Search

Introduction Despite being an occupational hazard, environmental exposure to lead (Pb) has been and will continue to be a major public health concern, because this metal is widely present in [...], BACKGROUND: The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain [beta]-amyloid (A[beta]) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. OBJECTIVES: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. METHODS: Female APP/PS1 mice at 8 wk of age were administered either 50 mg/kg Pb-acetate (PbAc) (i.e., 27 mg Pb/kg) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immuno-staining. In addition, A[beta] perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. RESULTS: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to A[beta]40, higher A[beta]40/A[beta]42 ratios, strikingly lower A[beta]40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. DISCUSSION: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384

This article presents a cooperative learning unit that could be beneficial for students with and without disabilities in general physical education settings. A description of this unit, helpful resources, and recommendations are provided for planning and implementing this unit. Keywords: Cooperative learning, physical education, disabilities, In physical education (PE) programs around the world, students with disabilities are commonly educated in general settings alongside their peers without disabilities (Haegele et al., 2017). Many students with disabilities [...]

Serotonin (5-HT) neurons constitute a tiny fraction of neurons in the brain (300 000 out of a billion neurons in human brain [0.03%]), yet they send projections to virtually all [...]

I feel closer to her,' William Carlos Williams said about Denise Levertov, 'than to any of the modern poets' (Interviews with Williams 40). Given Levertov's contemporaries, many of whom were [...]

Non-O157 Shiga toxin-producing Escherichia coli (STEC), which encompasses all STEC serogroups other than O157, causes an estimated 219,000 US infections annually (1). Typical symptoms are diarrhea, abdominal cramps, and vomiting, [...]

We studied the floral reproductive biology and nectar chemistry of Jaltomata grandiflora (Solanaceae), an apparently rare perennial of Michoacan, Mexico. During day 1, flowers are pistillate (stigma receptive, anthers not yet presenting pollen); flowers close for the night. Early in the morning of day 2, the corolla re-opens, stamens elongate to five times their earlier length, and anthers dehisce; the dehisced anthers remain about 2 mm from the stigma for much of day 2. In the afternoon of day 2, the corolla again closes, the corolla-androecium abscises, and only then can pollen be seen on the stigma. Protogyny and herkogamy likely promote outcrossing during days 1 and 2, respectively. Autonomous self-pollination takes place at the end of the corolla's life and allows fruit and seed production in the absence of pollinators but results in fruits that are lighter and contain fewer seeds than fruits resulting from manual self-pollinations. Carbohydrates from floral nectar samples were separated and quantified using hydrophilic interaction liquid chromatography coupled with corona charged aerosol detection. In nectar, mean sucrose concentration (0.482 mg/mg nectar), is about 10 and five times higher than glucose (0.043 mg/mg nectar) and fructose (0.095 mg/mg nectar) concentrations. Key words: autogamy, HILIC-Z, nectar chemistry, protogyny, self-compatible, self-pollination, Introduction Study of plant reproductive biology is elemental to understanding systematics, evolution, and ecology (Ornduff 1969; Anderson et al. 2002; Charlesworth 2006). Due to higher biodiversity, species of tropical areas [...]

Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine [CD8.sup.+] T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate ([Tex.sup.int]) and effector ([Tex.sup.eff]) exhausted T cell subsets derived from progenitor exhausted T cells ([Tex.sup.prog]) in tumors. A comprehensive CRISPR tiling screen of the 50C57-coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with an sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo antitumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies., Introduction Cell therapies using T lymphocytes possessing antitumor specificity have demonstrated robust clinical activity in hematological malignancies (1-4), with more limited success observed in solid tumors (5-7). The reduced effectiveness [...]

Chatbots are 'computer agents that can interact with the user' in a way that feels like human-to-human conversation. (1) While the use of chatbots for reference service in academic libraries is a topic of interest for both library professionals and researchers, little is known about how they are used in library reference service, especially in academic libraries in Canada. This article aims to fill this gap by conducting a web-based survey of 106 academic library websites in Canada and analyzing the prevalence and characteristics of chatbot and live chat services offered by these libraries. The authors found that only two libraries were using chatbots for reference service. For live chat services, the authors found that 78 libraries provided this service. The article discusses possible reasons for the low adoption of chatbots in academic libraries, such as accessibility, privacy, cost, and professional identity issues. The article also provides a case study of the authors' institution, the University of Calgary, which integrated a chatbot service in 2021. The article concludes with suggestions for future research on chatbot use in libraries., INTRODUCTION With the recent launch of artificial intelligence (AI) chatbots (e.g., ChatGPT and Bing-Chat), and Springshare's introduction of a library-focused chatbot product, it seems probable that more libraries will adopt [...]

