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Isabelle P Sico,1 Amber Oberle,2 Sheila M Thomas,3 Thomas Barsanti,3 Lisa Egbuonu-Davis,3 Daniel T Kennedy,3 Leah L Zullig,1,4,5 Hayden B Bosworth1,4– 7 1Department of Population Health Science, Duke University School of Medicine, Durham, NC, USA; 2Division of Pulmonary, Allergy and Critical Care, Duke University, Durham, NC, USA; 3Medical Affairs, Sanofi, Bridgewater, NJ, USA; 4Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA Medical Center, Durham, NC, USA; 5Division of General Internal Medicine, Duke University, Durham, NC, USA; 6School of Nursing, Duke University, Durham, NC, USA; 7Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USACorrespondence: Hayden B BosworthDuke University School of Medicine, 411 West Chapel Hill Street, Suite 600, Durham, NC, 27701, USATel +1 919-286-6936Email Hayden.bosworth@duke.eduAbstract: Moderate-to-severe asthma represents about a quarter of the nearly 10% of Americans diagnosed with asthma. Many patients with moderate-to-severe asthma have uncontrolled symptoms that lead to exacerbations requiring oral corticosteroids. There are many factors contributing to poor asthma control, including poor adherence to prescribed therapies, the under-prescribing of biologics and therapeutic inertia. We convened an eight-member panel from fields of primary care, pulmonology, immunology, health services and clinical research, behavioral science and pharmaceutical medical affairs, with the goal of identifying contributing factors and solutions to therapeutic inertia with asthma biologics. We used the Capability, Opportunity, and Motivation (COM-B) model to classify patient and provider behavior towards therapeutic inertia. The model incorporates existing behavior theories and is driven by the interaction of capability, opportunity, and motivation. We used a Delphi method to identify and develop six primary solutions: 1) integration of patient-centered outcomes into asthma management practice; 2) provider education about asthma treatment; 3) moderate-to-severe asthma care delivery redesign; 4) harmonized, evidence-based protocol for the management of moderate-to-severe asthma; 5) designated coordinator approach for optimal asthma management; and 6) a case coordination digital support tool. Integration of patient-centered outcomes into asthma management practice and provider education were identified as having the highest potential to impact therapeutic and clinical inertia. The COM-B model is effective in identifying improvement within therapeutic inertia targeting the capabilities, opportunities, and motivations of patients, providers, and payer systems.Keywords: asthma, COM-B, clinical inertia, therapeutic inertia

Stephanie M Thomas,1 Holly B Cassells2 1Vital Life Wellness Center, 2Ila Faye School of Nursing, University of the Incarnate Word, San Antonio, TX, USA Abstract: Elevated blood pressure (BP) and prehypertension increase the risk of cardiovascular diseases, a national health concern. This article presents a quality improvement project implemented within a primary care setting that aimed at lowering cardiovascular risk by improving the identification, treatment, and follow-up of patients with elevated BP. This project was designed and implemented to address the identified deficiencies contributing to poor identification and follow-up of patients with elevated BP. The intervention was multi-pronged and comprised a staff educational program, introduction of a new method for measuring BP using the BpTRU™ device, and patient educational intervention. A significant improvement in staff BP knowledge scores was achieved following the intervention (p

CeCd3As3 is a rare-earth triangular-lattice antiferromagnet with large interlayer separation. Our field-dependent heat capacity measurements at dilution fridge temperatures allow us to trace the field evolution of the spin-excitation gaps throughout the antiferromagnetic and paramagnetic regions. The distinct gap evolution places strong constraints on the microscopic pseudospin model, which, in return, yields a close quantitative description of the gap behavior. This analysis provides crucial insights into the nature of the magnetic state of CeCd3As3, with a certainty regarding its stripe order and low-energy model parameters that sets a compelling paradigm for exploring and understanding the rapidly growing family of the rare-earth-based triangular-lattice systems.

The transverse voltage generated by a temperature gradient in a perpendicularly applied magnetic field, termed the Nernst effect, has promise for thermoelectric applications and for probing electronic structure. In magnetic materials, an anomalous Nernst effect (ANE) is possible in a zero magnetic field. We report a colossal ANE in the ferromagnetic metal UCo0.8Ru0.2Al, reaching 23 microvolts per kelvin. Uranium's 5f electrons provide strong electronic correlations that lead to narrow bands, a known route to producing a large thermoelectric response. In addition, uranium's strong spin-orbit coupling produces an intrinsic transverse response in this material due to the Berry curvature associated with the relativistic electronic structure. Theoretical calculations show that in UCo0.8Ru0.2Al at least 148 Weyl nodes, and two nodal lines, exist within 60 millielectron volt of the Fermi level. This work demonstrates that magnetic actinide materials can host strong Nernst and Hall responses due to their combined correlated and topological nature.

