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Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.

Conservation of North American migratory birds requires information about their movements and regulating factors throughout the annual cycle. Over the past 10 or more years, improvements in tracking technology and quantitative approaches to assessing resulting data have yielded advances in understanding many aspects of North American bird migration with relevance to conservation. To date, much of the synthesis of this information has focused on describing patterns and drivers of migration without directly addressing how these advances can inform migratory bird conservation. We begin by describing broad patterns of migration behavior observed in North American birds and briefly summarize the technological advances that have characterized different eras of bird migration research that have provided data relevant to conservation. We then illustrate how data derived from migration studies can inform conservation strategies, including addressing regulating factors outside the breeding period for North American migratory birds, and highlight how different types of migration data have shaped conservation of three well-studied species. Lastly, we discuss critical knowledge gaps and future directions for research needed to better inform North American migratory bird conservation. In particular, we highlight how further technological developments could contribute to the development of effective conservation action in the context of climate change. We also recommend that future research and conservation efforts incorporate means of evaluating the success of conservation actions that target North American migratory birds outside the breeding period.

Abstract Background It has been hypothesized that low access to healthy and nutritious food increases health disparities. Low-accessibility areas, called food deserts, are particularly commonplace in lower-income neighborhoods. The metrics for measuring the food environment’s health, called food desert indices, are primarily based on decadal census data, limiting their frequency and geographical resolution to that of the census. We aimed to create a food desert index with finer geographic resolution than census data and better responsiveness to environmental changes. Materials and methods We augmented decadal census data with real-time data from platforms such as Yelp and Google Maps and crowd-sourced answers to questionnaires by the Amazon Mechanical Turks to create a real-time, context-aware, and geographically refined food desert index. Finally, we used this refined index in a concept application that suggests alternative routes with similar ETAs between a source and destination in the Atlanta metropolitan area as an intervention to expose a traveler to better food environments. Results We made 139,000 pull requests to Yelp, analyzing 15,000 unique food retailers in the metro Atlanta area. In addition, we performed 248,000 walking and driving route analyses on these retailers using Google Maps’ API. As a result, we discovered that the metro Atlanta food environment creates a strong bias towards eating out rather than preparing a meal at home when access to vehicles is limited. Contrary to the food desert index that we started with, which changed values only at neighborhood boundaries, the food desert index that we built on top of it captured the changing exposure of a subject as they walked or drove through the city. This model was also sensitive to the changes in the environment that occurred after the census data was collected. Conclusions Research on the environmental components of health disparities is flourishing. New machine learning models have the potential to augment various information sources and create fine-tuned models of the environment. This opens the way to better understanding the environment and its effects on health and suggesting better interventions.

The cytosolic enzyme NGLY1 (N-glycanase 1) is a central mediator of glycoprotein catabolism. The enzyme acts to cleave N-linked glycans from modified substrate asparagine residues prior to degradation of misfolded proteins by the proteasome, playing a key and well-conserved role in the ER-associated degradation/ERAD pathway. In a clinical context, NGLY1 disorder represents a rare congenital disorder of deglycosylation where mutations in the NGLY1 gene result in the loss of enzyme function. Patients with NGLY1 disorder present with a broad and varied array of symptoms, which can include moderate to profound levels of developmental delay, seizures, and complex movement disorders, as well as alacrima. Our recent results highlight a causal link between NGLY1 inhibition and macroautophagy/autophagy induction.

