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Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and endocrine glands on the brain, accumulating data suggest that dysfunction of other organs, such as gut, liver, kidney and lung, substantially affects the development and clinical manifestation of age-related brain pathologies. In this Review, a framework is provided to indicate how organ dysfunction can alter brain homeostasis and promote neurodegeneration, with a focus on dementia. We delineate the associations of subclinical dysfunction in specific organs with dementia risk and provide suggestions for public health promotion and clinical management. Peripheral organ dysfunction can have considerable effects on brain health, contributing to neurodegeneration and dementia. This Review explores how clinical and subclinical dysfunction of specific organ systems can impact brain health and discusses the implications for dementia prevention. Key points: Brain health is a worldwide priority, and dementia is the biggest threat to healthy brain ageing. The brain requires a supportive environment maintained by healthy organ systems to function optimally and to confer resilience to neurodegenerative diseases such as Alzheimer disease and Parkinson disease. Increasing evidence links subclinical dysfunction of the cardiovascular, pulmonary, renal, gastrointestinal, hepatic and endocrine systems with age-related cognitive decline and dementia. Cardiovascular, renal and hepatic dysfunction as well as changes in the gut microbiome have been associated with the presence of Alzheimer disease biomarkers in human research. Pathways that might lead from organ dysfunction to brain dysfunction include systemic endothelial dysfunction, reduced peripheral clearance of wastes (including amyloid-β and tau), systemic inflammation and alterations in the microbiome. Future research needs to explore mechanisms that link peripheral organ dysfunction to risk of age-related neurodegenerative and cerebrovascular diseases and to elucidate whether improving organ function reduces this risk. [ABSTRACT FROM AUTHOR]

As is true of many complex tasks, the work of discovering, describing, and understanding the diversity of life on Earth (viz., biological systematics and taxonomy) requires many tools. Some of this work can be accomplished as it has been done in the past, but some aspects present us with challenges which traditional knowledge and tools cannot adequately resolve. One such challenge is presented by species complexes in which the morphological similarities among the group members make it difficult to reliably identify known species and detect new ones. We address this challenge by developing new tools using the principles of machine learning to resolve two specific questions related to species complexes. The first question is formulated as a classification problem in statistics and machine learning and the second question is an out-of-distribution (OOD) detection problem. We apply these tools to a species complex comprising Southeast Asian stream frogs (Limnonectes kuhlii complex) and employ a morphological character (hind limb skin texture) traditionally treated qualitatively in a quantitative and objective manner. We demonstrate that deep neural networks can successfully automate the classification of an image into a known species group for which it has been trained. We further demonstrate that the algorithm can successfully classify an image into a new class if the image does not belong to the existing classes. Additionally, we use the larger MNIST dataset to test the performance of our OOD detection algorithm. We finish our paper with some concluding remarks regarding the application of these methods to species complexes and our efforts to document true biodiversity. [ABSTRACT FROM AUTHOR]

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing. [ABSTRACT FROM AUTHOR]

