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OBJECTIVE In the era of modern medicine with an armamentarium full of state-of-the art technologies at our disposal, the incidence of wrong-level spinal surgery remains problematic. In particular, the thoracic spine presents a challenge for accurate localization due partly to body habitus, anatomical variations, and radiographic artifact from the ribs and scapula. The present review aims to assess and describe thoracic spine localization techniques. METHODS The authors performed a literature search using the PubMed database from 1990 to 2020, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 27 articles were included in this qualitative review. RESULTS A number of pre- and intraoperative strategies have been devised and employed to facilitate correct-level localization. Some of the more well-described approaches include fiducial metallic markers (screw or gold), metallic coils, polymethylmethacrylate, methylene blue, marking wire, use of intraoperative neuronavigation, intraoperative localization techniques (including using a needle, temperature probe, fluoroscopy, MRI, and ultrasonography), and skin marking. CONCLUSIONS While a number of techniques exist to accurately localize lesions in the thoracic spine, each has its advantages and disadvantages. Ultimately, the localization technique deployed by the spine surgeon will be patient-specific but often based on surgeon preference.

With their extensive coverage, marine low clouds greatly impact global climate. Presently, marine low clouds are poorly represented in global climate models, and the response of marine low clouds to changes in atmospheric greenhouse gases and aerosols remains the major source of uncertainty in climate simulations. The eastern North Atlantic (ENA) is a region of persistent but diverse subtropical marine boundary layer clouds, whose albedo and precipitation are highly susceptible to perturbations in aerosol properties. In addition, the ENA is periodically impacted by continental aerosols, making it an excellent location to study the cloud condensation nuclei (CCN) budget in a remote marine region periodically perturbed by anthropogenic emissions, and to investigate the impacts of long-range transport of aerosols on remote marine clouds. The Aerosol and Cloud Experiments in Eastern North Atlantic (ACE-ENA) campaign was motivated by the need of comprehensive in situ measurements for improving the understanding of marine boundary layer CCN budget, cloud and drizzle microphysics, and the impact of aerosol on marine low cloud and precipitation. The airborne deployments took place from 21 June to 20 July 2017 and from 15 January to 18 February 2018 in the Azores. The flights were designed to maximize the synergy between in situ airborne measurements and ongoing long-term observations at a ground site. Here we present measurements, observation strategy, meteorological conditions during the campaign, and preliminary findings. Finally, we discuss future analyses and modeling studies that improve the understanding and representation of marine boundary layer aerosols, clouds, precipitation, and the interactions among them.

Oncology nurse navigators (ONNs) rely on assessment tools to identify patient priorities so that care may be expedited along the cancer continuum. Few nonproprietary assessment tools exist for ONNs who work in rural and other resource-poor settings to reliably identify and track patient needs and barriers for seamless and timely oncology care.

Objective We leveraged the Massachusetts perinatal quality collaborative (PQC) to address the COVID-19 pandemic. Our goals were to: (1) implement perinatal practices thought to reduce mother-to-infant SARS-CoV-2 transmission while limiting disruption of health-promoting practices and (2) do so without inequities attributable to race/ethnicity, language status, and social vulnerability. Methods Main outcomes were cesarean and preterm delivery, rooming-in, and breastfeeding. We examined changes over time overall and according to race/ethnicity, language status, and social vulnerability from 03/20-07/20 at 11 hospitals. Results Of 255 mothers with SARS-CoV-2, 67% were black or Hispanic and 47% were non-English speaking. Cesarean decreased (49% to 35%), while rooming-in (55% to 86%) and breastfeeding (53% to 72%) increased. These changes did not differ by race/ethnicity, language, or social vulnerability. Conclusions Leveraging the Massachusetts PQC led to rapid changes in perinatal care during the COVID-19 crisis in a short time, representing a novel use of statewide PQC structures.

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood–brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.

Acute Medicine is a specialty that is not defined by a single organ system and sits at the interface between primary and secondary care. In order to document improvements in the quality of care delivered a system of metrics is required. A number of frameworks for measurements exist to quantify quality of care at the level of patients, teams and organisations, such as measures of population health, patient satisfaction and cost per patient. Measures can capture whether care is safe, effective, patient-centred, timely, efficient and equitable. Measurement in Acute Medicine is challenged by the often-transient nature of the contact between Acute Medicine clinicians and patients, the lack of diagnostic labels, a low degree of standardisation and difficulties in capturing the patient experience in the context. In a time of increasing ecological and financial constraints, reflecting about the most appropriate metrics to document the impact of Acute Medicine is required.