Yb14MnSb11 is a magnetic Zintl compound as well as being one of the best high temperature p-type thermoelectric materials. According to the Zintl formalism, which defines intermetallic phases where cations and anions are valence satisfied, this structure type is nominally made up of 14 Yb2+, 1 MnSb49-, 1 Sb37-, and 4 Sb3- atoms. When Mn is replaced by Mg or Zn, the Zintl defined motifs become 13 Yb2+, 1 Yb3+, 1 (Mg, Zn)Sb410-, 1 Sb37-, and 4 Sb3-. The predicted existence of Yb3+ based on simple electron counting rules of the Zintl formalism calls the Yb valence of these compounds into question. X-ray absorption near-edge structure, magnetic susceptibility, and specific heat measurements on single crystals of the three analogs show signatures of intermediate valence Yb behavior and in particular, reveal the heavy fermion nature of Yb14MgSb11. In these isostructural compounds, Yb can exhibit a variety of electronic configurations from intermediate (M=Zn), mostly 2+ (M=Mn), to 3+ (M=Mg). In all cases, there is a small amount of intermediate valency at the lowest temperatures. The amount of intermediate valency is constant for M=Mn, Mg and temperature dependent for M=Zn. The evolution of the Yb valence correlated to the transport properties of these phases is highlighted. The presence of Yb in this structure type allows for fine tuning of the carrier concentration and thereby the possibility of optimized thermoelectric properties along with unique magnetic phenomena.

In light of a detailed characterization of genetic aberrations in cancer, nucleic acid targeting represents an attractive therapeutic approach with significant translational potential. Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer deaths worldwide with stagnant 5-year survival rates. Advances in conventional treatment have done little to improve survival and combined chemoradiation is associated with significant adverse effects. Recent reports have characterized the genetic alterations in HNSCC and demonstrated that mutations confer resistance to conventional and molecular targeted therapies. The ability to use specific nucleic acid sequences to inhibit cancer-associated genes including non-druggable targets facilitates personalized medicine approaches with less adverse effects. Additionally, advances in drug delivery mechanisms have increased the transfection efficiency aiding in greater therapeutic responses. Given these advances, the stage has been set to translate the information garnered from genomic studies into personalized treatment strategies. Genes involved in the tumor protein 53 and epidermal growth factor receptor pathways have been extensively investigated and many promising preclinical studies have shown tumor inhibition through genetic modulation. We, and others, have demonstrated that targeting oncogene expression with gene therapy approaches is feasible in patients. Other methods such as RNA interference have proven to be effective and are potential candidates for clinical studies. This review summarizes the major advances in sequence-specific gene modulation in the preclinical setting and in clinical trials in head and neck cancer patients.

Heavy fermion (HF) materials exhibit a rich array of phenomena due to the strong Kondo coupling between their localized moments and itinerant electrons. A central question in their study is to understand the interplay between magnetic order and charge transport, and its role in stabilizing new quantum phases of matter. Particularly promising in this regard is a family of tetragonal intermetallic compounds CeTX2 (where T denotes transition metal and X denotes pnictogen), which includes a variety of HF compounds showing T-linear electronic specific heat Ce∼γT, with γ∼20-500mJmol-1K-2, reflecting an effective-mass enhancement ranging from small to modest. Here, we study the low-temperature field-tuned phase diagram of high-quality CeAgBi2 using magnetometry and transport measurements. We find an antiferromagnetic transition at TN=6.4K with weak magnetic anisotropy and the easy axis along the c axis, similar to previous reports (TN=6.1K). This scenario, along with the presence of two anisotropic Ruderman-Kittel-Kasuya-Yosida interactions, leads to a rich field-tuned magnetic phase diagram, consisting of five metamagnetic transitions of both first and second order. In addition, we unveil an anomalous Hall contribution for fields H

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors.