Developing a mathematical understanding of autocatalysis in reaction networks has both theoretical and practical implications. We review definitions of autocatalytic networks and prove some properties for minimal autocatalytic subnetworks (MASs). We show that it is possible to classify MASs in equivalence classes, and develop mathematical results about their behavior. We also provide linear-programming algorithms to exhaustively enumerate them and a scheme to visualize their polyhedral geometry and combinatorics. We then define cluster chemical reaction networks, a framework for coarse-graining real chemical reactions with positive integer conservation laws. We find that the size of the list of minimal autocatalytic subnetworks in a maximally connected cluster chemical reaction network with one conservation law grows exponentially in the number of species. We end our discussion with open questions concerning an ecosystem of autocatalytic subnetworks and multidisciplinary opportunities for future investigation. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to estimate the global burden of pancreatic cancer from 1990 to 2019. Methods: We reconstructed the Global Burden of Diseases (GBD) study results for pancreatic cancer across 204 countries and territories. Our study generated estimates for key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and cost. Linear regression analysis of the natural logarithm of age-standardized outcomes was used to calculate annual percent change. Results: In 2019, there were a total of 530,296 incident and 442,101 prevalent cases of pancreatic cancer, resulting in 531,107 deaths and 11.5 million DALYs lost. The age-standardized incidence and prevalence of pancreatic cancer has increased from 5.22 (95% CI 4.97–5.40) to 6.57 (CI 6.00–7.09) per 100,000 people per year, and 4.1 (95% CI 3.95–4.26) to 5.4 (CI 4.96–5.87), respectively. This equated to 10 million (95% CI 9.5 to 10.4 million) incident cases of pancreatic cancer. The number of DALYs lost as a result of pancreatic cancer was 225 million years (95% CI 216–234 million years). Mortality from pancreatic cancer increased over the study period from 3.7 (95% CI 3.54–3.83) to 6.9 (95% CI 6.36–7.32). Incidence, prevalence, DALYs, and mortality were higher in countries with a higher socio-demographic index. Conclusions: Pancreatic cancer is rising around the world and is associated with a high economic burden. Programs aimed at reducing modifiable risk factors are needed. [ABSTRACT FROM AUTHOR]

Background: Within the spectrum of Lewy body disorders (LBD), both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by gait and balance disturbances, which become more prominent under dual-task (DT) conditions. The brain substrates underlying DT gait variations, however, remain poorly understood in LBD. Objective: To investigate the relationship between gray matter volume loss and DT gait variations in LBD. Methods: Seventy-nine participants including cognitively unimpaired PD, PD with mild cognitive impairment, PD with dementia (PDD), or DLB and 20 cognitively unimpaired controls were examined across a multi-site study. PDD and DLB were grouped together for analyses. Differences in gait speed between single and DT conditions were quantified by dual task cost (DTC). Cortical, subcortical, ventricle, and cerebellum brain volumes were obtained using FreeSurfer. Linear regression models were used to examine the relationship between gray matter volumes and DTC. Results: Smaller amygdala and total cortical volumes, and larger ventricle volumes were associated with a higher DTC across LBD and cognitively unimpaired controls. No statistically significant interaction between group and brain volumes were found. Adding cognitive and motor covariates or white matter hyperintensity volumes separately to the models did not affect brain volume and DTC associations. Conclusion: Gray matter volume loss is associated with worse DT gait performance compared to single task gait, across cognitively unimpaired controls through and the LBD spectrum. Impairment in DT gait performance may be driven by age-related cortical neurodegeneration. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases. [ABSTRACT FROM AUTHOR]

Although a decrease in stroke admissions during the SARS-CoV-2 pandemic has been observed, detailed analyses of the evolution of stroke metrics during the pandemic are lacking. We analyzed changes in stroke presentation, in-hospital systems-of-care, and treatment time metrics at two representative Comprehensive Stroke Centers (CSCs) during the first year of Coronavirus disease 2019 pandemic. From January 2018 to May 2021, data from stroke presentations to two CSCs were obtained. The study duration was split into: period 0 (prepandemic), period 1 (Wave 1), period 2 (Lull), and period 3 (Wave 2). Acute stroke therapies rates and workflow times were compared among pandemic and prepandemic periods. Analyses were adjusted for age, sex, comorbidities, and pre-morbid care needs. There was a significant decrease in monthly hospital presentations of stroke during Wave 1. Both centers reported declines in reperfusion therapies during Wave 1, slowly catching up but never to pre pandemic numbers, and dropping again in Wave 2. Both CSCs experienced in-hospital workflow delays during Waves 1 and 2, and even during the Lull period. Our results highlight the need for proactive strategies to reduce barriers to workflow and hospital avoidance for stroke patients during crisis periods. [ABSTRACT FROM AUTHOR]

