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Background. Parkinson’s disease (PD) causes difficulties with hand movements, which few studies have addressed therapeutically. Training with action observation (AO) and motor imagery (MI) improves performance in healthy individuals, particularly when the techniques are applied simultaneously (AO + MI). Both AO and MI have shown promising effects in people with PD, but previous studies have only used these separately. Objective. This article describes the development and pilot testing of an intervention combining AO + MI and physical practice to improve functional manual actions in people with PD. Methods. The home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team, including people with PD, and further developed through focus groups and initial field testing. Preliminary data on feasibility were obtained via a six-week pilot randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual). Usage and adherence data were recorded during training, and semistructured interviews were conducted with participants. Exploratory outcome measures included dexterity and timed action performance. Results. Usage and qualitative data provided preliminary evidence of acceptability and usability. Exploratory outcomes also suggested that subjective and objective performance of manual actions should be tested in a larger trial. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. Conclusions. The results indicate that a larger RCT is warranted, and the findings also have broader relevance for the feasibility and development of AO + MI interventions for PD and other conditions.

BACKGROUND: Safely and effectively discharging a patient from the hospital requires working within a multidisciplinary team. However, little is known about how perceptions of responsibility among the team impact discharge communication practices. OBJECTIVE: Our study attempts to understand residents’ perceptions of who is primarily responsible for discharge education, how these perceptions affect their own reported communication with patients, and how residents envision improving multidisciplinary communication around discharges. DESIGN: A multi-institutional cross-sectional survey. PARTICIPANTS: Internal medicine (IM) residents from seven US residency programs at academic medical centers were invited to participate between March and May 2019, via email of an electronic link to the survey. MAIN MEASURES: Data collected included resident perception of who on the multidisciplinary team is primarily responsible for discharge communication, their own reported discharge communication practices, and open-ended comments on ways discharge multidisciplinary team communication could be improved. KEY RESULTS: Of the 613 resident responses (63% response rate), 35% reported they were unsure which member of the multidisciplinary team is primarily responsible for discharge education. Residents who believed it was either the intern’s or the resident’s primary responsibility had 4.28 (95% CI, 2.51–7.30) and 3.01 (95% CI, 1.66–5.71) times the odds, respectively, of reporting doing discharge communication practices frequently compared to those who were not sure who was primarily responsible. To improve multidisciplinary discharge communication, residents called for the following among team members: (1) clarifying roles and responsibilities for communication with patients, (2) setting expectations for communication among multidisciplinary team members, and (3) redefining culture around discharges. CONCLUSIONS: Residents report a lack of understanding of who is responsible for discharge education. This diffusion of ownership impacts how much residents invest in patient education, with more perceived responsibility associated with more frequent discharge communication. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06508-4.

No consensus guidelines exist for timing of enterostomy closure in neonatal isolated intestinal perforation (IIP). This study evaluated neonates with IIP closed during the initial admission (A1) versus a separate admission (A2) comparing total length of stay and total hospital cost.Using 2012 to 2017 Pediatric Health information System (PHIS) data, 359 neonates with IIP were identified who underwent enterostomy creation and enterostomy closure. Two hundred sixty-five neonates (A1) underwent enterostomy creation and enterostomy closure during the same admission. Ninety-four neonates (A2) underwent enterostomy creation at initial admission and enterostomy closure during subsequent admission. For the A2 neonates, total hospital length of stay was calculated as the sum of hospital days for both admissions. A1 neonates were matched to A2 neonates in a 1:1 ratio using propensity score matching. Multivariate models were used to compare the two matched pair groups for length of stay and cost comparisons.Prior to matching, the basic demographics of our study population included a median birthweight of 960 g, mean gestational age of 29.5 weeks, and average age at admission of 4 days. Eighty-seven pairs of neonates with IIP were identified during the matching process. Neonates in A2 had 91% shorter total hospital length of stay compared to A1 neonates (HR: 1.91; 95% CI for HR: 1.44-2.53; p .0001). The median length of stay for A1 was 95 days (95% CI: 78-102 days) versus A2 length of stay of 67 days (95% CI: 56-76 days). Adjusting for the same covariates, A2 neonates had a 22% reduction in the average total cost compared A1 neonates (RR: 0.78; 95% CI for RR: 0.64-0.95; p-value = 0.014). The average total costs were $245,742.28 for A2 neonates vs. $315,052.21 for A1 neonates (p 0.001).Neonates with IIP have a 28 day shorter hospital length of stay, $75,000 or 24% lower total hospital costs, and a 22 day shorter post-operative course following enterostomy closure when enterostomy creation and closure is performed on separate admissions.Prognosis Study.Level II.

