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Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]1.5, FDR.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH1.3, FDR.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r.6; P .05).This study was limited by a small sample size and predominantly female FFA patients.Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition.

Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

Background e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown. Research Question What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior? Study Design and Methods CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ2 test, and multivariable analyses were used for statistical analysis. Results A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC. Interpretation EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding.

Introduction Research into the role of ultrasound elastography to assess compromised placental tissue is ongoing. There is particular interest in evaluating its potential in the investigation of changes associated with uteroplacental dysfunction. To date, there is limited data on how different maternal and fetal considerations, such as advancing gestational age, amniotic fluid Index (AFI) and maternal body mass index (BMI) may influence shear wave velocity (SWV) measurements. This study aimed to evaluate longitudinal changes in SWV throughout gestation and model these changes with other developing fetal and maternal physiological and biological characteristics. Methods The study utilised 238 singleton pregnancies and collected longitudinal data at repeated intervals in the 3rd trimester representing 629 individual data points. Linear mixed model regression analysis was used to identify significant predictors for SWV. Results From a total of ten variables selected for modelling, only gestational age, AFI, BMI, and sample depth were found to be significant predictors of placental SWV, and gestational age and AFI were found to have only a minimal impact on SWV. Discussion Sophisticated statistical modelling demonstrates that many of the expected maternal and fetal changes in the 3rd trimester have no or minimal impact on placental SWV. Understanding which factors influence placental SWV is essential to ascertain the technique's utility in managing pregnancies complicated by placental dysfunction in the future.

Evidence-based standardization of the perioperative management of patients undergoing complex spine surgery can improve outcomes such as enhanced patient satisfaction, reduced intensive care and hospital length of stay, and reduced costs. The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) tasked an expert group to review existing evidence and generate recommendations for the perioperative management of patients undergoing complex spine surgery, defined as surgery on 2 or more thoracic and/or lumbar spine levels. Institutional clinical management protocols can be constructed based on the elements included in these clinical practice guidelines, and the evidence presented.

Objectives The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. Background In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. Methods Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. Results In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. Conclusions Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

PURPOSE: To investigate the relationship between macro-vasculature features and the standardized uptake value (SUV) of positron emission tomography (PET), which is a surrogate for the metabolic activity of a lung tumor. METHODS: We retrospectively analyzed a cohort of 90 lung cancer patients who had both chest CT and PET-CT examinations before receiving cancer treatment. The SUVs in the medical reports were used. We quantified three macro-vasculature features depicted on CT images (i.e., vessel number, vessel volume, and vessel tortuosity) and several tumor features (i.e., volume, maximum diameter, mean diameter, surface area, and density). Tumor size (e.g., volume) was used as a covariate to adjust for possible confounding factors. Backward stepwise multiple regression analysis was performed to develop a model for predicting PET SUV from the relevant image features. The Bonferroni correction was used for multiple comparisons. RESULTS: PET SUV was positively correlated with vessel volume (R=0.44, p0.05). After adjusting for tumor size, PET SUV was significantly correlated with vessel tortuosity (R=0.299, p=0.004) and vessel number (R=0.224, p=0.035), but only marginally correlated with vessel volume (R=0.187, p=0.079). The multiple regression model showed a performance with an R-Squared of 0.391 and an adjusted R-Squared of 0.355 (p

PURPOSE The potential to compute volume metrics of emphysema from planar scout images was investigated in this study. The successful implementation of this concept will have a wide impact in different fields, and specifically, maximize the diagnostic potential of the planar medical images. METHODS We investigated our premise using a well-characterized chronic obstructive pulmonary disease (COPD) cohort. In this cohort, planar scout images from computed tomography (CT) scans were used to compute lung volume and percentage of emphysema. Lung volume and percentage of emphysema were quantified on the volumetric CT images and used as the "ground truth" for developing the models to compute the variables from the corresponding scout images. We trained two classical convolutional neural networks (CNNs), including VGG19 and InceptionV3, to compute lung volume and the percentage of emphysema from the scout images. The scout images (n = 1,446) were split into three subgroups: (1) training (n = 1,235), (2) internal validation (n = 99), and (3) independent test (n = 112) at the subject level in a ratio of 8:1:1. The mean absolute difference (MAD) and R-square (R2) were the performance metrics to evaluate the prediction performance of the developed models. RESULTS The lung volumes and percentages of emphysema computed from a single planar scout image were significantly linear correlated with the measures quantified using volumetric CT images (VGG19: R2 = 0.934 for lung volume and R2 = 0.751 for emphysema percentage, and InceptionV3: R2 = 0.977 for lung volume and R2 = 0.775 for emphysema percentage). The mean absolute differences (MADs) for lung volume and percentage of emphysema were 0.302 ± 0.247L and 2.89 ± 2.58%, respectively, for VGG19, and 0.366 ± 0.287L and 3.19 ± 2.14, respectively, for InceptionV3. CONCLUSIONS Our promising results demonstrated the feasibility of inferring volume metrics from planar images using CNNs.

