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There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2 years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS. [ABSTRACT FROM AUTHOR]

Acetylene, ethene, and ethane are products from the degradation of trichloroethene (TCE) in contaminated aquifers. However, the volatility of these gases makes it challenging to avoid excessive losses during sampling. The objective of this study was to compare the quantification of acetylene, ethene, and ethane using passive vapor diffusion (PVD) samplers vs. conventional low‐flow groundwater collection. Samples were obtained from 8 to 13 monitoring wells at three sites that show potential for biotic and abiotic degradation of TCE in fractured rock aquifers. Method reporting limits (MRLs) for the PVD samplers were 0.25 μg/L for acetylene (0.0094 μM) and 0.28 μg/L for ethene and ethane (0.0099 and 0.0092 μM, respectively); the MRLs for conventional low‐flow groundwater samples were ~40% higher. For two of the sites, the maximum concentrations of acetylene, ethene, and ethane obtained with the PVD samplers were comparable to the conventional low‐flow samples. The frequency of detection for these gases with the PVD samplers was also comparable to conventional low‐flow groundwater sampling. For one of the sites with higher levels of acetylene (maximum of 13 μg/L), the concentrations from the PVD samplers were approximately twofold higher than those with conventional low‐flow groundwater sampling. Based on robust detection of acetylene, ethene, and/or ethane, it appears likely that degradation of TCE is occurring at the three sites that were sampled. The use of PVD samplers can reduce the possibility of false negative results to provide another line of evidence in support of natural attenuation. [ABSTRACT FROM AUTHOR]

The article discusses the burden of respiratory syncytial virus (RSV) infections in older adults globally, highlighting the significant impact on hospitalizations and deaths. It also examines the efficacy and safety of three RSV vaccines approved for older adults, with data from clinical trials and real-world observational studies. The text provides recommendations for RSV vaccination in older adults with specific risk factors and chronic conditions, as well as considerations for travelers, including timing of vaccination and destination-specific risks. The article emphasizes the need for further research on vaccine effectiveness, safety, and optimal dosing regimens to inform broader vaccination strategies. [Extracted from the article]

The evidence base for psychological benefits of GnRHA for adolescents with gender dysphoria (GD) was deemed "low quality" by the UK National Institute of Health and Care Excellence. Limitations identified include inattention to clinical importance of findings. This secondary analysis of UK clinical study data uses Reliable and Clinically Significant Change approaches to address this gap. The original uncontrolled study collected data within a specialist GD service. Participants were 44 12–15-year-olds with GD. Puberty was suppressed using "triptorelin"; participants were followed-up for 36 months. Secondary analysis used data from parent-report Child Behavior Checklists and Youth Self-Report forms. Reliable change results: 15–34% of participants reliably deteriorated depending on the subscale, time point and parent versus child report. Clinically significant change results: 27–58% were in the borderline (subclinical) or clinical range at baseline (depending on subscale and parent or child report). Rates of clinically significant change ranged from 0 to 35%, decreasing over time toward zero on both self-report and parent-report. The approach offers an established complementary method to analyze individual level change and to examine who might benefit or otherwise from treatment in a field where research designs have been challenged by lack of control groups and low sample sizes. [ABSTRACT FROM AUTHOR]

People with MS may be at heightened risk of intimate partner violence (IPV) compared to the general population; however, little is known about the prevalence of IPV among people with MS or its effects on MS-specific clinical outcomes. Additionally, while MS clinicians often discuss family planning with patients, many clinicians may have received little training in detecting and responding to IPV. Moreover, no studies have investigated how to implement IPV case-finding and resource provision in the MS clinical setting. Overall, there are several scholarly, educational, and implementation-related gaps in IPV-associated care for people with MS. This article aims to summarize the available literature on IPV in people with MS, identify future research questions, and aid MS clinicians in safely addressing IPV while awaiting vital MS-specific knowledge. [ABSTRACT FROM AUTHOR]

Aerobic cometabolism is a viable method for treating groundwater contaminated with 1,4-dioxane. Although at least one biochemical pathway by which 1,4-dioxane is used as a sole source of carbon and energy has been elucidated, comparatively little is known about the products formed during cometabolic degradation. The objective of this study was to identify the main products formed during cometabolism of 1,4-dioxane by the mixed propanotrophic culture ENV487. During biodegradation of 14C-1,4-dioxane, soluble products accumulated that were concentrated by lyophilization and then separated into fractions using high-performance liquid chromatography. Formate accounted for 51% of the 14C-labeled compounds recovered, based on co-elution with authentic material. The identity of formate as the main product was confirmed using a formate dehydrogenase assay. Other products identified that represented at least 4% of the 14C products recovered included acetate, glycerate, glycolaldehyde, ethylene glycol, and glycolate. All these compounds are readily biodegradable in an aquifer environment. This is consistent with the expectation that the endpoint for aerobic cometabolism of 1,4-dioxane by propanotrophs in a mixed culture environment is carbon dioxide. [ABSTRACT FROM AUTHOR]