As complex systems, maritime vessels generate and require the utilization of large amounts of data for maximum efficiency. Designing, developing, and deploying these systems in a digital world requires rethinking how people interact and utilize technology throughout all areas of the industry. With growing interests in Industry 4.0, there are broad opportunities for the incorporation and development of new digital solutions that will support the improvement and optimization of next generation systems. However, while different technologies have been deployed with various levels of success the current challenge is not generating data but being able to harmoniously integrate different data streams into the decision‐making process. To support the development of next generation vessels, a comprehensive understanding of Maritime 4.0 is necessary. Current conceptions of 4.0 within the industry remain ambiguous and based on our research, have demonstrated a divergence in the levels of technological maturity and digital solutions in different industry sectors. This study leverages current state‐of‐the‐art literature and a series of interviews to formulate a descriptive definition of Maritime 4.0 that incorporates technologies that can be integrated to support decision‐making. Through a rigorous, empirically grounded, and contextually relevant approach, the contribution of this study is the establishment of an organized set of technologies and characteristics related to 4.0 and establishment of a practical definition.

Partnered gay, bisexual and other men who have sex with men (GBMSM) are less likely to engage in HIV and STI testing. We enrolled 51 male couples from a larger study of home HIV testing to test the feasibility of a dyadic home STI testing intervention delivered via telehealth, consisting of two telehealth sessions delivered via video-chat. In the first session, an interventionist demonstrated the specimen collection kits. In the second session, an interventionist delivered the STI results. Participants reported very high levels of acceptability of the intervention: 92% reported the telehealth calls quality as very good, 99% reported the sample collection instructions were clear, and 96% of respondents returned specimens for collection. 9% of participants tested positive for chlamydia or gonorrhea, and all were linked to care. The intervention has the potential to surmount economic, physical and stigma-related barriers to attending clinics for STI testing, but these results need to be further tested in more diverse samples of male couples.

Background Chronic lung disease remains a burden for extremely preterm infants. The changes in ventilation over time and optimal ventilatory management remains unknown. Newer, non-invasive technologies provide insight into these patterns. Methods This single-center prospective cohort study enrolled infants ≤32 0/7 weeks. We obtained epochs of transcutaneous carbon dioxide (TcCO2) measurements twice each week to describe the pattern of hypercarbia throughout their hospitalization. Results Patterns of hypercarbia varied based on birth gestational age and post-menstrual age (PMA) (p = 0.03), regardless of respiratory support. Infants receiving the most respiratory support had values 16–21 mmHg higher than those on room air (p

OBJECTIVE We evaluated the efficacy of a combined short-wavelength-enriched white light and exercise fatigue countermeasure during breaks for flight controllers working overnight shifts. METHODS Twenty NASA flight controllers were studied for two blocks of nightshifts in ISS mission control, randomized to either the control or countermeasure condition. The countermeasure constituted passive exposure to blue-enriched polychromatic lighting for three 20-minute intervals, which included 10 minutes of exercise and occurred before and twice during their shifts. Alertness, performance, and mood were evaluated. RESULTS Flight controllers reported being significantly more alert (P

Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE. Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA. Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = – 0.54). In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.

Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH).Premature neonates (1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders.We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P 0.01) and an increased length of stay (88.2 d versus 74.4 d, P 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P 0.01).Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization.III.

Background: The cause of subsequent surgery after anterior cruciate ligament (ACL) reconstruction varies, but if risk factors for specific subsequent surgical procedures can be identified, we can better understand which patients are at greatest risk. Purpose: To report the incidence and types of subsequent surgery that occurred in a cohort of patients 6 years after their index ACL reconstruction and to identify which variables were associated with the incidence of patients undergoing subsequent surgery after their index ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: Patients completed a questionnaire before their index ACL surgery and were followed up at 2 and 6 years. Patients were contacted to determine whether any underwent additional surgery since baseline. Operative reports were obtained, and all surgical procedures were categorized and recorded. Logistic regression models were constructed to predict which patient demographic and surgical variables were associated with the incidence of undergoing subsequent surgery after their index ACL reconstruction. Results: The cohort consisted of 3276 patients (56.3% male) with a median age of 23 years. A 6-year follow-up was obtained on 91.5% (2999/3276) with regard to information on the incidence and frequency of subsequent surgery. Overall, 20.4% (612/2999) of the cohort was documented to have undergone at least 1 subsequent surgery on the ipsilateral knee 6 years after their index ACL reconstruction. The most common subsequent surgical procedures were related to the meniscus (11.9%), revision ACL reconstruction (7.5%), loss of motion (7.8%), and articular cartilage (6.7%). Significant risk factors for incurring subsequent meniscus-related surgery were having a medial meniscal repair at the time of index surgery, reconstruction with a hamstring autograft or allograft, higher baseline Marx activity level, younger age, and cessation of smoking. Significant predictors of undergoing subsequent surgery involving articular cartilage were higher body mass index, higher Marx activity level, reconstruction with a hamstring autograft or allograft, meniscal repair at the time of index surgery, or a grade 3/4 articular cartilage abnormality classified at the time of index ACL reconstruction. Risk factors for incurring subsequent surgery for loss of motion were younger age, female sex, low baseline Knee injury and Osteoarthritis Outcome Score symptom subscore, and reconstruction with a soft tissue allograft. Conclusion: These findings can be used to identify patients who are at the greatest risk of incurring subsequent surgery after ACL reconstruction.

