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+ + + +Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood. - Conditions: Covid-19
Interventions: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA)
Sponsors: Vachira Phuket Hospital
Recruiting
UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease
Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 ÎŒg
Sponsors: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH
Recruiting
Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers. - Conditions: COVID-19
Interventions: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin)
Sponsors: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France
Not yet recruiting
High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk - Conditions: Cardiovascular Diseases; Long Covid19
Interventions: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa
Sponsors: Federal University of ParaĂba; City University of New York
Recruiting
SGB for COVID-induced Parosmia - Conditions: COVID-19-Induced Parosmia
Interventions: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection
Sponsors: Washington University School of Medicine
Recruiting
Effects of Physiotherapy Via Video Calls in Patients With COVID-19 - Conditions: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function
Interventions: Behavioral: Exercise training
Sponsors: Chulabhorn Hospital
Active, not recruiting
Investigating the Effectiveness of Vimida - Conditions: Long COVID; Post COVID-19 Condition
Interventions: Behavioral: vimida
Sponsors: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock
Not yet recruiting
Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Exercise session; Behavioral: Control session
Sponsors: University of Nove de Julho
Not yet recruiting
Reducing Respiratory Virus Transmission in Bangladeshi Classrooms - Conditions: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection
Interventions: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units
Sponsors: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh
Not yet recruiting
SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19 - Conditions: Anxiety; COVID-19 Pandemic
Interventions: Behavioral: Mindfulness
Sponsors: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International
Not yet recruiting
Development of a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018Âź adjuvant - NDV-HXP-S is a Newcastle disease virus (NDV) vectored vaccine candidate which expresses the S-antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This vaccine candidate is under evaluation in human clinical studies with and without cytosine phosphate guanine (CpG) 1018Âź adjuvant. Existing potency methods for NDV-HXP-S do not allow for quantification of the S-antigen when the adjuvant is present. To support evaluation of NDV-HXP-S with CpG 1018Âź adjuvant, an inhibitionâŠ
Syringa reticulata potently inhibits the activity of SARS-CoV-2 3CL protease - The ongoing coronavirus infectious disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still urgently requires effective treatments. The 3C-like (3CL) protease of SARS-CoV-2 is a highly conserved cysteine protease that plays an important role in the viral life cycle and host inflammation, providing an ideal target for developing broad-spectrum antiviral drugs. Herein, we describe the discovery of a large number of herbs mainly produced inâŠ
A Case Report of Drug Interactions Between Nirmatrelvir/Ritonavir and Tacrolimus in a Patient With Systemic Lupus Erythematosus - Nirmatrelvir/ritonavir is a treatment for COVID-19 consisting of nirmatrelvir, which has anti-SARS-CoV-2 activity, and ritonavir, a booster to maintain blood levels. Ritonavir is known to be a potent inhibitor of cytochrome P450 3A (CYP3A), and interactions with CYP3A-metabolized drugs, such as the immunosuppressant tacrolimus, can be problematic. Ritonavirâs inhibition of CYP3A is irreversible due to covalent binding, and its inhibitory effects are expected to persist until replaced by newâŠ
Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice - Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of the disease caused by new SARS-CoV-2 variants in elderly individuals and immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights the need for alternative platforms for booster vaccines. In our previous study, we assessed the boost effect of theâŠ
Preparation and characterization of a fluorogenic ddRFP-M biosensor as a specific SARS-CoV-2 main protease substrate - The conventional peptide substrates of SARS-CoV-2 main protease (Mpro) are frequently associated with high cost, unstable kinetics, and multistep synthesis. Hence, there is an urgent need to design affordable and stable Mpro substrates for pharmacological research. Herein, we designed a functional Mpro substrate based on a dimerization-dependent red fluorescent protein (ddRFP) for the evaluation of Mpro inhibitors in vitro. The codon-optimized DNA fragment encoding RFP-A(1) domain, a polypeptideâŠ
Neutralizing antibodies to block viral entry and for identification of entry inhibitors - Neutralizing antibodies (NAbs) are naturally produced by our immune system to combat viral infections. Clinically, neutralizing antibodies with potent efficacy and high specificity have been extensively used to prevent and treat a wide variety of viral infections, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), Dengue Virus (DENV) and Hepatitis B Virus (HBV). An overwhelmingly large subset of clinically effective NAbs operates byâŠ
Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion - CONCLUSION: Overall, our studies not only identify PVRL4 as an intrinsic broad-spectrum antiviral ISG, but also provide a candidate host-directed target for antiviral therapy against various viruses including SARS-CoV-2 and its variants in the future.