ABSTRACT Ordinarily, in federal court, only case-ending judgments can be appealed. The writ of mandamus is one exception to that so-called final judgment rule. Mandamus permits a litigant who is [...]

INTRODUCTION 1684 I. THE GENDER OF PATENT LAW 1689 A. Women's Representation in Patent Practice 1690 B. Gender Bias in Patent Law 1693 II. EMPIRICAL METHODOLOGY 1698 III. THE GENDER [...], This Article presents an empirical study of gender diversity--or, more accurately, the lack thereof--among the lawyers who handle patent cases in the federal courts, focusing on appellate litigation at the Federal Circuit and the Supreme Court. Drawing on two original datasets, the Article finds that, over the past decade, 87.4% of oral arguments in patent appeals at the Federal Circuit have been presented by men. The numbers are similar at the Supreme Court: over the past thirty years, more than 90% of arguments in patent cases have been delivered by male attorneys. The typical explanation for these sorts of gender gaps is that men are disproportionality represented in the science and technology fields that underlie patent practice. But a closer look at the numbers shows that gender parity exists in specific areas of patent litigation. Until a recent retirement, half of the Federal Circuit's twelve active judges were women, and the women on the court tend to have more pre-appointment experience in patent law than their male counterparts. In addition, the data collected for this study demonstrate that, when the government becomes involved in patent litigation (usually because a case involves the Patent and Trademark Office), women present oral argument at the Federal Circuit 48.5% of the time--more than five times as frequently as the rate for private-sector litigants. The story this Article tells--of women being largely absent from high-level patent litigation--is actually a story about gender inequality among the lawyers hired by large corporations, particularly the Federal Circuit's most frequent litigants, including Apple, Amazon, Google, and Samsung, all of which have been represented by women in less than 15% of their arguments over the past decade. Figuring out why women rarely litigate patent appeals for private-sector clients is challenging, but the disparity between law firms and the government parallels inequalities in law practice more generally. To that end, this Article suggests both small steps that would increase gender balance among the lawyers arguing patent cases as well as broader structural reforms that would improve diversity across the bar.

Since its emergence in late 2019, more than 481 million COVID-19 cases have been confirmed worldwide (2) and >79 million cases reported in the United States (2). Numerous variants of [...]

THE RIGHT TO DO WRONG: MORALITY AND THE LIMITS OF LAW. By Mark Osiel. Cambridge, MA and London, England: Harvard University Press. 2019. Pp 502. $45 (hardback). CONTENTS Introduction 118 [...]

The views expressed in this editorial are those of the author(s) and do not necessarily reflect the position of the Canadian Medical Association or its subsidiaries, the journal's editorial board [...]

We describe a case of endogenous endophthalmitis caused by sequence type 66-K2 hypervirulent Klebsiella pneumoniae in a diabetic patient with no travel history outside the United States. Genomic analysis showed [...]

Resistance represents a major challenge for antibody-based therapy for COVID-19.sup.1-4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern--B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)--and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19. An engineered IgM antibody administered intranasally in mice shows high prophylactic efficacy and therapeutic efficacy against SARS-CoV-2, and is also effective against multiple variants of concern that are resistant to IgG-based therapeutics., Author(s): Zhiqiang Ku [sup.1] , Xuping Xie [sup.2] , Paul R. Hinton [sup.3] , Xinli Liu [sup.4] , Xiaohua Ye [sup.1] , Antonio E. Muruato [sup.5] [sup.6] , Dean C. [...]