Although testosterone replacement therapy is an effective treatment for hypogonadism, there are safety concerns regarding potential cardiovascular risks and fertility preservation.To assess the effect of selective estrogen receptor modulator (SERM), aromatase inhibitor, and human chorionic gonadotropin (hCG) on total testosterone (TT) levels and hypogonadism.We performed a systematic literature review from 1987 to 2019 via PubMed, Cochrane review, and Web of Science. Terms used were infertility, hypogonadism, alternative to testosterone therapy, selective estrogen receptor modulator, aromatase inhibitor, and human chorionic gonadotropin. Studies that reported an effect of TT and hypogonadism after treatment of each medication were selected. Hypogonadal symptoms were assessed by the Androgen Deficiency of The Aging Male (ADAM) questionnaire. Aggregated data were analyzed via Chi-squared analysis.From literature, 25 studies were selected; of which, 12 evaluated efficacy of aromatase inhibitor, 8 evaluated SERMs, and 5 evaluated hCG effects. For SERMs, 512 patients with mean age 42.3 ± 1.94 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P .0001 [180.5-216.1 95% confidence interval {CI}]). For aromatase inhibitor, 375 patients with mean age 54.1 ± 0.67 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P .0001 [180.5-216.1 95% CI]). SERMs also showed ADAM before treatment vs after treatment (4.95 ± 0.28 vs 5.50 ± 0.19, P .0001 [0.523-0.581 95% CI]). For hCG, 196 patients with mean age 41.7 ± 1.5 years showed mean TT before treatment vs after treatment (284.5 ± 13.6 [ng/dl] vs 565.6 ± 39.7 [ng/dl], P .0001 [275.2-287.0 95% CI]). In addition, hCG also showed ADAM before treatment vs after treatment (28.1 ± 2.0 vs 30.9 ± 2.3, P .0001 [2.313 95% CI]).Non-testosterone therapies are efficacious in hypogonadal men. Our results show statistically significant improvement in TT and ADAM scores in all 3 medications after treatment. Future studies are warranted to elucidate the relationship between improved hypogonadism and erectile function in the setting of non-testosterone-based treatment. Raheem OA, Chen TT, Le TV, et al. Efficacy of Non-Testosterone-Based Treatment in Hypogonadal Men: A Review. Sex Med Rev 2021;9:381-392.

PURPOSE Intracavitary brachytherapy is critical in treatment of cervical cancer with the highest rates of local control and survival. Only about 50% of graduating residents express confidence to develop a brachytherapy practice with caseload as the greatest barrier. We hypothesize that virtual reality (VR)-based intracavitary brachytherapy simulation will improve resident confidence, engagement, and proficiency. METHODS We created a VR training video of an intracavitary brachytherapy case performed by a board-certified gynecologic radiation oncologist and medical physicist. Residents performed a timed intracavitary procedure on a pelvic simulator before and after viewing the VR simulation module on a commercially available VR headset while five objective measures of implant quality were recorded. The residents completed a pre- and postsimulation questionnaire assessing self-confidence, procedural knowledge, and perceived usefulness of the session. RESULTS There were 14 residents, including five postgraduate year (PGY)-2, three PGY-3, four PGY-4, and two PGY-5, who participated in the VR curriculum. There were improvements in resident confidence (1.43–3.36), and subjective technical skill in assembly (1.57–3.50) and insertion (1.64–3.21) after the simulation. Average time of implant decreased from 5:51 to 3:34 (p = 0.0016). Median technical proficiencies increased from 4/5 to 5/5. Overall, the residents found VR to be a useful learning tool and indicated increased willingness to perform the procedure again. CONCLUSIONS VR intracavitary brachytherapy simulation improves residents’ self-confidence, subjective and objective technical skills, and willingness to perform brachytherapy. Furthermore, VR is an immersive, engaging, time-efficient, inexpensive, and enjoyable tool that promotes residents interest in brachytherapy.

African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions, however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection. We queried a prospectively maintained institutional review board-approved database of men undergoing prostate biopsy for untreated prostate cancer. We included all consecutive patients from October 2017 to February 2020. Statistical analysis including Kaplan–Meier Curves, Fisher’s exact test, and Forest plot was performed. From 246 consecutive patients, 166 were AA and 80 were non-AA. There were similar distributions of PSA, PSAD, and number of targetable lesions between the AA and non-AA cohort (p &gt, 0.05 for all). We found no difference in location on MRI between race groups. There was similar cancer detection, focusing on anterior lesions and rate of positive Gleason grade (≥GG1) and clinically significant (≥GG2) cancer between cohorts. In a predominant AA cohort of veterans, we found similar distribution of location for MRI-targeted lesions, along with rates of tumor detection and aggressiveness of disease. In this single payer veteran population, we did not identify specific biologic differences inherent to tumor detection between AA and non-AA patients.

Background In atopic dermatitis (AD), some studies have shown an association with increased cardiovascular disease in certain populations. However, other investigations found modest or no association. Despite conflicting results, molecular profiling studies in both AD skin and blood have demonstrated upregulation of atherosclerosis and cardiovascular risk-related markers. However, the underlying mechanisms connecting AD to vascular inflammation/atherosclerosis are unknown. In this study, we aim to determine factors associated with vascular inflammation/atherosclerosis in AD patients. Methods We used 18-FDG PET-CT to characterize vascular inflammation in AD patients and healthy subjects. In parallel, we assessed their skin and blood immune profiles to determine AD-related immune biomarkers associated with vascular inflammation. We also assessed levels of circulating microparticles, which are known to be associated with increased cardiovascular risk. Results We found significant correlations between vascular inflammation and Th2-related products in skin and blood of AD patients as well as atherosclerosis-related markers that were modulated by dupilumab. Circulating levels of endothelial microparticles were significantly higher in severe AD patients and tended to correlate with vascular inflammation assessed by PET-CT. Conclusion Vascular inflammation in AD is associated with enhanced Th2 response and clinical severity, which may explain cardiovascular comorbidities observed in select AD populations. Larger prospective studies are needed to further evaluate vascular inflammation and cardiovascular events and mortality in AD patients. Finally, as dupilumab treatment demonstrated significant modulation of atherosclerosis-related genes in AD patients compared to placebo, these data suggest that modulation of vascular inflammation with systemic treatment should be explored in patients with AD.