Background In 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted a 16-h limit on consecutive hours for first-year resident physicians. We sought to examine the effect of these work-hour regulations on physician safety. Methods All medical students matched to a US residency program from 2002 to 2007 and 2014 to 2017 were invited to participate in prospective cohort studies. Each month participants reported hours of work, extended duration shifts, and adverse safety outcomes, including motor vehicle crashes, percutaneous injuries, and attentional failures. The incidence of each outcome was compared before and after the 2011 ACGME work-hour limit. Hypotheses were tested using generalized linear models adjusted for potential confounders. Results Of all first-year resident physicians nationwide, 13% participated in the study, with 80,266 monthly reports completed by 15,276 first-year resident physicians. Following implementation of the 16-h 2011 ACGME work-hour limit, the mean number of extended duration (≥24-h) shifts per month decreased from 3.9 to 0.2. The risk of motor vehicle crash decreased 24% (relative risk [RR] 0.76; 0.67-0.85), percutaneous injury risk decreased more than 40% (relative risk 0.54; 0.48-0.61), and the rate of attentional failures was reduced 18% (incidence rate ratio [IRR] 0.82; 0.78-0.86). Extended duration shifts and prolonged weekly work hours were associated with an increased risk of adverse safety outcomes independent of cohort. Conclusions The 2011 ACGME work-hour limit was associated with meaningful improvements in physician safety and health. Surveillance is needed to monitor the ongoing impact of work hours on physician safety, health, and well-being.

Aims: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. Methods: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. Results: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. Conclusions: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures. (Less)

FMX101 4% topical minocycline foam has been shown to be an effective and safe treatment for acne vulgaris (AV).To further evaluate the efficacy and safety of FMX101 4% in treating moderate to severe acne vulgaris.A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Coprimary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (Investigator's Global Assessment score of 0 or 1 with a ≥2-grade improvement).There were 1488 participants in the intent-to-treat population. The FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P .0001) and a greater rate of treatment success based on Investigator's Global Assessment (P .0001) versus the foam vehicle group at week 12. FMX101 4% was generally safe and well tolerated.The efficacy and safety of FMX101 4% were not characterized in participants with mild AV.FMX101 4% topical minocycline foam was effective and safe for the treatment of moderate to severe AV.

Objectives To describe feasibility, adherence, acceptability, and outcomes of a cognitive-behavioral-based physical therapy (CBPT-ACLR) intervention for improving postoperative recovery after anterior cruciate ligament reconstruction (ACLR). Design Pilot study. Setting Academic medical center. Participants Eight patients (mean age [SD] = 20.1 [2.6] years, 6 females) participated in a 7-session telephone-based CBPT-ACLR intervention beginning preoperatively and lasting 8 weeks after surgery. Main outcome measures At 6 months, patients completed Knee Injury and Osteoarthritis Outcome Score (KOOS) sports/recreation and quality of life (QOL) subscales, International Knee Documentation Committee (IKDC), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), and Knee Self-Efficacy Scale (K-SES), return to sport (Subjective Patient Outcome for Return to Sports), and satisfaction. Minimal clinically important difference (MCID) was used for meaningful change. Results Seven (88%) patients completed all sessions. Seven (88%) patients exceeded MCID on the TSK, 6 (75%) on the PCS, 5 (63%) on the KOOS sports/recreation subscale, 4 (50%) on the IKDC, and 3 (38%) on the KOOS QOL subscale. Three (38%) patients returned to their same sport at the same level of effort and performance. All patients were satisfied with their recovery. Conclusions A CBPT-ACLR program is feasible and acceptable for addressing psychological risk factors after ACLR.

Maritime vessels are complex systems that generate and require the utilization of large amounts of data for maximum efficiency. The successful utilization of sensors and IoT in the industry requires a forward-thinking approach to leverage the benefits of Industry 4.0 in a more comprehensive manner. While processes and manufacturing processes can be improved and advanced through such efforts, in order the industry to be able to benefit from data generation, integrated approaches are necessary. In order to develop truly value-added vessels, we introduce a descriptive approach for understanding Maritime 4.0.

