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Chronic, excessive alcohol consumption is associated with cerebrovascular hypoperfusion, which has the potential to interfere with cognitive processes. Magnetic resonance pulsed continuous arterial spin labeling (PCASL) provides a noninvasive approach for measuring regional cerebral blood flow (CBF) and was used to study 24 men and women with Alcohol Use Disorder (AUD) and 20 age- and sex-matched controls. Two analysis approaches tested group differences: a data-driven, regionally-free method to test for group differences on a voxel-by-voxel basis and a region of interest (ROI) approach, which focused quantification on atlas-determined brain structures. Whole-brain, voxel-wise quantification identified low AUD-related cerebral perfusion in large volumes of medial frontal and cingulate cortices. The ROI analysis also identified lower CBF in the AUD group relative to the control group in medial frontal, anterior/middle cingulate, insular, and hippocampal/amygdala ROIs. Further, years of AUD diagnosis negatively correlated with temporal cortical CBF, and scores on an alcohol withdrawal scale negatively correlated with posterior cingulate and occipital gray matter CBF. Regional volume deficits did not account for AUD CBF deficits. Functional relevance of attenuated regional CBF in the AUD group emerged with positive correlations between episodic working memory test scores and anterior/middle cingulum, insula, and thalamus CBF. The frontolimbic and insular cortical neuroconstellation with dampened perfusion suggests a mechanism of dysfunction associated with these brain regions in AUD.

This survey investigated diagnostic and antimicrobial stewardship practices related to molecular respiratory panel testing in adults with lower respiratory tract infections at acute care hospitals. Most respondents reported use of rapid respiratory panels, but related stewardship practices were uncommon and the real-world impact of respiratory panels were difficult to quantify.

Background The cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking. Methods Magnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no/low drinking youths age 12 to 21 years at induction into this 5-site, NCANDA (National Consortium on Alcohol and NeuroDevelopment in Adolescence) study. Over the 3- to 4-year longitudinal examination yielding 2043 magnetic resonance imaging scans, 328 youths remained no/low drinkers, whereas 220 initiated substantial drinking after initial neuroimaging. Results Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V and VI, crus II, lobule VIIB, and lobule X declined faster with age in male youths than in female youths, whereas white matter volumes in crus I and crus II and lobules VIIIA and VIIIB expanded faster in female youths than in male youths; cerebrospinal fluid volume expanded faster in most cerebellar regions of male youths than female youths. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated cerebrospinal fluid volumes expansion of anterior lobules relative to youths who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana in alcohol effects on cerebellar gray matter trajectories. Conclusions Alcohol use–related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youths who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected by youthful drinking may be vulnerable to age–alcohol interactions in later adulthood.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.MethodsParticipants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.ResultsThe prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.ConclusionsThe sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.

The U.S. Food & Drug Administration (FDA) regulates the marketing of manufacturers’ in vitro diagnostic tests (IVDs), including assays for the detection of SARS-CoV-2. The U.S. government’s Clinical Laboratory Improvement Amendments (CLIA) of 1988 regulates the studies that a clinical diagnostic laboratory needs to perform for an IVD before placing it into use. Until recently, the FDA has authorized the marketing of SARS-CoV-2 IVDs exclusively through the Emergency Use Authorization (EUA) pathway. The regulatory landscape continues to evolve, and IVDs will eventually be required to pass through conventional non-EUA FDA review pathways once the emergency declaration is terminated, in order to continue to be marketed as an IVD in the United States. When FDA regulatory status of an IVD changes or is anticipated to change, the laboratory should review manufacturer information and previously performed internal verification studies to determine what, if any, additional studies are needed before implementing the non-EUA version of the IVD in accordance with CLIA regulations. Herein, the College of American Pathologists’ Microbiology Committee provides guidance for how to approach regulatory considerations when an IVD is converted from EUA to non-EUA status.

While the incidence of COVID-associated pulmonary aspergillosis (CAPA) in COVID-19 patients admitted to the ICU in Europe is widely published (incidence up to 30%) (1), data on CAPA from the United States is lacking or has not been well described (2, 3).….

Background Among the neurological consequences of alcoholism is peripheral neuropathy. Relative to human immunodeficiency virus (HIV) or diabetes-related neuropathies, neuropathy associated with alcohol use disorders (AUD) is understudied. In both the diabetes and HIV literature, emerging evidence supports a central nervous system (CNS) component to peripheral neuropathy. Methods In seeking a central substrate for AUD-related neuropathy, the current study was conducted in 154 individuals with AUD (43 women, age 21 to 74 years) and 99 healthy controls (41 women, age 21 to 77 years) and explored subjective symptoms (self-report) and objective signs (perception of vibration, deep tendon ankle reflex, position sense, 2-point discrimination) of neuropathy separately. In addition to regional brain volumes, risk factors for AUD-related neuropathy, including age, sex, total lifetime ethanol consumed, nutritional indices (i.e., thiamine, folate), and measures of liver integrity (i.e., γ-glutamyltransferase), were evaluated. Results The AUD group described more subjective symptoms of neuropathy and was more frequently impaired on bilateral perception of vibration. From 5 correlates, the number of AUD-related seizures was most significantly associated with subjective symptoms of neuropathy. There were 15 correlates of impaired perception of vibration among the AUD participants: Of these, age and volume of frontal precentral cortex were the most robust predictors. Conclusions This study supports CNS involvement in objective signs of neuropathy in AUD.