Background: Acetabular component malposition is a major cause of dislocation following total hip arthroplasty (THA). Intellijoint HIP is an imageless navigation tool that has been shown to provide accurate intraoperative measurement of cup position during primary THA without substantially increasing operative time. However, its accuracy in revision THA has not been evaluated. This study therefore aims to assess the accuracy of Intellijoint HIP in measuring cup inclination and anteversion in comparison with computed tomography (CT) during revision THA. Methods: Intellijoint HIP was used to measure the position of the preexisting cup in 53 consecutive patients undergoing revision THA between December 2018 and February 2020. Two authors blinded to the intraoperative navigation measurements also independently measured cup position using preoperative CT according to Murray's radiographic definitions. Pearson correlation coefficients with 95% confidence intervals (CIs), paired t tests and Bland-Altman plots were used to assess agreement between navigation-and CT-measured cup position. Statistical analysis was performed using GraphPad Prism, with p values less than 0.05 indicating statistical significance. Results: There was excellent agreement between navigation and CT measurements for both cup inclination (r = 0.89, 95% CI 0.81-0.93) and anteversion (r = 0.93, 95% CI 0.88-0.96), with the mean absolute difference being 5.2[degrees] (standard deviation [SD] 4.0[degrees]) for inclination and 4.8[degrees] (SD 5.4[degrees]) for anteversion. The navigation measurement was within 10[degrees] of the radiographic measurement in 47 of 53 (88.7%) cases for inclination and 46 of 53 (86.8%) cases for anteversion. Conclusion: Imageless navigation demonstrated excellent correlation and agreement with CT measurements for both inclination and anteversion over a wide range of acetabular component positions. Contexte: La malposition de la composante acetabulaire est une cause majeure de luxation apres une intervention pour prothese totale de la hanche (PTH). Intellijoint HIPMD est un outil de navigation sans image qui offre une mesure peroperatoire precise de la cupule aceta-bulaire lors d'une PTH primaire, sans prolonger indument le temps operatoire. Par contre, sa precision lors d'une revision de PTH n'a pas ete verifiee. Cette etude vise donc a evaluer la capacite d'Intellijoint HIP a mesurer precisement l'inclinaison et l'anteversion de la cupule acetabulaire en comparaison avec la tomodensitometrie (TDM) lors d'une revision de PTH. Methodes: Intellijoint HIP a ete utilise pour mesurer la position de la cupule preexistante chez 53 patients consecutifs soumis a une revision de leur PTH entre decembre 2018 et fevrier 2020. Deux auteurs non informes des mesures peroperatoires obtenues avec l'outil de navigation ont aussi mesure de facon independante la position de la cupule a l'aide d'une TDM preoperatoire selon les definitions radiographiques de Murray. Nous avons utilise les coefficients de correlation de Pearson avec des intervalles de confiance (IC) a 95 %, des tests t apparies et des graphiques Bland-Altman pour evaluer la concordance entre la position ace-tabulaire mesuree avec l'outil de navigation et par TDM. L'analyse statistique a ete effectuee avec GraphPad Prism et les valeurs p inferieures a 0,05 indiquaient une portee statistique. Resultats: On a observe une excellente concordance entre les mesures obtenues avec l'outil de navigation et par TDM pour l'inclinaison (r = 0,89, IC a 95 % 0,81-0,93) et l'anteversion de la cupule (r = 0,93, IC a 95 % 0,88-0,96),l'ecart absolu moyen etant de 5,2[degrees] (ecart-type [E.-T.] 4,0 [degrees]) pour l'inclinaison et de 4,8 [degrees] (E.-T. 5,4 [degrees]) pour l'anteversion. La mesure au moyen de l'outil de navigation s'est retrouvee a l'interieur d'une limite de 10 [degrees] par rapport a la mesure radiographique dans 47 cas sur 53 (88,7 %) pour l'inclinaison et 46 cas sur 53 (86,8 %) pour l'anteversion. Conclusion: La navigation sans image a donne lieu a une correlation et une concordance excellentes avec les mesures par TDM pour l'inclinaison comme pour l'anteversion et ce, dans un vaste eventail de positions de la composante acetabulaire., Dislocation following total hip arthroplasty (THA) is a common complication associated with substantial morbidity and increased health care expenditures. A 2009 study of more than 50 000 revision THAs found [...]