Objective: The incidence of lymphogranuloma venereum (LGV) in Europe is increasing. However, diagnosing LGV in a hospital setting is rare. We analysed the diagnostic process and clinical characteristics of patients with LGV in a hospital setting. Design and setting: A retrospective observational study conducted in a teaching hospital in Amsterdam, The Netherlands. All adult patients with LGV between November 2010 and February 2019 were included. Clinical data were retrieved from electronic patient records. Results: 40 patients were included. 90% of patients were men who have sex with men (MSM) and 62,5% were HIV positive. The most common presenting symptoms were rectal bleeding (47,5%), anal symptoms (30%) and change in bowel habits (25%). The mean time from first consultation to diagnosis was 28 days (range: 0 to 332, median 16,5 days). Diagnostic delay was increased by clinical presentation (ie anogenital syndrome) and the number of specialists involved. Diagnostic procedures not leading to the diagnosis were performed in 98% of cases. Conclusion: To prevent late complications, unnecessary diagnostic procedures and further transmission, early testing for LGV should be incorporated in the work-up of every patient reporting MSM-activity presenting with anorectal symptoms or inguinal lymphadenopathy.

Renal Cell Carcinoma (RCC) is the most common form of kidney cancer, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. There are limited curable treatments available for metastatic ccRCC because this disease is unresponsive to conventional targeted systemic pharmacotherapy. Exosomes (Exo) are small extracellular vesicles (EVs) secreted from cancer cells with marked roles in tumoral signaling and pharmacological resistance. Ketoconazole (KTZ) is an FDA approved anti-fungal medication which has been shown to suppress exosome biogenesis and secretion, yet its role in ccRCC has not been identified. A time-course, dose-dependent analysis revealed that KTZ selectively decreased secreted Exo in tumoral cell lines. Augmented Exo secretion was further evident by decreased expression of Exo biogenesis (Alix and nSMase) and secretion (Rab27a) markers. Interestingly, KTZ-mediated inhibition of Exo biogenesis was coupled with inhibition of ERK1/2 activation. Next, selective inhibitors were employed and showed ERK signaling had a direct role in mediating KTZ’s inhibition of exosomes. In sunitinib resistant 786-O cells lines, the addition of KTZ potentiates the efficacy of sunitinib by causing Exo inhibition, decreased tumor proliferation, and diminished clonogenic ability of RCC cells. Our findings suggest that KTZ should be explored as an adjunct to current RCC therapies.

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

The premise of catch-and-release angling is that most fish survive fisheries interactions. Therefore, it is common for anglers, management agencies, and other organizations to share information on handling practices and other strategies that are believed to improve fish welfare and survival. Recent media coverage has sensationalized the use of carbonated beverages to treat bleeding fish, an intervention that is purported to stop bleeding but has yet to be validated scientifically. We captured Northern Pike (Esox lucius) via hook and line, experimentally injured their gills in a standardized manner, and treated them with either Mountain Dew, Coca Cola, or carbonated lake water and observed the duration and intensity of bleeding, as well as overall blood loss (using gill colour as a proxy) while the fish was held in a lake water bath. As a control, we had a group of experimentally injured fish that did not have liquid poured over their gills before the observation period. All treatments and the control were conducted at two different water temperatures (11-18 °C and 24-27 °C) to determine if the effects of pouring carbonated beverages over injured gills is temperature dependent. When compared to the control, we found that the duration and intensity of bleeding increased regardless of the type of carbonated beverages used in this study, and there was no effect of water temperature. Use of chilled versus ambient temperature beverages similarly had no influence on outcomes. As such, there is no scientific evidence to support the use of carbonated beverages for reducing or stopping blood loss for fish that have had their gills injured during recreational angling based on the context studied here. This study reinforced the need to scientifically test angler anecdotes and theories when it comes to best practices for catch-and-release fishing.

PURPOSE Physical impairment after critical illness is recognized as a part of the post-intensive care syndrome (PICS). About one third of intensive care unit (ICU) survivors suffer from long-term physical disability, yet the underlying pathophysiological mechanisms remain poorly understood. The pro-inflammatory alarmin, high mobility group box 1 (HMGB1), promotes muscle dysfunction in experimental models, and HMGB1 stays elevated in some patients after ICU discharge. Accordingly, we investigated the relationship between HMGB1 plasma levels and physical performance in ICU survivors. METHODS Prospective cohort study of 100 ICU survivors from the general ICU at the Karolinska University Hospital, Sweden. Patients returned for follow up at 3 (58 patients) and 6 months (51 patients) after ICU discharge. Blood samples were collected, and a 6-minute walk test (6-MWT), a handgrip-strength test (HST), and a timed-stands test (TST) were performed. RESULTS Compared to reference values of the different physical tests, 16% of patients underperformed at all tests at 3 months and 12% at 6 months. All test results, except hand-grip strength left, improved significantly over the follow-up period (P