Consumption of poultry products is increasing worldwide, leading to an increased demand for safe, fresh, high-quality products. To ensure consumer safety and meet quality standards, poultry products must be routinely checked for fecal matter, food fraud, microbiological contamination, physical defects, and product quality. However, traditional screening methods are insufficient in providing real-time, nondestructive, chemical and spatial information about poultry products. Novel techniques, such as hyperspectral imaging (HSI), are being developed to acquire real-time chemical and spatial information about products without destruction of samples to ensure safety of products and prevent economic losses. This literature review provides a comprehensive overview of HSI applications to poultry products. The studies used for this review were found using the Google Scholar database by searching the following terms and their synonyms: “poultry” and “hyperspectral imaging”. A total of 67 studies were found to meet the criteria. After all relevant literature was compiled, studies were grouped into categories based on the specific material or characteristic of interest to be detected, identified, predicted, or quantified by HSI. Studies were found for each of the following categories: food fraud, fecal matter detection, microbiological contamination, physical defects, and product quality. Key findings and technological advancements were briefly summarized and presented for each category. Since the first application to poultry products 20 yr ago, HSI has been shown to be a successful alternative to traditional screening methods.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 8,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation and promiscuity in incorporating foreign glycoproteins into its virions. In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity and efficacy in mice. We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of Ifnar-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection against lethal SFTSV challenge. Additionally, passive transfer of sera from immunized Ifnar-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects mice against challenge with the closely related Heartland virus despite low neutralizing titers to the virus. Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate.ImportanceTick borne diseases are a growing threat to human health. Severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses are recently recognized, highly-pathogenic, tick-transmitted viruses. The fatality rates for individuals infected with SFTSV or HRTV are high and there are no therapeutics or vaccines available. The recent introduction of the tick vector for SFTSV (Haemaphysalis longicornis) to the eastern half of the United States and Austrailia raises concerns for SFTSV outbreaks outside East Asia. Here we report the development of a potential vaccine for SFTSV and HRTV based on the viral vector platform that has been successfully used for an Ebola vaccine. We demonstrate that the rVSV-SFTSV protects from lethal SFTSV or HRTV challenge when given as a single dose. We evaluated possible pathogenic effects of the vaccine and show that it is safe in immune compromised animlas and when introduced into the central nervous system.

This qualitative study, undertaken in England, explored young carers’ perspectives on the nature of their caring responsibilities. The findings are significant, particularly in the context of England's Care Act 2014, which seeks to prevent children engaging in ‘excessive’ or ‘inappropriate’ caring. Our research placed children at the heart of the debate on what constitutes appropriate care. The findings raise key questions regarding effective implementation of contemporary child policy, duties of care towards children in caring roles and priorities for child protection and family support policy and practices, with the potential to inform thinking around child's well-being in wider contexts.

The objective of this study is to use a portable visible spectral imaging system (443-726 nm) to detect poultry thawed from frozen at the pixel level using multivariate analysis methods commonly used in machine learning (decision tree, logistic regression, linear discriminant analysis (LDA), k-nearest neighbors (KNN), support vector machines (SVM)). The selection of the most suitable method is based on the amount of data required to build an accurate model, computational speed, and the robustness of the model. The training set consists of pixel spectra from packages of chicken thighs without plastic lidding to evaluate the robustness of the models when implemented on the test set with and without plastic lidding. Data subsets were created by randomly selecting 1, 5, 10, 20, and 50% of the pixel spectra of each sample for both the training and test data sets. The subsets of pixel spectra and the full training set were used to train the machine learning algorithms to evaluate how the amount of data influences computational time. Logistic regression was found to be the best algorithm for detecting poultry thawed from frozen with and without plastic lidding film. Although logistic regression and SVM both performed with the same high accuracy and sensitivity for all training subset sizes, the computational time needed to implement SVM makes it the less suitable algorithm for detecting poultry thawed from frozen with and without plastic lidding film.

This study investigates the novel application of hyperspectral imaging techniques to SolarBlack, a thermal control coating developed for the European Space Agency. A range of hyperspectral imaging techniques are presented as a novel method of surface characterization for thermal control coatings, and potentially a wide range of other materials. Spatially resolved Fourier-transform infrared imaging and visible/near-infrared imaging in combination with principal component analysis of the SolarBlack thermal control coating confirmed the presence of periodic variations in reflectance and thermal emittance. This periodicity is due to the rastering nature of the coating process.