Abstract Background Pregnancy-related mortality in the United States is the greatest among all high-income countries, and Georgia has one of the highest maternal mortality rates—almost twice the national rate. Furthermore, inequities exist in rates of pregnancy-related deaths. In Georgia, non-Hispanic Black women are nearly 3 times more likely to die from pregnancy-related complications than non-Hispanic White women. Unlike health equity, a clear definition of maternal health equity is lacking, overall and in Georgia specifically, but is needed to reach consensus and align stakeholders for action. Therefore, we used a modified Delphi method to define maternal health equity in Georgia and to determine research priorities based on gaps in understanding of maternal health in Georgia. Methods Thirteen expert members of the Georgia Maternal Health Research for Action Steering Committee (GMHRA-SC) participated in an iterative, consensus-driven, modified Delphi study comprised of 3 rounds of anonymous surveys. In round 1 (web-based survey), experts generated open-ended concepts of maternal health equity and listed research priorities. In rounds 2 (web-based meeting) and 3 (web-based survey), the definition and research priorities suggested during round 1 were categorized into concepts for ranking based on relevance, importance, and feasibility. Final concepts were subjected to a conventional content analysis to identify general themes. Results The consensus definition of maternal health equity created after undergoing the Delphi method is: maternal health equity is the ultimate goal and ongoing process of ensuring optimal perinatal experiences and outcomes for everyone as the result of practices and policies free of interpersonal or structural bias that tackle current and historical injustices, including social, structural, and political determinants of health impacting the perinatal period and life course. This definition highlights addressing the current and historical injustices manifested in the social determinants of health, and the structural and political structures that impact the perinatal experience. Conclusion The maternal health equity definition and identified research priorities will guide the GMHRA-SC and the broader maternal health community for research, practice, and advocacy in Georgia.

Abstract The expanding application of deep brain stimulation (DBS) therapy both drives and is informed by our growing understanding of disease pathophysiology and innovations in neurosurgical care. Neurophysiological targeting, a mainstay for identifying optimal, motor responsive targets, has remained largely unchanged for decades. Utilizing deep learning-based computer vision and related computational methods, we developed an effective and simple intraoperative approach to objectively correlate neural signals with movements, automating and standardizing the otherwise manual and subjective process of identifying ideal DBS electrode placements. Kinematics are extracted from video recordings of intraoperative motor testing using a trained deep neural network and compared to multi-unit activity recorded from the subthalamic nucleus. Neuro-motor correlations were quantified using dynamic time warping with the strength of a given comparison measured by comparing against a null distribution composed of related neuro-motor correlations. This objective measure was then compared to clinical determinations as recorded in surgical case notes. In seven DBS cases for treatment of Parkinson’s disease, 100 distinct motor testing epochs were extracted for which clear clinical determinations were made. Neuro-motor correlations derived by our automated system compared favorably with expert clinical decision making in post-hoc comparisons, although follow-up studies are necessary to determine if improved correlation detection leads to improved outcomes. By improving the classification of neuro-motor relationships, the automated system we have developed will enable clinicians to maximize the therapeutic impact of DBS while also providing avenues for improving continued care of treated patients.

Abstract Background Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy. Methods We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4–6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021. Results All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207–811] AU/ml vs. 820.75 [IQR, 459–1313] AU/ml; P