Working memory (WM), a core cognitive function, enables the temporary holding and manipulation of information in mind to support ongoing behavior. Neurophysiological recordings conducted in nonhuman primates have revealed neural correlates of this process in a network of higher-order cortical regions, particularly the prefrontal cortex (PFC). Here, we review the circuit mechanisms and functional importance of WM-related activity in these areas. Recent neurophysiological data indicates that the absence of these neural correlates at different stages of WM is accompanied by distinct behavioral deficits, which are characteristic of various disease states/normal aging and which we review here. Finally, we discuss emerging evidence of electrical stimulation ameliorating these WM deficits in both humans and non-human primates. These results are important for a basic understanding of the neural mechanisms supporting WM, as well as for translational efforts to developing therapies capable of enhancing healthy WM ability or restoring WM from dysfunction. [ABSTRACT FROM AUTHOR]

A pedestrian crossing a street during rush hour often looks and listens for potential danger. When they hear several different horns, they localize the cars that are honking and decide whether or not they need to modify their motor plan. How does the pedestrian use this auditory information to pick out the corresponding cars in visual space? The integration of distributed representations like these is called the assignment problem, and it must be solved to integrate distinct representations across but also within sensory modalities. Here, we identify and analyze a solution to the assignment problem: the representation of one or more common stimulus features in pairs of relevant brain regions—for example, estimates of the spatial position of cars are represented in both the visual and auditory systems. We characterize how the reliability of this solution depends on different features of the stimulus set (e.g., the size of the set and the complexity of the stimuli) and the details of the split representations (e.g., the precision of each stimulus representation and the amount of overlapping information). Next, we implement this solution in a biologically plausible receptive field code and show how constraints on the number of neurons and spikes used by the code force the brain to navigate a tradeoff between local and catastrophic errors. We show that, when many spikes and neurons are available, representing stimuli from a single sensory modality can be done more reliably across multiple brain regions, despite the risk of assignment errors. Finally, we show that a feedforward neural network can learn the optimal solution to the assignment problem, even when it receives inputs in two distinct representational formats. We also discuss relevant results on assignment errors from the human working memory literature and show that several key predictions of our theory already have support. Author summary: Human and animal behavior relies on the integration of distinct sources of information about the same objects in the world—for instance, social behavior requires the correct integration of people with their words, even when multiple people are talking over each other. We formalize this integration process and show that it relies on at least partial redundancy between these different sources of information. In the case of integrating vocalizations with their source, this redundancy could be provided by the distinct representations of spatial position in the visual and auditory systems. Then, we show that the necessity of this integration process produces a trade-off between the representation of redundant information (for reliable integration) and the representation of non-redundant information (which is to be integrated), with implications for modular organization in the brain. Finally, we show that a simple feedforward neural network can integrate as reliably as predicted by our theory—as well as make predictions from our theory that can be tested in neural data. Overall, this work provides insight into how the brain makes sense of its distributed and sometimes distinct representations of the world. [ABSTRACT FROM AUTHOR]

Neural activity in the lateral intraparietal cortex (LIP) correlates with both sensory evaluation and motor planning underlying visuomotor decisions. We previously showed that LIP plays a causal role in visually-based perceptual and categorical decisions, and preferentially contributes to evaluating sensory stimuli over motor planning. In that study, however, monkeys reported their decisions with a saccade to a colored target associated with the correct motion category or direction. Since LIP is known to play a role in saccade planning, it remains unclear whether LIP's causal role in such decisions extend to decision-making tasks which do not involve saccades. Here, we employed reversible pharmacological inactivation of LIP neural activity while two male monkeys performed delayed match to category (DMC) and delayed match to sample (DMS) tasks. In both tasks, monkeys needed to maintain gaze fixation throughout the trial and report whether a test stimulus was a categorical match or nonmatch to the previous sample stimulus by releasing a touch bar. LIP inactivation impaired monkeys' behavioral performance in both tasks, with deficits in both accuracy and reaction time (RT). Furthermore, we recorded LIP neural activity in the DMC task targeting the same cortical locations as in the inactivation experiments. We found significant neural encoding of the sample category, which was correlated with monkeys' categorical decisions in the DMC task. Taken together, our results demonstrate that LIP plays a generalized role in visual categorical decisions independent of the task-structure and motor response modality. [ABSTRACT FROM AUTHOR]