Objective Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. Methods HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. Results 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). Conclusions HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.

Galidesivir (BCX4430) is an adenosine nucleoside analog that is broadly active in cell culture against several RNA viruses of various families. This activity has also been shown in animal models of viral disease associated with Ebola, Marburg, yellow fever, Zika, and Rift Valley fever viruses. In many cases, the compound is more efficacious in animal models than cell culture activity would predict. Based on favorable data from in vivo animal studies, galidesivir has recently undergone evaluation in several phase I clinical trials, including against severe acute respiratory syndrome coronavirus 2, and as a medical countermeasure for the treatment of Marburg virus disease.

Several arenaviruses, including Lassa and Lujo viruses in Africa and five New World arenavirus (NWA) species in the Americas, cause life-threatening viral hemorrhagic fevers. In the absence of licensed antiviral therapies, these viruses pose a significant public health risk. The envelope glycoprotein complex (GPC) mediates arenavirus entry through a pH-dependent fusion of the viral and host endosomal membranes. It thus is recognized as a viable target for small-molecule fusion inhibitors. Here, we report on the antiviral activity and pre-clinical development of the novel broad-spectrum arenavirus fusion inhibitors, ARN-75039 and ARN-75041. In Tacaribe virus (TCRV) pseudotyped and native virus assays, the ARN compounds were active in the low to sub-nanomolar range with selectivity indices exceeding 1000. Pharmacokinetic analysis of the orally administered compounds revealed an extended half-life in mice supporting once-daily dosing, and the compounds were well tolerated at the highest tested dose of 100 mg/kg. In a proof-of-concept prophylactic efficacy study, doses of 10 and 35 mg/kg of either compound dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues. Additionally, in contrast to surviving mice that received ribavirin or placebo, animals treated with ARN-75039 or ARN-75041 were cured of TCRV infection. In a follow-up study with ARN-75039, impressive therapeutic efficacy was demonstrated under conditions where treatment was withheld until after the onset of disease. Taken together, the data strongly support the continued development of ARN-75039 as a candidate therapeutic for the treatment of severe arenaviral diseases.

Aims: Cervical cancer incidence and mortality rates are approximately 55% higher in the Rio Grande Valley (RGV) along the Texas–Mexico border compared with the average rates in the US. Our aim was to improve cervical cancer prevention efforts in the RGV through a comprehensive multilevel intervention initiative focused on community education, patient navigation, and training of local providers. Methods: We initiated a program in the RGV which consisted of (1) community education, (2) patient navigation, and (3) a training/mentoring program for local medical providers including hands-on training courses coupled with telementoring using Project ECHO® (Extension for Community Health Outcomes). We assessed the number of women undergoing cervical cancer screening, diagnosis, and treatment at three participating clinics caring for underserved women in the region. Results: From November 2014 to October 2018, 14,846 women underwent cervical cancer screening. A total of 2030 (13.7%) women underwent colposcopy for abnormal results (179% increase over baseline) and 453 women underwent loop electrosurgical excision procedures (LEEPs) for treatment of cervical dysplasia. Invasive cancer was diagnosed in 39 women who were navigated to a gynecologic oncologist for treatment. Seven local medical providers were trained to perform colposcopy and/or LEEP. Project ECHO telementoring videoconferences were held every 2 weeks for a total 101 sessions with an average of 22 participants per session and a total of 180 patient cases presented and discussed. Conclusions: Our program led to a large number of women undergoing diagnosis and treatment of cervical dysplasia in the RGV. If sustained, we anticipate these efforts will decrease cervical cancer rates in the region. The program is currently being expanded to additional underserved areas of Texas and globally to low- and middle-income countries.

The diagnosis of prostate cancer is challenging due to the heterogeneity of its presentations, leading to the over diagnosis and treatment of non-clinically important disease. Accurate diagnosis can directly benefit a patient's quality of life and prognosis. Towards addressing this issue, we present a learning model for the automatic identification of prostate cancer. While many prostate cancer studies have adopted Raman spectroscopy approaches, none have utilised the combination of Raman Chemical Imaging (RCI) and other imaging modalities. This study uses multimodal images formed from stained Digital Histopathology (DP) and unstained RCI. The approach was developed and tested on a set of 178 clinical samples from 32 patients, containing a range of non-cancerous, Gleason grade 3 (G3) and grade 4 (G4) tissue microarray samples. For each histological sample, there is a pathologist labelled DP - RCI image pair. The hypothesis tested was whether multimodal image models can outperform single modality baseline models in terms of diagnostic accuracy. Binary non-cancer/cancer models and the more challenging G3/G4 differentiation were investigated. Regarding G3/G4 classification, the multimodal approach achieved a sensitivity of 73.8% and specificity of 88.1% while the baseline DP model showed a sensitivity and specificity of 54.1% and 84.7% respectively. The multimodal approach demonstrated a statistically significant 12.7% AUC advantage over the baseline with a value of 85.8% compared to 73.1%, also outperforming models based solely on RCI and median Raman spectra. Feature fusion of DP and RCI does not improve the more trivial task of tumour identification but does deliver an observed advantage in G3/G4 discrimination. Building on these promising findings, future work could include the acquisition of larger datasets for enhanced model generalization., Comment: 19 pages, 8 tables, 18 figures