BACKGROUND: Wernicke’s encephalopathy (WE) is a neurological condition resulting from thiamine deficiency. Although commonly associated with alcoholism, non-alcoholic WE has been described in individuals with Human Immunodeficiency Virus (HIV) infection, but subclinical WE may be underdiagnosed. The current study questioned whether presence of subclinical WE signs underlies cognitive and motor deficits in HIV individuals as observed in alcoholism. SETTING: 56 HIV positive individuals (HIV+) and 53 HIV negative controls (HIV−) were assessed on 6 cognitive and motor domains: attention/working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function. METHODS: Based on a rating scheme by Caine et al, HIV+ individuals were categorized by subclinical WE risk factors (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state). Performance was expressed as age- and education-corrected Z-scores standardized on controls. RESULTS: Sorting by Caine criteria yielded 20 HIV+ as Caine 0 (i.e., meeting no criteria), 22 as Caine 1 (i.e., meeting one criterion), and 14 as Caine 2 (i.e., meeting two criteria). Comparison among HIV+ Caine subgroups revealed a graded effect: Caine 0 performed at control levels, Caine 1 showed mild to moderate deficits on some domains, and Caine 2 showed the most severe deficits on each domain. CONCLUSION: This graded severity pattern of performance among Caine subgroups suggests that signs of subclinical WE can partly explain the heterogeneity in HIV-related cognitive and motor impairment. This study highlights the utility of Caine criteria in identifying potential causes of HIV-related neurocognitive disorders and has implications for disease management.

Background Children who develop malaria after returning to a setting in which the disease is not endemic are at high risk for critical delays in diagnosis and initiation of antimalarial therapy. We assessed the clinical impact of the implementation of malaria rapid diagnostic testing (RDT) on the management of children with malaria at an urban US children’s hospital that serves a large immigrant population. Methods This was a retrospective cohort study of all children diagnosed with laboratory-confirmed malaria at the Children’s Hospital of Philadelphia (CHOP) between 2000 and 2014. RDT using a US Food and Drug Administration–approved immunochromatographic assay was introduced at CHOP on August 1, 2007. We compared clinical management and outcomes of patients with malaria diagnosed before and after RDT introduction. Results We analyzed 82 pediatric malaria cases (32 before and 50 after RDT implementation). The majority of these patients had traveled to West Africa (91.5%) and were infected with Plasmodium falciparum (80.5%). The mean time to a positive result decreased from 10.4 to 0.9 hours (P < .001) after the introduction of RDT for patients with P falciparum. The mean time to antimalarial therapy decreased from 13.1 to 6.9 hours (P =; .023) in hospitalized patients. We found no significant reduction in the mean number of clinical signs of severe malaria between 0 and 48 hours of hospitalization and no difference in the need for exchange transfusion, time to resolution of parasitemia, or length of hospital stay. Conclusions Implementation of RDT for malaria was associated with shorter times to malaria diagnosis and initiation of antimalarial therapy. The results of this study support RDT in the optimal management of patients with malaria who present in settings in which the disease is not endemic.

Neuropathy, typically diagnosed by the presence of either symptoms or signs of peripheral nerve dysfunction, remains a frequently reported complication in the antiretroviral (ART)-treated HIV population. This study was conducted in 109 healthy controls and 57 HIV-infected individuals to investigate CNS regions associated with neuropathy. An index of objective neuropathy was computed based on 4 measures: deep tendon ankle reflex, vibration sense (great toes), position sense (great toes), and 2-point discrimination (feet). Subjective neuropathy (self-report of pain, aching, or burning; pins and needles; or numbness in legs or feet) was also evaluated. Structural MRI data were available for 126/166 cases. The HIV relative to the healthy control group was impaired on all 4 signs of neuropathy. Within the HIV group, an objective neuropathy index of 1 (bilateral impairment on 1 measure) or 2 (bilateral impairment on at least 2/4 measures) was associated with older age and a smaller volume of the cerebellar vermis. Moderate to severe symptoms of neuropathy were associated with more depressive symptoms, reduced quality of life, and a smaller volume of the parietal precuneus. This study is consistent with the recent contention that ART-treated HIV-related neuropathy has a CNS component. Distinguishing subjective symptoms from objective signs of neuropathy allowed for a dissociation between the precuneus, a brain region involved in conscious information processing and the vermis, involved in fine tuning of limb movements. Graphical Abstract In HIV patients, objective signs of neuropathy correlated with smaller cerebellar vermis (red) volumes whereas subjective symptoms of neuropathy were associated with smaller precuneus (blue) volumes.

Many neurological diseases are characterized by gradual deterioration of brain structure and function. Large longitudinal MRI datasets have revealed such deterioration, in part, by applying machine and deep learning to predict diagnosis. A popular approach is to apply Convolutional Neural Networks (CNN) to extract informative features from each visit of the longitudinal MRI and then use those features to classify each visit via Recurrent Neural Networks (RNNs). Such modeling neglects the progressive nature of the disease, which may result in clinically implausible classifications across visits. To avoid this issue, we propose to combine features across visits by coupling feature extraction with a novel longitudinal pooling layer and enforce consistency of the classification across visits in line with disease progression. We evaluate the proposed method on the longitudinal structural MRIs from three neuroimaging datasets: Alzheimer's Disease Neuroimaging Initiative (ADNI, N=404), a dataset composed of 274 normal controls and 329 patients with Alcohol Use Disorder (AUD), and 255 youths from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). In all three experiments our method is superior to other widely used approaches for longitudinal classification thus making a unique contribution towards more accurate tracking of the impact of conditions on the brain. The code is available at https://github.com/ouyangjiahong/longitudinal-pooling., Accepted by Journal of Biomedical and Health Informatics (JBHI)