Complex mixtures of contaminants at hazardous waste sites often pose significant challenges for remediation. For example, within the largest industrial area in northeastern Brazil, one of the sites is contaminated with at least 26 chemicals, six of which are present in the part per million range: chlorobenzene (CB), 1,2‐dichlorobenzene (1,2‐DCB), 4‐nitrotoluene (4‐NT), 2,6‐dinitrotoluene (2,6‐DNT), 4‐isopropylaniline (4‐IPA), and 1,2‐dichloroethane (1,2‐DCA). Other chemicals of concern include 2,4‐dinitrotoluene (2,4‐DNT), 2‐ and 3‐nitrotoluene (NT), and 1,4‐dioxane. The objective of this study was to evaluate remediation strategies that include aerobic and anaerobic biodegradation, along with chemical reduction and oxidation. In microcosms prepared with site soil and groundwater, aerobic biodegradation of CB, 1,2‐DCB, 2‐NT, 3‐NT, and 4‐NT was demonstrated, while the dinitrotoluene isomers, 1,2‐DCA, and 1,4‐dioxane were recalcitrant. 2,6‐DNT, 2,4‐DNT, and 4‐NT were readily reduced to amino‐toluenes under anaerobic conditions by microbes with lactate serving as the electron donor or using zero valent iron. Amino‐toluenes were amenable to chemical oxidation and/or aerobic biodegradation. This suggests a sequential treatment strategy may be the most effective remediation approach, consisting of aerobic biodegradation, followed by anaerobic reduction (abiotic or biotic) and then aerobic biodegradation and/or chemical oxidation. This approach was the most effective in a continuous flow column experiment using site soil. Batch tests with mixtures of contaminants as well as groundwater exposed to chemical oxidation revealed modest to no inhibitory effects. While these mixtures may slow the rate of biodegradation, a remediation strategy that incorporates aerobic and anaerobic biodegradation is achievable. [ABSTRACT FROM AUTHOR]

The objective of this work was to field‐demonstrate the Min‐Trap® sampler technology, a new in‐situ passive monitoring tool that offers distinct advantages for collecting mineralogical data. The Min‐Trap consists of a solid porous medium (e.g., silica sand) contained within a water‐permeable mesh and support housing that is deployed inside a monitoring well. The porous medium serves as a solid substrate upon which target minerals passively form. Analysis of the sample medium using chemical, microscopic, spectroscopic, or other techniques can provide direct evidence of geochemical conditions and the formation of target minerals in‐situ. The abiotic degradation of chlorinated volatile organic compounds via the reducing power stored in reactive minerals (e.g., iron sulfides) is a recognized important process, and Min‐Traps are well suited to document the formation of these minerals during remediation. Min‐Traps were tested in multiple wells at two field sites undergoing active remediation where reactive iron sulfide minerals were expected to be actively forming. Min‐Trap samples were analyzed by a variety of analytical techniques, including total iron, acid volatile sulfide (AVS), chromium extractable sulfide (CrES; also known as chromium reducible sulfur; CRS), weak acid soluble (WAS) iron, strong acid soluble (SAS) iron, and scanning electron microscopy–energy dispersive X‐ray spectroscopy (SEM‐EDS). The results provided direct verification of iron sulfide minerals in all cases (n = 9) where they were expected or interpreted to be possibly present based on groundwater data. Min‐Traps offer the potential for lifecycle cost savings because they do not require the collection of soil core samples, they can aid in better remedy implementation and performance, and they can potentially support earlier transition from active to passive remedy phases. [ABSTRACT FROM AUTHOR]