Objective: Diabetes is a leading cause of chronic kidney disease (CKD), and new drug classes including SGLT-2 inhibitors and GLP-1 receptor agonists have shown renal benefits for those with type 2 diabetes (T2D). This study evaluated T2D patients’ awareness regarding CKD and renoprotective drugs across household income and educational attainment. Method: In an online survey in September 2020, 2,008 adults with T2D not currently being treated for kidney disease rated their level of agreement with statements about CKD risk and renoprotective drugs. Demographic information was collected. Result: The majority (58%) of patients strongly agreed that diabetes increases risk of CKD. Those with an income of $100k and a bachelor’s degree or higher (65%). Only 30% of patients indicated strong concern about CKD risk, and 25% were aware that some T2D drugs have renal benefits. Among those earning $50k-$100k, patients with a high school diploma were more concerned about their risk (44%) than those with some college (24%) or a bachelor’s degree or higher (29%). Those earning >$100k with a bachelor’s degree or higher were more likely to indicate strong awareness that some T2D drugs are renoprotective (34%) than those earning $100k with some college (20%). Conclusion: While few T2D patients are aware that some T2D drugs have renoprotective effects, those with higher education and income are more likely to be aware. These findings emphasize the importance of informing patients about renal health and therapeutic options, in efforts to increase accessibility of SGLT-2 and GLP-1 therapies to all who would benefit. Disclosure J. Stevenson: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, LifeScan, Medtronic, Roche Diabetes Care, Senseonics, Tandem Diabetes Care. E. Ye: Other Relationship; Self; dQ&A. S. Suhl: Other Relationship; Self; dQ&A has several clients (>10) in the diabetes field. R. Gowen: Other Relationship; Self; dQ&A. J. Tait: Other Relationship; Self; dQ&A Market Research Inc. C. Florissi: Other Relationship; Self; Abbott Diabetes, Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly Diabetes, Medtronic, Roche Diabetes Care, Senseonics, Tandem Diabetes Care. R. Wood: Research Support; Self; Abbott Diabetes, American Diabetes Association, Ascensia Diabetes Care, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk Inc., Sanofi.

Background: Surface imaging is a promising, noninvasive approach to assess regional perfusion in craniovascular disorders such as migraine. Methods: We used optical imaging to examine differences in facial blood volume at baseline and in response to ammonia inhalation (a noxious stimulus), as well as standardized measures of cardiovascular autonomic function, in healthy, non-headache controls ( n = 43) and in interictal migraine subjects ( n = 22). Results: Resting facial cutaneous oscillation (FCO) frequency was significantly different in migraine compared to healthy controls. Following ammonia inhalation, healthy controls showed a significant increase in resting FCO frequency, whereas this response was not significant in the migraine group. Standardized autonomic reflex parameters did not differ significantly between study groups, and facial cutaneous activity did not correlate with standardized cardiovascular autonomic reflex parameters, suggesting potentially different regulation. Conclusions: This approach to the assessment of craniofacial hemodynamic function appears to exhibit differing mechanisms from previously available techniques, and represents a promising new physiological biomarker for the study of craniofacial vascular function in migraine and potentially other craniovascular disorders.

The increasing visibility of mental health challenges for academic and graduate trainee populations has led to discussion of the role higher education institutions should play to address trainee mental health, particularly during the COVID-19 pandemic and ongoing racial injustice. To address the growing concern about training impacts on medical and biomedical doctoral trainee mental health, a cross-sectional study (n=957) was conducted using institutional annual survey data analyzed by type of training program, race/ethnicity, and survey year on measures of depression, anxiety, hazardous alcohol use, problems related to substance use, and suicidal ideation. Results indicated significant differences for rates of depression, anxiety, and suicidal ideation, with biomedical doctoral trainees showing greater incidence than medical doctoral trainees, and underrepresented minority trainees showing greater incidence than well-represented trainees. The concerningly high rates of depression, anxiety, and suicidal ideation among these trainee populations suggest that medical and biomedical doctoral training environments must be transformed in addition to expanding mental health support resources.