Government responses to COVID-19 have dramatically altered the social quality of daily circumstances. Consequently, theoretical questions about social cohesion require recalibration as we explore new models of social quality. Central to this article is trust, one of the fundamental tenets of social cohesion. We present data from interviews with 40 women in midlife (45-64 years) regarding their everyday experiences of 'life in lockdown' during the pandemic. Key themes focus on women's (dis)trust in individuals (e.g., politicians, public health experts, family, themselves) and systems (e.g., politics, medicine, the media). This study provides insights into the differential impact of the pandemic in shaping public trust and hence social cohesion-in authority, institutions, and 'each other'-with important lessons for how future efforts can rebuild trust in post-pandemic times. Keywords: Australia, COVID-19, midlife women, pandemic, social quality, social cohesion, trust, The purpose of this article is to explore how COVID-19 countermeasures and associated restrictions on 'social life' have altered the nature of trust-in governments, the media, 'experts,' and the wider [...]

Introduction: Brief Cognitive Behavioral Therapy for Chronic Pain (Brief CBT-CP) is a biopsychosocial treatment designed to improve access to nonpharmacological pain care in primary care. Results from a clinical demonstration project in Veterans Health Administration (VHA) clinics showed rapid improvement in pain outcomes following Brief CBT-CP treatment in Primary Care Behavioral Health (PCBH). As part of this larger project, the current work aimed to understand patients' perspectives of Brief CBT-CP via a self-report survey completed posttreatment. Method: Thirty-four primary care patients received Brief CBT-CP as part of their usual VHA care and subsequently completed an anonymous survey that included questions regarding treatment modality, intervention content, utility, and satisfaction, as well as global assessment of change in pain-related functioning. Results: Participants reported that Brief CBT-CP content was useful (91%) and that they were satisfied with the intervention overall (89%), including appointment length, frequency of encounters, and comprehensibility of content. On average (M = 4.50, SD = 1.71), participants reported 'somewhat better' to 'moderately better' pain-related functioning following treatment. Exploratory descriptive analysis indicated that self-reported change in function following treatment may vary by patient characteristics, including gender and opioid use history. Discussion: Patients were receptive to Brief CBT-CP, were satisfied with their experience during treatment, and reported benefit in pain-related functioning after treatment. Further development and evaluation of Brief CBT-CP as a feasible biopsychosocial treatment option for pain in primary care clinics using the PCBH model of integration is warranted. Public Significance Statement This study showed that patients who completed Brief Cognitive Behavioral Therapy for Chronic Pain found treatment to be highly acceptable in terms of the length and frequency of appointments, understandability and utility of treatment content, and impact on pain-related functioning. This protocol is well suited for delivery in integrated primary care settings and may serve to extend the reach of safe, behavioral treatments for chronic pain. Keywords: chronic pain, primary health care, mental health services, primary care behavioral health, cognitive behavioral therapy, Recommendations for chronic pain management increasingly emphasize nonpharmacological interventions due to safety concerns over opioids (Dowell et al., 2016). Psychological therapies are effective treatments for chronic pain (Williams et al., [...]

Underwater explosions pose a significant threat to waterborne infrastructure. The potential for damage to nearby infrastructure is dependent on parameters such as the peak incident pressure, energy flux density, radial standoff distance, and dynamic material strength and structural response. Bubble screens have been shown to be an effective means to attenuate specific shock wave characteristics such as the peak incident pressure and energy flux density to safe levels. This paper presents a comprehensive, rational design approach for protecting waterborne infrastructure using bubble screens. The paper presents an improved methodology to predict peak incident pressure and energy flux density produced by shock waves, which includes depth effects. In addition, the damage potential to various structural materials is established based on the equivalent dynamic loads and dynamic material strength. The results are compiled to form a step-by-step procedure for the design and implementation of a bubble screen system. Key words: underwater explosion (UNDEX), shock wave, peak incident pressure, energy flux density, waterborne infrastructure. Les explosions sous l'eau representent une menace importante pour les infrastructures liees a l'eau. Le risque de dommages a l'infrastructure a proximite d'une explosion sous l'eau depend de parametres tels que la pression incidente maximale, la densite du flux energetique, la distance de securite radiale, la resistance dynamique des materiaux et la reponse structurelle. Les rideaux de bulles s'averent un moyen efficace afin d'attenuer les caracteristiques specifiques des ondes de choc, comme la pression incidente maximale et la densite du flux energetique a des niveaux sans danger. Le present document presente une approche globale et rationnelle de conception pour la protection des infrastructures liees a l'eau a l'aide de rideaux de bulles. Le document presente une methodologie amelioree pour predire la pression incidente maximale et la densite de flux energetique produites par les ondes de choc, ce qui comprend les effets de profondeur. De plus, les dommages possibles aux divers materiaux structuraux sont determines en fonction des charges dynamiques equivalentes et de la resistance dynamique du materiau. Les resultats sont compiles pour former une procedure etape par etape pour la conception et la mise en reuvre d'un systeme de rideau a bulles. [Traduit par la Redaction] Mots-cles : explosion sous l'eau (<< underwater explosion, UNDEX >>), onde de choc, pression incidente maximale, densite de flux energetique, infrastructure liee a l'eau., Introduction A major concern with waterborne infrastructure is the vulnerability to underwater explosions (UNDEX) caused by construction or military activities. Extreme loads due to UNDEX are significantly more destructive than [...]