Abstract Background Lung ultrasound (LUS) is a clinician-performed evidence-based imaging modality that has multiple advantages in the evaluation of dyspnea caused by multiple disease processes, including COVID-19. Despite these advantages, few hospitalists have been trained to perform LUS. The aim of this study was to increase adoption and implementation of LUS during the 2020 COVID-19 pandemic by using recurrent assessments of RE-AIM outcomes to iteratively revise our implementation strategies. Methods In an academic hospital, we implemented guidelines for the use of LUS in patients with COVID-19 in July 2020. Using a novel “RE-AIM dashboard,” we used an iterative process of evaluating the high-priority outcomes of Reach, Adoption, and Implementation at twice monthly intervals to inform revisions of our implementation strategies for LUS delivery (i.e., Iterative RE-AIM process). Using a convergent mixed methods design, we integrated quantitative RE-AIM outcomes with qualitative hospitalist interview data to understand the dynamic determinants of LUS Reach, Adoption, and Implementation. Results Over the 1-year study period, 453 LUSs were performed in 298 of 12,567 eligible inpatients with COVID-19 (Reach = 2%). These 453 LUS were ordered by 43 out of 86 eligible hospitalists (LUS order adoption = 50%). However, the LUSs were performed/supervised by only 8 of these 86 hospitalists, 4 of whom were required to complete LUS credentialing as members of the hospitalist procedure service (proceduralist adoption 75% vs 1.2% non-procedural hospitalists adoption). Qualitative and quantitative data obtained to evaluate this Iterative RE-AIM process led to the deployment of six sequential implementation strategies and 3 key findings including (1) there were COVID-19-specific barriers to LUS adoption, (2) hospitalists were more willing to learn to make clinical decisions using LUS images than obtain the images themselves, and (3) mandating the credentialing of a strategically selected sub-group may be a successful strategy for improving Reach. Conclusions Mandating use of a strategically selected subset of clinicians may be an effective strategy for improving Reach of LUS. Additionally, use of Iterative RE-AIM allowed for timely adjustments to implementation strategies, facilitating higher levels of LUS Adoption and Reach. Future studies should explore the replicability of these preliminary findings.

Abstract Background Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes. Methods We conducted an RCT to evaluate the efficacy and safety of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was the number of desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction. Results Overall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0–1) and 1 (0–2) in the DEX and control groups, respectively (P = 0.29). Median desaturation time was 1 (0–2) and 1 (0–3) minutes in the DEX and control groups, respectively (P = 0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P = 0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P = 0.009). Conclusion Dexmedetomidine sedation during bronchoscopy did not show differences in oxygen saturation and transcutaneous CO2 level in comparison to propofol. Moreover, DEX sedation required a significantly higher number of rescue boluses, due to inadequate sedation and was associated with a higher rate of adverse events. Trial registration NCT04211298, registration date: 26.12.2019.

Abstract Background Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the performance of echocardiographic PASP as an indicator of pulmonary hypertension in LT candidates, in order to assess the necessity of RHC. Methods From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015–2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods—echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. Results The mean value of PASP estimated by echocardiography was 49.5 ± 20.0 mmHg, compared to 42.5 ± 18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson’s correlation: r = 0.609, p

Summary: Background: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans. Methods: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case–control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of neighborhood-level disadvantage: area deprivation index (ADI) and isolation index (ISOL). We used logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for comparing VLWH with matched controls. We performed analyses for the entire U.S. and separately for each U.S. Census division. Findings: Overall, living in minority-segregated neighborhoods was associated with a higher risk of HIV (OR: 1.88 (95% CI: 1.79–1.97) while living in higher ADI neighborhoods was associated with a lower risk of HIV (OR: 0.88; 95% CI: 0.84–0.92). The association between living in a higher ADI neighborhood and HIV was inconsistent across divisions, while living in minority-segregated neighborhoods was consistently associated with increased risk across all divisions. In the interaction model, individuals from low ADI and high ISOL neighborhoods had a higher risk of HIV in three divisions: East South Central; West South Central, and Pacific. Interpretation: Our results suggest that residential segregation may prevent people in disadvantaged neighborhoods from protecting themselves from HIV independent from access to health care. There is the need to advance knowledge about the neighborhood-level social-structural factors that influence HIV vulnerability toward developing interventions needed to achieve the goal of ending the HIV epidemic. Funding: US National Cancer Institute.