CDK4/6 inhibitors arrest the cell cycle in G1-phase. They are approved to treat breast cancer and are also undergoing clinical trials against a range of other tumour types. To facilitate these efforts, it is important to understand why a cytostatic arrest in G1 causes long-lasting effects on tumour growth. Here we demonstrate that a prolonged G1-arrest following CDK4/6 inhibition downregulates replisome components and impairs origin licencing. This causes a failure in DNA replication after release from that arrest, resulting in a p53-dependent withdrawal from the cell cycle. If p53 is absent, then cells bypass the G2-checkpoint and undergo a catastrophic mitosis resulting in excessive DNA damage. These data therefore link CDK4/6 inhibition to genotoxic stress; a phenotype that is shared by most other broad-spectrum anti-cancer drugs. This provides a rationale to predict responsive tumour types and effective combination therapies, as demonstrated by the fact that CDK4/6 inhibition induces sensitivity to chemotherapeutics that also cause replication stress.

Glycans are responsible for many biological activities; however, their structures are incredibly diverse and complex often rendering the field of glycomics unsolvable by a single analytical technique. The development of multiple chemical derivatization strategies and bioinformatic software are responsible for some of the greatest analytical gains in the field of glycomics. The INLIGHT(™) strategy is a chemical derivatization technique using hydrazide chemistry to derivatize the reducing end of N-linked glycans and incorporates either a natural (NAT – (12)C(6)) or stable-isotope label (SIL – (13)C(6)) to carry out relative quantification. Here we present GlycoHunter, a user-friendly software created in MATLAB that enables researchers to accurately and efficiently process MS1 glycomics data where a NAT and SIL pair are generated for relative quantification, including but not limited to, INLIGHT(™). GlycoHunter accepts the commonly used data files formats imzML or mzXML, and effectively identifies all peak pairs associated with NAT and SIL labeled N-linked glycans using MS1 data. It also includes the ability to tailor the search parameters and export the results for further analysis using Skyline or Excel.

Deep learning (DL) has recently achieved considerable successes in a wide range of applications, such as speech recognition, machine translation and visual recognition. This tutorial provides guidelines and useful strategies to apply DL techniques to address pixel-wise classification of spectral images. A one-dimensional convolutional neural network (1-D CNN) is used to extract features from the spectral domain, which are subsequently used for classification. In contrast to conventional classification methods for spectral images that examine primarily the spectral context, a three-dimensional (3-D) CNN is applied to simultaneously extract spatial and spectral features to enhance classificationaccuracy. This tutorial paper explains, in a stepwise manner, how to develop 1-D CNN and 3-D CNN models to discriminate spectral imaging data in a food authenticity context. The example image data provided consists of three varieties of puffed cereals imaged in the NIR range (943–1643 nm). The tutorial is presented in the MATLAB environment and scripts and dataset used are provided. Starting from spectral image pre-processing (background removal and spectral pre-treatment), the typical steps encountered in development of CNN models are presented. The example dataset provided demonstrates that deep learning approaches can increase classification accuracy compared to conventional approaches, increasing the accuracy of the model tested on an independent image from 92.33 % using partial least squares-discriminant analysis to 99.4 % using 3-CNN model at pixel level. The paper concludes with a discussion on the challenges and suggestions in the application of DL techniques for spectral image classification.

Hyperspectral imaging (HSI) emerges as a non-destructive and rapid analytical tool for assessing food quality, safety, and authenticity. This work aims to investigate the potential of combining the spectral and spatial features of HSI data with the aid of deep learning approach for the pixel-wise classification of food products. We applied two strategies for extracting spatial-spectral features: (1) directly applying three-dimensional convolution neural network (3-D CNN) model, (2) first performing principal component analysis (PCA) and then developing 2-D CNN model from the first few PCs. These two methods were compared in terms of efficiency and accuracy, exemplified through two case studies, i.e., classification of four sweet products and differentiation between white stripe (&ldquo, myocommata&rdquo, ) and red muscle (&ldquo, myotome&rdquo, ) pixels on salmon fillets. Results showed that combining spectral-spatial features significantly enhanced the overall accuracy for sweet dataset, compared to partial least square discriminant analysis (PLSDA) and support vector machine (SVM). Results also demonstrated that spectral pre-processing techniques prior to CNN model development can enhance the classification performance. This work will open the door for more research in the area of practical applications in food industry.

