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•We describe the phenotypes of mouse models of XLSA, the SLC25A38 anemia, and XLPP.•XLSA and SLC25A38-CSA are conditionally synthetically lethal with pyridoxine deficiency.

Admiralty Law The Admiralty Law Committee continued to advance its four core functions in the 2020-21 fiscal year: 1) to advance the practice of admiralty and maritime law by providing [...]

CONTEXTE : La pandemie de maladie a coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) est associee a une mortalite elevee dans les unites de soins intensifs (USI). Nous avons voulu decrire les caracteristiques cliniques et les issues des patients gravement atteints de la maladie a coronavirus 2019 (COVID-19) en contexte canadien. METHODES : Nous avons procede a l'etude retrospective d'une serie de cas graves d'infection au SRAS-CoV-2 confirmee en laboratoire hospitalises dans l'une des 6 USI du Vancouver metropolitain, en Colombie-Britannique (Canada), entre le 21 fevrier et le 14 avril 2020. Les donnees demographiques, les renseignements sur la prise en charge et les resultats ont ete recueillis a partir des dossiers medicaux, electroniques ou non, des patients. RESULTATS : Entre le 21 fevrier et le 14 avril 2020, 117 patients ont ete admis dans une USI avec un diagnostic confirme de COVID-19. L'age median etait de 69 ans (ecart interquartile [EI] 60-75 ans); et 38 (32,5 %) etaient des femmes. Au moins une comorbidite etait presente chez 86 patients (73,5 %). La ventilation mecanique a ete necessaire chez 74 patients (63,2 %). La duree de la ventilation mecanique a ete de 13,5 jours (EI 8-22 jours) dans l'ensemble et de 11 jours (II 6-16) chez les patients qui ont recu leur conge de l'USI. Du tocilizumab a ete administre a 4 patients et de l'hydroxychloroquine a 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) etaient decedes, 12 (10,3 %) etaient toujours a l'USI, 16 (13,7 %) avaient obtenu leur conge de l'USI, mais restaient hospitalises, et 71 (60,7 %) avaient pu retourner a la maison. INTERPRETATION : Dans cette etude, la mortalite chez les patients gravement malades de la COVID-19 hospitalises dans une USI a ete moins elevee que chez les patients d'etudes precedentes. Ces resultats donnent a penser que le pronostic des cas graves de COVID-19 pourrait ne pas etre aussi sombre que ce qui avait d'abord ete rapporte., Le coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) est responsable de la maladie a coronavirus 2019 (COVID-19), qui a maintenant le statut de pandemie selon l'Organisation mondiale de la [...]

BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), now characterized as a pandemic by the World Health Organization. (1) Infection rates and deaths worldwide increased exponentially. [...]

In naive individuals, sensory neurons directly detect and respond to allergens, leading to both the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response1,2. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch3–7. Although these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naive state is unknown. Here we describe a γδ T cell–IL-3 signalling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal γδ T cell subset8, termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This γδ T cell–IL-3 signalling axis further acts by means of STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens on first exposure. This pathway may explain individual differences in allergic susceptibility and opens new therapeutic avenues for treating allergic diseases.

Epilepsy patients often experience acute repetitive seizures, known as seizure clusters, which can progress to prolonged seizures or status epilepticus if left untreated. Predicting the onset of seizure clusters is crucial to enable patients to receive preventative treatments. Additionally, studying the patterns of seizure clusters can help predict the seizure type (isolated or cluster) after observing a just occurred seizure. This paper presents machine learning models that use bivariate intracranial EEG (iEEG) features to predict seizure clustering. Specifically, we utilized relative entropy (REN) as a bivariate feature to capture potential differences in brain region interactions underlying isolated and cluster seizures. We analyzed a large ambulatory iEEG dataset collected from 15 patients and spanned up to 2 years of recordings for each patient, consisting of 3341 cluster seizures (from 427 clusters) and 369 isolated seizures. The dataset’s substantial number of seizures per patient enabled individualized analyses and predictions. We observed that REN was significantly different between isolated and cluster seizures in majority of the patients. Machine learning models based on REN: 1) predicted whether a seizure will occur soon after a given seizure with up to 69.5% Area under the ROC Curve (AUC), 2) predicted if a seizure is the first one in a cluster with up to 55.3% AUC, outperforming baseline techniques. Overall, our findings could be beneficial in addressing the clinical burden associated with seizure clusters, enabling patients to receive timely treatments and improving their quality of life.