Introduction and Objectives: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. Materials and Methods: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. Results: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. Conclusions: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

IntroductionEpidemiologic and public health interest in structural racism has grown dramatically, producing both increasingly sophisticated questions, methods, and findings, coupled with concerns of atheoretical and ahistorical approaches that often leave the actual production of health or disease ambiguous. This trajectory raises concerns as investigators adopt the term “structural racism” without engaging with theories and scholars with a long history in this area. This scoping review aims to build upon recent work by identifying current themes about the incorporation of structural racism into (social) epidemiologic research and practice with respect to theory, measurement, and practices and methods for trainees and public health researchers who are not already deeply grounded in this work.MethodsThis review uses methodological framework and includes peer-review articles written in English published between January 2000–August 2022.ResultsA search of Google Scholar, manual collection, and referenced lists identified a total of 235 articles; 138 met the inclusion criteria after duplicates were removed. Results were extracted by, and organized into, three broad sections: theory, construct measurement, and study practice and methods, with several themes summarized in each section.DiscussionThis review concludes with a summary of recommendations derived from our scoping review and a call to action echoing previous literature to resist an uncritical and superficial adoption of “structural racism” without attention to already existing scholarship and recommendations put forth by experts in the field.

The neurotrophic signaling of glial cell line-derived neurotrophic factor (GDNF) with its canonical receptor, the receptor tyrosine kinase RET, coupled together with the GDNF family receptor alpha 1 is important for dopaminergic neuron survival and physiology in cell culture experiments and animal models. This prompted the idea to try GDNF/RET signaling as a therapeutic approach to treat Parkinson’s disease with the hallmark of dopaminergic cell death in the substantia nigra of the midbrain. Despite several clinical trials with GDNF in Parkinson’s disease patients, which mainly focused on optimizing the GDNF delivery technique, benefits were only seen in a few patients. In general, the endpoints did not show significant improvements. This suggests that it will be helpful to learn more about the basic biology of this fascinating but complicated GDNF/RET signaling system in the dopaminergic midbrain and about recent developments in the field to facilitate its use in the clinic. Here we will refer to the latest publications and point out important open questions in the field.

La yerba mate (Ilex paraguariensis A. St. -Hil.) es un cultivo primario y de gran importancia para el noreste de Argentina. En los últimos años, la enfermedad conocida como “mal de la tela”, cuyo agente causal es Ceratobasidium niltonsouzanum, está ocasionando importantes daños en la producción; y debido a la poca información existente su manejo resulta muy difícil.Al inicio de la enfermedad los signos incluyen cordones de micelios blancos visibles sobre las ramas y hojas infectadas. Las hojas se necrosan, se secan y quedan colgando de las ramas por la hifa del hongo. A partir de hojas y ramas sintomáticas, muestreadas de distintas partes de la provincia de Misiones, fue aislado el agente causal para su posterior caracterización morfológica y molecular. Las colonias fueron aisladas y crecieron rápidamente sobre medios de APG (agar papa glucosado), presentando un color blanquecino al inicio, tornándose luego de un color castaño. Con la caracterización morfológica se pudo determinar que el hongo se encuentra distribuido en distintas partes de la provincia de Misiones, afectando las plantaciones con distintos niveles de incidencia. Pruebas de patogenicidad, conducidas en laboratorio, permitieron conocer el progreso de la enfermedad bajo condiciones ambientales favorables. El objetivo del presente trabajo fue contribuir al conocimiento de la enfermedad, con la descripción de síntomas y signos, condiciones predisponentes y caracteres morfológicos y moleculares del agente causal del “mal de la tela”.

Synthetic mimics of glycoproteins and proteoglycans have wide applications in biomedicine, yet preparation has been challenged by their high grafting and glycosylation densities. Here the authors show one-pot dual-catalysis polymerization of glycan-bearing α-amino acid N-carboxyanhydrides to form glycopolypeptide brushes.