Evidence of fluctuations in transport have long been predicted in 3He. They are expected to contribute only within 100μK of Tc and play a vital role in the theoretical modeling of ordering; they encode details about the Fermi liquid parameters, pairing symmetry, and scattering phase shifts. It is expected that they will be of crucial importance for transport probes of the topologically nontrivial features of superfluid 3He under strong confinement. Here we characterize the temperature and pressure dependence of the fluctuation signature, by monitoring the quality factor of a quartz tuning fork oscillator. We have observed a fluctuation-driven reduction in the viscosity of bulk 3He, finding data collapse consistent with the predicted theoretical behavior. Early theoretical work predicted that fluctuations above the superfluid transition in liquid 3He should be observable in viscosity. Baten et al. document the reduction of the viscosity due to fluctuations, by monitoring the quality factor of a resonator immersed in 3He as a function of pressure and temperature. [ABSTRACT FROM AUTHOR]

The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response. How the immune response is involved in the response to multiple myeloma after treatment is not fully understood. Here the authors investigate how lenalidomide treatment in newly diagnosed MM patients affects the immune microenvironment in the blood and bone marrow and compare between responses to treatment. [ABSTRACT FROM AUTHOR]

Coralsnakes of the genus Micrurus are a diverse group of venomous snakes ranging from the southern United States to southern South America. Much uncertainty remains over the genus diversity, and understanding Micrurus systematics is of medical importance. In particular, the widespread Micrurus nigrocinctus spans from Mexico throughout Central America and into Colombia, with a number of described subspecies. This study provides new insights into the phylogenetic relationships within M. nigrocinctus by examining sequence data from a broad sampling of specimens from Mexico, Guatemala, Honduras, Nicaragua, Costa Rica, and Panama. The recovered phylogenetic relationships suggest that M. nigrocinctus is a species complex originating in the Pliocene and composed of at least three distinct species-level lineages. In addition, recovery of highly divergent clades supports the elevation of some currently recognized subspecies to the full species rank while others may require synonymization. [ABSTRACT FROM AUTHOR]

Severe forms of dilated cardiomyopathy (DCM) are associated with point mutations in the alternative splicing regulator RBM20 that are frequently located in the arginine/serine-rich domain (RS-domain). Such mutations can cause defective splicing and cytoplasmic mislocalization, which leads to the formation of detrimental cytoplasmic granules. Successful development of personalized therapies requires identifying the direct mechanisms of pathogenic RBM20 variants. Here, we decipher the molecular mechanism of RBM20 mislocalization and its specific role in DCM pathogenesis. We demonstrate that mislocalized RBM20 RS-domain variants retain their splice regulatory activity, which reveals that aberrant cellular localization is the main driver of their pathological phenotype. A genome-wide CRISPR knockout screen combined with image-enabled cell sorting identified Transportin-3 (TNPO3) as the main nuclear importer of RBM20. We show that the direct RBM20-TNPO3 interaction involves the RS-domain, and is disrupted by pathogenic variants. Relocalization of pathogenic RBM20 variants to the nucleus restores alternative splicing and dissolves cytoplasmic granules in cell culture and animal models. These findings provide proof-of-principle for developing therapeutic strategies to restore RBM20's nuclear localization in RBM20-DCM patients. The authors show that loss-of-interaction with the nuclear importer, TNPO3, causes cytoplasmic mislocalization of RBM20 variants linked to severe cases of dilated cardiomyopathy. Restoring their nuclear localization alleviates the disease phenotype. [ABSTRACT FROM AUTHOR]

Purpose: The emergence of the COVID-19 (SARS-CoV-2) pandemic has led to public health restrictions and a shift towards virtual care and telehealth. The aim of this study was to explore barriers and facilitators of virtual care from the perspective of neurological and psychiatric patients. Methods: One-on-one interviews were conducted remotely using telephone and online video teleconferencing. There was a total of 57 participants, and a thematic content analysis was conducted using NVivo software. Results: The two main themes were (1) virtual health service delivery and (2) virtual physician/patient interaction, with subthemes around how virtual care improved accessibility of care for patients and improved patient-centered care; how privacy and technical issues impact patients using virtual care; and the need for relationality and connection between health care providers and patients while using virtual care. Conclusions: This study showed that virtual care can increase accessibility and efficiency for patients and providers, indicating its potential for ongoing use in the delivery of clinical care. Virtual care was found to be an acceptable mode of healthcare delivery from the perspective of patients; however, there is a continued need for relationship-building between care providers and patients. [ABSTRACT FROM AUTHOR]