This article explores the way judicial review of administrative action in Aotearoa New Zealand engenders a form of dialogical accountability; that is, a relational form of accountability as conceptualised by Bovens. In particular, the article explains the current practice and experience in a way attentive to its expressive character, highlighting the features of judicial review – both procedural infrastructure and substantive doctrinal norms – that foster and support this dynamic relationship of dialogue between actor and forum. The articular concludes with some reflections on the virtue of viewing judicial review in dialogical terms and implications for its place within the myriad of other accountability conversations operating within modern government in New Zealand.

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions.

A retrospective chart review was completed to examine psychological treatment duration and response among pediatric patients with a disorder of gut-brain interaction including functional abdominal pain and irritable bowel syndrome. Cognitive behavioral therapy (CBT) was delivered via telehealth with a licensed psychologist or supervised psychology trainee embedded in a pediatric gastroenterology clinic. Participants were 22 youth (mean age = 14.36 years) who received CBT via telehealth between February and September of 2021, after completing an initial evaluation between February and July of 2021. Patients completed reliable and valid self-report measures of functional disability and pain during treatment. A unique CBT model was employed with an initial focus on psychoeducation and function regardless of level of severity of functional impairment. Consistent with study hypotheses, nonparametric statistical analyses demonstrated statistically significant reductions in functional disability and pain following implementation of the CBT model via telehealth. Contrary to predictions, there was no relation found between severity of functional impairment and duration of treatment.

An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. How this survival mechanism affects brain metabolism, which in a resting human amounts to 20% of the overall energy demand, is only beginning to be understood. Here, we review and extend a previous hypothesis that this survival mechanism has a major role in the development of Alzheimer’s disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. We propose that the pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer’s disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. Although more studies are needed on the role of fructose metabolism and its metabolite, uric acid, in Alzheimer’s disease, we suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.

Pathogenic microorganisms contaminating potable water are a serious water quality concern because they have severe consequences for human and environmental health. Managing water contamination requires the availability of fast and highly sensitive point‐of‐use detection systems responsive to a wide concentration range. In the present work, this goal is achieved by realizing a cascade‐structured biosensor that exploits innovative stimuli‐responsive materials such as gold nanorods (AuNRs) and photosensitive nematic liquid crystals (NLCs). The cascade structure is fabricated by interfacing a glass substrate in a back‐to‐front arrangement, hosting an array of bioactivated AuNRs and an NLC cell. The AuNRs array integrates microfluidic channels, allowing direct water sampling and the analysis of reduced water volumes with high sensitivity. The biosensor combines in the same device two independent optical transducers: a bioactive AuNRs array (plasmonic biosensor), sensitive to refractive index alterations, and an NLC cell that detects the presence of pathogens by responding to light intensity variations. The plasmonic biosensor performs exceptionally well for very low concentrations of bacteria. In contrast, the NLC biosensor works for high‐concentration bacteria, thus providing a cascade‐like detection system able to detect bacteria in a wide concentration range from 10 to 109CFU mL−1. A new early warning system that detects the presence of harmful pathogens dispersed in potable water is realized by harnessing the capabilities of antibody‐functionalized gold nanorod arrays and light‐sensitive liquid crystals, providing a robust and efficient detection mechanism.