In the dynamic environment of today's manufacturing industry, companies need to be changeable, i.e. capable of adapting to changes quickly and cost-effectively. In this context, the diagnosability characteristic, allowing fast and economic ramp-ups of new manufacturing settings, becomes particularly relevant. Depending on their diagnosability requirements, companies can exploit different technologies and applications. In this study, five diagnosability requirements have been identified. Through a literature review, the five requirements have been further investigated; thus, the extent to which these five requirements can be fulfilled, and their enabling technologies and applications has been specified. Finally, a case study has been conducted to show how diagnosability requirements are fulfilled differently in three manufacturing contexts.

Sleep deficiency and undiagnosed or untreated sleep disorders are pervasive among employed adults, yet often ignored in the context of workplace health promotion programs among employers. Smartphone applications (app) are a promising, scalable approach to improving sleep among employees. In this randomized clinical trial, we evaluate the dayzz app, a personalized sleep training program that promotes healthy sleep and sleep disorders awareness through personalized, comprehensive sleep improvement solutions. In a sample of daytime employees affiliated with a large healthcare organization, we evaluated the dayzz app in a parallel-group, randomized, waitlist control trial. Participants were randomly assigned to either use the dayzz app throughout the study or the waitlist control condition where they would receive the dayzz app at the end of the study period. We collected data on employee sleep (e.g., sleep duration, sleep health behavioral changes); workplace outcomes (e.g., employee presenteeism, absenteeism, and performance); and healthcare utilization (e.g., mental health, ambulatory visits, and emergency room visits), throughout the study. Results show that those assigned to the experimental condition exhibited an increase in healthy sleep behaviors; an increase in sleep duration; a trend toward a more regular sleep schedule; and a significant increase in overall sleep quality. Regarding workplace outcomes, results showed that those in the experimental condition also demonstrated a trend toward less absenteeism and significantly lower presenteeism; and those in the experimental condition reported lower healthcare utilization. Results from this randomized clinical trial demonstrate that a workplace sleep wellness program can be beneficial to both the employee and employer.

Sleep deficiency is a hidden cost of our 24-7 society, with 70% of adults in the US admitting that they routinely obtain insufficient sleep. Further, it is estimated that 50-70 million adults in the US have a sleep disorder. Undiagnosed and untreated sleep disorders are associated with diminished health for the individual and increased costs for the employer. Research has shown that adverse impacts on employees and employers can be mitigated through sleep health education and sleep disorder screening and treatment programs. Smartphone applications (app) are increasingly commonplace and represent promising, scalable modalities for such programs. The dayzz app is a personalized sleep training program that incorporates assessment of sleep disorders and offers a personalized comprehensive sleep improvement solution. Using a sample of day workers affiliated with a large institution of higher education, we will conduct a single-site, parallel-group, randomized, waitlist control trial. Participants will be randomly assigned to either use the dayzz app throughout the study or receive the dayzz app at the end of the study. We will collect data on feasibility and acceptability of the dayzz app; employee sleep, including sleep behavioral changes, sleep duration, regularity, and quality; employee presenteeism, absenteeism, and performance; employee mood; adverse and safety outcomes; and healthcare utilization on a monthly basis throughout the study, as well as collect more granular daily data from the employee during pre-specified intervals. Our results will illuminate whether a personalized smartphone app is a viable approach for improving employee sleep, health, and productivity.

INTRODUCTION AND OBJECTIVE:Neurogenic and idiopathic detrusor overactivity (DO) is currently treated with onabotulinumtoxin A (BoNT/A) as third line therapy. In cases of treatment failure, alternat...

Introduction: Neuropilin-1 (NRP1) is a transmembrane receptor present in vascular smooth muscle cells (VSMC) that mediates the inhibition of Rho signaling by binding the Class 3 Semaphorin (SEMA) ligand SEMA3A. Hypothesis: We hypothesize that loss of NRP1 in VSMC mitigates SEMA3A-induced Rho inhibition, thereby increasing vascular tone and blood pressure in vivo . Methods: Male and female adult mice (8-12 weeks) with inducible, smooth muscle cell-specific deletion of NRP1 (SM22a-Cre ERT2 X Nrp1 flox/flox ) were examined. Following recombination using 4-hydroxy tamoxifen (SM- NRP1 KO), systolic blood pressure (SBP) was measured using a tail cuff and compared to age- and sex-matched mice that did not receive tamoxifen (control). Aortic vascular reactivity and expression of key proteins in the Rho signaling cascade were measured using ex vivo tension myography and western blotting, respectively. Results: SBP was significantly increased in SM- NRP1 KO mice following recombination compared to control mice (SBP: 136.5 ± 10.9 vs 112.9 ± 5.6 mmHg; p=0.0006). Contractile responses in aortas of SM- NRP1 KO mice to phenylephrine (p=0.025), KCl (p=0.012), and the thromboxane agonist U44619 (p=0.019) were significantly enhanced compared to controls. Expression of total myosin light chain and LIMK-2 proteins were increased in SM- NRP1 KO compared to control aortas. In vitro , treatment of murine primary VSMC expressing NRP1 with SEMA3A decreased angiotensin II-induced Rho-GTP activation. Additionally, control and SM- NRP1 KO mice (starting at 2 weeks post-recombination) were administered angiotensin II (490 ng/kg/day) for 4 weeks. While there was no significant difference in SBP at weeks 1 and 2, SM- NRP1 KO mice had significantly lower SBP at weeks 3 and 4 following angiotensin II infusion compared to controls (Week 4 SBP: 150 ± 1.4 vs 130.5 ± 2.5 mmHg; p=0.02), suggesting a low ejection fraction and cardiac dysfunction in these mice. In support of this observation, mRNA expression of atrial natriuretic peptide was increased in hearts of angiotensin II-infused SM- NRP1 KO mice. Conclusion: Our data suggest that VSMC NRP1 regulates basal tone and blood pressure, and that loss of NRP1 causes hypertension and exacerbates cardiac dysfunction.