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.

Time series spectral imaging facilitates a comprehensive understanding of the underlying dynamics of multi-component systems and processes. Most existing classification strategies focus exclusively on the spectral features and they tend to fail when spectra between classes closely resemble each other. This work proposes a hybrid approach of principal component analysis (PCA) and deep learning (i.e., long short-term memory (LSTM) model) for incorporating and utilizing the combined multi-temporal and spectral information from time series spectral imaging datasets. An example data, consisting of times series spectral images of casein-based biopolymers, was used to illustrate and evaluate the proposed hybrid approach. Compared to using partial least squares discriminant analysis (PLSDA), the proposed PCA-LSTM method applying the same spectral pretreatment achieved substantial improvement in the pixel-wise classification (i.e., accuracy increased from 59.97% of PLSDA to 85.73% of PCA-LSTM). When projecting the pixel-wise model to object-based classification, the PCA-LSTM approach produced an accuracy of 100%, correctly classifying the whole 21 film samples in the independent test set, while PLSDA only led to an accuracy of 80.95%. The proposed method is powerful and versatile in utilizing distinctive characteristics of time dependencies from multivariate time series dataset, which could be adapted to suit non-congruent images over time sequences as well as spectroscopic data. ispartof: ANALYTICA CHIMICA ACTA vol:1143 pages:9-20 ispartof: location:Netherlands status: published

BackgroundParkinson’s disease (PD) causes difficulties with everyday manual activities, but few studies have addressed these therapeutically. Training with action observation (AO) and motor imagery (MI) can significantly improve performance in healthy individuals, particularly when these techniques are applied simultaneously (AO+MI). Both AO and MI have shown promising effects in PD, but previous studies have used these separately. This article describes the development and pilot testing of an intervention combining AO+MI and physical practice to improve functional manual actions in PD.MethodsThe home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team including people with PD, and further developed through focus groups and initial testing. The intervention was then tested in a six-week randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual).Results and ConclusionsUsage and qualitative data provided preliminary evidence of acceptability and usability, indicating that a feasibility RCT is warranted. Exploratory analyses suggested potential improvements in manual actions. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. The findings also have broader relevance for AO+MI interventions in PD and other populations.

Objectives: To evaluate and analyze the efficacy of implementation of hemorrhage-control training into the formal medical school curriculum. We predict this training will increase the comfort and confidence levels of students with controlling major hemorrhage and they will find this a valuable skill set for medical and other healthcare professional students. Methods: After IRB and institutional approval was obtained, hemorrhage-control education was incorporated into the surgery clerkship curriculum for 96 third-year medical students at the University of Arkansas for Medical Sciences using the national Stop The Bleed program. Using a prospective study design, participants completed pre- and post-training surveys to gauge prior experiences and comfort levels with controlling hemorrhage and confidence levels with the techniques taught. Course participation was mandatory; survey completion was optional. The investigators were blinded as to the individual student’s survey responses. A knowledge quiz was completed following the training. Results: Implementation of STB training resulted in a significant increase in comfort and confidence among students with all hemorrhage-control techniques. There was also a significant difference in students’ perceptions of the importance of this training for physicians and other allied health professionals. Conclusion: Hemorrhage-control training can be effectively incorporated into the formal medical school curriculum via a single 2-hour Stop The Bleed course, increasing students’ comfort level and confidence with controlling major traumatic bleeding. Students value this training and feel it is a beneficial addition to their education. We believe this should be a standard part of undergraduate medical education.

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Importantly, interferon (IFN)-γ-related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ-dominant AML subtypes.

Social support plays an important role in both mental and physical well-being. This study used patient-reported outcomes to better understand the effect of social support and diabetes communities on the behaviors and health outcomes of those living with diabetes. People with diabetes (n=4,717) from an opted-in U.S. research panel were surveyed about their level of social support using the Interpersonal Support Evaluation List-12 (ISEL-12). Physical activity level was determined using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and health and demographic information were collected. Findings show that higher levels of support are associated with better glycemic control, healthier lifestyle choices, and lower rates of diabetes complications and comorbidities. Notably, when controlling for overall level of social support and evaluating participants within one SD of the ISEL-12 mean, diabetes community members are more likely than those not in a community to have high diet adherence (≥80%) and high levels of physical activity. These diabetes community members are also less likely to have A1c >7, heart/circulation problems, high blood pressure, and cholesterol/triglyceride problems. These findings emphasize the importance of social support on the overall health of those with diabetes and suggest that diabetes communities are an important tool for managing diabetes. Disclosure S. Suhl: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. J.B. Rost: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. K.C. Stoner: Other Relationship; Self; Various companies and organizations. R. Gowen: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. C. Florissi: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. R. Wood: Consultant; Self; Abbott, ADOCIA, American Diabetes Association, Ascensia Diabetes Care, Boehringer Ingelheim Pharmaceuticals, Inc., CeQur Corporation, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. Employee; Self; dQ&A Market Research Inc.