Objective: Many US youth experienced accelerated weight gain during the early COVID‐19 pandemic. Using an ambulatory electronic health record data set, the authors compared children's rates of BMI change in three periods: pre‐pandemic (January 2018‐February 2020), early pandemic (March‐December 2020), and later pandemic (January‐November 2021). Methods: This study used mixed‐effects models to examine differences in rates of change in BMI, weight, and obesity prevalence among the three periods. Covariates included time as a continuous variable, a variable indicating in which period each BMI was taken, sex, age, and initial BMI category. Results: In a longitudinal cohort of 241,600 children aged 2 through 19 years with ≥4 BMI measurements, the monthly rates of BMI change (kilograms per meters squared) were 0.056 (95% CI: 0.056‐0.057) in the pre‐pandemic period, 0.104 (95% CI: 0.102‐0.106) in the early pandemic, and 0.035 (95% CI: 0.033‐0.036) in the later pandemic. The estimated prevalence of obesity in this cohort was 22.5% by November 2021. Conclusions: In this large, geographically diverse cohort of US youth, accelerated rates of BMI change observed during 2020 were largely attenuated in 2021. Positive rates indicate continued weight gain rather than loss, albeit at a slower rate. Childhood obesity prevalence remained high, which raises concern about long‐term consequences of excess weight and underscores the importance of healthy lifestyle interventions. [ABSTRACT FROM AUTHOR]

The article discusses the development and recommendation of a new dengue vaccine called TAK-003. The vaccine is recommended by the World Health Organization (WHO) for children aged 6 to 16 years in areas with high dengue transmission intensity. TAK-003 is a live attenuated vaccine that provides protection against dengue serotypes 1 and 2, but its efficacy against serotypes 3 and 4 is unclear. The article also mentions that TAK-003 may be beneficial for travelers who have previously had dengue, but its use in dengue-naïve travelers is uncertain. The vaccine is administered in two doses, with the second dose given at least 3 months after the first dose. The article emphasizes the need for further research and data on the vaccine's efficacy and safety, especially for seronegative individuals and older age groups. [Extracted from the article]

Neurons in parietal cortex exhibit task-related activity during decision-making tasks. However, it remains unclear how long-term training to perform different tasks over months or even years shapes neural computations and representations. We examine lateral intraparietal area (LIP) responses during a visual motion delayed-match-to-category task. We consider two pairs of male macaque monkeys with different training histories: one trained only on the categorization task, and another first trained to perform fine motion-direction discrimination (i.e., pretrained). We introduce a novel analytical approach—generalized multilinear models—to quantify low-dimensional, task-relevant components in population activity. During the categorization task, we found stronger cosine-like motion-direction tuning in the pretrained monkeys than in the category-only monkeys, and that the pretrained monkeys' performance depended more heavily on fine discrimination between sample and test stimuli. These results suggest that sensory representations in LIP depend on the sequence of tasks that the animals have learned, underscoring the importance of considering training history in studies with complex behavioral tasks. Posterior parietal cortex supports visual categorization in macaque monkeys. Here, the authors quantify low-dimensional neural population activity using tensor regression to find that long term training history impacts encoding of categorization. [ABSTRACT FROM AUTHOR]

Categorization is an essential cognitive and perceptual process for decision-making and recognition. The posterior parietal cortex, particularly the lateral intraparietal (LIP) area has been suggested to transform visual feature encoding into abstract categorical representations. By contrast, areas closer to sensory input, such as the middle temporal (MT) area, encode stimulus features but not more abstract categorical information during categorization tasks. Here, we compare the contributions of the medial superior temporal (MST) and LIP areas in category computation by recording neuronal activity in both areas from two male rhesus macaques trained to perform a visual motion categorization task. MST is a core motion-processing region interconnected with MT and is often considered an intermediate processing stage between MT and LIP. We show that MST exhibits robust decision-correlated motion category encoding and working memory encoding similar to LIP, suggesting that MST plays a substantial role in cognitive computation, extending beyond its widely recognized role in visual motion processing. [ABSTRACT FROM AUTHOR]

Objective: There have been conflicting reports concerning weight gain among adults during the COVID-19 epidemic. Although early studies reported large weight increases, several of these analyses were based on convenience samples or self-reported information. The objective of the current study is to examine the pandemic-related weight increase associated with the pandemic through May 2021.Methods: A total of 4.25 million adults (18 to 84 years) in an electronic health record database who had at least two weight measurements between January 2019 and February 2020 and one after June 2020 were selected. Weight changes before and after March 2020 were contrasted using mixed-effects regression models.Results: Compared with the pre-pandemic weight trend, there was a small increase (0.1 kg) in weight in the first year of the pandemic (March 2020 through March 2021). Weight changes during the pandemic varied by sex, age, and initial BMI, but the largest mean increase across these characteristics was < 1.3 kg. Weight increases were generally greatest among women, adults with BMI of 30 or 35 kg/m2 , and younger adults.Conclusions: The results indicate that the mean weight gain among adults during the COVID-19 pandemic may be small. [ABSTRACT FROM AUTHOR]