FEOpti-ACVP: identification of novel anti-coronavirus peptide sequences based on feature engineering and optimization - Anti-coronavirus peptides (ACVPs) represent a relatively novel approach of inhibiting the adsorption and fusion of the virus with human cells. Several peptide-based inhibitors showed promise as potential therapeutic drug candidates. However, identifying such peptides in laboratory experiments is both costly and time consuming. Therefore, there is growing interest in using computational methods to predict ACVPs. Here, we describe a model for the prediction of ACVPs that is based on theâŠ
Taming the cytokine storm: small molecule inhibitors targeting IL-6/IL-6α receptor - Given the increasing effectiveness of immune-based therapies, management of their associated toxicities is of utmost importance. Cytokine release syndrome (CRS), characterized by elevated levels of cytokine, poses a significant challenge following the administration of antibodies and CAR-T cell therapies. CRS also contributes to multiple organ dysfunction in severe viral infections, notably in COVID-19. Given the pivotal role of IL-6 cytokine in initiating CRS, it has been considered a mostâŠ
How can we promote vaccination of the mass population?-Lessons from the COVID-19 vaccination defaults - While vaccines are pivotal in combating COVID-19, concerns about side effects and complex procedures have hindered complete vaccination. Prior studies suggest that individuals defaulted to opt-out exhibit higher COVID-19 vaccination rates compared to those in opt-in systems. However, these studies were conducted in countries with a tolerant attitude towards vaccination and default changes, targeting specific age groups, and did not address potential deterrents like the increase in cancellationâŠ
Nanobody engineering for SARS-CoV-2 neutralization and detection - In response to the ongoing COVID-19 pandemic, the quest for coronavirus inhibitors has inspired research on a variety of small proteins beyond conventional antibodies, including robust single-domain antibody fragments, i.e., ânanobodies.â Here, we explore the potential of nanobody engineering in the development of antivirals and diagnostic tools. Through fusion of nanobody domains that target distinct binding sites, we engineered multimodular nanobody constructs that neutralize wild-typeâŠ
Effect of rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report - Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. AâŠ
SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release via ATP/P2Y2 and ERK1/2 signaling pathways in human bronchial epithelia - The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner ofâŠ
Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis - CONCLUSION: ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.
Methotrexate Inhibits the Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Receptor Binding Domain to the Host-Cell Angiotensin-Converting Enzyme-2 (ACE-2) Receptor - As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus mutates, finding effective drugs becomes more challenging. In this study, we use ultrasensitive frequency locked microtoroid optical resonators in combination with in silico screening to search for COVID-19 drugs that can stop the virus from attaching to the human angiotensin-converting enzyme 2 (hACE2) receptor in the lungs. We found 29 promising candidates that could block the binding site and selected four of them thatâŠ
Legal Weed in New York Was Going to Be a Revolution. What Happened? - Lawsuits. Unlicensed dispensaries. Corporations pushing to get in. The messy rollout of a law that has tried to deliver social justice with marijuana. - link
The Snake with the Emoji-Patterned Skin - In the wild, ball pythons are usually brown and tan. In America, breeding them to produce eye-catching offspring has become a lucrative, frenetic, andâfor someâtroubling enterprise. - link
Matt Gaetzâs Chaos Agenda - The Florida Republican is among the most brazen and controversial figures in Donald Trumpâs G.O.P. Heâs also among the most influential. - link
The Trials of Alejandro Mayorkas - The Secretary of Homeland Security has been forced to respond to an unprecedented flow of migrants to the U.S.-Mexico border. Why are Republicans in Congress impeaching him for it? - link
Is the Media Prepared for an Extinction-Level Event? - Ads are scarce, search and social traffic is dying, and readers are burned out. The future will require fundamentally rethinking the pressâs relationship to its audience. - link
+The hostâs return to The Daily Show is a coda to a golden age. +
++Jon Stewartâs return to The Daily Show has been, on the metrics, a success. According to Comedy Central, his first episode back on February 12 was watched by 1.85 million total viewers across premiere simulcasts and encores, up 110 percent from Trevor Noahâs final episode in 2022. Itâs also a major improvement on Stewartâs last show. The Problem with Jon Stewart, which ran on Apple TV+ from 2021 to 2023, was routinely drawing in audiences as low as 40,000 people. +
++âJon Stewartâ and âThe Daily Showâ on their own are flawed brands. âJon Stewart on The Daily Show,â on the other hand? Thatâs a combination of such heady nostalgia that the viewers pour in. +
++Still, Stewartâs first episode proved that his appeal is not just pure nostalgia. There is some kind of alchemy that occurs when Jon Stewart gets behind that old Daily Show desk. He knows the format of the show so well; he plays it like a virtuoso. +