Despite the significant impact of radiation-induced redox reactions on the accessibility and lifetimes of actinide oxidation states, fundamental knowledge of aqueous actinide metal ion radiation chemistry is limited, especially for the late actinides. A quantitative understanding of these intrinsic radiation-induced processes is essential for investigating the fundamental properties of these actinides. We present here a picosecond electron pulse reaction kinetics study into the radiation-induced redox chemistry of trivalent berkelium (Bk(III)) and californium (Cf(III)) ions in acidic aqueous solutions at ambient temperature. New and first-of-a-kind, second-order rate coefficients are reported for the transient radical-induced reduction of Bk(III) and Cf(III) by the hydrated electron (eaq–) and hydrogen atom (H•), demonstrating a significant reactivity (up to 1011M–1s–1) indicative of a preference of these metals to adopt divalent states. Additionally, we report the first-ever second-order rate coefficients for the transient radical-induced oxidation of these elements by a reaction with hydroxyl (•OH) and nitrate (NO3•) radicals, which also exhibited fast reactivity (ca. 108M–1s–1). Transient Cf(II), Cf(IV), and Bk(IV) absorption spectra are also reported. Overall, the presented data highlight the existence of rich, complex, intrinsic late actinide radiation-induced redox chemistry that has the potential to influence the findings of other areas of actinide science.

Increased utilization of pediatric psychology services has been demonstrated following integration into urban pediatric gastroenterology clinics; however, examination within rural health systems is lacking. Utilization of pediatric psychology services was assessed through a retrospective analysis of Electronic Health Record data contrasting referrals occurring six months pre- and post-integration of pediatric psychology in an outpatient pediatric gastroenterology clinic within a rural setting. Significant increases in the number of referrals to pediatric psychology and number of billed initial visits were observed after integration, as was a significant decrease in time to be seen. Patients with public insurance were 3.1 times more likely to complete a billed initial visit compared with patients with nonpublic insurance. The current findings support the integration of pediatric psychology within rural outpatient pediatric gastroenterology clinics to increase utilization and allow more traditionally underserved families to benefit from these services.

The pursuit of common educational expectations, or standards, among t Instates has long been a conversation met with strong opinions-- for and against. On the one hand, it can be [...]

Background: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation--Survival Using Glucose Algorithm Regulation) study. Results: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level [less than or equal to] 6.1 mmol/L v. [less than or equal to] 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU. Une version francaise de ce resume est disponible a l'adresse www.cmaj.ca/cgi/content/full/180/8/821/DC1 CMAJ 2009;180(8):821-7, Hyperglycemia is associated with adverse outcomes, including increased mortality, in acutely ill patients. (1-7) In 2001, a randomized trial involving patients admitted to a surgical intensive care unit (ICU) showed [...]

WHERE WILL THE NEXT GENERATION of Catholic leaders come from? As the average age of priests and religious continues to climb, this question must not be ignored. Finding ways to [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.annemergmed.2006.10.016 Byline: Baruch Krauss (a)(c), Dean R. Hess (b)(c) Abstract: Although it is standard of care for patient safety monitoring in anesthesia, capnography is not routinely used for emergency department procedural sedation and analgesia. We discuss the use of capnography as a diagnostic monitoring modality for procedural sedation and analgesia, focusing on the physiology and interpretation of the CO.sub.2 waveform and recognition of normal, abnormal, and drug-induced ventilatory patterns. Author Affiliation: (a) Division of Emergency Medicine, Children's Hospital, Boston, MA (b) Division of Respiratory Care, Massachusetts General Hospital, Boston, MA (c) Harvard Medical School, Boston, MA. Article History: Received 14 July 2006; Revised 26 September 2006; Accepted 23 October 2006 Article Note: (footnote) Supervising editor: Richard M. Levitan, MD Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Available online January 12, 2007. Reprints not available from the authors.

Abstract This article reviews the strengths and limitations of static as well as dynamic risk assessment of sexually violent predators. Static risk assessment is a powerful and useful risk assessment [...]

This article uses data from Statistics New Zealand's Linked Employer-Employee Data (LEED) over the six year period April 1999-March 2005 in order to derive and analyse estimates of two-way worker and firm fixed effects components of job earnings rates. The fixed effects estimates reflect the portable earnings premium that each worker receives in whichever firm they work for, and the time-invariant premium that each firm pays to all the workers it employs. We focus on three issues. First, how much of the variation in job earnings rates is attributable to observable worker demographic factors (age and gender), unobserved worker effects and unobserved firm effects? Second, how much compositional change occurred during this period of substantial employment growth? Third, what is the aggregate pattern of sorting of workers and firms across jobs?