The age- and time-dependent effects of binge-drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume development was examined using longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Non-binge drinkers (n=177) were matched to binge drinkers (n=164) on potential confounders. Number of binge drinking episodes in the past year was linked to decreased volumes for total gray matter, frontal, parietal, temporal, and occipital lobes (psps

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10, these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan–Killiany cortical parcellations (26 of 34 with P

Background Episodic memory deficits occur in alcohol use disorder (AUD), but their anatomical substrates remain in question. Although persistent memory impairment is classically associated with limbic circuitry disruption, learning and retrieval of new information also relies on frontal systems. Despite AUD vulnerability of frontal lobe integrity, relations between frontal regions and memory processes have been under-appreciated. Methods Participants included 91 AUD (49 with a drug diagnosis history) and 36 controls. Verbal and visual episodic memory scores were age- and education-corrected. Structural magnetic resonance imaging (MRI) data yielded regional frontal lobe (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and total hippocampal volumes. Results AUD were impaired on all memory scores and had smaller precentral frontal and hippocampal volumes than controls. Orbital, superior, and inferior frontal volumes and lifetime alcohol consumption were independent predictors of episodic memory in AUD. Selectivity was established with a double dissociation, where orbital frontal volume predicted verbal but not visual memory, whereas inferior frontal volumes predicted visual but not verbal memory. Further, superior frontal volumes predicted verbal memory in AUD alone, whereas orbital frontal volumes predicted verbal memory in AUD+drug abuse history. Conclusions Selective relations among frontal subregions and episodic memory processes highlight the relevance of extra-limbic regions in mnemonic processes in AUD. Memory deficits resulting from frontal dysfunction, unlike the episodic memory impairment associated with limbic dysfunction, may be more amenable to recovery with cessation or reduction of alcohol misuse and may partially explain the heterogeneity in episodic memory abilities in AUD.

Longitudinal MRIs are often used to capture the gradual deterioration of brain structure and function caused by aging or neurological diseases. Analyzing this data via machine learning generally requires a large number of ground-truth labels, which are often missing or expensive to obtain. Reducing the need for labels, we propose a self-supervised strategy for representation learning named Longitudinal Neighborhood Embedding (LNE). Motivated by concepts in contrastive learning, LNE explicitly models the similarity between trajectory vectors across different subjects. We do so by building a graph in each training iteration defining neighborhoods in the latent space so that the progression direction of a subject follows the direction of its neighbors. This results in a smooth trajectory field that captures the global morphological change of the brain while maintaining the local continuity. We apply LNE to longitudinal T1w MRIs of two neuroimaging studies: a dataset composed of 274 healthy subjects, and Alzheimer's Disease Neuroimaging Initiative (ADNI, N=632). The visualization of the smooth trajectory vector field and superior performance on downstream tasks demonstrate the strength of the proposed method over existing self-supervised methods in extracting information associated with normal aging and in revealing the impact of neurodegenerative disorders. The code is available at \url{https://github.com/ouyangjiahong/longitudinal-neighbourhood-embedding.git}., Provisional Accepted by Medical Image Computing and Computer Assisted Intervention (MICCAI) 2021

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.

Presence of bias (in datasets or tasks) is inarguably one of the most critical challenges in machine learning applications that has alluded to pivotal debates in recent years. Such challenges range from spurious associations between variables in medical studies to the bias of race in gender or face recognition systems. Controlling for all types of biases in the dataset curation stage is cumbersome and sometimes impossible. The alternative is to use the available data and build models incorporating fair representation learning. In this paper, we propose such a model based on adversarial training with two competing objectives to learn features that have (1) maximum discriminative power with respect to the task and (2) minimal statistical mean dependence with the protected (bias) variable(s). Our approach does so by incorporating a new adversarial loss function that encourages a vanished correlation between the bias and the learned features. We apply our method to synthetic data, medical images (containing task bias), and a dataset for gender classification (containing dataset bias). Our results show that the learned features by our method not only result in superior prediction performance but also are unbiased. The code is available at https://github.com/QingyuZhao/BR-Net/., Comment: WACV 2021

IMPORTANCE: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood. OBJECTIVE: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents. DESIGN, SETTING, AND PARTICIPANTS: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking. EXPOSURES: Self-reported alcohol consumption in the past year summarized by categorical drinking levels. MAIN OUTCOMES AND MEASURES: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope. RESULTS: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t(154) = –2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r(156) = –0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t(152) = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence. CONCLUSIONS AND RELEVANCE: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.