While the stochastic, "blinking" nature of fluorescent systems has enabled the super-resolution of their localization by the fitting of their point-spread functions (PSFs), this strategy cannot be exploited for similar resolution of "nonblinking" systems, such as those that might be encountered in a coherent Raman experiment. An alternative method for subdiffraction-limited imaging lies in the exploitation of optical heterodyning. For example, if a Gaussian PSF (a TEM00 mode) of a point emitter is displaced with respect to the origin of the optical system, photons in the higher-order TEM modes carry information about that displacement. Information concerning the displacement can be extracted from photons in these higher-order modes. These photons can be collected by optical heterodyning, which exploits the large gain in a detector's response to an optical signal from an emitter coupled to a local oscillator, which is prepared in the TEM of interest, e.g., TEM10. We have generalized and developed the heterodyning technique to localize point emitters via the detection of higher-order spatial modes. We have developed a theoretical approach to find a practical estimation limit of the localization parameters using a realistic model that accounts for shot noise, background noise, and Gaussian noise. To demonstrate the applicability of the method, we designed experiments in which a laser is a surrogate for one and two point emitters. Using the Fisher information and its accompanying Cramér-Rao lower bound, we demonstrate super-resolution localization in these cases: we show that objects can be localized to roughly 2-3 orders of magnitude of their point-spread function's size for a given optical system. Finally and most importantly, it is suggested that the results will ultimately be generalizable to multiple emitters and, most importantly, to "nonblinking" molecular systems, which will be essential for broadening the scope of super-resolution measurements beyond the limits of fluorescence-based techniques.

Objective To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear. Methods A prospectively maintained AS database from the Southeast Louisiana Veterans Administration Medical Center, New Orleans, Lousiana was queried. We identified men with low- and very low-risk PCa (Gleason 3 + 3, PSA Results From a total of 274 men on AS (70% AA), 158 men met inclusion criteria (104 AA [66%]). All patients underwent at least 2 biopsies, and 29% underwent 3 or more biopsies. The median follow-up was 2.7 years. At 3 years on AS protocol, 57% AA and 61% Caucasians demonstrated no evidence of upgrading or treatment. No significant difference was observed between upgrading or progression to treatment when comparing racial groups. Seven (4%) patients in this cohort died from non PCa-specific causes, but no patients demonstrated metastasis or death from PCa over the course of study. Conclusion AA men with low-risk PCa can be safely followed with the same AS protocol as non-AA men. Further analysis with longer follow up is ongoing.

A significant limitation in biodiversity conservation has been the effective implementation of laws and regulations that protect species' habitats from degradation. Flexible, efficient, and effective monitoring and enforcement methods are needed to help conservation policies realize their full benefit. As remote sensing data become more numerous and accessible, they can be used to identify and quantify land-cover changes and habitat loss. However, these data remain underused for systematic conservation monitoring in part because of a lack of simple tools. We adapted 2 algorithms that automatically identify differences between pairs of images. We used free, publicly available satellite data to evaluate their ability to rapidly detect land-cover changes in a variety of land-cover types. We compared algorithm predictions with ground-truthed results at 100 sites of known change in the United States. We also compared algorithm predictions to manually created polygons delineating anthropogenic change in 4 case studies involving imperiled species' habitat: oil and gas development in the range of the Greater Sage Grouse (Centrocercus urophasianus); sand mining operations in the range of the dunes sagebrush lizard (Sceloporus arenicolus); loss of Piping Plover (Charadrius melodus) coastal habitat after Hurricane Michael (2018); and residential development in St. Andrew beach mouse (Peromyscus polionotus peninsularis) habitat. Both algorithms effectively discriminated between pixels corresponding to land-cover change and unchanged pixels as indicated by area under a receiver operating characteristic curve0.90. The algorithm that was most effective differed among the case-study habitat types, and both effectively delineated habitat loss as indicated by low omission (min. = 0.0) and commission (min. = 0.0) rates, and moderate polygon overlap (max. = 47%). Our results showed how these algorithms can be used to help close the implementation gap of monitoring and enforcement in biodiversity conservation. We provide a free online tool that can be used to run these analyses (https://conservationist.io/habitatpatrol).Respaldo a la Conservación de Hábitat con la Detección Automatizada de Cambio en Google Earth Resumen Una limitación significativa en la conservación de la biodiversidad ha sido la implementación efectiva de las leyes y regulaciones que protegen los hábitats de las especies de la degradación. El monitoreo flexible, eficiente y efectivo y los métodos de aplicación son necesarios para que las normas de conservación puedan llevar a cabo su potencial completo. Conforme los datos de telemetría se vuelven cada vez más numerosos y accesibles, su uso puede extenderse a la identificación y cuantificación de los cambios en la cobertura del suelo y la pérdida del hábitat. Sin embargo, estos datos todavía están subutilizados en cuanto al monitoreo sistemático de la conservación en parte debido a la falta de herramientas simples y sencillas. Adaptamos dos algoritmos que identifican automáticamente las diferencias entre pares de imágenes. Utilizamos datos satelitales gratuitos y disponibles para el público para con ellos evaluar la habilidad que tienen los algoritmos para detectar rápidamente los cambios en la cobertura del suelo dentro de una variedad de tipos de cobertura de suelo. Comparamos las predicciones algorítmicas con los resultados de algunas investigaciones en 100 sitios con cambios conocidos en los Estados Unidos. También comparamos las predicciones algorítmicas con polígonos creados manualmente que delinean el cambio antropogénico en cuatro estudios de caso que involucran al hábitat de una especie en peligro: desarrollos de petróleo y gas en la distribución de Centrocercus urophasianus; minas de arena en la distribución de Sceloporus arenicolus; la pérdida del hábitat costero de Charadrius melodus después del huracán Michael (2018); y los desarrollos residenciales en el hábitat de Peromyscus polionotus peninsularis. Ambos algoritmos discriminaron efectivamente entre los píxeles que correspondían al cambio en la cobertura del suelo y los píxeles sin cambio así indicados por el área bajo la curva de característica de receptor operante0.90. El algoritmo más efectivo difirió entre los tipos de hábitat para los estudios de caso, mientras que ambos algoritmos delinearon efectivamente la pérdida de hábitat así indicada por la baja tasa de omisión (min. = 0.0) y comisión (min. = 0.0) y el traslape moderado de polígonos (max. = 47%). Nuestros resultados mostraron cómo pueden usarse estos algoritmos para ayudar a cerrar la brecha en la implementación del monitoreo y aplicación en la conservación de la biodiversidad. Proporcionamos una herramienta gratuita en línea que puede usarse para realizar estos análisis: https://conservationist.io/habitatpatrol.

Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for vaccine targeting, including the oral cavity, stomach, and small intestine. However, currently available oral vaccines are effectively limited to live-attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges,including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent advances in oral biologic delivery that offer promise as future platforms for the administration of oral vaccines.

Preclinical studies show a link between subthalamic nucleus (STN) deep brain stimulation (DBS) and neuroprotection of nigrostriatal dopamine (DA) neurons, potentially through brain-derived neurotrophic factor (BDNF) signaling. However, the question of whether DBS of the STN can be disease-modifying in Parkinson's disease (PD) remains unanswered. In particular, the impact of STN DBS on α-synuclein (α-syn) aggregation, inclusion-associated neuroinflammation, and BDNF levels has yet to be examined in the context of synucleinopathy. To address this, we examined the effects of STN DBS on BDNF using the α-syn preformed fibril (PFF) model in male rats. While PFF injection resulted in accumulation of phosphorylated α-syn (pSyn) inclusions in the substantia nigra pars compacta (SNpc) and cortical areas, STN DBS did not impact PFF-induced accumulation of pSyn inclusions in the SNpc. In addition, nigral pSyn inclusions were associated with increased microgliosis and astrogliosis; however, the magnitude of these processes was not altered by STN DBS. Total BDNF protein was not impacted by pSyn inclusions, but the normally positive association of nigrostriatal and corticostriatal BDNF was reversed in rats with PFF-induced nigrostriatal and corticostriatal inclusions. Despite this, rats receiving both STN DBS and PFF injection showed increased BDNF protein in the striatum, which partially restored the normal corticostriatal relationship. Our results suggest that pathologic α-syn inclusions disrupt anterograde BDNF transport within nigrostriatal and corticostriatal circuitry. Further, STN DBS has the potential to exert protective effects by modifying the long-term neurodegenerative consequences of synucleinopathy.SIGNIFICANCE STATEMENTAn increase in brain-derived neurotrophic factor (BDNF) has been linked to the neuroprotection elicited by subthalamic nucleus (STN) deep brain stimulation (DBS) in neurotoxicant models of Parkinson's disease (PD). However, whether STN DBS can similarly increase BDNF in nigrostriatal and corticostriatal circuitry in the presence of α-synuclein (α-syn) inclusions has not been examined. We examined the impact of STN DBS on rats in which accumulation of α-syn inclusions is induced by injection of α-syn preformed fibrils (PFFs). STN DBS significantly increased striatal BDNF protein in rats seeded with α-syn inclusions and partially restored the normal corticostriatal BDNF relationship. These findings suggest that STN DBS can drive BDNF in the parkinsonian brain and retains the potential for neuroprotection in PD.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Background Pathologic fibrosis is characterized by dysregulation of gene expression with excessive extracellular matrix production. The genetic basis for solid organ fibrosis is well described in the literature. However, there is a paucity of evidence for similar processes in the musculoskeletal (MSK) system. The purpose of this review is to provide an overview of existing evidence of genetic predisposition to pathologic fibrosis in the cardiac, pulmonary, and MSK systems, and to describe common genetic variants associated with these processes. Methods A comprehensive search of several databases from 2000 to 2019 was conducted using relevant keywords in the English language. Genes reported as involved in idiopathic fibrotic processes in the heart, lung, hand, shoulder, and knee were recorded by 2 independent authors. Results Among 2373 eligible studies, 52 studies investigated genetic predisposition in terms of variant analysis with the following organ system distribution: 36 pulmonary studies (69%), 15 hand studies (29%), and 1 knee study (2%). Twenty-two percent of gene variants identified were associated with both pulmonary and MSK fibrosis (ie, ADAM, HLA, CARD, EIF, TGF, WNT, and ZNF genes). Genetic variants known to be involved in the MSK tissue development or contractility properties in muscle were identified in the pulmonary fibrosis. Conclusion Despite shared genetic variations in both the lung and hand, there remains limited information about genetic variants associated with fibrosis in other MSK regions. This finding establishes the necessity of further studies to elucidate the genetic determinants involved in the knee, shoulder, and other joint fibrotic pathways. Level of evidence Level III.

Minimally invasive glaucoma surgery (MIGS) has become a reliable standard of care for the treatment of glaucoma when combined with cataract surgery. This review describes the MIGS procedures currently combined with and without cataract surgery with a focus on visual outcomes based on the literature and the experience of the ASCRS Glaucoma Clinical Committee.