The contributed papers in this special issue each provide valuable perspectives on how social processes are relevant to academic motivation. Yet a critical question remains: How can this research lead to concrete guidance for educators who wish to create motivating and equitable classrooms? We propose this complex task can be simplified by encouraging educators to address students' concerns about how they are viewed by instructors in school. Our review of the literature suggests that two meta-concerns are particularly important to address for students from groups marginalized in education: whether instructors may (1) see them as limited in academic potential and (2) narrowly define them by their academic success. We argue that effective teaching practices address these concerns by communicating two corresponding messages: (1) inclusive expectations, "I recognize your potential for academic growth" and (2) broad regard, "I regard you as a whole person, with a range of personal values, social identities, and relationships." These messages can shift students away from a "narrow" sense of self, in which their value is defined by current academic performance, and towards an "expansive" sense of self, in which students feel both academically capable and valued for more than just their academic success. We present evidence that novice instructors can use this framework to develop or adapt practices that are attuned to marginalized students' two meta-concerns and enhance student motivation and engagement. Throughout this commentary, we describe how this framework can build on the important theoretical advances presented elsewhere in this special issue. [ABSTRACT FROM AUTHOR]

Introduction: In clinical practice, tube feedings have been delayed after the percutaneous endoscopic gastrostomy (PEG) tube placement. Previous studies, including a meta-analysis in 2008, have shown that it is safe to start tube feeding ≤ 4 h of PEG tube placement. However, it is still a common practice to delay the initiation of tube feeding up to 24 h after PEG tube placement. We have performed an updated analysis of studies comparing early versus delayed tube feedings following PEG placement.Major databases like PubMed, EMBASE, and Web of Science were searched in June 2022 for randomized controlled trial (RCT) studies reporting on comparative outcomes with early (< or = 4 h) versus delayed (> 4 h) feeding after PEG tube placement in adult patients. The primary outcomes in our study include complication rates and mortality rates within 72 h of the procedure. The outcomes were reported as pooled odds ratio (95% confidence interval (CI) (Moole et al. in Indian J Gastroenterol. 35:323–330, 2016), p value, I2 values).A total of 212 individuals in the early feeding group and 215 individuals in the late feeding group were analyzed from six studies. The pooled odds ratio of total complication events between early and late feed groups was 0.86 (CI 0.51–1.45, p = 0.58). The pooled odds ratio of fever, vomiting, and local infection was 0.94 (CI 0.186–4.74, p = 0.94), 1.0 (CI 0.38–2.65, p = 0.9), and 1.25 (0.36–4.3, p = 0.72), respectively, between early and late feeding post-PEG tube placement. In conclusion, this meta-analysis confirms that early feeding ≤ 4 h after PEG placement does not increase the odds of poor outcomes or mortality, and it is a well-tolerated, safe, and effective alternative to delayed feeding. Furthermore, early feeding may decrease hospital stays and healthcare costs.Methods: In clinical practice, tube feedings have been delayed after the percutaneous endoscopic gastrostomy (PEG) tube placement. Previous studies, including a meta-analysis in 2008, have shown that it is safe to start tube feeding ≤ 4 h of PEG tube placement. However, it is still a common practice to delay the initiation of tube feeding up to 24 h after PEG tube placement. We have performed an updated analysis of studies comparing early versus delayed tube feedings following PEG placement.Major databases like PubMed, EMBASE, and Web of Science were searched in June 2022 for randomized controlled trial (RCT) studies reporting on comparative outcomes with early (< or = 4 h) versus delayed (> 4 h) feeding after PEG tube placement in adult patients. The primary outcomes in our study include complication rates and mortality rates within 72 h of the procedure. The outcomes were reported as pooled odds ratio (95% confidence interval (CI) (Moole et al. in Indian J Gastroenterol. 