A series of quantitative decision frameworks were developed to aid in the evaluation of Monitored Natural Attenuation (MNA) as a remedy for 1,4‐dioxane, chlorinated ethanes, and chlorinated ethenes. The end product is an updated version of BioPIC, a successful, existing decision framework for MNA of chlorinated ethenes. In evaluating MNA, the goal is to follow existing protocols but also incorporate more recent insights that have increased the potential viability of this technology for a wider number of contaminants. This includes data supporting the first line of evidence for MNA (decreasing concentration trends over time at appropriate sampling locations), as well as data that will serve as secondary and tertiary lines of evidence for MNA. For the BioPIC update, a similar lines of evidence approach was developed, using information from literature and project‐specific data to identify the relevant lines of evidence. As part of the update, a model for predicting contaminant trends over time and distance, including a method to estimate site‐specific biodegradation rate constants for chlorinated ethenes, chlorinated ethanes, and 1,4‐dioxane, has been included within BioPIC. The quantitative software tool provides step‐by‐step technical guidance for collecting and evaluating other lines of evidence, including data associated with targeted 14C assays, isotope fractionation, biomarkers for degradation, geochemical parameters, and co‐contaminant concentrations, to improve the MNA evaluation process. Article Impact Statement: This paper describes a new technical framework to help evaluate monitored natural attenuation as a remedy for an expanded set of compounds. [ABSTRACT FROM AUTHOR]

Summary: Background: Weight control programs for children monitor BMI changes using BMI z‐scores that adjust BMI for the sex and age of the child. It is, however, uncertain if BMIz is the best metric for assessing BMI change. Objective: To identify which of 6 BMI metrics is optimal for assessing change. We considered a metric to be optimal if its short‐term variability was consistent across the entire BMI distribution. Subjects: 285 643 2‐ to 17‐year‐olds with BMI measured 3 times over a 10‐ to 14‐month period. Methods: We summarized each metric's variability using the within‐child standard deviation. Results: Most metrics' initial or mean value correlated with short‐term variability (|r| ~ 0.3 to 0.5). The metric for which the within‐child variability was largely independent (r = 0.13) of the metric's initial or mean value was the percentage of the 50th expressed on a log scale. However, changes in this metric between the first and last visits were highly (r ≥ 0.97) correlated with changes in %95th and %50th. Conclusions: Log %50 was the metric for which the short‐term variability was largely independent of a child's BMI. Changes in log %50th, %95th, and %50th are strongly correlated. [ABSTRACT FROM AUTHOR]

1,4-Dioxane is a pervasive and persistent contaminant in numerous aquifers. Although the median concentration in most contaminant plumes is in the microgram per liter range, a subset of sites have contamination in the milligram per liter range. Most prior studies that have examined 1,4-dioxane concentrations in the hundreds of milligrams per liter range have been performed with industrial wastewater. The main objective of this study was to evaluate aerobic biodegradation of 1,4-dioxane in microcosms prepared with soil and groundwater from a site where concentrations range from ~ 1500 mg·L−1 in the source zone, to 450 mg·L−1 at a midpoint of the groundwater plume, and to 6 mg·L−1 at a down-gradient location. Treatments included biostimulation with propane, addition of propane and a propanotrophic enrichment culture (ENV487), and unamended. The highest rates of biodegradation for each location in the plume occurred in the bioaugmented treatments, although indigenous propanotrophs also biodegraded 1,4-dioxane to below 25 µg·L−1. Nutrient additions were required to sustain biodegradation of propane and cometabolism of 1,4-dioxane. Among the unamended treatments, biodegradation of 1,4-dioxane was detected in the mid-gradient microcosms. An isolate was obtained that grows on 1,4-dioxane as a sole source of carbon and energy and identified through whole-genome sequencing as Pseudonocardia dioxivorans BERK-1. In a prior study, the same strain was isolated from an aquifer in the southeastern United States. Monod kinetic parameters for BERK-1 are similar to those for strain CB1190. [ABSTRACT FROM AUTHOR]

The article discusses the provisions of the new Commercial Real Estate Receivership Act in Florida. Other topics include the duty of a receiver in the management of properties involved in litigation, the state's use of the U.S. federal Uniform Commercial Real Estate Receivership Act as basis for the new law, and the use of the general principle of contracts in the state.