Abstract This study investigates the impact of media on color sense: our ability to see different colors and use them to interpret the world. Specifically, we examine the role of color in the cultural construction of the Orient—an ‘imagined geography’ used to justify colonial domination—in two turn-of-the-twentieth-century types of color(ed) photographs: photochromes, where a printer added color, and autochromes, where colors were captured during exposure. While most research on visual Orientalism has focused on content, we use machine learning methods to study the most important formal element of visual Orientalism: color. After using K-means clustering to extract sixteen dominant colors from each photograph in our dataset, we train three different random forest classification algorithms to make a distinction between (A) the two color media (B) photochromes of the Orient and the Occident; and (C) autochromes of the Orient and the Occident. Subsequently, we apply Shapley Additive Explanations, an explainable AI method, to interpret the output of the classifiers. This allows us to examine how specific features (colors) impacted the classifiers’ predictions. While the algorithm can easily separate photochromes from autochromes (0.95) and Oriental from Occidental photochromes (0.93), it struggles with the same task in the autochrome collection (0.68). These findings support three interconnected conclusions: (1) color sense became mediated in the late nineteenth century, (2) in photochromes, the presence and absence of specific colors was a vital aspect of visual Orientalism, (3) the autochrome, where color was derived from light, provided a more objective picture of countries in the near and middle East than the photochrome.

Abstract De novo mutations (DNMs) are drivers of genetic disorders. However, the study of DNMs is hampered by technological limitations preventing accurate quantification of ultra-rare mutations. Duplex Sequencing (DS) theoretically has T. Blood MF and substitution spectrum were similar to those reported in blood cells with an orthogonal method. The sperm MF was in the same order of magnitude and had a strikingly similar spectrum to DNMs from publicly available whole genome sequencing data from human pedigrees (1.2 × 10− 8 per bp). DS revealed much larger numbers of insertions and deletions in sperm over blood, driven by an abundance of putative extra-chromosomal circular DNAs. The study indicates the strong potential of DS to characterize human DNMs to inform factors that contribute to disease susceptibility and heritable genetic risks.

Abstract Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca2+/calmodulin-dependent protein kinase II. We have previously observed an association between high impact variants in LRRC7 and Intellectual Disability; also three individual cases with variants in LRRC7 had been described. We identify here 33 individuals (one of them previously described) with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in LRRC7. The clinical spectrum involves intellectual disability, autism, ADHD, aggression and, in several cases, hyperphagia-associated obesity. A PDZ domain variant interferes with synaptic targeting of Densin-180 in primary cultured neurons. Using in vitro systems (two hybrid, BioID, coimmunoprecipitation of tagged proteins from 293T cells) we identified new candidate interaction partners for the LRR domain, including protein phosphatase 1 (PP1), and observed that variants in the LRR reduced binding to these proteins. We conclude that LRRC7 encodes a major determinant of intellectual development and behaviour.

Abstract Plant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI). Individuals with higher healthful PDI had lower BMI and fasting glucose and higher HDL-C, while those with higher unhealthful PDI had higher BMI, triacylglycerol and fasting glucose and lower HDL-C. Unhealthful PDI was associated with higher levels of several amino acids and biogenic amines previously associated with cardiometabolic diseases and an opposite pattern was observed for healthful PDI. Furthermore, healthful PDI was associated with higher levels of glycerophosphocholines containing very long-chain fatty acids. Glutamate, isoleucine, proline, tyrosine, α-aminoadipate and kynurenine had a statistically significant mediation effect on the associations between PDI scores and LDL-C, HDL-C and fasting glucose. These findings contribute to the growing evidence supporting the role of plant-based diets in promoting metabolic health and shed light on the potential mechanisms explaining their beneficial health effects.

Behavioral neuroscience requires precise and unbiased methods for animal behavior assessment to elucidate complex brain–behavior interactions. Traditional manual scoring methods are often labor-intensive and can be prone to error, necessitating advances in automated techniques. Recent innovations in computer vision have led to both marker- and markerless-based tracking systems. In this protocol, we outline the procedures required for utilizing Augmented Reality University of Cordoba (ArUco) markers, a marker-based tracking approach, to automate the assessment and scoring of rodent engagement during an established intracortical microstimulation-based nose-poking go/no-go task. In short, this protocol involves detailed instructions for building a suitable behavioral chamber, installing and configuring all required software packages, constructing and attaching an ArUco marker pattern to a rat, running the behavioral software to track marker positions, and analyzing the engagement data for determining optimal task durations. These methods provide a robust framework for real-time behavioral analysis without the need for extensive training data or high-end computational resources. The main advantages of this protocol include its computational efficiency, ease of implementation, and adaptability to various experimental setups, making it an accessible tool for laboratories with diverse resources. Overall, this approach streamlines the process of behavioral scoring, enhancing both the scalability and reproducibility of behavioral neuroscience research. All resources, including software, 3D models, and example data, are freely available at https://github.com/tomcatsmith19/ArucoDetection.