The 1983-1984 die-off of the long-spined sea urchin Diadema antillarum stands out as a catastrophic marine event because of its detrimental effects on Caribbean coral reefs. Without the grazing activities of this key herbivore, turf and macroalgae became the dominant benthic group, inhibiting coral recruitment and compromising coral reef recovery from other disturbances. In the decades that followed, recovery of D. antillarum populations was slow to non-existent. In late January 2022, a new mass mortality of D. antillarum was first observed in the U.S. Virgin Islands. We documented the spread and extent of this new die-off using an online survey. Infected individuals were closely monitored in the lab to record signs of illness, while a large population on Saba, Dutch Caribbean, was surveyed weekly before and during mortality to determine the lethality of this event. Within four months the die-off was distributed over 1,300 km from north to south and 2,500 km east to west. Whereas the 1983-1984 die-off advanced mostly with the currents, the 2022 event has appeared far more quickly in geographically distant areas. First die-off observations in each jurisdiction were often close to harbor areas, which, together with their rapid appearance, suggests that anthropogenic factors may have contributed to the spread of the causative agent. The signs of illness in sick D. antillarum were very similar to those recorded during the 1983-1984 die-off: lack of tube feet control, slow spine reaction followed by their loss, and necrosis of the epidermis were observed in both lab and wild urchins. Affected populations succumbed fast; within a month of the first signs of illness, a closely monitored population at Saba, Dutch Caribbean, had decreased from 4.05 individuals per m2 to 0.05 individuals per m2. Lethality can therefore be as high as 99%. The full extent of the 2022 D. antillarum die-off event is not currently known. The slower spread in the summer of 2022 might indicate that the die-off is coming to a (temporary) standstill. If this is the case, some populations will remain unaffected and potentially supply larvae to downstream areas and augment natural recovery processes. In addition, several D. antillarum rehabilitation approaches have been developed in the past decade and some are ready for large scale implementation. However, active conservation and restoration should not distract from the primary goal of identifying a cause and, if possible, implementing actions to decrease the likelihood of future D. antillarum die-off events.

IntroductionThe vaginal microbiome is a dynamic ecosystem that is important for women's health. Its composition has been associated with risk for menopausal symptoms, sexually transmitted infections, gynecologic cancer, and preterm birth. Conventional risk factors for a vaginal microbiome linked with these adverse health outcomes include sexual behaviors, hygiene practices, individual social factors, and stress levels. However, there has been limited research on socio-contextual determinants, and whether neighborhood context modifies the association with individual socioeconomic factors.MethodsSocioeconomically diverse pregnant African American women in Atlanta, Georgia (n = 439) provided residential addresses and first trimester vaginal swab samples, which underwent sequencing, taxonomic classification, and assignment into mutually exclusive CST (community state types) via hierarchical clustering. Linear probability models were used to estimate prevalence differences (PD) for the associations of neighborhood factors with vaginal microbiome CST and to evaluate for additive interaction with maternal level of education, health insurance type, and recruitment hospital.ResultsFactors such as higher (vs. lower) maternal education, private (vs. public) insurance, and private (vs. public) hospital were associated with higher prevalence of Lactobacillus-dominant vaginal microbiome CSTs typically associated with better health outcomes. When considering the joint effects of these individual socioeconomic status and residential neighborhood factors on vaginal microbiome CST, most combinations showed a greater than additive effect among the doubly exposed; however, in the case of local income homogeneity and local racial homogeneity, there was evidence of a crossover effect between those with less-advantaged individual socioeconomic status and those with more-advantaged individual socioeconomic status. Compared to women at the public hospital who lived in economically diverse neighborhoods, women at the private hospital who lived in economically diverse neighborhoods had a 21.9% higher prevalence of Lactobacillus-dominant CSTs, while women at the private hospital who lived in less economically diverse neighborhoods (the doubly exposed) had only an 11.7% higher prevalence of Lactobacillus-dominant CSTs, showing a crossover effect (interaction term p-value = 0.004).DiscussionIn this study, aspects of residential neighborhood context were experienced differently by women on the basis of their individual resources, and the joint effects of these exposures on vaginal microbiome CST showed a departure from simple additivity for some factors.

Abstract Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation. Design/Setting/Participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers. Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs. Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT (R −0.3, P = .04) and LOT (R −0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT (R –0.003, P = .98, R = −0.059, P = .69) or LOT (R +0.073, P = .62, R −0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average. Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time.