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

Pinpointing subcellular protein localizations from microscopy images is easy to the trained eye, but challenging to automate. Based on the Human Protein Atlas image collection, we held a competition to identify deep learning solutions to solve this task. Challenges included training on highly imbalanced classes and predicting multiple labels per image. Over 3 months, 2,172 teams participated. Despite convergence on popular networks and training techniques, there was considerable variety among the solutions. Participants applied strategies for modifying neural networks and loss functions, augmenting data and using pretrained networks. The winning models far outperformed our previous effort at multi-label classification of protein localization patterns by ~20%. These models can be used as classifiers to annotate new images, feature extractors to measure pattern similarity or pretrained networks for a wide range of biological applications., The 2018 Human Protein Atlas Image Classification competition sought to improve automated classification of protein subcellular localizations from fluorescence images. The winning strategies involved innovative deep learning approaches for multi-label classification.

There are strong individual differences in performance during sleep deprivation. We assessed whether baseline features of Psychomotor Vigilance Test (PVT) performance can be used for classifying participants’ relative attentional vulnerability to total sleep deprivation. In a laboratory, healthy adults (n = 160, aged 18–30 years) completed a 10-min PVT every 2 h while being kept awake for ≥24 hours. Participants were categorized as vulnerable (n = 40), intermediate (n = 80), or resilient (n = 40) based on their number of PVT lapses during one night of sleep deprivation. For each baseline PVT (taken 4–14 h after wake-up time), a linear discriminant model with wrapper-based feature selection was used to classify participants’ vulnerability to subsequent sleep deprivation. Across models, classification accuracy was about 70% (range 65–76%) using stratified 5-fold cross validation. The models provided about 78% sensitivity and 86% specificity for classifying resilient participants, and about 70% sensitivity and 89% specificity for classifying vulnerable participants. These results suggest features derived from a single 10-min PVT at baseline can provide substantial, but incomplete information about a person’s relative attentional vulnerability to total sleep deprivation. In the long term, modeling approaches that incorporate baseline performance characteristics can potentially improve personalized predictions of attentional performance when sleep deprivation cannot be avoided.

Recent progress in the performance of intermediate temperature (500–600°C) protonic ceramic fuel cells (PCFCs) has demonstrated both fuel flexibility and increasing power density that approach commercial application requirements. Under the U.S. DOE ARPA-E REBELS program, the Colorado School of Mines (Mines), in collaboration with Fuel Cell Energy (FCE), is developing durable, kW-scale PCFC stacks and system concepts. Results from cell scale-up efforts are reviewed. Several cells have been tested for over 6,000 hours, and we demonstrate excellent performance and exceptional durability (

The unique and beneficial characteristics of solid oxide fuel cell (SOFC) technology hold much promise for their eventual widespread adoption in numerous commercial building applications. Nevertheless, cost and durability challenges remain that currently limit SOFC technology penetration in stationary energy applications. Under the U.S. DOE ARPA-E INTEGRATE program, the Colorado School of Mines and its partners are developing a novel hybrid stationary power system comprised of an intermediate temperature (600-degreeC), metal-supported solid oxide fuel cell stack integrated with a high efficiency stationary engine and novel balance-of-point (BOP) equipment.

