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Pyruvate kinase deficiency, the most common genetic lesion in the glycolytic pathway, leads to chronic hemolytic anemia. Mitapivat, an oral agent, can activate some mutant enzymes and restore red-cell ATP generation. In this trial, hemoglobin levels increased from baseline by 1.5 g per deciliter or more at 24 weeks in 40% of the patients with pyruvate kinase deficiency who received mitapivat.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle β-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10−16) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. National Heart, Lung, and Blood Institute, National Institutes of Health.

Both trademark and unfair competition laws and state right of publicity laws protect against unauthorized uses of a person’s identity. Increasingly, however, these rights are working at odds with one another and can point in different directions with regard to who controls a person’s name, likeness, and broader indicia of identity. This creates what I call an “identity thicket” of overlapping and conflicting rights over a person’s identity. Current jurisprudence provides little to no guidance on the most basic questions surrounding this thicket, such as what right to use a person’s identity, if any, flows from the transfer of marks that incorporate indicia of a person’s identity, and whether such transfers can empower a successor company to bar a person from using their own identity, and, if so, when. Part of the challenge for mediating these disputes is that both right of publicity and trademark laws are commonly thought of as concerned solely with market-based interests. But this is not the case. As I have documented elsewhere, the right of publicity has long been directed at protecting both the economic and the noneconomic interests of identity-holders. And, as I demonstrate here, it turns out that the same is true for trademark and unfair competition laws, which have long protected a person’s autonomy and dignity interests as well as their market-based ones. After documenting and developing this overlooked aspect of trademark law, I suggest a number of broader insights of this more robust account of trademark law both for addressing the identity thicket and for trademark law more generally. First, I suggest that recognizing a personality-based facet of trademark law suggests a basis to limit the alienation of personal marks in some contexts. Second, this understanding shores up trademark’s negative spaces, especially when truthful information is at issue. Third, recognizing trademark’s personality-based interests provides a partial explanation (and limiting principle) for some of its expansionist impulses. Finally, I contend that recognizing this broader vision of trademark law provides significant guidance as to how to navigate the identity thicket. I employ trademark preemption analysis to mediate disputes between trademark and right of publicity laws. Trademark preemption provides an avenue out of the thicket, but only if trademark law’s robust theory of personality is recognized. A failure to do so risks leaving us with one of two bad options: a right of publicity that acts as a “mutant” trademark law, swallowing up and obstructing legitimate rights to use trademarks, or, alternatively, with a shallow husk of trademark law (rooted solely in commercial interests) that swallows up publicity claims at the expense of personal autonomy and dignity. Trademark law already provides us with the tools to avoid both of these unsavory paths — if only we reclaim its lost personality.

In patients with heart failure, guideline directed medical therapy improves outcomes and requires close patient monitoring. Pulmonary artery pressure monitors permit remote assessment of cardiopulmonary haemodynamics and facilitate early intervention that has been shown to decrease heart failure hospitalization. Pressure sensors implanted in the pulmonary vasculature are stabilized through passive or active interaction with the anatomy and communicate with an external reader to relay invasively measured pressure by radiofrequency. A body mass index  > 35 kg/m 2  and chest circumference > 165 cm prevent use due to poor communication. Pulmonary vasculature anatomy is variable between patients and the pulmonary artery size, angulation of vessels and depth of sensor location from the chest wall in heart failure patients who may be candidates for pressure sensors remains largely unexamined. The present study analyses the size, angulation, and depth of the pulmonary artery at the position of implantation of two pulmonary artery pressure sensors: the CardioMEMS sensor typically implanted in the left pulmonary artery and the Cordella sensor implanted in the right pulmonary artery. Thirty-four computed tomography pulmonary angiograms from patients with heart failure were analysed using the MIMICS software. Distance from the bifurcation of the pulmonary artery to the implant site was shorter for the right pulmonary artery (4.55 ± 0.64 cm vs. 7.4 ± 1.3 cm) and vessel diameter at the implant site was larger (17.15 ± 2.87 mm vs. 11.83 ± 2.30 mm). Link distance (length of the communication path between sensor and reader) was shorter for the left pulmonary artery (9.40 ± 1.43 mm vs. 12.54 ± 1.37 mm). Therefore, the detailed analysis of pulmonary arterial anatomy using computed tomography pulmonary angiograms may alter the choice of implant location to reduce the risk of sensor migration and improve readability by minimizing sensor-to-reader link distance.