++He eases into his monologue with no rush, breaking out the same Borscht Belt voices and self-deprecating barbs he used to play with in 2015, talking in the same relaxed patter that builds to the same crescendo of righteousness. He is so delighted by the chance to play a gotcha reel (in this case, members of the Trump family repeating âI canât recallâ during depositions after a discussion of Bidenâs allegedly failing memory) that he almost manages to make the old trick feel new again. He almost manages to make you think, âWow, Jon Stewart could have done something with the Trump era.â Almost. +
++Jon Stewartâs great satirical gift is his ability to puncture hypocrisy, which is why he became one of the most trusted sources of news in America during the 2000s. George W. Bush was Stewartâs perfect foil: a president who talked of compassionate conservatism and grand existential battles of good versus evil while lying to the public and embroiling America in dirty, vicious wars that dragged on for decades. No one could puncture Bushâs pieties as well as Jon Stewart. Nothing was more satisfying to watch than Stewartâs mugging face, eyes wide with faux shock, next to a video montage that promised to expose, once and for all, that Bush administration doublespeak. +
++Stewartâs version of The Daily Show lost some of its urgency during the Obama administration, as the brand of liberal centrism he championed ascended to cultural primacy and he lost his ability to position himself as the scrappy outsider unmasking a lying president. Still, most presidents have their hypocrisies, and Stewart found plenty to puncture during the Obama years: his initially tepid support of gay marriage, the drone warfare, the IRS targeting of Tea Party groups. He left The Daily Show in 2015, just before Trump became the Republican candidate and the liberal consensus worldview of Daily Show viewers shattered. +
++Stewart, by and large, sat out the Trump years, so we donât know for sure what his comedy would have looked like in that troubled era. We did, however, watch all the comedians who came up on The Daily Show try and fail to grapple with Trump, a president who never bothered to veil his indiscretions, who was so straightforwardly villainous that he had no hypocrisy there to be exposed. Stephen Colbert, Samantha Bee, John Oliver, Trevor Noah â the more they talked about Trump, the more they seemed to become less funny and more earnest. They could not make his actions more absurd by hyperbole. Sarcasm was no longer attractive to audiences, who craved clear demarcations between the comedians who were on their side and those on Trumpâs side. Robbed of their most effective weapons, liberal comics ended up spending the Trump years like much of the left did: alternating between rage and tears. +
++âFor the last 20 years we [the left] have owned the cultural terrain of comedy and irony, arguably to good effect,â Nick Marx, a media scholar who studies political humor, told me in 2022. âThe Trump era made liberals forget that. It made our comedians want to act like paternal figures who would pat us on the head.â +
++As liberal comedy faltered, right-wing comedy rushed to fill the power vacuum. Conservative comedians now position themselves as the truly edgy and transgressive ones, the people speaking truth to the power of liberal elitists, the heirs apparent to the tradition begun by Jon Stewart. +
++âThereâs a rebelliousness in the way people think of this right-wing comedy, right?â Matt Sienkiewicz said in 2022. Sienkiewicz co-authored Thatâs Not Funny: How the Right Makes Comedy Work for Them alongside Marx. âEven if it really is regressive and pointing back to old dominant ideas. But it can be branded as being the opposite of Stephen Colbert crying about January 6 during his monologue, which is very much not cool to the teens.â +
++Stewartâs return comes not during the Trump era but during the Biden presidency, just as the country begins to stare down the possibility of a second Trump term. Biden is the sort of traditional president Stewart excels at handling; itâs not surprising that the sharpest moment of his first episode came when he criticized Bidenâs administration for trying to shame the press out of covering criticism of Bidenâs age. But Stewart has yet to prove his ability to cover a man like Donald Trump, especially in a moment when the right has successfully positioned itself as the home of transgressive comedy. +
++As good as Jon Stewartâs ratings were on his first night, The Daily Show wasnât the most-watched show on late-night. Over on Fox News, Gutfeld! got 2.2 million views. No matter how skillful Stewartâs performance has been, itâs hard to avoid the sense that heâs delivering a coda to a golden age that ended long ago. +
+Garland v. Cargill asks whether gun makers can evade the ban on machine guns with a device called a bump stock. +
++On February 28, the Supreme Court will hear a case that could effectively make it legal for civilians to own automatic weapons capable of firing as many as nine bullets every second. +
++The case, known as Garland v. Cargill, involves bump stocks, devices that use a gunâs recoil to repeatedly fire the weapon. Bump stocks cause a semiautomatic firearmâs trigger to buck against the shooterâs finger, as the gunâs recoil causes it to jerk back and forth â repeatedly âbumpingâ the trigger and causing the gun to fire as if it were fully automatic. +
++A âsemiautomaticâ weapon refers to a gun that loads a bullet into the chamber or otherwise prepares itself to fire again after discharging a bullet, but that will not fire a second bullet until the shooter pulls the trigger a second time. An âautomaticâ weapon, by contrast, will fire a continuous stream of bullets â though the shooter often must hold down the trigger to do so. +