Background The demographic of Northern Territory prison population differs than elsewhere in Australia and the prevalence of hepatitis B and hepatitis C may therefore be somewhat different from other jurisdictions. There has been no study which has specifically described the serological results of a large proportion of prisoners in Northern Territory correctional facilities over an extended period of time. Methods This retrospective longitudinal study reviewed serological results and testing rates for hepatitis B, and hepatitis C performed in correctional facilities in the Northern Territory of Australia between July 1st, 2003 and June 30th, 2017. Results The proportion of positive records over 14 years for hepatitis B surface antigen (HBsAg) was 641/12,066 (5.3, 95% CI 4.9–5.7), for hepatitis B core antibody (anti-HBc) 4937/12,138 (40.1, 95%CI 39.8–41.6), for hepatitis B surface antibody (anti-HBs) 6966/13,303 (52.4, 95% CI 51.5–53.2), and for hepatitis C antibody 569/12,153 (4.7, 95% CI 4.3–5.1). The proportion of prisoners tested for hepatitis B and hepatitis C has decreased since 2015, while a high proportion of prisoners remain non-immune to hepatitis B. Conclusion There is a relatively high proportion of positive serological markers of hepatitis B, and a lower proportion of positive hepatitis C serology in the Northern Territory’s correctional facilities compared to overall Australian rates. As the proportion of prisoners tested for hepatitis B and C has decreased recently, and a high proportion of prisoners remain non-immune to hepatitis B, there are opportunities to increase testing and vaccination rates in this population.

Rotational malreduction is a common yet underreported postoperative complication following intramedullary nailing of long bone fractures. In most situations, this can be prevented at the time of initial surgery with meticulous preoperative planning, careful use of intraoperative fluoroscopy, and awareness of risk factors for malrotation. However, rotational alignment remains difficult to assess by clinical examination so a high index of suspicion is always necessary. Here, the authors review the literature on this complication and report on 3 such cases of femoral and the tibial malrotation, methods for calculating femoral version and tibial torsion, and techniques for correcting these deformities.

OBJECTIVES: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians. METHODS: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs. Resident-physicians worked 4-week EDWRs with shifts of 24+ hours every third or fourth shift, or an RCWR in which most shifts were ≤16 consecutive hours. Participants completed a daily sleep and work log and the 10-minute Psychomotor Vigilance Task and Karolinska Sleepiness Scale 2 to 5 times per shift approximately once per week as operational demands allowed. RESULTS: Overall, the mean (± SE) number of attentional failures was significantly higher (P =.01) on the EDWR (6.8 ± 1.0) compared with RCWR (2.9 ± 0.7). Reaction time and subjective alertness were also significantly higher, by ∼18% and ∼9%, respectively (both P CONCLUSIONS: Performance impairment due to EDWR is improved by limiting shift duration. These data and their correlation with SME rates highlight the impairment of neurobehavioral performance due to extended-duration shifts and have important implications for patient safety.

Individual comorbidities have distinct contributions to nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (allo-HCT). We studied the impact of comorbidities individually and in combination in a single-center cohort of 573 adult patients who underwent CD34-selected allo-HCT following myeloablative conditioning. Pulmonary disease, moderate to severe hepatic comorbidity, cardiac disease of any type, and renal dysfunction were associated with increased NRM in multivariable Cox regression models. A Simplified Comorbidity Index (SCI) composed of the 4 comorbidities predictive of NRM, as well as age >60 years, stratified patients into 5 groups with a stepwise increase in NRM. NRM rates ranged from 11.4% to 49.9% by stratum, with adjusted hazard ratios of 1.84, 2.59, 3.57, and 5.38. The SCI was also applicable in an external cohort of 230 patients who underwent allo-HCT with unmanipulated grafts following intermediate-intensity conditioning. The area under the receiver operating characteristic curve (AUC) of the SCI for 1-year NRM was 70.3 and 72.0 over the development and external-validation cohorts, respectively; corresponding AUCs of the Hematopoietic Cell Transplantation–specific Comorbidity Index (HCT-CI) were 61.7 and 65.7. In summary, a small set of comorbidities, aggregated into the SCI, is highly predictive of NRM. The new index stratifies patients into distinct risk groups, was validated in an external cohort, and provides higher discrimination than does the HCT-CI.

Plastics pollution is causing an environmental crisis, prompting the development of new approaches for recycling, and upcycling. Here, we review challenges and opportunities in chemical and biological catalysis for plastics deconstruction, recycling, and upcycling. We stress the need for rigorous characterization and use of widely available substrates, such that catalyst performance can be compared across studies. Where appropriate, we draw parallels between catalysis on biomass and plastics, as both substrates are low-value, solid, recalcitrant polymers. Innovations in catalyst design and reaction engineering are needed to overcome kinetic and thermodynamic limitations of plastics deconstruction. Either chemical and biological catalysts will need to act interfacially, where catalysts function at a solid surface, or polymers will need to be solubilized or processed to smaller intermediates to facilitate improved catalyst–substrate interaction. Overall, developing catalyst-driven technologies for plastics deconstruction and upcycling is critical to incentivize improved plastics reclamation and reduce the severe global burden of plastic waste. Plastics are invaluable materials for modern society, although they result in the generation of large amounts of litter at the end of their life cycle. This Review explores the challenges and opportunities associated with the catalytic transformation of waste plastics, looking at both chemical and biological approaches to transforming such spent materials into a resource.