Objective: This study compared the importance of age at adiposity rebound versus childhood BMI to subsequent BMI levels in a longitudinal analysis.Methods: From the electronic health records of 4.35 million children, a total of 12,228 children were selected who were examined at least once each year between ages 2 and 7 years and reexamined after age 14 years. The minimum number of examinations per child was six. Each child's rebound age was estimated using locally weighted regression (lowess), a smoothing technique.Results: Children who had a rebound age < 3 years were, on average, 7 kg/m2 heavier after age 14 years than were children with a rebound age ≥ 7 years. However, BMI after age 14 years was more strongly associated with BMI at the rebound than with rebound age (r = 0.57 vs. -0.44). Furthermore, a child's BMI at age 3 years provided more information on BMI after age 14 years than did rebound age. In addition, rebound age provided no information on subsequent BMI if a child's BMI at age 6 years was known.Conclusions: Although rebound age is related to BMI after age 14 years, a child's BMI at age 3 years provides more information and is easier to obtain. [ABSTRACT FROM AUTHOR]

The article examines longitudinal trends in body mass index (BMI) among children and adolescents aged 2–19 years before and during the COVID-19 pandemic in the United States. The study shows that during the COVID-19 pandemic, there was a significant increase in BMI among this age group, particularly among those with overweight or obesity, emphasizing the need for efforts to prevent excess weight gain and promote healthy behaviors during public health emergencies.

Background With the integration of quality improvement (QI) into competency-based models of physician training, there is an increasing requirement for medical students and residents to demonstrate competence in QI. There may be factors that commonly facilitate or inhibit the desired outcomes of QI curricula in undergraduate and postgraduate medical education. The purpose of this review was to synthesise attributes of QI curricula in undergraduate and postgraduate medical education associated with curricular outcomes. Methods A realist synthesis of peer-reviewed and grey literature was conducted to identify the common contexts, mechanisms, and outcomes of QI curricula in undergraduate and postgraduate medical education in order to develop a programme theory to articulate what works, for whom, and in what contexts. Results 18854 records underwent title and abstract screening, full texts of 609 records were appraised for eligibility, data were extracted from 358 studies, and 218 studies were included in the development and refinement of the final programme theory. Contexts included curricular strategies, levels of training, clinical settings, and organisational culture. Mechanisms were identified within the overall QI curricula itself (eg, clear expectations and deliverables, and protected time), in the didactic components (ie, content delivery strategies), and within the experiential components (eg, topic selection strategies, working with others, and mentorship). Mechanisms were often associated with certain contexts to promote educational and clinical outcomes. Conclusion This research describes the various pedagogical strategies for teaching QI to medical learners and highlights the contexts and mechanisms that could potentially account for differences in educational and clinical outcomes of QI curricula. Educators may benefit from considering these contexts and mechanisms in the design and implementation of QI curricula to optimise the outcomes of training in this competency area. [ABSTRACT FROM AUTHOR]

Obesity* is a recognized risk factor for severe COVID-19 (1,2), possibly related to chronic inflammation that disrupts immune and thrombogenic responses to pathogens (3) as well as to impaired lung function from excess weight (4). Obesity is a common metabolic disease, affecting 42.4% of U.S. adults (5), and is a risk factor for other chronic diseases, including type 2 diabetes, heart disease, and some cancers.† The Advisory Committee on Immunization Practices considers obesity to be a high-risk medical condition for COVID-19 vaccine prioritization (6). Using data from the Premier Healthcare Database Special COVID-19 Release (PHD-SR),§ CDC assessed the association between body mass index (BMI) and risk for severe COVID-19 outcomes (i.e., hospitalization, intensive care unit [ICU] or stepdown unit admission, invasive mechanical ventilation, and death). Among 148,494 adults who received a COVID-19 diagnosis during an emergency department (ED) or inpatient visit at 238 U.S. hospitals during March-December 2020, 28.3% had overweight and 50.8% had obesity. Overweight and obesity were risk factors for invasive mechanical ventilation, and obesity was a risk factor for hospitalization and death, particularly among adults aged <65 years. Risks for hospitalization, ICU admission, and death were lowest among patients with BMIs of 24.2 kg/m2, 25.9 kg/m2, and 23.7 kg/m2, respectively, and then increased sharply with higher BMIs. Risk for invasive mechanical ventilation increased over the full range of BMIs, from 15 kg/m2 to 60 kg/m2. As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity. These findings highlight the clinical and public health implications of higher BMIs, including the need for intensive COVID-19 illness management as obesity severity increases, promotion of COVID-19 prevention strategies including continued vaccine prioritization (6) and masking, and policies to ensure community access to nutrition and physical activities that promote and support a healthy BMI. [ABSTRACT FROM AUTHOR]