++The Trump administration issued a regulation banning bump stocks in 2018, after a gunman used one to kill 60 people and wound hundreds more during a country music festival in Las Vegas. A 1986 law makes it a crime to own a âmachinegun,â and the Trump administration determined that this law extends to bump stocks. +
++But federal courts have divided on whether federal law defines the term âmachinegunâ broadly enough to include bump stocks, and the law does appear to be genuinely ambiguous on this point. +
++If this case, which was brought by an individual gun owner who wants to own bump stocks, had arisen just a few years ago, it would have been a slam dunk victory for the government. The Supreme Courtâs decision in Chevron v. Natural Resources Defense Council (1984) generally calls for judges to defer to a federal agencyâs reading of an ambiguous federal law, so Chevron calls for the courts to defer to the governmentâs interpretation of what constitutes a âmachinegun.â +
++But the Court is likely to overrule Chevron in a pair of cases it heard in January, shifting final authority over a simply enormous array of policy questions away from the executive branch of government and to the Court itself. And that means that the fate of the current ban on bump stocks most likely rests entirely upon whether five justices want such a ban to exist. +
++Federal law defines a âmachinegunâ to include âany weapon which shoots, is designed to shoot, or can be readily restored to shoot, automatically more than one shot, without manual reloading, by a single function of the trigger.â The plaintiff in Cargill makes two separate arguments that this definition doesnât extend to bump stocks. +
++One of these arguments is fairly plausible, while the other is not. +
++Starting with the plaintiffâs weaker argument, his lawyers claim that a gun equipped with a bump stock does not fire âautomatically.â The US Court of Appeals for the Fifth Circuit, a far-right court that routinely issues dubiously reasoned decisions implementing conservative policy goals, agreed with this argument, concluding that the bump stocks at issue in this case do not allow automatic fire because they only function if the shooter maintains âmanual, forward pressure on the barrel and manual, backward pressure on the trigger ledge.â +
++The problem with this argument is that it proves far too much. If a gun cannot be an automatic weapon if it requires the shooter to maintain continuous pressure on some part of the gun, then virtually all automatic weapons do not qualify as âmachineguns.â +
++As the Justice Department explains in its brief to the justices, most traditional machine guns âfire only by maintaining constant rearward pressure on the triggerâ â that is, the shooter must hold down the trigger or the gun stops firing. As the DOJ argues, there is âno meaningful differenceâ between a weapon that requires continuous pressure on the trigger and one that requires continuous pressure on some other part of the gun. Both types of guns should be considered automatic weapons because both kinds of guns continue firing until the shooter stops making the gun fire. +
++The Cargill plaintiffâs stronger argument, meanwhile, turns on the federal lawâs statement that a machine gun must engage in automatic fire âby a single function of the trigger.â Federal judges are quite divided on how to read this provision, which does appear to be genuinely ambiguous. +
++Some courts, like the left-leaning DC Circuit, concluded that this reference to âa single function of the triggerâ should be read to mean âa single pull of the trigger from the perspective of the shooter.â Thus, as that court said in Guedes v. ATF (2019), a semiautomatic weapon equipped with a bump stock counts as a machine gun because âthe shooter engages in a single pull of the trigger with her trigger finger, and that action, via the operation of the bump stock, yields a continuous stream of fire as long she keeps her finger stationary and does not release it.â +
++Alternatively, much of the Fifth Circuit concluded that a bump stock-equipped gun does not count as a machine gun because the trigger itself moves back and forth while such a gun is being fired. Although these judges conceded that bump stocks allow semiautomatic weapons to be rapidly fired, they claimed that âthe fact remains that only one bullet is fired each time the shooter pulls the trigger.â +
++Both sides of this case can point to competing rules guiding how statutes should be interpreted to support their preferred outcome. +
++Many judges whoâve ruled against the bump stock ban point to something called the ârule of lenityâ to justify that decision. Generally speaking, this rule establishes that, when a criminal law is ambiguous, it should be construed in favor of defendants. As the Supreme Court said in Rewis v. United States (1971), âambiguity concerning the ambit of criminal statutes should be resolved in favor of lenity.â +
++But the rule of lenity is also a very weak peg to hang any legal decision upon. Thatâs because, in Barber v. Thomas (2010), the Supreme Court concluded that âthe rule of lenity only applies if, after considering text, structure, history, and purpose, there remains a âgrievous ambiguity or uncertainty in the statute,â such that the Court must simply âguess as to what Congress intended.ââ +
++The Justice Department, meanwhile, points to a rule known as the âpresumption against ineffectivenessâ to justify leaving the bump stock ban in place. This rule holds that statutes generally should not be construed in ways that aid in âevasion of the law.â +