Posttraumatic stress disorder (PTSD) and depression are common following orthopedic trauma. This study examined the relationship between injury- and hospital-related variables and PTSD and depression at baseline and 12 months after orthopedic trauma. This longitudinal, prospective cohort study examined adult orthopedic trauma patients admitted ≥24 hours to a level I trauma center. Non-English/Spanish-speaking and cognitively impaired patients were excluded. The Primary Care PTSD screen and PTSD Checklist-Civilian version assessed PTSD, and the Patient Health Questionnaire 8-Item assessed depression. Demographic and hospital-related variables were examined (e.g., hospital length of stay, Injury Severity Score, Glasgow Coma Scale). For 160 participants, PTSD prevalence was 23% at baseline and 21% at 12 months. Depression prevalence was 28% at baseline and 29% at 12 months. Ventilation (P = 0.023, P = 0.006) and prolonged length of stay (P = 0.008, P = 0.003) were correlated with baseline PTSD and depression. Injury etiology (P = 0.008) and Injury Severity Score (P = 0.013) were associated with baseline PTSD. Intensive care unit admission (P = 0.016, P = 0.043) was also correlated with PTSD at baseline and 12 months. Ventilation (P = 0.002, P = 0.040) and prolonged length of stay (P

Purpose A phase 3 trial (MERCURY-1) investigated efficacy and safety of a once-daily, fixed-dose combination (FDC) of netarsudil and latanoprost, compared with each active component, in reducing elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). A planned 3-month analysis demonstrated the superiority of netarsudil/latanoprost FDC over its individual active components at every assessment. Herein, the 12-month efficacy and safety of netarsudil/latanoprost FDC are reported. Design Double-masked, randomized, active-controlled, parallel-group trial. Participants Patients had unmedicated IOP >20 to am and met other standard criteria for OAG or OHT. Methods Randomization to once-daily netarsudil 0.02%/latanoprost 0.005% FDC (n = 238), netarsudil 0.02% only (n = 243), or latanoprost 0.005% only (n = 237). Patients instilled study drug into each eye between 8:00 pm and 10:00 pm . Main Outcome Measures IOP was obtained at 8:00 am , 10:00 am , and 4:00 pm on day 1 (baseline); at weeks 2 and 6; and at months 3, 6, 9, and 12. Ocular and systemic safety were evaluated up to month 12. Results Netarsudil/latanoprost FDC maintained statistically superior IOP lowering compared to its components at every assessment for 12 months. Least squares mean diurnal IOP (± standard error) at month 12 was 16.2 ± 0.23 mmHg for netarsudil/latanoprost FDC, 17.9 ± 0.20 mmHg for netarsudil, and 17.6 ± 0.18 mmHg for latanoprost (P Conclusions Results at 12 months revealed superior efficacy for netarsudil/latanoprost FDC compared with the individual components, netarsudil and latanoprost, at every time point assessed and an ocular tolerability profile similar to that of netarsudil alone.

Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. In vitro 3D-models of skeletal muscle provide a controllable, high throughput environment and mitigating many of the ethical and methodological constraints present during in vivo experimentation. This work aimed to determine if mechanical loading would offset dexamethasone (DEX) induced skeletal muscle atrophy, in muscle engineered using the C2C12 murine cell line. Mechanical loading successfully offset myotube atrophy and functional degeneration associated with DEX regardless of whether the loading occurred before or after 24 h of DEX treatment. Furthermore, mechanical load prevented increases in MuRF-1 and MAFbx mRNA expression, critical regulators of muscle atrophy. Overall, we demonstrate the application of tissue engineered muscle to study skeletal muscle health and disease, offering great potential for future use to better understand treatment modalities for skeletal muscle atrophy. Electronic supplementary material The online version of this article (10.1007/s10974-020-09589-0) contains supplementary material, which is available to authorized users.

Pain after lumbar spine fusion surgery is often difficult to control in the immediate postoperative period. Historically, opioids have been the mainstay of treatment, but are associated with many unwanted side effects as well as increased hospital length of stay. The ultrasound-guided erector spinae plane block (ESP) is a relatively safe and simple regional option for the management of acute postoperative pain after spine surgery without the technical difficulty or complications noted with paravertebral injection (eg, pneumothorax, hematoma). To date, there have been reports of preoperative placement of ESP block prior to spine surgery with some success. We present a report of two cases that highlight the efficacy of the ESP block as an early postoperative "rescue" regional anesthetic technique in lumbar spine surgery. These cases demonstrate the potential effectiveness of a "rescue" use of the ESP block in patients having uncontrolled or poorly controlled pain in the early postoperative period with no evidence of significant side effects.

Male sexual dysfunction has many different causes and is often multifactorial in nature. We aim to review the effects that testosterone (T), estrogen, thyroid hormone, prolactin (PRL), and cortisol have on male sexual function. T deficiency can cause decreased libido and diminished erectile function. Estrogen is necessary for sexual drive but is postulated to inhibit erectile function when elevated. Hyperthyroidism is associated with premature ejaculation (PE), hypothyroidism is associated with delayed ejaculation (DE), and both are associated with erectile dysfunction (ED). Hyperprolactinemia is associated with ED and can cause fertility issues. The role of corticosteroids is largely unknown. While hormonal disorders can largely influence male sexual health, resolution of sexual dysfunction is achieved in most cases by normalization of hormone levels.