Rationale For Review: In response to increased concerns about emerging infectious diseases, GeoSentinel, the Global Surveillance Network of the International Society of Travel Medicine in partnership with the US Centers for Disease Control and Prevention (CDC), was established in 1995 in order to serve as a global provider-based emerging infections sentinel network, conduct surveillance for travel-related infections and communicate and assist global public health responses. This review summarizes the history, past achievements and future directions of the GeoSentinel Network.Key Findings: Funded by the US CDC in 1996, GeoSentinel has grown from a group of eight US-based travel and tropical medicine centers to a global network, which currently consists of 68 sites in 28 countries. GeoSentinel has provided important contributions that have enhanced the ability to use destination-specific differences to guide diagnosis and treatment of returning travelers, migrants and refugees. During the last two decades, GeoSentinel has identified a number of sentinel infectious disease events including previously unrecognized outbreaks and occurrence of diseases in locations thought not to harbor certain infectious agents. GeoSentinel has also provided useful insight into illnesses affecting different traveling populations such as migrants, business travelers and students, while characterizing in greater detail the epidemiology of infectious diseases such as typhoid fever, leishmaniasis and Zika virus disease.Conclusions: Surveillance of travel- and migration-related infectious diseases has been the main focus of GeoSentinel for the last 25 years. However, GeoSentinel is now evolving into a network that will conduct both research and surveillance. The large number of participating sites and excellent geographic coverage for identification of both common and illnesses in individuals who have traversed international borders uniquely position GeoSentinel to make important contributions of travel-related infectious diseases in the years to come. [ABSTRACT FROM AUTHOR]

With funding from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program, The University of Chicago Center for Asian Health Equity partnered with a federally qualified health center (FQHC) to implement multiple evidence-based interventions (EBIs) in order to improve colorectal cancer (CRC) screening uptake. The purpose of this study is to determine the effectiveness and cost of implementing a provider reminder system entered manually and supplemented with patient reminders and provider assessment and feedback. The FQHC collected demographic characteristics of the FQHC and outcome data from January 2015 through December 2015 (preimplementation period) and cost from January 2016 through September 2017 (implementation period). Cost data were collected for the implementation period. We report on the demographics of the eligible population, CRC screening order, completion rates by sociodemographic characteristics, and, overall, the effectiveness and cost of implementation. From the preimplementation phase to the implementation phase, there was a 21.2 percentage point increase in CRC screens completed. The total cost of implementing EBIs was $40908.97. We estimated that an additional 283 screens were completed because of the interventions, and the implementation cost of the interventions was $144.65 per additional screen. With the interventions, CRC screening uptake in Chicago increased for all race/ethnicity and demographic backgrounds at the FQHC, particularly for patients aged 50 to 64 years and for Asian, Hispanic, and uninsured patients. [ABSTRACT FROM AUTHOR]

Whenever the retinal image changes, some neurons in visual cortex increase their rate of firing whereas others decrease their rate of firing. Linking specific sets of neuronal responses with perception and behavior is essential for understanding mechanisms of neural circuit computation. We trained mice of both sexes to perform visual detection tasks and used optogenetic perturbations to increase or decrease neuronal spiking primary visual cortex (VI). Perceptual reports were always enhanced by increments in VI spike counts and impaired by decrements, even when increments and decrements in spiking were generated in the same neuronal populations. Moreover, detecting changes in cortical activity depended on spike count integration rather than instantaneous changes in spiking. Recurrent neural networks trained in the task similarly relied on increments in neuronal activity when activity has costs. This work clarifies neuronal decoding strategies used by cerebral cortex to translate cortical spiking into percepts that can be used to guide behavior. [ABSTRACT FROM AUTHOR]

BMI z (BMIz) score based on the Centers for Disease Control and Prevention growth charts is widely used, but it is inaccurate above the 97th percentile. We explored the performance of alternative metrics based on the absolute distance or % distance of a child's BMI from the median BMI for sex and age. We used longitudinal data from 5628 children who were first examined <12 years to compare the tracking of three BMI metrics: distance from median, % distance from median and % distance from median on a log scale. We also explored the effects of adjusting these metrics for age differences in the distribution of BMI. The intraclass correlation coefficient (ICC) was used to compare tracking of the metrics. Metrics based on % distance (whether on the original or log scale) yielded higher ICCs compared with distance from median. The ICCs of the age-adjusted metrics were higher than that of the unadjusted metrics, particularly among children who were (1) overweight or had obesity, (2) younger and (3) followed for >3 years. The ICCs of the age-adjusted metrics were also higher compared with that of BMIz among children who were overweight or obese. Unlike BMIz, these alternative metrics do not have an upper limit and can be used for assessing BMI in all children, even those with very high BMIs. The age-adjusted % from median (on a log or linear scale) works well for all ages, while unadjusted % from median is better limited to older children or short follow-up periods. [ABSTRACT FROM AUTHOR]