This chapter describes the transport processes of radiative energy in a thin luminescent paint, including the absorption of excitation light through the paint layer and the luminescent radiation from the paint layer. The response of a photodetector to the luminescent emission is discussed.

This chapter describes image and data analysis techniques for PSP and TSP. For quantitative measurements, cameras should be calibrated to establish the accurate relationship between the image plane and the 3D object space (Euclidean space) and then map data in images onto a surface grid in the object space. Analytical camera calibration techniques, especially the Direct Linear Transformation (DLT) and an optimization calibration method, are discussed. For PSP and TSP measurements, an ideal camera should have a linear response to the luminescent radiance. A simple effective technique is described to determine the radiometric response function of a camera. The self-illumination of PSP and TSP may cause a significant error near a conjuncture of surfaces when a strong exchange of the radiative energy occurs between neighboring surfaces. The numerical methods for correcting the self-illumination are described and the errors associated with the self-illumination are estimated.

Ureteral reconstruction with autologous tissue grafts is often limited by tissue availability and donor site morbidity. This study investigates the performance of acellular, bi-layer silk fibroin (BLSF) scaffolds in a porcine model of ureteroplasty. Tubular ureteroplasty with BLSF grafts in combination with transient stenting for 8 weeks was performed in adult female, Yucatan, mini-swine (N = 5). Animals were maintained for 12 weeks post-op with imaging of neoconduits using ultrasonography and retrograde ureteropyelography carried out at 2 and 4 weeks intervals. End-point analyses of ureteral neotissues and unoperated controls included histological, immunohistochemical (IHC), histomorphometric evaluations as well as ex vivo functional assessments of contraction/relaxation. All animals survived until scheduled euthanasia and displayed mild hydronephrosis (Grades 1-2) in reconstructed collecting systems during the 8 weeks stenting period with one animal presenting with a persistent subcutaneous fistula at 2 weeks post-op. By 12 weeks of scaffold implantation, unstented neoconduits led to severe hydronephrosis (Grade 4) and stricture formation in the interior of graft sites in 80% of swine. Bulk scaffold extrusion into the distal ureter was also apparent in 60% of swine contributing to ureteral obstruction. However, histological and IHC analyses revealed the formation of innervated, vascularized neotissues with a-smooth muscle actin+ and SM22α+ smooth muscle bundles as well as uroplakin 3A+ and pan-cytokeratin + urothelium. Ex vivo contractility and relaxation responses of neotissues were similar to unoperated control segments. BLSF biomaterials represent emerging platforms for tubular ureteroplasty, however further optimization is needed to improve in vivo degradation kinetics and mitigate stricture formation.

This chapter describes the intensity-based methods that are widely used in PSP and TSP measurements. A generic camera-based system is first described, which includes illumination sources, optical filters, digital cameras (CCD and CMOS cameras), and data acquisition and processing units. Then, a generic laser-scanning system is briefly described for PSP and TSP measurements. Furthermore, the basic data processing for the intensity-based methods is described. Uncertainty analysis of the intensity-based methods for PSP and TSP is a major topic of this chapter, including system modeling, error propagation, sensitivity coefficients, total uncertainty, elemental error sources, and measurement limits.

This chapter describes the response of the luminescent emission of PSP (or TSP) to time-varying excitation light and the luminescent lifetime measurement methodologies, including the pulse method, phase method, amplitude demodulation method, and gated intensity ratio method. Uncertainty analysis of the lifetime-based methods for PSP is given, and typical lifetime measurements are described. Compared to the intensity-based method, the intrinsic advantage of the lifetime-based method is that a relation between the luminescent lifetime and pressure is not dependent on the illumination intensity. The lifetime-based methods were applied earlier to a laser-scanning system for PSP and TSP. Currently, multi-gated digital cameras with LED lights for illumination (particularly with the single-shot two-gate lifetime method) are popular for PSP and TSP lifetime measurements.