Introduction: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are useful clinical biomarkers for prognosis in several malignancies. Their predictive value has been less clearly demonstrated with prostate cancer (PCa), particularly, their utility within active surveillance (AS) protocols. We aim to evaluate NLR and PLR in AS patients.Methods: We identified 98 patients who met inclusion criteria in our cohort of 274 men diagnosed with PCa on AS. Patients were then categorized into high and low NLR and PLR groups.Results: The 2.5 and 5-year Gleason upgrading free probability for our high NLR cohort was 73.9%(CI 56.3% to 97.0%) and 46.2%(CI 22.4% to 95.1%) compared to 76.3%(CI 65.7% to 88.7%) and 61.7%(CI 47.7% to 80.0%) in the low NLR cohort(p = .73). The 2.5 and 5-year Gleason upgrading free probability for our High PLR cohort was 73.5%(CI 57.3% to 94.2%) and 60.1(CI 41.4% to 87.4%) compared to 76.8%(CI 65.8% to 89.65) and 58.1%(CI 42.2% to 80.1%) in our low PLR group(p = .41). A multivariant analysis demonstrated these groups were not significant predictors of upgrading or treatment.Conclusion: Despite their usefulness in many types of malignancy, NLR and PLR were not predictors of upgrading or treatment in men on AS for localized PCa in our cohort.

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.

Introduction About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. Methods Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. Results Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. Conclusions AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed., Graphical abstract

A human has over 200 muscles in the body, creating a high degree of flexibility and redundancy in movement. This paper exploits this high degree of redundancy for the actuation and control of Supernumerary Robotic Limbs (SuperLimbs), which are attached to a human body. SuperLimbs containing many active joints tend to be too heavy to wear comfortably. Since SuperLimbs are attached to a human body at their base, Superlimbs can be positioned directly by moving the base with movements of the human body. No active joints are needed for the SuperLimbs in certain directions if the human body can generate the same movements as the SuperLimbs, thus allowing for the design of reduced-actuator Superlimbs. Here, we present a method for quantifying the usable degrees of freedom (DOFs) of a human body for a specific task so that the number of Superlimb actuators can be reduced. The high degree of redundant human DOFs can also be utilized for communication and control. Human's fingers are often redundant for performing a task, e.g. holding a box. Although both hands are busy, some combination of the finger forces is still available for generating signal patterns. An algorithm is developed for generating coded finger force patterns without interfering with the performance of the primary task. Both methods are implemented on a simple SuperLimb and a human subject demonstrates the usefulness of the methods.

OBJECTIVES/HYPOTHESIS Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting. STUDY DESIGN Prospective individual cohort study. METHODS This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain). RESULTS Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the

Summary: Background: To evaluate trends in frequency, mortality and treatment for non-traumatic vascular emergencies (VE) in the US. Methods: VE in the Nationwide Inpatient Sample (2005–2014) were identified. ICD-9 CM diagnosis and procedures codes captured six common VE. Results: 228,210,504 emergency admissions with 317,396 procedures for VE were estimated. Mean age was 67.8 years and were primarily men (56.1 %; p < 0.0001). The commonest VE was Acute Limb Ischemia (ALI) (82.4 %) followed by ruptured AAA (10.8 %) and Acute Mesenteric Ischemia (4.71 %). VE increased from 132.8 per 100,000 admissions in 2005 to 153.6 in 2014 (p < 0.001), with mortality decrease for all VE (13.8 % vs. 9.1 %; p

1. Participatory approaches are widely used by researchers to gather data and insight about how the environment is perceived, valued and used. The participatory activities may be creating information as part of curiosity-driven blue-skies research or to inform policy/practice decision-making. \ud 2. The quality and usability of data derived from participatory approaches are heavily influenced by how activities are conducted. We share a set of features and processes that underpin the generation of high-quality data, based on our collective experience of developing and undertaking participatory activities with an environmental and conservation focus.\ud 3. We propose four general features: (1) depth and breadth of engagement; (2) robustness of the approach; (3) allowing space for surprises; and (4) usability across contexts. We also provide a practical toolbox of processes, and associated facilitation techniques, which can be employed to maximise participant engagement and generate quality data.\ud 4. The features and processes are a practical guide for project leaders/teams to consider in the context of their work, rather than a set of inflexible rules. They should be relevant regardless of the participatory methods used, or the research, policy or practice setting being addressed.

Background : While obesity has become an increasingly prevalent health concern in the United States, little emphasis has been placed on utilizing patient reported outcome measures (PROM) to investigate its impact on life from the patients’ perspective. The purpose of the study was to determine the association between patients’ body mass index (BMI) and three Patient-Reported Outcome Measurement Information System (PROMIS) computer adaptive test scores: upper extremity physical function (UE) or lower extremity physical function (PF), pain interference (PI), and depression (D). Methods : Patients were recruited from two sports medicine orthopedic surgery clinics. PROMIS questionnaires were administered to patients arriving for their first visit. Patients were stratified into BMI groupings according to the National Institute of Health standards. Patients’ BMI, sex, race, ethnicity, and injury were determined retroactively. Data were analyzed using a Pearson correlation and a least significant difference post hoc test. Results : A total of 833 patients completed the set of PROMIS questionnaires that were retrospectively analyzed. BMI was found to have a correlation with PROMIS-UE (R=–0.111, P

Background The ability to automatically count animals is important to design appropriate environmental policies and to monitor their populations in relation to biodiversity and maintain balance among species. Out of all living mammals on Earth, 60% are livestock, 36% humans, and only 4% are animals that live in the wild. In a relatively short period, development of human civilization caused a loss of 83% of wildlife and 50% of plants. The rate of species extinction is accelerating. Traditional wildlife surveys provide rough population estimates. However, emerging technologies, such as aerial photography, allow to perform large-scale surveys in a short period of time with high accuracy. In this paper, we propose the use of computer vision, through deep learning (DL) architecture, together with aerial photography and density maps, to count the population of Steller sea lions and African elephants with high precision. Results We have trained two deep learning models, a basic UNet without any feature extractor (Model-1) and another with the EfficientNet-B5 feature extractor (Model-2). We measured the model’s prediction accuracy, using Root Mean Square Error (RMSE) for the predicted and actual animal count. The results showed an RMSE of 1.88 and 0.60 to count Steller sea lions and African elephants, respectively, regardless of complex background, different illumination conditions, heavy overlapping and occlusion of the animals. Conclusions Our proposed solution performed very well in the counting prediction problem, with relatively low training parameters and minimum annotation. The approach adopted, combining DL and density maps, provided better results than state-of-art deep learning models used for counting, indicating that the proposed method has the potential to be used more widely in large-scale wildlife surveying projects and initiatives.