Abstract NOAA Daily Optimum Interpolation Sea Surface Temperature (DOISST) and other similar sea surface temperature (SST) products indicate that the globally averaged SST set a new daily record in March 2023. The record‐high SST in March was immediately broken in April, and new daily records were set again in July and August 2023. The SST anomaly (SSTA) persisted at a record high from mid‐March to the remainder of 2023. Our analysis indicates that the record‐high SSTs, and associated marine heatwaves (MHWs) and even super‐MHWs, are attributed to three factors: (a) a long‐term warming trend, (b) a shift to the warm phase of the multi‐decadal Pacific‐Atlantic‐Arctic (PAA) mode, and (c) the transition from the triple‐dip succession of La Niña events to the 2023–24 El Niño event.

This study explores the development and validation of an airflow model to support climate prediction for Citrus Under Protective Screens (CUPS) in California. CUPS is a permeable screen structure designed to protect a field of citrus trees from large insects including the vector that causes the devastating citrus greening disease. Because screen structures modify the environmental conditions (e.g., temperature, relative humidity, airflow), farm management and treatment strategies (e.g., pesticide spraying events) must be modified to account for these differences. Toward this end, we develop a model for predicting wind speed and direction in a commercial-scale research CUPS, using a computational fluid dynamics (CFD) model. We describe the model and validate it in two ways. In the first, we model a small-scale replica CUPS under controlled conditions and compare modeled and measured airflow in and around the replica structure. In the second, we model the full-scale CUPS and use historical measurements to “back test” the model’s accuracy. In both settings, the modeled airflow values fall within statistical confidence intervals generated from the corresponding measurements of the conditions being modeled. These findings suggest that the model can aid decision support and smart agriculture solutions for farmers as they adapt their farm management practices for CUPS structures.

Sodium dependent multivitamin transporter (SMVT) deficiency is a very rare autosomal recessive disorder characterized by multisystemic clinical manifestations due to combined biotin, panthotenic acid and lipoic acid deficiency. About 10 families have been described so far. Accurate diagnosis is crucial because of the possibility of a supplementation treatment with proven efficacy. Here we describe 4 new patients (3 additional families) originating from the same world region (Algeria, Maghreb). All patients, born form consanguineous parents, were homozygous carriers of the same intronic variation, outside of canonical sites, in the SLC5A6 gene encoding SMVT. RNA study in one family allowed confirming the pathogenic effect of the variation and re-classifying this variant of uncertain significance as pathogenic, opening the possibility of genetic counseling and treatment. The identification of the same variation in three distinct and apparently unrelated families is suggestive of a founder effect. The phenotype of all patients was very similar, with systematic optic atrophy (initially considered as a very rare sign), severe cyclic vomiting, and rapidly progressive mixed axonal and demyelinating sensory motor neuropathy.

Background: Thoracic ultrasound is a valuable tool that helps diagnose cardiopulmonary disorders and guide management in intensive care unit patients. Intensive care unit nurses were trained to perform thoracic ultrasound examinations, after which they were named ‘UltraNurses’ for clinical recognizability. UltraNurses demonstrated rapid learning trajectories, but the impact on clinical-decision making remained unknown. The aim of this study was to investigate the effects of UltraNurse ultrasound on clinical management. Methods: This was a prospective observational single center study within a mixed medical and surgical intensive care unit. All adult patients with an indication for UltraNurse thoracic ultrasound were included. The study consisted of three steps: pre- and post- data collection, with the ultrasound examination conducted in-between these two steps. The examination consisted of a standardized ultrasound protocol aimed at the lungs and cardiac output. Primary outcome was what percentage of ultrasounds led to a change of management. Secondary outcomes included: percentage of changes executed within first 8 hours, frequency of pathology found, percentage of diagnosis change, and frequency of UltraNurse ultrasounds per shift. Results: A total of 102 ultrasound examinations were performed in 65 patients (89% mechanically-ventilated). Ultrasound examinations suggested changes of management in 26% of cases, of which 96% were executed within 8 hours. Most changes were within the nursing scope (56%), specifically: 44% of examinations changed fluid management. UltraNurse ultrasound detected pathology in 97% of cases. In 7% of cases, the diagnosis was changed, sometimes leading to life-saving interventions. UltraNurses performed one thoracic ultrasound examination per four shifts. Conclusion: In adult intensive care unit patients, UltraNurse thoracic ultrasound led to a change of management in more than a quarter of the cases, of which almost all were executed within the first 8 hours. Study registration: Netherlands Trial Registration NL9047, VUmc 2020.011 (prospectively registered on: 13–11–2020)