Alcohol use disorder (AUD) is associated with neuroadaptations in brain stress and reward circuits. It is not known whether such neuroadaptations are affected by number of days of alcohol abstinence and whether they influence heavy drinking during the early treatment phase. The authors used a novel functional MRI (fMRI) approach to assess brain responses during sustained exposure to standardized visual stimuli of stressful, alcohol cue, and neutral control images combined with prospective assessment of drinking outcomes during early outpatient treatment, in two related studies.In study 1, 44 treatment-entering patients with AUD and 43 demographically matched healthy control subjects participated in the fMRI experiment to identify dysfunctional responses associated with chronic alcohol abuse. In study 2, 69 treatment-entering patients with AUD were assessed for whether fMRI responses at treatment initiation were influenced by alcohol abstinence and were prospectively predictive of early heavy drinking outcomes.Relative to control subjects, patients with AUD showed significant hyperreactivity in the ventromedial prefrontal cortex (vmPFC) in response to neutral images, but significant hypoactivation in the vmPFC and ventral striatum in response to stress images and to alcohol cues relative to response to neutral images. In study 2, this specific prefrontal-ventral striatal dysfunction was associated with fewer days of alcohol abstinence and also predicted greater number heavy drinking days during the subsequent 2 weeks of treatment engagement.Number of days of alcohol abstinence at treatment initiation significantly affected functional disruption of the prefrontal-striatal responses to stress images and to alcohol cues in patients with AUD, and the severity of this disruption in turn predicted greater heavy drinking during early treatment. Treatments that target this functional prefrontal-striatal pathology could improve early treatment outcomes in AUD.

Parkinson’s disease (PD) is a progressive neurological disorder primarily affecting motor function resulting in tremor at rest, rigidity, bradykinesia, and postural instability. The physical severity of PD impairments can be quantified through the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a widely used clinical rating scale. Accurate and quantitative assessment of disease progression is critical to developing a treatment that slows or stops further advancement of the disease. Prior work has mainly focused on dopamine transport neuroimaging for diagnosis or costly and intrusive wearables evaluating motor impairments. For the first time, we propose a computer vision-based model that observes non-intrusive video recordings of individuals, extracts their 3D body skeletons, tracks them through time, and classifies the movements according to the MDS-UPDRS gait scores. Experimental results show that our proposed method performs significantly better than chance and competing methods with an \(F_1\)-score of 0.83 and a balanced accuracy of 81%. This is the first benchmark for classifying PD patients based on MDS-UPDRS gait severity and could be an objective biomarker for disease severity. Our work demonstrates how computer-assisted technologies can be used to non-intrusively monitor patients and their motor impairments. The code is available at https://github.com/mlu355/PD-Motor-Severity-Estimation.

Minor artifacts introduced during image acquisition are often negligible to the human eye, such as a confined field of view resulting in MRI missing the top of the head. This cropping artifact, however, can cause suboptimal processing of the MRI resulting in data omission or decreasing the power of subsequent analyses. We propose to avoid data or quality loss by restoring these missing regions of the head via variational autoencoders (VAE), a deep generative model that has been previously applied to high resolution image reconstruction. Based on diffusion weighted images (DWI) acquired by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), we evaluate the accuracy of inpainting the top of the head by common autoencoder models (U-Net, VQVAE, and VAE-GAN) and a custom model proposed herein called U-VQVAE. Our results show that U-VQVAE not only achieved the highest accuracy, but also resulted in MRI processing producing lower fractional anisotropy (FA) in the supplementary motor area than FA derived from the original MRIs. Lower FA implies that inpainting reduces noise in processing DWI and thus increases the quality of the generated results. The code is available at https://github.com/RdoubleA/DWI-inpainting.

The tracking of dynamic functional connectivity (dFC) states in resting-state fMRI scans aims to reveal how the brain sequentially processes stimuli and thoughts. Despite the recent advances in statistical methods, estimating the high dimensional dFC states from a small number of available time points remains a challenge. This paper shows that the challenge is reduced by linear covariance shrinkage, a statistical method used for the estimation of large covariance matrices from small number of samples. We present a computationally efficient formulation of our approach that scales dFC analysis up to full resolution resting-state fMRI scans. Experiments on synthetic data demonstrate that our approach produces dFC estimates that are closer to the ground-truth than state-of-the-art estimation approaches. When comparing methods on the rs-fMRI scans of 162 subjects, we found that our approach is better at extracting functional networks and capturing differences in rs-fMRI acquisition and diagnosis.

Postural stability is a multi-factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet standing in 151 AUD and 96 control men and women, age 25-75. Structural equation (seq) path analysis estimated contributions from age, diagnosis, and sensory perception to sway and measures of ADL and roadside ataxia testing. Whether eyes were open or closed, older AUD and control participants had longer sway paths than younger ones; older men had longer sway paths than older women. Although each sensory ability tested declined with aging, different factor constellations influenced ADL, ataxia scores, or sway path. Seq-path analysis indicated that ADL was strongly dependent on sensory (but not cognitive) systems with sway-path length accounting for upwards of 25% of variance. Within the AUD group, an index of historically-experienced withdrawal symptoms was a common predictor of stability regardless of vision condition. The greatest variance measured by the seq-path model was for predicting platform sway and simple ataxia testing of one-leg standing even though these measures were affected by different predictor variables: strong predictors of one-leg standing were diagnosis and age (R2 = 39.6%-43.2%), whereas strong predictors of sway-path length were sensory factors and withdrawal index (R2 = 22.0%-22.9%). These findings present evidence for appreciating selective factors that contribute to declining postural stability and to liability for compromised quality of life in AUD.

BACKGROUND. In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4-day) intragastric ethanol (EtOH) on wild-type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment. METHODS. Herein, we used similar voxel-based comparisons of Magnetic Resonance Images collected in EtOH-exposed relative to control animals to test the hypothesis that regardless of the intoxication protocol or the rat strain, the hippocampi, thalami, and colliculi would be affected. RESULTS. Two experiments [binge (4-day) intragastric EtOH in Fisher 344 rats and chronic (1-month) vaporized EtOH in Wistar rats] showed similarly affected brain regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum. While most of these regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to show response to each proximal alcohol exposure but at diminished levels with repeated exposures. CONCLUSIONS. Given the high metabolic rate of these enduringly affected regions, the current findings suggest that EtOH per se may affect cellular respiration leading to brain volume deficits. Further, responsivity greatly diminished likely reflecting neuroadaptation to repeated alcohol exposure. In summary, this unbiased, in vivo based approach demonstrating convergent brain systems responsive to two EtOH exposure protocols in two rat strains highlights regions that warrant further investigation in both animal models of alcoholism and in humans with Alcohol Use Disorder.