35:323–330, 2016), p value, I2 values).A total of 212 individuals in the early feeding group and 215 individuals in the late feeding group were analyzed from six studies. The pooled odds ratio of total complication events between early and late feed groups was 0.86 (CI 0.51–1.45, p = 0.58). The pooled odds ratio of fever, vomiting, and local infection was 0.94 (CI 0.186–4.74, p = 0.94), 1.0 (CI 0.38–2.65, p = 0.9), and 1.25 (0.36–4.3, p = 0.72), respectively, between early and late feeding post-PEG tube placement. In conclusion, this meta-analysis confirms that early feeding ≤ 4 h after PEG placement does not increase the odds of poor outcomes or mortality, and it is a well-tolerated, safe, and effective alternative to delayed feeding. Furthermore, early feeding may decrease hospital stays and healthcare costs.Results: In clinical practice, tube feedings have been delayed after the percutaneous endoscopic gastrostomy (PEG) tube placement. Previous studies, including a meta-analysis in 2008, have shown that it is safe to start tube feeding ≤ 4 h of PEG tube placement. However, it is still a common practice to delay the initiation of tube feeding up to 24 h after PEG tube placement. We have performed an updated analysis of studies comparing early versus delayed tube feedings following PEG placement.Major databases like PubMed, EMBASE, and Web of Science were searched in June 2022 for randomized controlled trial (RCT) studies reporting on comparative outcomes with early (< or = 4 h) versus delayed (> 4 h) feeding after PEG tube placement in adult patients. The primary outcomes in our study include complication rates and mortality rates within 72 h of the procedure. The outcomes were reported as pooled odds ratio (95% confidence interval (CI) (Moole et al. in Indian J Gastroenterol. 35:323–330, 2016), p value, I2 values).A total of 212 individuals in the early feeding group and 215 individuals in the late feeding group were analyzed from six studies. The pooled odds ratio of total complication events between early and late feed groups was 0.86 (CI 0.51–1.45, p = 0.58). The pooled odds ratio of fever, vomiting, and local infection was 0.94 (CI 0.186–4.74, p = 0.94), 1.0 (CI 0.38–2.65, p = 0.9), and 1.25 (0.36–4.3, p = 0.72), respectively, between early and late feeding post-PEG tube placement. In conclusion, this meta-analysis confirms that early feeding ≤ 4 h after PEG placement does not increase the odds of poor outcomes or mortality, and it is a well-tolerated, safe, and effective alternative to delayed feeding. Furthermore, early feeding may decrease hospital stays and healthcare costs. [ABSTRACT FROM AUTHOR]

The relationship between head impact and subsequent brain injury for American football players is not well-defined, especially for youth. The objective of this study is to quantify and assess Head Impact Exposure (HIE) metrics among youth and collegiate football players. This multi-season study enrolled 639 unique athletes (354 collegiate; 285 youth, ages 9–14), recording 476,209 head impacts (367,337 collegiate; 108,872 youth) over 971 sessions (480 collegiate; 491 youth). Youth players experienced 43 and 65% fewer impacts per competition and practice, respectively, and lower impact magnitudes compared to collegiate players (95th percentile peak linear acceleration (PLA, g) competition: 45.6 vs 61.9; 95th percentile PLA practice: 42.6 vs 58.8; 95th percentile peak rotational acceleration (PRA, rad·s−2) competition: 2262 vs 4422; 95th percentile PRA practice: 2081 vs 4052; 95th percentile HITsp competition: 25.4 vs 32.8; 95th percentile HITsp practice: 23.9 vs 30.2). Impacts during competition were more frequent and of greater magnitude than during practice at both levels. Quantified comparisons of head impact frequency and magnitude between youth and collegiate athletes reveal HIE differences as a function of age, and expanded insight better informs the development of age-appropriate guidelines for helmet design, prevention measures, standardized testing, brain injury diagnosis, and recovery management. [ABSTRACT FROM AUTHOR]