The highly automated macromolecular crystallography beamline AMX/17-ID-1 is an undulator-based high-intensity (>5 × 1012 photons s−1), micro-focus (7 µm × 5 µm), low-divergence (1 mrad × 0.35 mrad) energy-tunable (5–18 keV) beamline at the NSLS-II, Brookhaven National Laboratory, Upton, NY, USA. It is one of the three life science beamlines constructed by the NIH under the ABBIX project and it shares sector 17-ID with the FMX beamline, the frontier micro-focus macromolecular crystallography beamline. AMX saw first light in March 2016 and started general user operation in February 2017. At AMX, emphasis has been placed on high throughput, high capacity, and automation to enable data collection from the most challenging projects using an intense micro-focus beam. Here, the current state and capabilities of the beamline are reported, and the different macromolecular crystallography experiments that are routinely performed at AMX/17-ID-1 as well as some plans for the near future are presented.

The key challenge for rechargeable Ca batteries originates from the severe passivation of the calcium metal anode in electrolyte solutions. Here, the authors demonstrate the feasibility and elucidate the electrochemical properties of calcium-tin (Ca–Sn) alloy anodes for rechargeable Ca batteries.

Abstract Background Efforts to improve the impact of long-lasting insecticidal nets (LLINs) should be informed by understanding of the causes of decay in effect. Holes in LLINs have been estimated to account for 7–11% of loss in effect on vectorial capacity for Plasmodium falciparum malaria in an analysis of repeated cross-sectional surveys of LLINs in Kenya. This does not account for the effect of holes as a cause of net attrition or non-use, which cannot be measured using only cross-sectional data. There is a need for estimates of how much these indirect effects of physical damage on use and attrition contribute to decay in effectiveness of LLINs. Methods Use, physical integrity, and survival were assessed in a cohort of 4514 LLINs followed for up to 4 years in Kenya. Flow diagrams were used to illustrate how the status of nets, in terms of categories of use, physical integrity, and attrition, changed between surveys carried out at 6-month intervals. A compartment model defined in terms of ordinary differential equations (ODEs) was used to estimate the transition rates between the categories. Effects of physical damage to LLINs on use and attrition were quantified by simulating counterfactuals in which there was no damage. Results Allowing for the direct effect of holes, the effect on use, and the effect on attrition, 18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years in the counterfactual without physical damage. Nets that were in use were more likely to be in a damaged state than unused nets but use made little direct difference to LLIN lifetimes. Damage was reported as the reason for attrition for almost half of attrited nets, but the model estimated that almost all attrited nets had suffered some damage before attrition. Conclusions Full quantification of the effects of damage will require measurement of the supply of new nets and of household stocks of unused nets, and also of their impacts on both net use and retention. The timing of mass distribution campaigns is less important than ensuring sufficient supply. In the Kenyan setting, nets acquired damage rapidly once use began and the damage led to rapid attrition. Increasing the robustness of nets could substantially increase their lifetime and impact but the impact of LLIN programmes on malaria transmission is ultimately limited by levels of use. Longitudinal analyses of net integrity data from different settings are needed to determine the importance of physical damage to nets as a driver of attrition and non-use, and the importance of frequent use as a cause of physical damage in different contexts.