ABSTRACT Objectives: To clarify the benefits, risks and timing of glucose control and intensive insulin therapy in several groups, specifically the neurologic, cardiac and septic populations of patients, commonly seen [...]

Background: The proliferation of inhaler devices has resulted in a confusing number of choices for clinicians who are selecting a delivery device for aerosol therapy. There are advantages and disadvantages [...]

Objective: To test the hypothesis that the ratio of diffusing capacity of the lung for nitric oxide (DLNO) to diffusing capacity of the lung for carbon monoxide (DLCO) would be [...]

Genomic prediction (GP) has emerged an effective tool for addressing the many shortcomings of traditional selective breeding, thereby enhancing the selection process. In this study, we optimized GP methods using 5-fold cross-validation to estimate genome-estimated breeding values for the weight traits of olive flounder (Paralichthys olivaceus). To accomplish our goal, we determined the parentage of the target broodstock and the ability of 11 prediction models to predict the weight traits of 1.8-year-old olive flounders, which were genotyped using a 70 K single nucleotide polymorphism (SNP) array. Moreover, our optimization efforts toward the predictive ability of genomic best linear unbiased prediction (GBLUP), Bayesian B (BB), and random forest (RF) methods encompassed changes in various aspects such as fixed effects, SNP quantity, population size, and phenotypic data collected at different fish ages. Additionally, we assessed the predictive ability for the total length and body depth of fish using GBLUP, BB, and RF. Among the 11 prediction methods used in this study, the BB (0.675), Elastic Net (0.679), and RF (0.698) methods exhibited the highest predictive abilities, whereas the GBLUP (0.637) method demonstrated the lowest. Incorporating information regarding fish sex as a fixed effect substantially improved the predictive ability of GBLUP and BB. For mean models, utilizing 3000–5000 random SNP markers resulted in a higher predictive ability, similar to that obtained using 50,000 SNPs. Increasing the population size reduced the standard deviation of the predictive ability. Notably, phenotypic records from 1.8-year-old fish exhibited a significantly higher predictive ability than those from the other age groups. Furthermore, GBLUP, BB, and RF provided higher predictive abilities for length (0.655–0.852) and body depth (0.665–0.861). These findings may significantly shape future olive flounder genomic selection programs and offer valuable insights into GP in aquaculture.

The growing spread of pathogens, caused by anthropogenic activities, pushes the interest of the scientific community towards developing biosensors with improved performance for rapid, simple, and on-site pathogen detection. In this study, we present and discuss a label-free gold nanorod (Au NR) array for the rapid detection of Escherichia colicells in water, resulting in an effective optical transducer, based on the phenomenon of localized surface plasmon resonance (LSPR). Au NRs with different aspect ratios are functionalized with a suitable antibody by an electrostatic-linking method, resulting in two different Au NR-based bioconjugates. We investigate the ability of the two bioconjugates to detect and spectroscopically recognize E. colicells dispersed in water by specific antigen–antibody interaction. The results allow selecting the Au NR morphology more suited for preparing the Au NR bioactive array on a glass substrate with excellent optical and morphological properties. The antibody-functionalized Au NR array can detect E. colicells with high sensitivity and a limit of detection of 8.4 CFU mL−1, resulting in an excellent label-free spectroscopic biosensor. In addition, the multicolor thermoplasmonic properties of the Au NR array, triggered by appropriate light sources, are suited to enable on-demand photothermal disinfection, thus providing an extraordinary capacity for the biosensor to be both disinfected and, more importantly, reutilized.

The U.S. Court of Federal Claims recently held that certain payments made by an employer upon its employees' involuntary separation from employment are not wages subject to Federal Insurance Contributions [...]

Study objectives: Individual comparison of cardiac output via intermittent thermodilution and Fick technique over a wide range of cardiac outputs. Design: Prospective clinical investigation. Setting: Multidisciplinary ICUs of two teaching [...]

A survey is conducted among safety professionals from several United States industries on the extent to which technological developments over the last decade have affected their roles. Their personal narratives illustrate the importance of the Internet and use of machines which reduce personal injury.