SGLT2 inhibitors are not approved for people with type 1 diabetes in the U.S. due to elevated risk of diabetic ketoacidosis (DKA), prompting interest in ketone testing education. This study surveyed 4,612 people with type 1 diabetes across the U.S., EU, and Canada regarding their preferred method and duration of ketone testing education if they were to start a new therapy that increased DKA risk. Overall, a phone app was the preferred method of education, with some country-level differences apparent. In the U.S., Germany, and the Netherlands, 15-30 minutes was the most selected training time duration, while the remaining countries most commonly selected 1-2 hours. When considering the safety of SGLT2 therapy for type 1 patients, this data lends important insights into the feasibility and optimal composition of ketone test training. Disclosure J.B. Rost: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. S. Suhl: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. K.C. Stoner: Other Relationship; Self; Various companies and organizations. C. Florissi: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. R. Gowen: Employee; Self; This work was funded by dQ&A Diabetes Research, a provider of research services to multiple companies and patient organizations in the diabetes field. R. Wood: Consultant; Self; Abbott, ADOCIA, American Diabetes Association, Ascensia Diabetes Care, Boehringer Ingelheim Pharmaceuticals, Inc., CeQur Corporation, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. Employee; Self; dQ&A Market Research Inc.

Junín virus (JUNV) is one of five New World mammarenaviruses (NWMs) that causes fatal hemorrhagic disease in humans and is the etiological agent of Argentine hemorrhagic fever (AHF). The pathogenesis underlying AHF is poorly understood; however, a prolonged, elevated interferon-α (IFN-α) response is associated with a negative disease outcome. A feature of all NWMs that cause viral hemorrhagic fever is the use of human transferrin receptor 1 (hTfR1) for cellular entry. Here, we show that mice expressing hTfR1 develop a lethal disease course marked by an increase in serum IFN-α concentration when challenged with JUNV. Further, we provide evidence that the type I IFN response is central to the development of severe JUNV disease in hTfR1 mice. Our findings identify hTfR1-mediated entry and the type I IFN response as key factors in the pathogenesis of JUNV infection in mice.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human disease were observed including petechial rash, blood coagulation dysfunction, and various biochemistry and blood cell count abnormalities. Furthermore, we also demonstrated the utility of this model for anti-CCHFV therapeutic evaluation. The STAT2 knock-out hamster model of CCHFV infection may provide some further insights into clinical disease, viral pathogenesis, and pave the way for testing of potential drug and vaccine candidates.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus found throughout Eastern Europe, Africa, the Middle East and Asia. It is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. In humans, CCHFV can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. Currently, there is no widely available vaccine and although ribavirin has been suggested for the treatment of CCHFV, clinical efficacy in both animal models and humans is inconsistent suggesting more potent antivirals are needed for CCHFV. Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model. In this report we utilized the cynomolgus macaque model to evaluate the efficacy of once- and twice-daily favipiravir treatment against CCHFV infection. We found that favipiravir treatment suppressed viremia and viral shedding when treatment was initiated 24 h post-infection and viral burdens in key tissues trended lower in favipiravir-treated animals. Our data indicate that favipiravir has efficacy against CCHFV in vivo in a non-human primate model of infection.

INTRODUCTION Research data services have been adopted by many academic libraries. This study tracked the changes in research data management services and staffing among Association of American Universities (AAU) libraries over the past 5 years and compared them to the libraries’ goals for research data management (RDM) in their strategic plan. METHODS This quantitative study examined libraries at the 60 U.S. AAU institutions. In order to examine longitudinal changes, portions of Briney et.al. (2015a) were used as a basis for measuring data librarian staffing and services. These trends were compared to the contemporary strategic priorities of libraries interviewed by Meier (2016), as well as against strategic plans of 2014 and 2019 available online. RESULTS & DISCUSSION While there have been modest increases in libraries in the sample population offering data services, most of those gains have been among the libraries that did not consider RDM a priority in 2014. Interestingly, some of the libraries that mentioned RDM as a priority in 2014 have lost data librarian positions. Over half of the libraries in this study now provide or support a data repository. Many library strategic plans that mentioned RDM as an explicit goal 5 years ago now no longer mention it. CONCLUSION Data librarian positions, data services, and data repositories have now become common features of large research university libraries. However, research data services are no longer as prominent in many library strategic plans at institutions where such services are more established, and libraries instead seem to be moving on to the work of rethinking the nature of the services or expanding them. Data: https://scholarsphere.psu.edu/concern/generic_works/t1g05ff42r

Reducing hospital readmission rates has been increasingly important as a measure of hospital quality and safety performance. While in recent years hospitals have emphasized the importance of organi...

