs to run wild.
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+That, ultimately, is the bliss of the Ramona Quimby books: a safe and happy space, and a little girl running wild within it. It’s what makes the books such uncontested classics.
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+Thank you for everything, Beverly Cleary.
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+
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+Don’t miss our new video projects, returning series, and opportunities to get involved with our reporting.
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Thierry Henry hopes quitting social media inspires others to stand up to online abuse - The ex-Arsenal and Barcelona striker, who has 15 million followers across Facebook, Instagram and Twitter, on Friday said he would be disabling his accounts
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Indian Premier League 2021 | Mumbai Indians unveil new jersey - The defending champion start off their campaign against Royal Challengers Bangalore on April 9.
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ISSF World Cup | Vijayveer, Tejaswani win gold in 25m rapid fore pistol mixed event - On Friday, Sidhu won the individual silver medal in the 25 rapid fire pistol event ahead of Anish Bhanwala and Gurpreet.
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Ex-Tokyo Olympics chief again criticized for sexist comment - Yoshiro Mori, speaking at a party for a politician at a Tokyo hotel, referred to the politician’s aide as ‘way too old to be called a woman.’
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Gavaskar welcome to give me a ring and talk about my Test cricket: Bairstow - Bairstow had scores of 0, 0, 0 and 28 in the four innings that he played in England’s 1-3 Test series defeat against India, prompting Gavaskar to comment that he looked “uninterested”
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From The Hindu: National News
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Delhi Court appoints Local Commissioner to oversee sealing of lawyer’s computer - Advocate Mehmood Pracha, representing the accused in the north-east Delhi riots, will keep posession of the computer and has been asked not to tamper with it.
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Music varsity signs MoU with Sri Satya Sai University - Aim is to to develop suitable training systems and organise courses, seminars, workshops
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Four Kerala artists on an all-India trip to discover the country - Travelling in a car, they are funding the journey by holding roadside exhibitions and selling their works
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Rajasthan Assembly byelections | Congress releases list of candidates - The list of candidates was issued by All India Congress Committee general secretary Mukul Wasnik on Saturday.
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COVID-19 casts an unseen shadow over the Haridwar Kumbh Mela - Even with fewer numbers, SOP is conspicuous by its absence in this large congregation of humanity
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From BBC: Europe
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Coronavirus: France accuses UK of ‘blackmail’ over vaccine exports - The row over Covid vaccination supplies escalates after France’s foreign minister criticises the UK.
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Coronavirus: Germany tightens borders amid alarm over pandemic - France is to be classed a “high-risk” area as Germans are warned of a possible 100,000 infections a day.
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France was ‘blind’ to Rwanda genocide, French report says - French historians say France bears “heavy responsibilities” over the 1994 Rwanda massacres.
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Thierry Henry: Former Arsenal player takes action over racism and bullying - Former Arsenal and France striker Thierry Henry says he is disabling his social media accounts because of racism and bullying.
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UK professor shared info with fake Russian agent - Paul McKeigue shared information with a man who hinted he was a Russian agent, to discredit an NGO.
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From Ars Technica
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+
“Are schools safe?” is the wrong question to be asking - There’s no right answer on school safety, just a right answer for each community. - link
+
What will it take to get a giant cargo ship unstuck from the Suez Canal? - Tugboats, excavators, and cranes all may be enlisted to help the Ever Given. - link
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Apple pushes iOS 14.4.2, iPadOS 14.4.2, and watchOS 7.3.3 to supported devices - There are no new features in these updates, just a security fix. - link
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Experts sound alarm of possible new COVID surge as US cases once again rise - CDC director says she’s “deeply concerned about this trajectory.” - link
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Bias, subtweets, and kids: Key takeaways from Big Tech’s latest outing on the Hill - Won’t somebody please think of the children and/or censorship? - link
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From Jokes Subreddit
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A girl goes into the doctor’s office for a checkup. -
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+As she takes off her blouse, the doctor notices a red ‘H’ on her chest.