++It is also a very old rule. The DOJâs brief cites a 200-year-old Supreme Court decision, known as The Emily and the Caroline (1824), which warns against reading laws in ways that would render âthe law in a great measure nugatory and enable offenders to elude its provisions in the most easy manner.â (âNugatoryâ means that the law is inoperative or unable to function.) +
++âIn construing a statute, penal as well as others,â the Court explained in The Emily, âwe must look to the object in view, and never adopt an interpretation that will defeat its own purpose if it will admit of any other reasonable construction.â Thus, if a law can fairly be read in more than one way, a court should avoid reading it in a way that renders the law ineffective. +
++There is some recent evidence, moreover, that a majority of the justices may be sympathetic to the DOJâs argument that laws should not be read to make them ineffective â even though this very conservative Supreme Court tends to be sympathetic to arguments made by gun rights plaintiffs. +
++Last August, the Supreme Court temporarily blocked a lower courtâs decision permitting the sale of âghost guns,â firearms that are sold in a dismantled state in order to evade certain federal gun laws. +
++Federal law typically requires gun purchasers to submit to a background check, and it also requires guns to be marked with a serial number to help track the weapon if it is used in a crime. These requirements apply to âany weapon ⊠which will or is designed to or may readily be converted to expel a projectile by the action of an explosive.â To prevent gun sellers from evading this law by selling dismantled guns as individual parts, the same federal law also applies to âthe frame or receiver of any such weapon,â the skeletal part of a firearm that houses other components, such as the barrel or trigger mechanism. +
++Ghost guns seek to evade these requirements because they are sold dismantled, and the frame or receiver is sold incomplete â although often they can be completed with minimal work, such as drilling a single hole in the frame. +
++In any event, a majority of the justices decided, in Garland v. VanDerStok, to block a lower court decision that would have allowed these ghost guns to be sold without background checks or serial numbers. VanDerStok was a 5-4 decision, with Chief Justice John Roberts and Justice Amy Coney Barrett crossing over to vote with the Courtâs three Democratic appointees. +
++So thatâs, at least, some evidence that this Court will apply a presumption against ineffectiveness to gun laws like the one at issue in Cargill. +
++Regardless, the bump stocks case does turn on a genuinely ambiguous provision of federal law. That means that, in a world without Chevron, the question of whether gun manufacturers can sell devices that evade the ban on machine guns will turn on which outcome a majority of the justices prefer. +
++What True Detectiveâs fourth season gets wrong about True Detective. +
++To be a True Detective fan is to wrestle with uncomfortable contradictions. The first season is both a masterpiece of cosmic horror noir and a piece of art that feels like it was created not just by, but for men. It was a gritty treatise against toxic masculinity that still dehumanized women and ultimately reified the very thing it attempted to deconstruct. +
++For all its critical acclaim and influence on prestige drama in the years that followed, True Detective also generated a deeply toxic fanbase. These fans were men who missed the point but who saw themselves as a vital part of the showâs metatextuality, the real âtrue detectivesâ all along. Ever since, that first season has primarily been remembered, not for its incredible acting, its brilliant aesthetic touches, that legendary six-minute tracking shot, nor even the now-ubiquitous line, âTime is a flat circle,â but for the misogyny. Its two subsequent seasons have mostly been forgotten altogether. +
++All of these uneasy truths loom large over season four, True Detective: Night Country, 10 years after its progenitor. Every succeeding season of this anthology series has occupied a lose-lose position simply by not being season one. But season four, by virtue of being centered around two women â a local chief of police (Jodie Foster) and a state trooper (Kali Reis) trying to solve a mysterious set of murders in the unforgiving Alaskan north â has simultaneously raised the stakes for the series and revived all of True Detectiveâs messy paradoxes. +
++Night Countryâs new showrunner and writer/director Issa LĂłpez needed to accomplish two risky, ambitious goals: The season had to justify itself as a creative follow-up to a work thatâs very difficult to follow up, and rectify the notorious sexism of season one in a way that would hopefully allow the series to forge a new path. Its sixth episode, which aired Sunday on HBO, had to reconcile both goals in a satisfying finale. +
++To many among True Detectiveâs original fanbase, outrage at the second goal has precluded an objective view of how well itâs succeeding at the first. By the same token, many longtime fans are so eager to see the second project succeed that theyâre quick to dismiss all critiques of season fourâs creative aims as pure misogyny. +
++These seem like unbridgeable positions. But thereâs unfortunately a third view: that Night Countryâs creative flaws ultimately torpedo its efforts at feminist reclamation, shifting the season finale away from a compelling cosmic mystery and toward a hamfisted Me Too revenge plot that leaves a comic number of plot points unresolved and arguably weakens the whole series. +