Background Individuals with alcohol use disorder (AUD) have a heightened risk of contracting HIV infection. The effects of these two diseases and their comorbidity on brain structure have been well described, but their effects on brain function have never been investigated at the scale of whole-brain connectomes. Methods In contrast with prior studies that restricted analyses to specific brain networks or examined relatively small groups of participants, our analyses are based on whole-brain functional connectomes of 292 participants. Results Relative to participants without AUD, the functional connectivity between the anterior cingulate cortex and orbitofrontal cortex was lower for participants with AUD. Compared with participants without AUD+HIV comorbidity, the functional connectivity between the anterior cingulate cortex and hippocampus was lower for the AUD+HIV participants. Compromised connectivity between these pairs was significantly correlated with greater total lifetime alcohol consumption; the effects of total lifetime alcohol consumption on executive functioning were significantly mediated by the functional connectivity between the pairs. Conclusions Taken together, our results suggest that the functional connectivity of the anterior cingulate cortex is disrupted in individuals with AUD alone and AUD with HIV infection comorbidity. Moreover, the affected connections are associated with deficits in executive functioning, including heightened impulsiveness.

Resting-state functional connectivity states are often identified as clusters of dynamic connectivity patterns. However, existing clustering approaches do not distinguish major states from rarely occurring minor states and hence are sensitive to noise. To address this issue, we propose to model major states using a non-linear generative process guided by a Gaussian-mixture distribution in a low-dimensional latent space, while separately modeling the connectivity patterns of minor states by a non-informative uniform distribution. We embed this truncated Gaussian-Mixture model in a Variational AutoEncoder framework to obtain a general joint clustering and outlier detection approach, called tGM-VAE. When applied to synthetic data with known ground-truth, tGM-VAE is more accurate in clustering dynamic connectivity patterns than existing approaches. On the rs-fMRI data of 593 healthy adolescents from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study, tGM-VAE identified meaningful major connectivity states. The dwell time of these states significantly correlated with age.

An overarching goal of our research has been to develop a valid animal model of alcoholism with similar imaging phenotypes as those observed in humans with the ultimate objective of assessing the effectiveness of pharmacological agents. In contrast to our findings in humans with alcohol use disorders (AUD), our animal model experiments have not demonstrated enduring brain pathology despite chronic, high ethanol (EtOH) exposure protocols. Relative to healthy controls, older individuals with AUD demonstrate accelerating brain tissue loss with advanced age. Thus, this longitudinally controlled study was conducted in 4-month old (equivalent to ~16-year-old humans) and 17-month old (equivalent to ~45-year-old humans) male and female Fisher 344 rats to test the hypothesis that following equivalent alcohol exposure protocols, older relative to younger animals would exhibit more brain changes as evaluated using in vivo structural magnetic resonance imaging (MRI) and MR spectroscopy (MRS). At baseline, total brain volume as well as the volumes of each of the three constituent tissue types (i.e., cerebral spinal fluid (CSF), gray matter, white matter) were greater in old relative to young rats. Baseline metabolite levels (except for glutathione) were higher in older than younger animals. Effects of binge EtOH exposure on brain volumes and neurometabolites replicated our previous findings in Wistar rats and included ventricular enlargement and reduced MRS-derived creatine levels. Brain changes in response to binge EtOH treatment were more pronounced in young relative to older animals, negating our hypothesis. Higher baseline glutathione levels in female than male rats suggest that female rats are perhaps protected against the more pronounced changes in CSF and gray matter volumes observed in male rats due to superior metabolic homeostasis mechanisms. Additional metabolite changes including low inositol levels in response to high blood alcohol levels support a mechanism of reversible osmolarity disturbances due to temporarily altered brain energy metabolism.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

A generally accepted framework derived predominately from animal models asserts that repeated cycles of chronic intermittent ethanol (EtOH; CIE) exposure cause progressive brain adaptations associated with anxiety and stress that promote voluntary drinking, alcohol dependence, and further brain changes that contribute to the pathogenesis of alcoholism. The current study used CIE exposure via vapor chambers to test the hypothesis that repeated episodes of withdrawals from chronic EtOH would be associated with accrual of brain damage as quantified using in vivo magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS). The initial study group included 16 male (~325g) and 16 female (~215g) wild-type Wistar rats exposed to 3 cycles of 1-month in vapor chambers + 1 week of abstinence. Half of each group (n = 8) was given vaporized EtOH to blood alcohol levels approaching 250 mg/dL. Blood and behavior markers were also quantified. There was no evidence for dependence (i.e., increased voluntary EtOH consumption), increased anxiety, or an accumulation of pathology. Neuroimaging brain responses to exposure included increased cerebrospinal fluid (CSF) and decreased gray matter volumes, increased Choline/Creatine, and reduced fimbria-fornix fractional anisotropy (FA) with recovery seen after one or more cycles and effects in female more prominent than in male rats. These results show transient brain integrity changes in response to CIE sufficient to induce acute withdrawal but without evidence for cumulative or escalating damage. Together, the current study suggests that nutrition, age, and sex should be considered when modeling human alcoholism.