The first edition of the book “Pressure and Temperature Sensitive Paints” published by Springer in 2005 summarizes the early development of pressure- and temperature-sensitive paints (PSP and TSP) for aerodynamics, fluid mechanics, and heat transfer measurements. PSP and TSP as global optical techniques are able to provide quantitative high-resolution surface pressure, temperature, and heat-transfer data for complex aerodynamic flows. Since 2005, there has been significant progress with the PSP and TSP techniques, especially with techniques such as time-revolved PSP and TSP measurements in unsteady flows, lifetime-based PSP and TSP measurements on rotating and moving objects, aeroacoustic measurements, and PSP measurements in low-speed, low-pressure, and hypersonic flows. PSP and TSP measurements are now commonly being carried out in various facilities in major aerospace institutions, including subsonic, transonic, supersonic, and hypersonic facilities, in cryogenic wind tunnels and with rotating machinery. The goal of this second edition is to give an updated, systematic description of PSP and TSP with presentation of new results obtained after 2005. This second edition has 11 chapters and four appendices whose content is summarized in brief below.

Background: There is a critical gap in HIV prevention science around the development of interventions that help male couples form and adhere to safer sexual agreements. This paper reports the results of a randomized controlled trial (RCT) to assess the efficacy of Nexus , a telehealth delivered intervention that combines Couples’ HIV Counseling and Testing (CHTC) with home-based HIV-testing, examining the impact of the intervention on the couples’ formation and adherence to safer sexual agreements. Methods: Between 2016 and 2018, 424 male couples were recruited online from across the U.S and equally randomized to the intervention arm (a telehealth delivered CHTC session with two home HIV-testing kits) or a control arm (two home HIV-testing kits), with study assessments at baseline, 3 and 6 months. Outcomes included the formation and adherence to safer sexual agreements, dyadic discordance in reporting sexual agreements, breakage of sexual agreements, and perceptions of the benefit of PrEP. Findings: Couples randomized to the intervention arm had significantly greater odds of reporting a safer sexual agreement (3 months OR 1.87, 95%CI 1.21-2.90, p-value 0.005, and 6 months OR 1.84, p-value 0.007), lower odds of reporting discordant sexual agreements at 6 months (OR 0.62, p-value 0.048), and a significantly lower odds of reporting breaking their sexual agreement (3 months OR 0.51, p-value 0.035, and 6 months OR 0.23, p-value 0.000). By 6 months, couples in the intervention arm were less likely to say PrEP was beneficial to one (RRR 0.33, P=0.000) or both of them (RRR 0.29, P=0.000) than being beneficial to neither of the partners. Interpretation: The high levels of acceptability and efficacy of the intervention demonstrate strong potential for the scale-up of this efficacious intervention that leverages existing interventions (CHTC) and delivers them through a low-cost telehealth platform to create significant behavioral change among male couples. Trial Registration: The study was registered on ClinicalTrials.gov (NCT02335138) Funding: The study was supported by National Institutes of Health (Grant No. R01HD078131). Declaration of Interest: The authors declare no competing interests. Ethical Approval: Ethical approval was obtained from the University of Michigan (HUM00102906) Institutional Review Board.

Forest biomass is an essential indicator for monitoring the Earth’s ecosystems and climate. It is a critical input to greenhouse gas accounting, estimation of carbon losses and forest degradation, assessment of renewable energy potential, and for developing climate change mitigation policies such as REDD+, among others. Wall-to-wall mapping of aboveground biomass (AGB) is now possible with satellite remote sensing (RS). However, RS methods require extant, up-to-date, reliable, representative and comparable in situ data for calibration and validation. Here, we present the Forest Observation System (FOS) initiative, an international cooperation to establish and maintain a global in situ forest biomass database. AGB and canopy height estimates with their associated uncertainties are derived at a 0.25 ha scale from field measurements made in permanent research plots across the world’s forests. All plot estimates are geolocated and have a size that allows for direct comparison with many RS measurements. The FOS offers the potential to improve the accuracy of RS-based biomass products while developing new synergies between the RS and ground-based ecosystem research communities., Measurement(s)above-ground biomass • organic materialTechnology Type(s)tree species census • measurement methodFactor Type(s)geographic location • tree speciesSample Characteristic - Environmentforest biomeSample Characteristic - LocationEarth (planet) Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.9850571

We designed, developed and tested a series of benzalkylsilane molecules in self-assembled monolayers (SAMs) to investigate their degree of order and electrical properties when anchored to silicon substrates. The molecules consist of a silane anchoring group and a nitrogen-substituted benzene ring, separated by a propyl group and imine linkage. By varying fabrication procedures and the ring substituents, we obtained a vast range of rectification ratios, between 10-3100. The highest value was obtained for the molecule (E)-1-(4-cyanophenyl)-N-(3-(triethoxysilyl) propyl)methanimine. We assign the efficient rectification behavior to a highly ordered SAM and coupling between the delocalized lone pair of electrons from the nitrogen termination and the device electrode. These devices were employed for sensing applications allowing for sensitive detection of humidity. Overall, the utilization of these molecular devices will allow for functionable, cost efficient, and easily integrable devices.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P