Temporal lobe epilepsy is the most common form of focal epilepsy and can have various detrimental consequences within many neurologic domains. Recent evidence suggests that the piriform cortex may also be implicated in seizure physiology. The piriform cortex is a primary component of the olfactory network and is located at the junction of the frontal and temporal lobes, wrapping around the entorhinal sulcus. Similar to the hippocampus, it is a tri-layered allocortical structure, with connections to many adjacent regions including the orbitofrontal cortex, amygdala, peri- and entorhinal cortices, and insula. Both animal and human studies have implicated the piriform cortex as a critical node in the temporal lobe epilepsy network. It has additionally been shown that resection of greater than half of the piriform cortex may significantly increase the odds of achieving seizure freedom. Laser interstitial thermal therapy has also been shown to be an effective treatment strategy with recent evidence hinting that ablation of the piriform cortex may be important for seizure control as well. We propose that sampling piriform cortex in intracranial stereoelectroencephalography (sEEG) procedures with the use of a temporal pole or amygdalar electrode would be beneficial for further understanding the role of the piriform cortex in temporal lobe epilepsy.

Abstract We present comments on an article published by Confer et al. (Ecology and Evolution, 10, 2020). Confer et al. (2020) aggregate data from multiple studies of social pairing between Vermivora chrysoptera and V. cyanoptera, two wood warblers in the family Parulidae that hybridize extensively where they co‐occur. From analysis of these data, they conclude there is near‐complete reproductive isolation between these two species. In our reply, we show that this finding is not supported by other lines of evidence, and significant drawbacks of their study design preclude such strong conclusions. In our critique, we show that (a) coarse‐scale plumage classifications cannot be used to accurately estimate hybrid ancestry in Vermivora; (b) extra‐pair paternity is very high in Vermivora and is likely facilitating hybridization, yet was not considered by Confer et al. (2020), and we suggest this will have a substantial influence on the interpretation of reproductive isolation in the system; and (c) the central finding of strong total reproductive isolation is not compatible with the results of other long‐term studies, which demonstrate low isolation and high gene flow. We conclude with a more comprehensive interpretation of hybridization and reproductive isolation in Vermivora warblers.

The cellular glycocalyx is involved in diverse biological phenomena in health and disease. Yet, molecular level studies have been challenged by a lack of tools to precisely manipulate this heterogeneous structure. Engineering of the cell surface using insertion of hydrophobic-terminal materials has emerged as a simple and efficient method with great promise for glycocalyx studies. However, there is a dearth of information about how the structure of the material affects membrane insertion efficiency and resulting density, the residence time of the material, or what types of cells can be utilized. Here, we examine a panel of synthetic mucin structures terminated in highly efficient cholesterylamide membrane anchors for their ability to engineer the glycocalyx of five different cell lines. We examined surface density, residence time and half-life, cytotoxicity, and the ability be passed to daughter cells. We report that this method is robust for a variety of polymeric structures, long-lasting, and well-tolerated by a variety of cell lines.

Clinical assessments of movement disorders currently rely on the administration of rating scales, which, while clinimetrically validated and reliable, depend on clinicians’ subjective analyses, resulting in interrater differences. Intraoperative microelectrode recording for deep brain stimulation targeting similarly relies on clinicians’ subjective evaluations of movement-related neural activity. Digital motion tracking can improve the diagnosis, assessment, and treatment of movement disorders by generating objective, standardized measures of patients’ kinematics. Motion tracking with concurrent neural recording also enables motor neuroscience studies to elucidate the neurophysiology underlying movements. Despite these promises, motion tracking has seen limited adoption in clinical settings due to the drawbacks of conventional motion tracking systems and practical limitations associated with clinical settings. However, recent advances in deep learning based computer vision algorithms have made accurate, robust markerless motion tracking viable in any setting where digital video can be captured. Here, we review and discuss the potential clinical applications and technical limitations of deep learning based markerless motion tracking methods with a focus on DeepLabCut (DLC), an open-source software package that has been extensively applied in animal neuroscience research. We first provide a general overview of DLC, discuss its present usage, and describe the advantages that DLC confers over other motion tracking methods for clinical use. We then present our preliminary results from three ongoing studies that demonstrate the use of DLC for 1) movement disorder patient assessment and diagnosis, 2) intraoperative motor mapping for deep brain stimulation targeting and 3) intraoperative neural and kinematic recording for basic human motor neuroscience.