The Blood-Oxygen-Level-Dependent (BOLD) signal of resting-state fMRI (rs-fMRI) records the temporal dynamics of intrinsic functional networks in the brain. However, existing deep learning methods applied to rs-fMRI either neglect the functional dependency between different brain regions in a network or discard the information in the temporal dynamics of brain activity. To overcome those shortcomings, we propose to formulate functional connectivity networks within the context of spatio-temporal graphs. We train a spatio-temporal graph convolutional network (ST-GCN) on short sub-sequences of the BOLD time series to model the non-stationary nature of functional connectivity. Simultaneously, the model learns the importance of graph edges within ST-GCN to gain insight into the functional connectivities contributing to the prediction. In analyzing the rs-fMRI of the Human Connectome Project (HCP, N = 1,091) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N = 773), ST-GCN is significantly more accurate than common approaches in predicting gender and age based on BOLD signals. Furthermore, the brain regions and functional connections significantly contributing to the predictions of our model are important markers according to the neuroscience literature.

Functional connectivity between brain regions is often estimated by correlating brain activity measured by resting-state fMRI in those regions. The impact of factors (e.g., disorder or substance use) are then modeled by their effects on these correlation matrices in individuals. A crucial step in better understanding their effects on brain function could lie in estimating connectomes, which encode the correlation matrices across subjects. Connectomes are mostly estimated by creating a single average for a specific cohort, which works well for binary factors (such as sex) but is unsuited for continuous ones, such as alcohol consumption. Alternative approaches based on regression methods usually model each pair of regions separately, which generally produces incoherent connectomes as correlations across multiple regions contradict each other. In this work, we address these issues by introducing a deep learning model that predicts connectomes based on factor values. The predictions are defined on a simplex spanned across correlation matrices, whose convex combination guarantees that the deep learning model generates well-formed connectomes. We present an efficient method for creating these simplexes and improve the accuracy of the entire analysis by defining loss functions based on robust norms. We show that our deep learning approach is able to produce accurate models on challenging synthetic data. Furthermore, we apply the approach to the resting-state fMRI scans of 281 subjects to study the effect of sex, alcohol, and HIV on brain function.

Older individuals infected by Human Immunodeficiency Virus (HIV) are at risk for developing HIV-Associated Neurocognitive Disorder (HAND), i.e., from reduced cognitive functioning similar to HIV-negative individuals with Mild Cognitive Impairment (MCI) or to Alzheimer's Disease (AD) if more severely affected. Incompletely understood is how brain structure can serve to differentiate cognitive impairment (CI) in the HIV-positive (i.e., HAND) from the HIV-negative cohort (i.e., MCI and AD). To that end, we designed a multi-label classifier that labels the structural magnetic resonance images (MRI) of individuals by their HIV and CI status via two binary variables. Proper training of such an approach traditionally requires well-curated datasets containing large number of samples for each of the corresponding four cohorts (healthy controls, CI HIV-negative adults a.k.a. CI-only, HIV-positive patients without CI a.k.a. HIV-only, and HAND). Because of the rarity of such datasets, we proposed to improve training of the multi-label classifier via a multi-domain learning scheme that also incorporates domain-specific classifiers on auxiliary single-label datasets specific to either binary label. Specifically, we complement the training dataset of MRIs of the four cohorts (Control: 156, CI-only: 335, HIV-only: 37, HAND: 145) acquired by the Memory and Aging Center at the University of California - San Francisco with a CI-specific dataset only containing MRIs of HIV-negative subjects (Controls: 229, CI-only: 397) from the Alzheimer's Disease Neuroimaging Initiative and an HIV-specific dataset (Controls: 75, HIV-only: 75) provided by SRI International. Based on cross-validation on the UCSF dataset, the multi-domain and multi-label learning strategy leads to superior classification accuracy compared with one-domain or multi-class learning approaches, specifically for the undersampled HIV-only cohort. The 'prediction logits' of CI computed by the multi-label formulation also successfully stratify motor performance among the HIV-positive subjects (including HAND). Finally, brain patterns driving the subject-level predictions across all four cohorts characterize the independent and compounding effects of HIV and CI in the HAND cohort.

Background Life expectancy of successfully treated human immunodeficiency virus (HIV)–infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. Methods This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories. Results The HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups. Conclusions HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.

Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.

In the clinical microbiology laboratory, the focus when choosing new tests is often on performance, turnaround time, and labor needs. This review examines available rapid, multiplexed tests from a different perspective: that of the patient. It considers whether published evidence supports the notion that use of rapid, on-demand tests (as opposed to batched testing) leads to better patient outcomes and whether broad, syndrome-based, multiplexed panels translate into better patient care than narrower monoplex or duplex assays. Finally, we examine how synergy between the clinical microbiology and antimicrobial stewardship programs is necessary to ensure that rapid tests, if implemented, impact the patients they are designed to support.