Purpose: Brain herniation into arachnoid granulations (BHAG) of the dural venous sinuses is a recently described finding of uncertain etiology. The purpose of this study was to investigate the prevalence of BHAG in a cohort of patients with pulsatile tinnitus (PT) and to clarify the physiologic and clinical implications of these lesions. Methods: The imaging and charts of consecutive PT patients were retrospectively reviewed. All patients were examined with MRI including pre- and post-contrast T1- and T2-weighted sequences. Images were reviewed separately by three blinded neuroradiologists to identify the presence of BHAG. Their location, signal intensity, size, presence of arachnoid granulation, and associated dural venous sinus stenosis were documented. Clinical records were further reviewed for idiopathic intracranial hypertension, history of prior lumbar puncture, and opening pressure. Results: Two hundred sixty-two consecutive PT patients over a 4-year period met inclusion criteria. PT patients with BHAG were significantly more likely to have idiopathic intracranial hypertension than PT patients without BHAG (OR 4.2, CI 1.5–12, p = 0.006). Sixteen out of 262 (6%) patients were found to have 18 BHAG. Eleven out of 16 (69%) patients had unilateral temporal or occipital lobe herniations located in the transverse sinus or the transverse-sigmoid junction. Three out of 16 (19%) patients had unilateral cerebellar herniations and 2/16 (13%) patients had bilateral BHAG. Conclusion: In patients with PT, BHAG is a prevalent MRI finding that is strongly associated with the clinical diagnosis of IIH. The pathogenesis of BHAG remains uncertain, but recognition should prompt comprehensive evaluation for IIH. [ABSTRACT FROM AUTHOR]

We provide the conversion parameters to allow a 3 He melting curve thermometer to be used to calibrate secondary thermometers to the PLTS2000 temperature scale (Rusby et al. in J Low Temp Phys 149(3):156, 2007). Additional fits to the phase diagram of superfluid 3 He are also provided using the melting curve P, T measurements and of the phase diagram of superfluid 3 He (Greywall in Phys Rev B 33(11):7520, https://doi.org/10.1103/PhysRevB.33.7520, 1986) as a bridge. Further, the melting curve measurements of Osheroff and Yu (Phys Lett A 77(6):458, https://doi.org/10.1016/0375-9601(80)90539-3, 1980) are also used to extend the scale below 0.9 mK. [ABSTRACT FROM AUTHOR]

The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251–402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01–0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life. [ABSTRACT FROM AUTHOR]

Rivers are known to act as biogeographic barriers in several strictly terrestrial taxa, while possibly serving as conduits of dispersal for freshwater-tolerant or -dependent species. However, the influence of river systems on genetic diversity depends on taxa-specific life history traits as well as other geographic factors. In amphibians, several studies have demonstrated that river systems have only minor influence on their divergence. Here, we assess the role of the paleodrainage systems of the Sunda region (with a focus on the island of Sumatra) in shaping the evolutionary history of two genera of frogs (Sumaterana and Wijayarana) whose tadpoles are highly dependent on cascading stream habitats. Our phylogenetic results show no clear association between the genetic diversification patterns of both anurans genera and the existence of paleodrainage systems. Time-calibrated phylogenies and biogeographical models suggest that these frogs colonized Sumatra and diversified on the island before the occurrence of the Pleistocene drainage systems. Both genera demonstrate phylogenetic structuring along a north–south geographic axis, the temporal dynamics of which coincide with the geological chronology of proto Sumatran and -Javan volcanic islands. Our results also highlight the chronic underestimation of Sumatran biodiversity and call for more intense sampling efforts on the island. [ABSTRACT FROM AUTHOR]