Synapsin-I (SYN1) is a presynaptic phosphoprotein crucial for synaptogenesis and synaptic plasticity. Pathogenic SYN1 variants are associated with variable X-linked neurodevelopmental disorders mainly affecting males. In this study, we expand on the clinical and molecular spectrum of the SYN1-related neurodevelopmental disorders by describing 31 novel individuals harboring 22 different SYN1 variants. We analyzed newly identified as well as previously reported individuals in order to define the frequency of key features associated with these disorders. Specifically, behavioral disturbances such as autism spectrum disorder or attention deficit hyperactivity disorder are observed in 91% of the individuals, epilepsy in 82%, intellectual disability in 77%, and developmental delay in 70%. Seizure types mainly include tonic-clonic or focal seizures with impaired awareness. The presence of reflex seizures is one of the most representative clinical manifestations related to SYN1. In more than half of the cases, seizures are triggered by contact with water, but other triggers are also frequently reported, including rubbing with a towel, fever, toothbrushing, fingernail clipping, falling asleep, and watching others showering or bathing. We additionally describe hyperpnea, emotion, lighting, using a stroboscope, digestive troubles, and defecation as possible triggers in individuals with SYN1 variants. The molecular spectrum of SYN1 variants is broad and encompasses truncating variants (frameshift, nonsense, splicing and start-loss variants) as well as non-truncating variants (missense substitutions and in-frame duplications). Genotype-phenotype correlation revealed that epileptic phenotypes are enriched in individuals with truncating variants. Furthermore, we could show for the first time that individuals with early seizures onset tend to present with severe-to-profound intellectual disability, hence highlighting the existence of an association between early seizure onset and more severe impairment of cognitive functions. Altogether, we present a detailed clinical description of the largest series of individuals with SYN1 variants reported so far and provide the first genotype-phenotype correlations for this gene. A timely molecular diagnosis and genetic counseling are cardinal for appropriate patient management and treatment.

Abstract Background In cluster randomized trials (CRTs) or stepped wedge cluster randomized trials (SWCRTs) of malaria interventions, mosquito movement leads to contamination between trial arms unless buffer zones separate the clusters. Contamination can be accounted for in the analysis, yielding an estimate of the contamination range, the distance over which contamination measurably biases the effectiveness. Methods A previously described analysis for CRTs is extended to SWCRTs and estimates of effectiveness are provided as a function of intervention coverage. The methods are applied to two SWCRTs of malaria interventions, the SolarMal trial on the impact of mass trapping of mosquitoes with odor-baited traps and the AvecNet trial on the effect of adding pyriproxyfen to long-lasting insecticidal nets. Results For the SolarMal trial, the contamination range was estimated to be 146 m ( $$95\%$$ 95 % credible interval $$[0.052,\,0.923]$$ [ 0.052 , 0.923 ] km), together with a $$31.9\%$$ 31.9 % ( $$95\%$$ 95 % credible interval $$[15.3,\,45.8]\%$$ [ 15.3 , 45.8 ] % ) reduction of Plasmodium infection, compared to the $$30.0\%$$ 30.0 % reduction estimated without accounting for contamination. The estimated effectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination effects were minimal, with insufficient data from the cluster boundary regions to estimate the effectiveness as a function of coverage. Conclusions The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fly. An appropriate analysis makes buffer zones unnecessary, enabling the design of more cost-efficient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this.

Abstract Background In cluster randomized trials (CRTs) of interventions against malaria, mosquito movement between households ultimately leads to contamination between intervention and control arms, unless they are separated by wide buffer zones. Methods This paper proposes a method for adjusting estimates of intervention effectiveness for contamination and for estimating a contamination range between intervention arms, the distance over which contamination measurably biases the estimate of effectiveness. A sigmoid function is fitted to malaria prevalence or incidence data as a function of the distance of households to the intervention boundary, stratified by intervention status and including a random effect for the clustering. The method is evaluated in a simulation study, corresponding to a range of rural settings with varying intervention effectiveness and contamination range, and applied to a CRT of insecticide treated nets in Ghana. Results The simulations indicate that the method leads to approximately unbiased estimates of effectiveness. Precision decreases with increasing mosquito movement, but the contamination range is much smaller than the maximum distance traveled by mosquitoes. For the method to provide precise and approximately unbiased estimates, at least 50% of the households should be at distances greater than the estimated contamination range from the discordant intervention arm. Conclusions A sigmoid approach provides an appropriate analysis for a CRT in the presence of contamination. Outcome data from boundary zones should not be discarded but used to provide estimates of the contamination range. This gives an alternative to “fried egg” designs, which use large clusters (increasing costs) and exclude buffer zones to avoid bias.