Current guidelines recommend anticoagulation prior to cardioversion in patients with atrial fibrillation of48 h or unknown duration to reduce thromboembolic risk. Therapeutic anticoagulation with warfarin, with INR between 2 and 3, is consistently achieved in approximately 60% of patients.We evaluated outcomes and assessed differences in direct current cardioversion (DCCV) in patients treated with warfarin and novel oral anticoagulants (NOAC) at our institution.A retrospective analysis of consecutive DCCV at a tertiary referral over 18 months was conducted. Analysis of cardioversion records allowed completion of a standardised dataset. Clinical variables recorded included (1) CHADSVASC score, (2) anticoagulant use, and (3) bleeding complications.During this period 187 DCCVs were scheduled; 119 on warfarin and 68 on NOAC. DCCV was deferred in 26% (n = 31) of the warfarin group and 4.4% (n = 3) of the NOAC group (p = 0.0002). The average time interval between referral and DCCV was 144.43 and 109.32 days for the warfarin and NOAC groups, respectively (p value = 0.023). 7.56% (n = 9) of the warfarin population had a bleeding event compared to a 2.94% total bleeding rate in NOAC group (p = 0.213). Deferral of elective DCCV and additional anticoagulant monitoring was estimated at €1160 per procedure.In elective cardioversions, the group anticoagulated with NOAC was less likely to have subtherapeutic anticoagulation and hence deferred procedures and had reduced health care consumption when compared to the group anticoagulated with warfarin.

Objective In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. Methods ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged

Background Temple University Hospital recently implemented a protocol in which a urinalysis will reflex to culture only in the presence of pyuria. The purpose of this study is to compare appropriate antimicrobial use for patients with positive urine cultures before and after implementation of the urinalysis with reflex to culture protocol. Methods This is a single center, observational chart review. Adult internal medicine patients with a urinalysis and positive urine culture before and after the intervention were included in the pre- and post-intervention groups. Patients in the intensive care unit, undergoing urologic or surgical procedures, with leukopenia, being treated for another infection, who were discharged within 72 hours of the urine culture order, or pregnant were excluded. The primary endpoint was the percentage of patients with appropriate antimicrobial management of the positive urine culture before and after implementation of the protocol. Appropriate management was defined as antimicrobial treatment for a symptomatic urinary tract infection or no antimicrobial treatment for asymptomatic bacteriuria. Duration of therapy was also assessed. A sample size of 334 cultures was needed to detect a 15% difference in initiation of antibiotics between groups. Comparisons of categorical variables were analyzed by Chi-Square/Fisher exact test while continuous variables were analyzed by Wilcoxon test. Results Patient characteristics and outcomes are listed in the tables below. Table 1: Patient Characteristics Table 2: Outcomes Conclusion The urinalysis with reflex to culture intervention appeared to have minimal impact on the management of patients with a positive urine culture, with a possible increase in inappropriate management. Duration of therapy was significantly reduced by approximately one day with the intervention. Additional interventions to improve appropriate management of bacteriuria should be explored. Disclosures Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Allergan (Consultant)Astellas (Consultant)Merck (Consultant, Grant/Research Support)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant)

Ventilator-associated pneumonia (VAP) is one of the most common infections in the ICU. Prompt diagnosis is vital as mortality increases with delayed antibiotic therapy. However, accurate diagnosis is challenging due to non-specific clinical features in a complicated patient cohort. Microbiological culture data remains a crucial aspect in confirming diagnosis. Literature data comparing the benefit of invasive respiratory sampling to non-invasive is inconclusive. Differences in culturing practices translate in overidentification of organisms of unclear significance. Positive culture data in a low pre-test probability does not differentiate between true infection and colonization resulting in overtreatment. Furthermore, there are also opportunities for modifying the reporting of respiratory tract cultures that can better guide antimicrobial therapy. Under the umbrella of antimicrobial stewardship, diagnostic stewardship can be incorporated to create a systematic approach that would target culturing practices to match the right pre-test probability. Ideal outcome will be targeting cultures to the right patient population and minimizing unnecessary treatment.

Objectives The comorbidity of HIV infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy, a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical Wernicke's encephalopathy signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC). Design Sixty-one HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function. Methods Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical Wernicke's encephalopathy risk factors. Results Signs of subclinical Wernicke's encephalopathy were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALC Caine 2+ (i.e. meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e. meeting one criterion), HIV+ALC Caine 0 (i.e. meeting no criteria), and controls. Conclusion The high prevalence of subclinical signs of Wernicke's encephalopathy and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors, such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical Wernicke's encephalopathy signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity.

Volumes of thalamic nuclei are differentially affected by disease‐related processes including alcoholism and human immunodeficiency virus (HIV) infection. This MRI study included 41 individuals diagnosed with alcohol use disorders (AUD, 12 women), 17 individuals infected with HIV (eight women), and 49 healthy controls (24 women) aged 39 to 75 years. A specialized, high‐resolution acquisition protocol enabled parcellation of five thalamic nuclei: anterior [anterior ventral (AV)], posterior [pulvinar (Pul)], medial [mediodorsal (MD)], and ventral [including ventral lateral posterior (VLp) and ventral posterior lateral (VPl)]. An omnibus mixed‐model approach solving for volume considered the “fixed effects” of nuclei, diagnosis, and their interaction while covarying for hemisphere, sex, age, and supratentorial volume (svol). The volume by diagnosis interaction term was significant; the effects of hemisphere and sex were negligible. Follow‐up mixed‐model tests thus evaluated the combined (left + right) volume of each nucleus separately for effects of diagnosis while controlling for age and svol. Only the VLp showed diagnoses effects and was smaller in the AUD (p = .04) and HIV (p = .0003) groups relative to the control group. In the AUD group, chronic back pain (p = .008) and impaired deep tendon ankle reflex (p = .0005) were associated with smaller VLp volume. In the HIV group, lower CD4 nadir (p = .008) was associated with smaller VLp volume. These results suggest that the VLp is differentially sensitive to disease processes associated with AUD and HIV.