This paper describes the feasibility of using short-wave infrared (SWIR) spectrometry to classify concretes by their water-to-cement (w/c) ratios and predict their density. Concrete spectra of three w/c ratios (50%, 65%, 80%) were studied in the 1300–2200 nm range. A Partial Least Square Discriminant Analysis model was developed from the spectra of 36 samples, resulting in an 89% correct classification for the 18 validation samples, thereby demonstrating that SWIR spectrometry can detect differences in initial w/c ratios for hardened concretes. Additionally, differences in density and compressive strength as a function of the w/c ratio could be indirectly estimated through SWIR spectrometry.

Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient’s tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. The patient achieved a 2-year response to single agent imatinib that is ongoing. While PDGFR-α N848 K is rare among public sequencing databases our cases strongly suggests functional relevance and highlights the importance of studying rare variants in NSCLC.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a cause of serious hemorrhagic disease in humans. Humans infected with CCHFV develop a non-specific febrile illness and then progress to the hemorrhagic phase where case fatality rates can be as high as 30%. Currently there is lack of vaccines and the recommended antiviral treatment, ribavirin, has inconsistent efficacy in both human and animal studies. In this study we developed a model of CCHFV infection in type I interferon deficient mice using the clinical CCHFV isolate strain Hoti. Mice infected with strain Hoti develop a progressively worsening and ultimately fatal disease. We utilized this model along with our established model using the prototypical CCHFV strain 10200 to evaluate treatment with ribavirin or the antiviral favipiravir. While ribavirin treatment was able to suppress viral loads at early time points it was ultimately unable to prevent development of terminal disease in mice infected with either strain of CCHFV. In contrast, favipiravir showed clinical benefit even when administered late in the clinical progression of CCHF. Interestingly, in a small subset of mice, late-onset of CCHF was observed after favipiravir treatment was stopped and persistence of viral RNA in favipiravir treated survivors was also seen. Nevertheless, favipiravir showed significant clinical benefit against two distinct strains of CCHFV suggesting it may be a potent antiviral for treatment of human CCHFV infections.

Lassa virus, the cause of Lassa fever in humans, is endemic to West Africa. Treatment of Lassa fever is primarily supportive, although ribavirin has shown limited efficacy if administered early during infection. We tested favipiravir in Lassa virus–viremic macaques and found that 300 mg/kg daily for 2 weeks successfully treated infection.

Introduction Helicopter emergency medical services (HEMS) have provided benefit for severely injured patients. However, HEMS are likely overused for the transportation of both adult and pediatric trauma patients. In this study, we aim to evaluate the degree of overuse of helicopter as a mode of transport for head-injured children. In addition, we propose criteria that can be used to determine if a particular patient is suitable for air versus ground transport. Materials and methods We identified patients who were transported to our facility for head injuries. We included only those patients who were transported from another facility and who were seen by the neurosurgical service. We recorded a number of data points including age, gender, race, Glasgow Coma Score (GCS), and intubation status. We also collected data on a number of imaging findings such as mass effect, edema, intracranial hemorrhage, and skull fractures. Patients undergoing emergent nonneurosurgical intervention were excluded. Results Of the 373 patients meeting inclusion criteria, 116 (31.1%) underwent a neurosurgical procedure or died and were deemed appropriate for helicopter transport. The remaining 68.9% of patients survived their injuries without neurosurgical intervention and were deemed nonappropriate for helicopter transport. Multivariable logistic regression identified GCS 3–8 and/or presence of mass effect, edema, epidural hematoma (EDH), and open-depressed skull fracture as appropriate indications for helicopter transport. Conclusions The majority of patients transported to our facility by helicopter survived their head injury without need for neurosurgical intervention. Only those patients meeting clinical (GCS 3–8) or radiographic (mass effect, edema, EDH, open-depressed skull fracture) criteria should be transported by air. Level of Evidence Level III (Diagnostic Study).