++(Note: Spoilers for Sundayâs season four finale abound.) +
++To be fair to LĂłpez, this isnât the first season of True Detective to miss the mark by a mile. Season two, a hasty, shoddy 2015 follow-up from series creator and season one writer Nic Pizzolatto, featured all the worst parts of season one on speed â the tortured masculinity, the presentation of women as little more than sexy window-dressing, and a poor imitation of all of Matthew McConaugheyâs famous existential monologues as Rust Cohle shoehorned into vapid machismo nonsense from Colin Farrellâs dysfunctional detective. Perhaps to shift himself and HBO away from misplaced allegations of plagiarism, Pizzolatto cut out most of season oneâs mesmerizing Weird fiction elements: murky occult figures, arcane Lovecraftian rituals, and worship of the âYellow King.â +
++If season two had too little of the supernatural, 2019âs third season was a true return to form, with Pizzolatto returning to the deep South and to a cold case tinged with occult horror, floating on a sense of nonlinear time, and backed by a soul-filled T Bone Burnett soundtrack. But by then, the world was a much different place, and True Detective had to compete with a field of its own descendants â shows as disparate as 2017âs Mindhunter and 2018âs The Terror, each successful at cordoning off a sliver of True Detectiveâs genius for themselves. +
++Still, anchored by Mahershala Aliâs pitch-perfect turn as an aging detective who spends decades trying to solve a cold case, season three really clarified the True Detective formula: A labyrinthine mystery driven by deep characterization, replete with hints of a dark otherworldly version of reality, filmed with an attention to aesthetics, and written with a certain literary flourish. Perhaps most of all, True Detective has to have a philosophy â a commitment to engaging with those eldritch horrors, if only to nod to them and be on your way. +
++On paper, Night Country ticks a lot of those boxes. Inspired by the recently solved Dyatlov Pass incident (an avalanche did it), the season follows a quest to solve the gruesome deaths of a team of scientists. The group was found naked, frozen, and apparently terrified to death in the tundra near the small town of Ennis, Alaska. Populated mainly by Iñupiat residents whose water has turned black due to pollution from an evil mining plant, Ennis has plunged into its annual winter stretch of sunless polar night, and tensions are high as the local police begin their investigation. Sheriff Danvers (Foster) and Trooper Navarro (Reis) work to solve the murders while navigating their own rocky history. The brutal, still-unsolved murder of an Iñupiaq activist has unexpected connections to the current crime; the women quickly realize they have to bury their differences and work together to solve all the murders at once. +
+ ++Like season one, the finale brings us to a literal labyrinth, this time deep in the ice caves beneath Ennis. LĂłpez has exchanged the Yellow King for an unnamed divine feminine spirit, perhaps Sedna or Mother Nature. (Thereâs also a tongue-in-cheek reference to the âBlue Kingâ crab company throughout.) The locals all seem to be aware of âher,â and as our story progresses it becomes clear that some of them view the spirit of the murdered activist as synonymous with this ancient entity. In the final episode, we finally meet her â or at least we come as close to âherâ as we can get. +
++But the similarities to that first season are all surface. LĂłpez didnât originally plan to create Night Country as a part of the True Detective universe, and her efforts to incorporate callbacks to previous True Detective seasons make that painfully clear. Throughout season four, references to season one recur, but they usually lack context and arenât justified by anything happening around them. We learn a season four character had a relationship with Rust Cohleâs father; but so what? We learn our evil mining corporation has ties to evil corporate overlords from previous seasons ⊠and? There are spirals everywhere, but we gain no enhanced understanding of what this familiar motif means. +
++LĂłpez picks up on the well-known line, âYouâre asking the wrong question.â She has characters repeat variants of this statement over and over again throughout season four until it becomes preposterous, an annoying substitute for meaningful writing. Each reference, from âflat circleâ to Funyuns, is purely fan service, a distracting blip on the map that contributes nothing to our understanding of the True Detective universe. +
++The same goes for Night Countryâs over-the-top horror elements, which range from pointless jump scares to spectral phenomena that appear for no reason. Where season two was completely devoid of the supernatural, Night Country is so full of ghosts that they lose all significance. +
++Other aesthetic choices are so baffling as to be unintentionally hilarious. Night Country utilizes a bizarrely off-kilter soundtrack of somber minor-key covers of famous pop songs that are absolutely incongruous with the mood of the show, from Eagle-Eye Cherryâs 1997 bop âSave Tonightâ to eerie Christmas music. In the finale, we get a dark emo needle drop of âTwist and Shout,â and the gravely intoned âShake it up, babyâ lands with such unbelievable dissonance that I burst into laughter. +