Since their inception in the late nineteenth century, privacy rights have been widely understood to terminate with a person’s death. The “no-privacy-rights-for- the-dead” doctrine has been repeated for nearly 130 years. As demonstrated in this Article, the reality on the ground deviated from this common pronouncement even early on. The divergence is so great today that sustained consideration of postmortem privacy is essential. This is especially so given urgent calls to protect the digital assets of the dead and evolving technology that allows for the reanimation of deceased performers and loved ones. This Article provides a theoretical foundation for determining whether, when, and how the law should extend privacy rights after death. We begin by mapping what we call “postmortem privacy,” revealing both the surprisingly wide extension of privacy protections after a person’s death, and the haphazard, inconsistent, and at times incoherent state of the law. We then interrogate the array of interests that could justify postmortem privacy rights. We first situate this analysis in the law’s “jurisprudence of exclusion,” which withholds rights from entities that lack traits deemed essential for rights ascription. We then consider why, despite the initial impetus to deny rights to the dead, the law increasingly gravitates toward doing so. The best reasons to extend postmortem privacy are rooted not in the ongoing interests of the dead, but instead in the interests of the living and society. In particular, living individuals have interests in the treatment of their future deceased selves that we denominate the interests of the “future-decedents.” The living also have interests tied to their deceased relatives and loved ones that we designate the interests of the “relational-living.” Finally, society has a collective interest in treating the dead with respect. Postmortem privacy, however, must be bounded both to accommodate competing interests and also to ensure that it appropriately furthers its objectives. Accordingly, in its final part, this Article explores important limits on the scope of postmortem rights, including boundaries of eligibility, standing, temporal duration, and the competing interests of the living, including the freedom of speech. Ultimately, we conclude that there are convincing reasons to recognize postmortem privacy rights. However, the current law, by focusing on commercial value after death as the prime basis to extend rights, is off kilter. Postmortem privacy should be for everyone, not just the famous, and should empower survivors and future-decedents to limit the commercialization of the dead. Instead, the current system incentivizes unrelated companies to exploit and profit from the dead without meaningfully protecting postmortem privacy. Our analysis frames a markedly different normative and practical vision than the one we have today and provides a foundation on which to build a more coherent, fair, and predictable postmortem privacy.

This report proposes a stepwise process covering the range of considerations to systematically consider key choices for study design and data analysis for non-interventional studies with the central objective of fostering generation of reliable and reproducible evidence. These steps include (1) formulating a well defined causal question via specification of the target trial protocol; (2) describing the emulation of each component of the target trial protocol and identifying fit-for-purpose data; (3) assessing expected precision and conducting diagnostic evaluations; (4) developing a plan for robustness assessments including deterministic sensitivity analyses, quantitative bias analyses, and net bias evaluation; and (5) inferential analyses.

The right of publicity protects persons against unauthorized uses of their identity, most typically their names, images, or voices. The right is in obvious tension with freedom of speech. Yet courts seeking to reconcile the right with the First Amendment have to date produced only a notoriously confused muddle of inconsistent constitutional doctrine. In this Article, we suggest a way out of the maze. We propose a relatively straightforward framework for analyzing how the right of publicity should be squared with First Amendment principles. At the root of contemporary constitutional confusion lies a failure to articulate the precise state interests advanced by the right of publicity. We seek to remedy this deficiency by disaggregating four distinct state interests that the right of publicity is typically invoked to protect. We argue that in any given case the right of publicity is characteristically invoked to protect (one or more) of these four interests: the value of a plaintiff's performance, the commercial value of a plaintiff's identity, the dignity of a plaintiff, or the autonomous personality of a plaintiff. Plaintiffs' interests in their identity must always be weighed against defendants' constitutional interests in their speech. We therefore isolate three constitutional kinds of communication, each with a distinct form of First Amendment protection. A defendant's misappropriation of a plaintiff's identity can occur in public discourse, in commercial speech, or in what we call \"commodities.\" We then discuss how constitutional protections for these three kinds of speech should intersect with the four different interests that right of publicity claims are typically invoked to protect. The upshot is not a mechanical algorithm for producing correct constitutional outcomes, but an illumination of the constitutional stakes at issue in any given right of publicity action. We hope that by carefully surfacing the constitutional and policy stakes that beset the conflict between right(s) of publicity and the First Amendment, we have sketched a map that might substantially assist those who must navigate this tumultuous terrain.