From its invention to the internet age, photography has been considered universal, pervasive, and omnipresent. This anthology of essays posits how the question of when photography came to be everywhere shapes our understanding of all manner of photographic media. Whether looking at a portrait image on the polished silver surface of the daguerreotype, or a viral image on the reflective glass of the smartphone, the experience of looking at photographs and thinking with photography is inseparable from the idea of ubiquity—that is, the apparent ability to be everywhere at once. While photography’s distribution across cultures today is undeniable, the insidious logics and pervasive myths that have governed its spread demand our critical attention, now more than ever.

BACKGROUND: Prior studies using aggregated data suggest that better care coordination is associated with higher performance on measures of clinical care process; it is unclear whether this relationship reflects care coordination activities of health plans or physician practices. OBJECTIVE: Estimate within-plan relationships between beneficiary-reported care coordination measures and HEDIS measures of clinical process for the same individuals. DESIGN: Mixed-effect regression models in cross-sectional data. PARTICIPANTS: 2013 Medicare Advantage CAHPS respondents (n=152,069) with care coordination items linked to independently collected HEDIS data on clinical processes. MAIN MEASURES: Care coordination measures assessed follow-up, whether doctors had medical records during visits, whether doctors discussed medicines being taken, how informed doctors seemed about specialist care, and help received with managing care among different providers. HEDIS measures included mammography, colorectal cancer screening, cardiovascular LDL-C screening, controlling blood pressure, 5 diabetes care measures (LDL-C screening, retinal eye exam, nephropathy, blood sugar/HbA1c

BACKGROUND Septic arthritis of the native knee often results in irreversible joint damage leading to the need for total knee arthroplasty (TKA). The purpose of the present study was to examine the intermediate-term risk of periprosthetic joint infection (PJI), aseptic revision, and reoperation following primary TKA in patients with a history of septic arthritis of the native knee as compared with primary TKA performed for the treatment of osteoarthritis. METHODS We retrospectively identified 215 primary TKAs performed from 1971 to 2016 at a single institution in patients with a history of septic arthritis of the native knee. Each case was matched 1:1 based on age, sex, body mass index (BMI), and surgical year to a TKA for osteoarthritis. The mean age and BMI were 63 years and 30 kg/m2, respectively. The mean duration of follow-up was 9 years. RESULTS Survivorships free of PJI at 10 years were 90% and 99% for the septic arthritis and osteoarthritis groups, respectively (hazard ratio [HR] = 6.1; p < 0.01). Ten-year survivorships free of any aseptic revisions were 83% and 93% (HR = 2.5; p < 0.01), and survivorships free of any reoperation were 61% and 84% (HR = 2.9; p < 0.01) for the septic arthritis and osteoarthritis groups, respectively. In addition, as time from the diagnosis of native knee septic arthritis to TKA increased, the relative risk of subsequent infection decreased. Preoperative and 2-year postoperative Knee Society scores were similar between the groups (p = 0.16 and p = 0.19, respectively). CONCLUSIONS There was a 6.1-fold increased risk of PJI in patients undergoing TKA with a history of native knee septic arthritis when compared with controls undergoing TKA for the treatment of osteoarthritis, with a cumulative incidence of 9% at 10 years. Subgroup analysis of the septic arthritis cohort revealed a higher risk of any infection in patients who underwent TKA within the first 5 to 7 years after the diagnosis of septic arthritis as compared with those with a greater duration. Moreover, the 10-year rates of survival free of aseptic revision, any revision, and any reoperation were significantly worse in the native knee septic arthritis cohort. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The U.S. Endangered Species Act (ESA) is widely considered to be one of the strongest laws for 10 protecting imperiled wildlife, with nearly all species protected under the law still existing today. 11 Among the ESA’s strongest provisions, at least as written, is the requirement under section 7(a)(1) 12 that federal agencies use their authorities to help recover imperiled species. New initiatives like 13 30x30, the campaign to conserve at least thirty percent of U.S. lands and waters by 2030, offer 14 opportunities to reinvigorate and expand 7(a)(1) programs to play a significant role in biodiversity 15 conservation. To gauge the current status of 7(a)(1) plans and assess their effectiveness, we collected 16 all section 7(a)(1) materials available to the public through internet searches and direct requests to 17 agencies. We evaluated the scope of existing 7(a)(1) programs and found that despite the clear 18 potential benefits of strong programs, the section has been significantly underused by federal 19 agencies. Further, we show that existing plans are highly inconsistent in content and style, and we 20 trace that inconsistency to the lack of policy guidance for their creation and implementation. Based 21 on these findings, we recommend five strategies for improving 7(a)(1) implementation: establishment 22 of formal guidance from the federal wildlife agencies, tailored guidance from other federal agencies 23 to help them meet their 7(a)(1) obligation, dedicated funding, integration of 7(a)(1) into existing 24 initiatives and opportunities, and top-level executive branch coordination and cooperation.