Body size is a key biological trait, influencing the biomechanics, physiology, behaviour, and ecology of species. Describing variation in body size within and among co-occurring species within an ecological guild can provide important context for understanding the ecology of species and the structure of ecological communities. Here, we focus on a guild of carrion beetles (Coleoptera: Silphidae) co-occurring in southeastern Ontario, Canada. We examine how body size varies (i) among species, (it) within species, including among sexes, and (tit) across the active season, contrasting estimates of size based on mass with those based on morphological structure (elytron length). We find that body size varies significantly both within and among species. Five focal species show evidence for sexual dimorphism in size. All focal species show significant seasonal variation in size, but these patterns differ across species, and depend on our estimates of size. Overall, the observed variation in body size is most consistent with widespread environmental constraints on size and (or) diverse selective pressures favouring different sizes within and among species. We discuss possible selective pressures acting on size within and among species; however, the causes and consequences of the variation in body size that we describe remain to be discovered. Key words: body size, Silphidae, sexual dimorphism, resource partitioning, community ecology, carrion beetles, Coleoptera. La taille du corps est un caractere biologique cle qui influence la biomecanique, la physiologie, le comportement et l'ecologie des especes. La description des variations de la taille du corps entre especes cooccurrentes dans une meme guilde ecologique et au sein de ces especes peut fournir un important contexte pour mieux comprendre l'ecologie des especes et la structure des communautes ecologiques. Nous nous penchons sur une guilde de coleopteres necrophages (coleopteres : silphides) cooccurrents dans le sud-est de l'Ontario (Canada). Nous examinons les variations de la taille du corps (i) entre especes, (ii) au sein d'especes, y compris entre les sexes, et (iii) durant la periode d'activite, comparant des estimations de la taille reposant sur la masse a des estimations basees sur une structure morphologique (la longueur de l'elytre). Nous constatons que la taille du corps varie significativement tant au sein des especes qu'entre elles. Cinq especes focales presentent des signes de dimorphisme sexuel de la taille. Toutes les especes focales presentent des variations saisonnieres significatives de la taille, mais ces variations varient selon l'espece et dependent de nos estimations de la taille. Globalement, les variations observees de la taille du corps concordent le mieux avec des contraintes environnementales a grande echelle agissant sur la taille ou avec differentes pressions de selection qui favorisent differentes tailles au sein d'especes et entre elles. Nous abordons les pressions de selection possibles influant sur la taille au sein d'especes et entre elles; les causes et consequences des variations de la taille du corps que nous decrivons ne sont toutefois pas encore etablies. [Traduit par la Redaction] Mots-cles : taille du corps, silphides, dimorphisme sexuel, partage des ressources, ecologie des communautes, coleopteres necrophages, coleopteres., Introduction Body size is perhaps the most powerful predictor of biological form and function, permeating almost every facet of an organism's biology. Body size influences the biomechanics of organisms, including [...]

'To my knowledge,' Bruce D. Marshall notes in his foreword to this welcomed volume, 'no systematic theologian of his generation commented on the Bible as extensively as [Jenson] did.' Likewise, [...]