++To be clear, both Foster and Reis are fantastic. Fosterâs Sheriff Danvers keeps up a gruff loner hostility, pushing away her family, her partner, and her community, even as she works tirelessly to protect them all. When her exterior finally cracks open, itâs to reveal an unforgettable tapestry of grief and resilience. By contrast, Reisâs Navarro bleeds raw vulnerability throughout, running hot and then hotter as she gets closer to the truth in her long quest to find a killer, and perhaps an even more ancient quest to pursue the unknown spirit of the north. +
++As individual characters, they fully fit into the tradition of True Detectiveâs spiritually clashing sleuths who galvanize each other through a charged mix of loathing and shared desperation. Yet Danversâ cynicism and Navarroâs spirituality never satisfyingly cohere â a fundamental flaw that Night Country doesnât fully overcome. For all that Reis is excellent, when she and Foster are onscreen together she seems stifled, limited to churlishness and sarcasm. In episode six, Foster delivers an acting master class as her character finally reveals a little of her personal heartbreak, only to be met with a disconnected non-response from Navarro. Itâs as if LĂłpez didnât know how to follow her own mic drop, so didnât bother trying. Itâs a hesitance that encapsulates a season full of baffling choices and inconsistent characterizations. +
++Perhaps the most baffling choice of all comes in the finale, when we finally learn that the murders of the scientists were facilitated by the women of Ennis, as payback for the murder of the activist â who, it turns out, the scientists themselves murdered and covered up, years ago. The show fully glosses over the improbable way the women learn about this cover-up to barrel toward whatâs meant to be a righteous showstopper: They break into the science lab, armed to the teeth, and enact their vengeance, forcing the scientists to undress and fend for themselves in the brutal Arctic night. +
++This climax comes off as a ludicrous, unearned payoff, with undeveloped cardboard villagers standing in as mouthpieces for larger political stances, as they have throughout the season for environmental activism and post-Roe medical care. Here, though, itâs as if LĂłpez was determined to reverse-engineer a feminist morality play, even if it meant superseding all attempts at coherent storytelling. To add insult to injury, the biggest unresolved âmysteryâ of the show â the one weâre left to assume was the work of the mysterious Arctic god â involves a human tongue being dropped on the floor. Thatâs right. Weâre meant to believe âsheâ made her presence known by ⊠spectrally drop-kicking a tongue under a lab table. +
++(The seasonâs second-biggest mystery, Navarroâs fate at the end, gets left deliberately ambiguous in the finaleâs closing shot. Did she walk into the tundra for good, following the siren song of the ice goddess a la Frozen 2, or did she come back alive? We canât be certain, but the idea that sheâs now a ghost herself would feel more satisfying if Navarroâs struggle and escalating mental breakdown had felt less like a casual aside every now and then.) +
++This absurd plot resolution comes well after Pizzolatto himself reportedly shaded this season, calling the writing âstupid,â much to the delight of fanboys who couldnât wait to bash the show purely on the basis of its female representation. Who do we root for? Of course we want to root for Night Country under these conditions, and the show has won a high score of âuniversal acclaimâ on Metacritic. And yet Iâve got a dirty tongue backed by the worldâs worst Lana Del Rey album that begs to differ. +
++Whatâs most frustrating about all of this is that this mess neednât have happened. There are plenty of examples of better written, better directed female crime-solving duos in communities of sisters doing it for themselves. Last yearâs criminally underrated Australian dramedy Deadloch, for example, mined this formula for comedy gold and plenty of suspense alongside well-earned feminist proselytizing. But it did so by relying on whip-smart writing, a story that bears out the moral, and phenomenal acting and chemistry between its two leads â arguably the truest detectives of all in this farce. +
++The downgrade from Pizzolattoâs season one craft to the clunky sophomoric writing of season four was probably avoidable. If Night Country had just been allowed to be its own thing, without any pressure to either live up to season one or abide by its Weird parameters, it probably would have been a much better show. We canât fault HBO for wanting to revive one of its best franchises. But Night Country may ultimately go down as a reminder that sometimes itâs best to let sleeping eldritch creations lie. +
Dash, Thalassa and The Panther impress -
Irish Rockstar, Macron, Positano and Armory impress -
Daily Quiz | On history of the World Championships - With the 75th edition of Formula 1 World Championship going to commence from February 29 in Bahrain, hereâs a quiz on the history of the World Championships held so far
Bumrah likely to be rested, fit-again Rahul set to be back for Ranchi Test - The decision to rest Bumrah doesnât come as a surprise considering he bowled 80.5 overs in the first three Tests
Indiaâs show of bench strength eases transition concerns - With Shreyas Iyer struggling to meet the demands of test cricket and K.L. Rahul battling fitness issues, India have been left wondering how to plug the gaping hole in the middle order
SC examines divorced Muslim womenâs right to maintenance under Section 125 of the CrPC | Explained - The Supreme Court has decided to examine if a divorced Muslim woman can avail of maintenance under Section 125 CrPC despite existing personal laws â what is the case and what do judcial precedents stipulate?