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+“How did you get that mark on your chest?” asks the doctor.
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+“Oh, my boyfriend went to Harvard and he’s so proud of it he never takes off his Harvard sweatshirt, even when we make love,” she replies.
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+A couple of days later, another girl comes in for a checkup. As she takes off her blouse, he notices a blue ‘Y’ on her chest.
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+“How did you get that mark on your chest?” asks the doctor.
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+“Oh, my boyfriend went to Yale and he’s so proud of it that he never takes off his Yale sweatshirt, even when we make love,” she replies.
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+A couple of days later, another girl comes in for a checkup. As she takes off her blouse, he notices a green ‘M’ on her chest.
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+“Do you have a boyfriend at Michigan?” asks the doctor.
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+“No, but I have a girlfriend at Wisconsin, Why do you ask?”
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An old, tired-looking dog wandered into the yard. -
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+. I could tell from his collar and well-fed belly that he had a home. He followed me into the house, down the hall, and fell asleep on the couch. An hour later, he went to the door, and I let him out. The next day he was back, resumed his position on the couch and slept for an hour. This continued for several weeks. Curious, I pinned a note to his collar: “Every afternoon your dog comes to my house for a nap.” The next day he arrived with a different note pinned to his collar: “He lives in a home with four children – he’s trying to catch up on his sleep. Can I come with him tomorrow?”
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An Australian Army Recruit sends home a letter.. -
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+Dear Mum & Dad,
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+I am well. Hope youse are too. Tell me big brothers Doug and Phil that the Army is better than workin’ on the farm - tell them to get in quick smart before the jobs are all gone! I wuz a bit slow in settling down at first, because ya don’t hafta get outta bed until 6am. But I like sleeping in now, cuz all ya gotta do before brekky is make ya bed and shine ya boots and clean ya uniform. No cows to milk, no calves to feed, no feed to stack - nothin’!! Ya haz gotta shower though, but its not so bad, coz there’s lotsa hot water and even a light to see what ya doing!
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+At brekky ya get cereal, fruit and eggs but there’s no kangaroo steaks or possum stew like wot Mum makes. You don’t get fed again until noon and by that time all the city boys are dead because we’ve been on a ’route march’ - geez its only just like walking to the windmill in the back paddock!!
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+This one will kill me brothers Doug and Phil with laughter. I keep getting medals for shootin’ - dunno why. The bullseye is as big as a possum’s bum and it don’t move and it’s not firing back at ya like the Johnsons did when our big scrubber bull got into their prize cows before the Ekka last year! All ya gotta do is make yourself comfortable and hit the target! You don’t even load your own cartridges, they comes in little boxes, and ya don’t have to steady yourself against the rollbar of the roo shooting truck when you reload!
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+Sometimes ya gotta wrestle with the city boys and I gotta be real careful coz they break easy - it’s not like fighting with Doug and Phil and Jack and Boori and Steve and Muzza all at once like we do at home after the muster.
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+Turns out I’m not a bad boxer either and it looks like I’m the best the platoon’s got, and I’ve only been beaten by this one bloke from the Engineers - he’s 6 foot 5 and 15 stone and three pick handles across the shoulders and as ya know I’m only 5 foot 7 and eight stone wringin’ wet, but I fought him till the other blokes carried me off to the boozer.
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+I can’t complain about the Army - tell the boys to get in quick before word gets around how good it is.
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A girl tells her mother after school ‘Mum, I got a gold star today for reciting the whole alphabet! The rest of my class only knows 3 or 4 letters! -
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+‘Well done darling’ the girl’s mother replies. ‘That’s because you’re blonde.’ After returning from school the next day the girl tells her mother ‘I am the smartest student in my maths class! I can count up to 15! Everyone else stopped at about 5’ ‘Well done’ replies the mother again. ‘That’s because you’re blonde.’ The following day, the girl says to her mother. ‘Mum, today we measured our chests in class and mine is the largest! Is that because I’m blonde?’ ‘No darling, that’s because you’re 18.’
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