Abstract Background The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. Methods Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. Results A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p

Abstract Background Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD. Methods Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry. Measurements and main results Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13. Conclusion In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy. Trial registration clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114

Abstract Background Central airway obstruction and fistula are treated with a tracheobronchial Y stent. In the currently used self‐expandable metal Y stents, the delivery system is 8 mm in diameter and requires either a 9 mm tracheal tube or rigid bronchoscope to enable airway control during insertion. In this study we present a novel technique of laryngeal mask airway (LMA) assisted Y stent insertion, enabling airway control during deployment of the Y stent. Methods All procedures using LMA in assisting Y stent insertions between 2014–2020 were reviewed. Data collected included demographics, clinical diagnosis and disease characteristics, indication, procedural success rates, clinical outcome and survival. Results A total of 10 patients with a median age of 61.5 years (range 37–73) underwent LMA assisted Y stent insertion. Indications for stent insertion were malignant disease with central airway obstruction or fistula. In all cases airway patency was achieved leading to improvement of symptoms and performance status. No procedural complications were reported. The median survival was 4.5 weeks (range: 2–26). Conclusions LMA assisted Y stent insertion enables airway control during the procedure. In comparison to silicone Y stent insertion, the procedure is less cumbersome, shorter in duration and does not require the use of general anesthesia or rigid bronchoscopy. Key points Significant findings of the study LMA assisted Y stent insertion enables airway control during the implantation of metallic self‐expanding Y stent. The procedure does not require the use of general anesthesia or rigid bronchoscopy. What this study adds In this study we present the technique and outcomes of LMA assisted Y stent insertion. This method of Y stent insertion provides an additional treatment option for patients with central airway obstruction and fistula.

Varicella zoster virus (VZV) induces orofacial pain and female rats show greater pain than male rats. During the proestrus phase of the estrous cycle the VZV induce pain response is attenuated in female rats. A screen of gene expression changes in diestrus and proestrus female rats indicated neurexin 3α (Nrxn3α) was elevated in the central amygdala of proestrus rats vs. diestrus rats. GABAergic neurons descend from the central amygdala to the lateral parabrachial region and Nrxn3α is important for presynaptic γ-Aminobutyric acid (GABA) release. Thus, we hypothesized that the reduced orofacial pain in male rats and proestrus female rats is the result of increased Nrxn3α within the central amygdala that increases GABA release from axon terminals within the parabrachial and inhibits ascending pain signals. To test this hypothesis Nrxn3 α expression was knocked-down by infusing shRNA constructs in the central amygdala. Then GABA release in the parabrachial was quantitated concomitant with measuring the pain response. Results revealed that knockdown of Nrxn3α expression significantly increases the pain response in both male rats and proestrus female rats vs. diestrus rats. GABA release was significantly reduced in the parabrachial of male and proestrus female rats after Nrxn3α knockdown. Neuronal activity of excitatory neurons was significantly inhibited in the parabrachial after Nrxn3α knockdown. These results are consistent with the idea that Nrxn3 within the central amygdala controls VZV associated pain by regulating GABA release in the lateral parabrachial that then modulates ascending orofacial pain signals.