The 2000 CDC growth charts are based on national data collected between 1963 and 1994 and include a set of selected percentiles between the 3rd and 97th and LMS parameters that can be used to obtain other percentiles and associated z-scores. Obesity is defined as a sex- and age-specific body mass index (BMI) at or above the 95th percentile. Extrapolating beyond the 97th percentile is not recommended and leads to compressed z-score values. This study attempts to overcome this limitation by constructing a new method for calculating BMI distributions above the 95th percentile using an extended reference population. Data from youth at or above the 95th percentile of BMI-for-age in national surveys between 1963 and 2016 were modelled as half-normal distributions. Scale parameters for these distributions were estimated at each sex-specific 6-month age-interval, from 24 to 239 months, and then smoothed as a function of age using regression procedures. The modelled distributions above the 95th percentile can be used to calculate percentiles and non-compressed z-scores for extreme BMI values among youth. This method can be used, in conjunction with the current CDC BMI-for-age growth charts, to track extreme values of BMI among youth. [ABSTRACT FROM AUTHOR]

Objective: Several cross-sectional studies have shown that height in childhood is correlated with BMI and with body fatness, and two longitudinal studies have reported that childhood height is associated with adult BMI. This study explored this longitudinal association in an electronic health record database of 2.8 million children.Methods: Children were initially examined between the ages of 2 and 13.9 years and, on average, were reexamined 4 years later.Results: As expected, there was a cross-sectional correlation between height-for-age z score and BMI that increased from r = -0.06 (age of 2 years) to r = 0.37 (age of 9-10 years). In addition, height-for-age at the first visit was related to subsequent BMI and obesity, with the prevalence of subsequent obesity increasing about fourfold over six categories of height-for-age at the first visit. About 40% of this longitudinal association was independent of initial BMI, but its magnitude decreased with initial age. For example, the initial height-for-age of children who were 12 years of age or older was only weakly associated with subsequent BMI.Conclusions: Health professionals should recognize that greater childhood height-for-age before 12 years of age may be a marker for increased risk of subsequent obesity. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a neurodevelopmental genetic disorder in which maternal immune activation (MIA) and increased tumor necrosis factor-α (TNF-α) may contribute. Previous studies using iPSC-derived cerebral organoids and neuronal cells demonstrated developmental malformation and transcriptional dysregulations, including TNF receptors and their signaling genes, common to SZ patients with diverse genetic backgrounds. In the present study, we examined the significance of the common TNF receptor dysregulations by transiently exposing cerebral organoids from embryonic stem cells (ESC) and from representative control and SZ patient iPSCs to TNF. In control iPSC organoids, TNF produced malformations qualitatively similar in, but generally less pronounced than, the malformations of the SZ iPSC-derived organoids. TNF and SZ alone disrupted subcortical rosettes and dispersed proliferating Ki67+ neural progenitor cells (NPC) from the organoid ventricular zone (VZ) into the cortical zone (CZ). In the CZ, the absence of large ramified pan-Neu+ neurons coincided with loss of myelinated neurites despite increased cortical accumulation of O4+ oligodendrocytes. The number of calretinin+ interneurons increased; however, they lacked the preferential parallel orientation to the organoid surface. SZ and SZ+TNF affected fine cortical and subcortical organoid structure by replacing cells with extracellular matrix (ECM)-like fibers The SZ condition increased developmental vulnerability to TNF, leading to more pronounced changes in NPC, pan-Neu+ neurons, and interneurons. Both SZ- and TNF-induced malformations were associated with the loss of nuclear (n)FGFR1 form in the CZ and its upregulation in deep IZ regions, while in earlier studies blocking nFGFR1 reproduced cortical malformations observed in SZ. Computational analysis of ChiPseq and RNAseq datasets shows that nFGFR1 directly targets neurogenic, oligodendrogenic, cell migration, and ECM genes, and that the FGFR1-targeted TNF receptor and signaling genes are overexpressed in SZ NPC. Through these changes, the developing brain with the inherited SZ genome dysregulation may suffer increased vulnerability to TNF and thus, MIA. [ABSTRACT FROM AUTHOR]