After the 1973 decision Roe v. Wade, a crisis of meaning emerged in opinions of the United States Supreme Court dealing with reproduction and sex. The law became less intelligible [...]

Purpose To describe critical care patients with COVID-19 across England, Wales and Northern Ireland and compare them with a historic cohort of patients with other viral pneumonias (non-COVID-19) and with international cohorts of COVID-19. Methods Extracted data on patient characteristics, acute illness severity, organ support and outcomes from the Case Mix Programme, the national clinical audit for adult critical care, for a prospective cohort of patients with COVID-19 (February to August 2020) are compared with a recent retrospective cohort of patients with other viral pneumonias (non-COVID-19) (2017-2019) and with other international cohorts of critical care patients with COVID-19, the latter identified from published reports. Results 10,834 patients with COVID-19 (70.1% male, median age 60 years, 32.6% non-white ethnicity, 39.4% obese, 8.2% at least one serious comorbidity) were admitted across 289 critical care units. Of these, 36.9% had a PaO.sub.2/FiO.sub.2 ratio of [less than or equal to] 13.3 kPa ([less than or equal to] 100 mmHg) consistent with severe ARDS and 72% received invasive ventilation. Acute hospital mortality was 42%, higher than for 5782 critical care patients with other viral pneumonias (non-COVID-19) (24.7%), and most COVID-19 deaths (88.7%) occurred before 30 days. Meaningful international comparisons were limited due to lack of standardised reporting. Conclusion Critical care patients with COVID-19 were disproportionately non-white, from more deprived areas and more likely to be male and obese. Conventional severity scoring appeared not to adequately reflect their acute severity, with the distribution across PaO.sub.2/FiO.sub.2 ratio categories indicating acutely severe respiratory disease. Critical care patients with COVID-19 experience high mortality and place a great burden on critical care services., Author(s): Alvin Richards-Belle [sup.1], Izabella Orzechowska [sup.1], Doug W. Gould [sup.1], Karen Thomas [sup.1], James C. Doidge [sup.1], Paul R. Mouncey [sup.1], Michael D. Christian [sup.2], Manu Shankar-Hari [sup.3], David [...]

PURPOSE Hearing loss, the second most common disability in the United States, is under-diagnosed and under-treated. Identifying it in early stages could prevent its known substantial adverse outcomes. METHODS A multiple baseline design was implemented to assess a screening paradigm for identifying and referring patients aged [greater than or equal to] 55 years with hearing loss at 10 family medicine clinics in 2 health systems. Patients completed a consent form and the Hearing Handicap Inventory for the Elderly (HHI). An electronic alert prompted clinicians to screen for hearing loss during visits. RESULTS The 14,877 eligible patients during the study period had 36,701 encounters. Referral rates in the family medicine clinics increased from a baseline rate of 3.2% to 14.4% in 1 health system and from a baseline rate of 0.7% to 4.7% in the other. A general medicine comparison group showed referral rate increase from the 3.0% baseline rate to 3.3%. Of the 5,883 study patients who completed the HHI 25.2% (n = 1,484) had HHI scores suggestive of hearing loss; those patients had higher referral rates, 28% vs 9.2% (P CONCLUSION An electronic alert used to remind clinicians to ask patients aged [greater than or equal to] 55 years about hearing loss significantly increased audiology referrals for at-risk patients. Audiologic and audiogram data support the effectiveness of the prompt. Clinicians should consider adopting this method to identify patients with hearing loss to reduce its known and adverse sequelae., INTRODUCTION Hearing loss affects over 30% of those aged >55 years, with over one-half suffering morbidity that includes reduced quality of life. (1-14) Untreated hearing loss is a major risk [...]

The advent of a new class of aminoglycosides with increased translational readthrough of nonsense mutations and reduced toxicity offers a new therapeutic strategy for a subset of patients with hereditary kidney disease. The renal uptake and retention of aminoglycosides at a high intracellular concentration makes the kidney an ideal target for this approach. In this review, we explore the potential of aminoglycoside readthrough therapy in a number of hereditary kidney diseases and discuss the therapeutic window of opportunity for subclasses of each disease, when caused by nonsense mutations., Author(s): Fatima Tokhmafshan [sup.1] , Kyle Dickinson [sup.1] [sup.2] , Murielle M. Akpa [sup.1] , Emma Brasell [sup.3] , Pedro Huertas [sup.4] , Paul R. Goodyer [sup.1] [sup.2] [sup.3] [sup.5] [...]