Our study explored the relations between perceived everyday discrimination (PED), brooding rumination (dwelling on negative feelings), reflection rumination (attempting to understand a negative state), and depressive symptoms among adolescents. Previous research has identified PED as a risk factor for depressive symptoms across diverse populations, and there is evidence that brooding mediates the relation between PED and symptoms of depression in adolescents. However, we addressed a gap in the literature by examining how reflection, which is hypothesized to be a more adaptive coping response than brooding, is related to PED and depressive symptoms. Our sample of 232 adolescents (89 female) aged 13 to 16 (M = 14.18, SD = 0.54) identified as Black (46.5%), White (37.0%), Mixed Race (12.2%), Hispanic (1.7%), and Other (2.6%). Participants completed self-report measures of PED (attributable to any self-identified distinguishing characteristic), brooding and reflection, and depressive symptoms. In accordance with our hypotheses, we found that PED was positively associated with both brooding and reflection. Additionally, PED and brooding, but not reflection, were positively associated with depressive symptoms when accounting for the impact of the other variables in the model. Our results add to existing evidence that brooding is a less adaptive form of rumination than reflection. Further, our results corroborate previous findings that brooding plays a role in the association between PED and depressive symptoms. Testing the differential mediating effects of brooding and reflection in the relation between PED and adolescent depressive symptoms in a prospective study design will be an important direction for future research. Highlights: The results or our study indicate that perceived everyday discrimination (PED) and brooding are associated with adolescent depression. Brooding, but not reflection, was associated with adolescent depression, adding to existing evidence that brooding is a less adaptive form of rumination than reflection. Longitudinal studies are needed to test the differential mediating effects of brooding and reflection in the relation between PED and adolescent depression. Therapists working with adolescents should assess whether their clients experience PED based on a wide range of identities and characteristics, and whether they respond to these incidents by brooding. [ABSTRACT FROM AUTHOR]

In this paper, we show how the methods of systematic reviewing and meta-analysis can be used in conjunction with structural equation modeling to summarize the results of studies in a way that will facilitate the theory development and testing needed to advance prevention science. We begin with a high-level overview of the considerations that researchers need to address when using meta-analytic structural equation modeling (MASEM) and then discuss a research project that brings together theoretically important cognitive constructs related to depression to (a) show how these constructs are related, (b) test the direct and indirect effects of dysfunctional attitudes on depression, and (c) test the effects of study-level moderating variables. Our results suggest that the indirect effect of dysfunctional attitudes (via negative automatic thinking) on depression is two and a half times larger than the direct effect of dysfunctional attitudes on depression. Of the three study-level moderators tested, only sample recruitment method (clinical vs general vs mixed) yielded different patterns of results. The primary difference observed was that the dysfunctional attitudes → automatic thoughts path was less strong for clinical samples than it was for general and mixed samples. These results illustrate how MASEM can be used to compare theoretically derived models and predictions resulting in a richer understanding of both the empirical results and the theories underlying them. [ABSTRACT FROM AUTHOR]

Methodological impediments have presented challenges in identifying which individuals are at the highest risk of experiencing discrimination and its detrimental corollaries. In the current study, we examined whether adolescents' number of perceived reasons for everyday discriminations (i.e., number of identities and/or characteristics adolescents identify as the reasons(s) they are discriminated against) is associated with frequency of perceived everyday discriminations (PED) and depressive symptoms. Further, we evaluated indirect associations between number of perceived reasons for PEDs and depressive symptoms through frequency of PED, brooding, and reflection. The sample for this cross-sectional study consisted of 328 9th grade students between the ages of 13 and 16 (M = 14.19, SD = 0.56). Around 60% of the sample identified as male, and a majority of the adolescents identified their race as either Black (46%) or White (35%). Adolescents provided data on perceived reasons for PEDs, frequency of PED, brooding, reflection, and depressive symptoms using self-report measures. Adolescents' number of perceived reasons for PEDs was associated with frequency of PED and depressive symptoms. There were also multiple indirect associations between adolescents' number of perceived reasons for PEDs and depressive symptoms through frequency of PED, brooding, and reflection. Our results indicate that accounting for adolescents' number of perceived reasons for PEDs may be useful to both researchers and clinicians in identifying which individuals are at the greatest risk of experiencing PED and associated outcomes. Additional implications and future directions for research are discussed. [ABSTRACT FROM AUTHOR]