Highly public anti-Black violence may increase preterm birth in the general population of pregnant women via stress-mediated paths, particularly Black women exposed in early gestation. To examine spillover from racial violence in the US, we included a total of 49 high publicity incidents of the following types: police lethal force toward Black persons, legal decisions not to indict/convict officers involved, and hate crime murders of Black victims. National search interest in these incidents was measured via Google Trends to proxy for public awareness of racial violence. Timing of racial violence was coded in relation to a three-month preconception period and subsequent pregnancy trimesters, with the primary hypothesis being that first trimester exposure is associated with higher preterm birth odds. The national sample included 1.6 million singleton live births to US-born Black mothers and 6.6 million births to US-born White mothers from 2014 to 2017. Using a preregistered analysis plan, findings show that Black mothers had 5% higher preterm birth odds when exposed to any high publicity racial incidents relative to none in their first trimester, and 2–3% higher preterm birth odds with each log10 increase in national interest. However, post hoc sensitivity tests that included month fixed effects attenuated these associations to null. For White mothers, associations were smaller but of a similar pattern, and were attenuated when including month fixed effects. Highly public anti-Black violence may act as a national stressor, yet whether racial violence is associated with reproductive outcomes in the population is unknown and merits further research.

Post‐fledging brood division is a poorly understood, yet widespread suite of avian behaviours that includes both division of parental care and spatial division of a brood. For most species, the differences in parental care between adult males and females and the behavioural mechanisms explaining spatial patterns of brood division are unknown. We studied brood division in golden‐winged warblers Vermivora chrysoptera to describe the spatial and behavioural characteristics of brood division and assess hypotheses describing the potential benefits of brood division. Female golden‐winged warblers are known to travel farther from their nests than males within the post‐fledging period, although the mechanism resulting in this spatial pattern is unknown. From 2010 to 2012, we monitored radio‐marked golden‐winged warbler fledglings from fledging until independence from adult care at three sites in the western Great Lakes region of North America. We observed no significant differences in provisioning, parental attendance, daily distance traveled and fledgling begging between male‐ and female‐reared sub‐broods. We also did not observe a relationship between parental sex and fledgling sex or mass. However, female‐reared sub‐broods exhibited a unique period of relatively consistent directional movement on days 8–10 after fledging, which resulted in females traveling farther from the nests than males. Our observations were not fully consistent with any previously proposed hypotheses about the benefits of brood division. Brood division is a complex behaviour that may have a suite of benefits, including predation defense and provisioning efficiency, that are not fully understood.

Abstract Background Little is known about longitudinal patterns of adolescent health risk behavior initial engagement and persistence in low- and middle-income countries. Methods Birth to Twenty Plus is a longitudinal birth cohort in Soweto-Johannesburg, South Africa. We used reports from Black African participants on cigarette smoking, alcohol, cannabis, illicit drug, and sexual activity initial engagement and adolescent pregnancy collected over 7 study visits between ages 11 and 18 y. We fit Kaplan-Meier curves to estimate behavior engagement or adolescent pregnancy, examined current behavior at age 18 y by age of first engagement, and performed a clustering analysis to identify patterns of initial engagement and their sociodemographic predictors. Results By age 13 y, cumulative incidence of smoking and alcohol engagement were each > 21%, while the cumulative incidence of other behaviors and adolescent pregnancy were 65%, cannabis and illicit drug engagement were each > 16%; adolescent pregnancy was 31%. Rates of engagement were higher among males. Current risk behavior activity at age 18 y was generally unrelated to age of initial engagement. We identified three clusters reflecting low, moderate, and high-risk patterns of initial risk behavior engagement. One-third of males and 17% of females were assigned to the high-risk cluster. Sociodemographic factors were not associated with cluster membership. Conclusions Among urban dwelling Black South Africans, risk behavior engagement across adolescence was common and clustered into distinct patterns of initial engagement which were unrelated to the sociodemographic factors assessed. Patterns of initial risk behavior engagement may inform the timing of primary and secondary public health interventions and support integrated prevention efforts that consider multiple behaviors simultaneously.