A management strategy evaluation (MSE) is used to estimate success at achieving conservation goals for marine mammals while also aiming to minimize impacts on commercial fisheries. It is intended to improve understanding of US import rules that require countries exporting fish and fish products to the USA to adhere to marine mammal bycatch standards 'comparable' to those used by the USA. The MSE framework is applied, for illustrative purposes, to export fisheries in Iceland that impact harbor porpoises (Phocoena phocoena), harbor seals (Phoca vitulina), and grey seals (Halichoerus grypus). Several management strategies are evaluated. The harbor porpoise population is estimated to be close to or above its maximum net productivity level (MNPL) and, according to the model, will continue to increase even if current levels of human-caused mortality are unchanged. In contrast, the grey seal and harbor seal populations are below MNPL, and bycatch mortality in the lumpfish (Cyclopterus lumpus) fishery will need to be reduced to allow them to recover to MNPL. Une evaluation des strategies de gestion (ESG) estutilisee pour estimer le succes vers l'atteinte d'objectifs de conservation des mammiferes marins visant aussi a minimiser les impacts sur les peches commerciales. L'objectif est d'ameliorer la comprehension des regles d'importation americaines qui exigent que les pays qui exportent des poissons et des produits du poisson vers les Etats-Unis respectent des normes concernant les prises accessoires de mammiferes marins << comparables >> aux normes utilisees par les EtatsUnis. Le cadre d'ESG est applique, a des fins d'illustration, aux peches vouees a l'exportation en Islande qui ont des impacts sur les marsouins communs (Phocoena phocoena), les phoques communs (Phoca vitulina) et les phoques gris (Halichoerus grypus). Plusieurs strategies de gestion sont evaluees. Il est estime que la population de marsouins communs se situe aux alentours ou au- dessus de son niveau de productivite nette maximum (NPNM) et, selon le modele, qu'elle continuera d'augmenter meme si les taux de mortalite causee par les humains demeurent inchanges. En revanche, les populations de phoques gris et de phoques communs sont sous leurs NPNM, et la mortalite associee aux prises accessoires dans la peche a la grosse poule de mer devra diminuer pour permettre un retour au NPNM. [Traduit par la Redaction], Introduction There is a long history of deliberate exploitation of marine mammals worldwide. Although commercial whaling and sealing have declined mainly due to a combination of regulation and resource depletion, [...]