The use of small Unmanned Aircraft Systems (sUAS ) as platforms for data capture has rapidly increased in recent years. However, while there has been significant investment in improving the aircraft, sensors, operations, and legislation infrastructure for such, little attention has been paid to supporting the management of the complex data capture pipeline sUAS involve. This paper reports on the outcomes of a four-year-long community-engagement-based investigation into what tools, practices, and challenges currently exist for particularly researchers using sUAS as data capture platforms. The key results of this effort are: (1) sUAS captured data – as a set that is rapidly growing to include data in a wide range of Physical and Environmental Sciences, Engineering Disciplines, and many civil and commercial use cases – is characterised as both sharing many traits with traditional remote sensing data and also as exhibiting – as common across the spectrum of disciplines and use cases – novel characteristics that require novel data support infrastructure. And (2), given this characterization of sUAS data and its potential value in the identified wide variety of use case, we outline eight challenges that need to be addressed in order for the full value of sUAS captured data to be realized. We then conclude that there would be significant value gained and costs saved across both commercial and academic sectors if the global sUAS user and data management communities were to address these challenges in the immediate to near future, so as to extract the maximal value of sUAS captured data for the lowest long-term effort and monetary cost.

The current review summarizes advances in rapid diagnostic testing that impacts infection prevention and antimicrobial stewardship programs.A variety of rapid diagnostic technologies to identify organisms in cultured blood are now available. When coupled with antimicrobial stewardship (ASP), these rapid technologies can optimize antimicrobial utilization and patient outcomes. Two rapid molecular panels that detect organisms related to pneumonia are available and may impact infection prevention surveillance definitions. Three molecular tests are available for the detection of meningitis and encephalitis pathogens. Still, the clinical impact of these broad, multiplexed panels need additional clarification. For Clostridioides difficile infections, ultrasensitive toxin A/B assays may provide enhanced sensitivity and specificity compared with enzyme immunoassay and molecular testing respectively. Finally, the adoption of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI TOF MS) for rapid organism identification is growing. Recent US Food and Drug Administration-clearance of a MALDI TOF MS platform for identification of Nocardia, Mycobacteria, and molds may expedite antimicrobial decisions for infections that traditionally required days to weeks for an identification.Tests with broad diagnostic scope and swift turnaround time are rapidly entering the market. Many impact infection prevention and ASP programs. Collaboration with the microbiology laboratory is crucial to ensure that new tests successfully optimize patient care.

Alcohol is a psychoactive substance consumed worldwide and directly responsible or at least contributing to the development of diseases such as alcohol use disorder (AUD), cirrhosis, fetal alcohol syndrome, cancer, and cardiovascular diseases. The past decades of research have revealed brain structural and functional abnormalities associated with mild to moderate cognitive impairment in recently detoxified AUD patients. Such functional compromise can be detectable even before the development of more chronic and severe neurological complications such as Korsakoff’s syndrome (KS) and alcohol-related dementia (ARD). Excessive alcohol consumption results in impairment in attention, executive functions, memory, visuospatial and motor skills, as well as deficits in metamemory processes, emotion recognition, and theory of mind abilities. As a consequence, early in abstinence, some AUD patients may not be cognitively able to benefit from therapies and could be at risk to relapse because cognitive impairment hampers efficient decision-making, motivation to change, and learning skills, in addition to challenging emotional and interpersonal interactions. This chapter describes the alcohol-related cognitive impairment observed in recently detoxified AUD patients. It then discusses potential cognitive recovery or persistence of these deficits with prolonged abstinence and their clinical implications in terms of treatment and abstinence or relapse. The specificity of the AUD cognitive and motor profile is contrasted with alcohol-related neurological complications (i.e., KS and ARD) and other neurocognitive disorders (i.e., Alzheimer’s disease and frontotemporal dementia). Finally, structural and functional brain abnormalities as well as their relationship with neuropsychological impairments are presented.

The primary purpose of this review is to provide a summary of new and emerging laboratory technologies and testing platforms that impact infection prevention and antimicrobial stewardship programs. This review also summarizes available data describing the clinical impact of implementing these new technologies. While there is ample evidence that rapid organism identification technologies for positive blood cultures can ameliorate antimicrobial utilization, an assay that also provides expedited antimicrobial susceptibility testing results is now available and its clinical impact is under investigation. For C. difficile infection diagnosis, data related to performance and impact of “ultrasensitive” toxin assays is emerging in the literature although their role in C. difficile infection diagnosis remains unclear. For hospital-acquired pneumonia, a variety of rapid, automated, multiplexed, “pneumonia” panels have become commercially available and may impact surveillance definitions for ventilator-associated events. Finally, recent FDA clearance of various biochemical and molecular carbapenemase detection tests will facilitate rapid characterization of carbapenem-resistant organisms. Innovations in infectious diseases diagnostics have been making swift strides, broadening diagnostic scope; increasing accuracy and sensitivity; and reducing turnaround time. Many of these innovations directly impact infection prevention and antimicrobial stewardship operations. Close collaboration between infection control, antimicrobial stewardship, and the microbiology laboratory is necessary to ensure that new tests improve patient outcomes.

The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15 years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248 d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing. We identified an AUD-related volume deficit and accelerated aging in the total corpus medullare. Novel deformation-based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I-V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I-V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume-based and surface-based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.