Sleep is crucial for maintaining the recovery and restoration of the body and brain. Less sleep is associated with poor mental and physical performance. Seasonal changes in sleep patterns can be observed. This paper examines seasonal effects on sleep timing, duration, and problems in two Cree First Nation communities in Saskatchewan, Canada. Data were available from a community survey of 588 adults aged 18 years and older (range: 18–78 years) with 44.2% males and 55.8% females. Results are presented using descriptive statistics and a binary logistic-regression model to identify the association between seasonal changes in sleep patterns, and demographic, social, and environmental factors. The participants reported sleeping the least during the spring and summer months and sleeping the most during the fall and winter months. This was further confirmed by sleep hours and the lower proportion of recommended hours of sleep during the spring and summer, and a higher proportion of longer sleep duration during the fall and winter months. There was no significant variation in sleeping onset and wake-up times by season. Overall, there were no significant differences in the prevalence of sleep deprivation, insomnia, and excessive daytime sleepiness by season. When stratified by age group and sex, some differences existed in the prevalence of sleep problems by season. More than two-thirds (68.6%) of the participants reported that there was a change in sleep patterns across seasons, and about 26.0% reported a very or extremely marked change in sleep patterns across seasons. Changes in sleep patterns by season were related to money left at the end of the month and damage caused by dampness in the house.

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children

Training recommendations for novice to intermediate lifters include loads that correspond to a 10RM, yet there has not been normative data established for college aged females. Therefore, the purpose of this study was to provide 10RM normative reference values for various strength exercises for 18 to 25-year-old females. The exercises for this study included were the Lat Pulldown, Bench Press, Seated Front Press, Preacher Curl, and the Leg Press. Every testing and training occurred using the same equipment and in the same facility. Testing occurred prior to the structured training program began and then again upon completion of 12 weeks of training. A total of 371 subjects (age = 19.86 +1.43years; height = 64.51 +2.90 inches; pre-test bodyweight = 151.19 +36.05 pounds; pre-test body fat percentage = 29.20 +8.89 percent body fat; post-test bodyweight = 153.66 +36.80 pounds; post-test body fat percentage = 30.76 +8.44 percent body fat; years of strength training experience = 2.28 +2.38 years), participated in the study. Bodyweight categories were derived based upon two established classification systems used in competitive lifting sports. Percentiles and performance rankings for each weight category were reported, where the weighted average method was used to determine the percentile break points. These norms provide a range of possible 10RM loads as well as a reference to the strength levels, which could be useful to more effectively assess and design resistance training programs.

This is the second of a two-part lesson introducing deep learning based computer vision methods for humanities research. This lesson digs deeper into the details of training a deep learning based computer vision model. It covers some challenges one may face due to the training data used and the importance of choosing an appropriate metric for your model. It presents some methods for evaluating the performance of a model.

This is the first of a two-part lesson introducing deep learning based computer vision methods for humanities research. Using a dataset of historical newspaper advertisements and the fastai Python library, the lesson walks through the pipeline of training a computer vision model to perform image classification.

Insomnia is a common problem in Canada and has been associated with increased use of health care services and economic burden. This paper examines the prevalence and risk factors for insomnia in two Cree First Nation communities in Saskatchewan, Canada. Five hundred and eighty-eight adults participated in a baseline survey conducted as part of the First Nations Sleep Health Collaborative Project. The prevalence of insomnia was 19.2% among participants with an Insomnia Severity Index score of ≥15. Following the definition of nighttime insomnia symptoms, however, the prevalence of insomnia was much higher, at 32.6%. Multivariate logistic regression modeling revealed that age, physical health, depression diagnosis, chronic pain, prescription medication use for any health condition, and waking up during the night due to terrifying dreams, nightmares, or flashbacks related to traumatic events were risk factors for insomnia among participants from two Saskatchewan Cree First Nation communities.

Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Millions of Americans aged 65 + are socially isolated and millions more report feeling lonely. Social isolation and loneliness in older adults were compounded by stay-at-home orders and other COVID-19 prevention measures. Although many Americans experienced no difficulties transitioning to the use of electronic devices as their primary means of communication and connection, some older adults were not similarly able to espouse this shift. Our aim was to reduce the impact of social isolation on older adults, increase their comfort in expressing feelings of loneliness, and assist them in acquiring technology skills and accessing telehealth and community supports. Participants received wellness calls for conversation, resource access and technology-based support. Most participants reported decreased loneliness and increased connectedness after the calls; half reported increased ease in expressing their feelings. Programs that provide phone-based support for older adults may reduce loneliness and increase social connectedness.