Background: The most effective surgical approach to total hip replacement (THR) remains controversial. Most studies that have compared approaches have reported only short-term outcome data. It is therefore unclear in the literature if a particular surgical approach offers long-term advantages. The aim of this study was to determine the effect of the 3 main surgical approaches to THR on patient-reported outcomes 5 years after surgery. Methods: All patients who underwent a THR for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach at The Ottawa Hospital in Ontario, Canada, were included in the study. All preoperative and postoperative scores for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) questionnaires were recorded. Analy sis of covariance was used to study the relationship between the amount of change in scores on the HOOS and WOMAC subscales (dependent variables) and the surgical approach. The confounding factors of age, sex, American Society of Anesthesiologists (ASA) class, Charnley classification and body mass index were included in the analysis. Results: There were 138 patients (37.6%) in the posterior approach group, 104 (28.3%) in the lateral approach group and 125 (34.1%) in the anterior approach group. There were no significant differences among the 3 groups in terms of Charnley classification, body mass index, sex, ASA class, surgical side and preoperative functional scores. We did not observe any sig nificant differences in the amount of change in the scores for HOOS and WOMAC subscales among the 3 groups. There were also no differences in the final postoperative scores. Conclusion: Our findings suggest that the choice of surgical approach in primary THR surgery without revision has no influence on functional outcomes and quality of life after 5 years. Further studies are needed to assess how patient age and sex may influence the functional outcome of individual surgical approaches. Contexte : L'approche chirurgicale la plus efficace pour l'arthroplastie totale de la hanche (ATH) n'a pas ete determinee. La plupart des etudes qui ont compare les differentes approches n'ont fait etat que de donnees a court terme. Donc, la litterature nous renseigne peu sur leurs bienfaits a long terme. Le but de cette etude est de verifer l'effet des 3 principales approches chirurgicales pour l'ATH sur les parametres rapportes par les patients 5 ans apres la chirurgie. Methodes : Tous les patients soumis a une ATH pour arthrose ou osteonecrose entre 2008 et 2012 par approche anterieure, posterieure ou laterale a l'Hopital d'Ottawa, en Ontario, au Canada, ont ete inclus dans l'etude; et tous les scores preoperatoires et postoperatoires des questionnaires HOOS (Hip Disability and Osteoarthritis Outcome Score) et WOMAC (Western Ontario and MacMaster Universities Osteoarthritis Index) ont ete enregistres. L'analyse de covariance a servi a etudier le lien entre l'ampleur des changements aux scores des sous-echelles HOOS et WOMAC (variables dependantes) et l'approche chirurgicale. L'analyse a aussi tenu compte de facteurs de confusion tels que l'age, le sexe, la classe ASA (American Society of Anesthesiologists), classification de Charnley et indice de masse corporelle. Resultats : Le groupe soumis a l'approche posterieure comptait 138 patients (37,6 %), a l'approche laterale 104 (28,3 %) et a l'approche anterieure 125 (34,1 %). Il n'y avait pas de differences significatives entre les 3 groupes aux plans de la classification de Charnley, de l'indice de masse corporelle, du sexe, de la classe ASA, du cote ou la chirurgie a ete effectuee et des parametres fonctionnels preoperatoires. Nous n'avons observe aucune difference significative quant a l'ampleur du changement aux scores des sous-echelles HOOS et WOMAC entre les 3 groupes; il en est alle de meme pour les scores postoperatoires finaux. Conclusion : Selon nos observations, le choix de l'approche chirurgicale pour l'ATH primaire sans revision n'exerce aucune influence sur les parametres fonctionnels et la qualite de vie apres 5 ans. Il faudra proceder a d'autres etudes pour evaluer l'influence potentielle de l'age et du sexe sur les parametres fonctionnels des differentes approches., Total hip replacement (THR) has become one of the most commonly performed orthopedic surgical procedures, and levels of patient satisfaction are generally high. (1) Nevertheless, some controversy still exists regarding [...]

Employing a cohort sequential design and multilevel modeling, the direct and indirect effects (via depressed mood, emotional wellbeing, and perceived support) of received network support on marital quality were assessed over a 7-year period (child age 7-14) on 96 married or cohabiting mothers of children with ASD. Findings indicated several significant direct and indirect effects affecting change within mothers over time, with effects varying by whether the support source was a spouse or partner, family members, or friends. In addition, one moderated mediation effect was noted, with the indirect effect of received spousal support on marital quality via perceived spousal support retaining significance only at low and moderate levels of child problem behavior severity. Study strengths, limitations, and clinical implications are discussed., Author(s): Paul R. Benson [sup.1] Author Affiliations: (1) grid.266685.9, 0000 0004 0386 3207, Department of Sociology, University of Massachusetts Boston, , 100 Morrissey Blvd., 02125, Boston, MA, USA Parenting a [...]

Over the past two decades, a few dozen lawyers have come to dominate practice before the U.S. Supreme Court. By many accounts, these elite lawyers--whose clients are often among the [...]

ABSTRACT Descriptions of the experimental design and research highlights obtained from a series of four multiagency field projects held near Cape Canaveral, Florida, are presented. The experiments featured a 3 [...]

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS. However, neither acute CBD nor a 2-week-long course of CBD administered immediately after a kindling protocol could halt the proepileptogenic plasticity observed in AS model mice. CBD had a dose-dependent sedative effect but did not have an impact on motor performance. CBD abrogated the enhanced intracortical local field potential power, including the delta and theta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. We believe our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS and will thus help guide the rational development of CBD as a treatment for AS., Introduction Deletions or mutations of the maternally inherited copy of the UBE3A gene cause Angelman syndrome (AS). Individuals with AS show developmental delay, motor dysfunction, minimal speech, highly penetrant EEG [...]