Newborn kidnapped in Karimnagar rescued within 24 hours, two including a woman arrested - The baby was born to a couple from Bihar
Telangana | TSPSC cancels Group-I notification; new notification likely today or tomorrow -
Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.
Probe underway into potential mid-air collision between two IndiGo aircrafts in November 2023, one bound for Hyderabad -
Alexei Navalnyâs widow vows to continue his work in fight for âfree Russiaâ - Yulia Navalnya releases a video calling on supporters to stand with her, as she meets European ministers in Brussels.
Navalnyâs âprincipled and fearlessâ widow - Yulia Navalnaya kept a low profile in the past, but her husbandâs death could see her take a more public role.
âLose-loseâ anxiety marks global security talks in Munich - The conflicts in Gaza and Ukraine underline deepening geopolitical tensions and economic uncertainties.
Determination and despair in Ukraine front-line town - In Lyman, eastern Ukraine, some want peace on any terms, while others still hope for victory.
US and UK ambassadors to Russia lay Navalny tributes - Diplomats in Moscow pay their respects to the Russian opposition leader who died in prison on Friday.
That time the Morgan Motor Company designed a modern coupe, the Aeromax - Morgan is still best known for making throwback roadsters and for still using wood. - link
SpaceX wants to take over a Florida launch pad from rival ULA - SpaceX now plans at least four Starship launch pads, two in Texas and two in Florida. - link
Flowers grown floating on polluted waterways can help clean up nutrient runoff - Cut-flower farms could be a sustainable option for mitigating water pollution. - link
New FDA-approved drug makes severe food allergies less life-threatening - Injections over several months allowed people to tolerate larger doses of trigger foods. - link
Elon Muskâs X allows China-based propaganda banned on other platforms - X accused of overlooking propaganda flagged by Meta and criminal prosecutors. - link
The phone rings at 1 a.m. -
++The husband picks it up and yells âhow the hell do I know? Iâm not a weathermanâ and slams down the phone. +
++âWho was that?â the wife says. +
++The husband replies âsome jerk who wants to know if the coast is clear.â +
+ submitted by /u/AssociationSubject85
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The bartender says âWe donât serve time travellers hereâ -
++A time traveller walks in a bar. +
+ submitted by /u/Raggedy-Man
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A man is preparing to board a trainâŠ.. -
++when he hears that the Pope is also going to be using that mode of transportation because he apparently wanted to try something different. +
++âThis is exciting,â the man thinks. âIâve always been a big fan of the Pope. Perhaps Iâll be able to see him in person.â +
++Imagine his surprise when the Pope sits down in the seat next to him. But the gentleman was too shy to speak to the Pontiff. +
++Shortly after taking his seat, the Pope began a crossword puzzle. +
++âThis is fantastic,â the man thinks. âIâm really good at crosswords. Perhaps, if the Pope gets stuck, heâll ask me for assistance.â +
++Almost immediately, the Pope turns to the gentleman and says, âExcuse me, but do you know a four letter word referring to intercourse that ends in âkâ?â +
++Only one word leaps to mind. The man feels uncomfortable. âMy goodness,â he thinks, âI canât tell the Pope that. There must be another word.â He thinks for a while, then it hits him and he says, âI think the word youâre looking for is âtalkâ.â +
++âOf course,â replies the Pope. âDo you have an eraser?â +
+ submitted by /u/vect77
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Few people remember Canada had two Prime-Ministers with the same surname. -
++Itâs Trudeau +
+ submitted by /u/trubol
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An ego and a superego walk into a bar. -
++The bartender says âIâm going to need to see some idâ. +
+ submitted by /u/Gil-Gandel
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