Precise measurements of the dissipation and resonant frequency of a torsion pendulum reveal an anomaly in the inferred viscosity and normal density of liquid 3 He near the superfluid transition. We present an argument that the anomaly originates in the large viscosity and large viscosity change of the normal component in the torsion tube in the vicinity of the superfluid transition. [ABSTRACT FROM AUTHOR]

A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess the prevalence and determinants of cognitive impairment, including the role of cerebral small vessel disease (CSVD) in Polish middle-aged cohort. A comprehensive set of clinical (hypertension, coronary heart disease, diabetes mellitus, hyperlipidaemia, body mass index, smoking status, alcohol intake) and socio-demographic data was collected in the PURE study in years 2007–2016, which was the basis for detailed analysis of risk factors of cognitive impairments in years 2016–2018 in the PURE-MIND sub-study. Five hundred forty-seven subjects (age range 39–65, mean 56.2 ± 6.5) underwent neuropsychological assessment with Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT) and Digit Symbol Substitution Test (DSST) followed by brain MRI. Mean MoCA score was 26.29 and 33% participants met criteria for mild cognitive impairment (MCI) (MoCA< 26). Seventy-three percent showed findings related to CSVD. Higher WMH burden and lacunar infarcts were associated with lower MoCA and DSST scores. Severe CSVD was associated with twofold incidence of MCI, and obesity increased its probability by 53% and hypertension by 37%. The likelihood of MCI was reduced in nonsmokers. One factor analysis showed the important role of lower level of education, older age, rural area of residence and hypertension. MCI and CSVD are highly prevalent in the middle-aged population in Poland. A greater importance should be given to potentially modifiable risk factors of dementia which are already present in mid-life. [ABSTRACT FROM AUTHOR]

The genus Oxybelis currently is composed of four taxa despite numerous studies suggesting and describing multiple taxa within the O. aeneus complex. Here, we utilize a multilocus molecular dataset (i.e., cyt b, ND4, 12S, 16S, cmos, PRLR, 3663 bp) to conduct phylogenetic analyses to assess the evolutionary history of Oxybelis. Our molecular analyses find three major lineages of Oxybelis (i.e., O. aeneus complex, O. brevirostris, O. fulgidus complex) with a sister relationship between O. brevirostris and the O. aeneus complex to the exclusion of the O. fulgidus complex. More specifically, O. aeneus appears to harbor at least five taxa currently unrecognized while O. fulgidus was found to be paraphyletic with respect to O. wilsoni, suggesting cryptic diversity and novel taxa in that clade as well. Additionally, we use morphological data in concert with our molecular analyses and the literature to support removing Oxybelis microphthalmus Barbour and Amaral, 1926; Oxybelis potosiensis Taylor, 1941; and Dryophis vittatus Girard, 1854 from the synonymy of O. aeneus. Finally, we describe two new species from Central America and northern South America. [ABSTRACT FROM AUTHOR]

While large-scale oil spills can cause acute mortality events in birds, there is increasing evidence that sublethal oil exposure can trigger physiological changes that have implications for individual performance and survival. Therefore, improved methods for identifying small amounts of oil on birds are needed. Because ultraviolet (UV) light can be used to identify thin crude oil films in water and on substrate that are not visually apparent under normal lighting conditions, we hypothesized that UV light could be useful for detecting small amounts of oil present on the plumage of birds. We evaluated black skimmers (Rynchops niger), brown pelicans (Pelecanus occidentalis), clapper rails (Rallus crepitans), great egrets (Ardea alba), and seaside sparrows (Ammodramus maritimus) exposed to areas affected by the Deepwater Horizon oil spill in the Gulf of Mexico as well as from reference areas from 20 June, 2010 to 23 February, 2011. When visually assessed without UV light, 19.6% of birds evaluated from areas affected by the spill were determined to be oiled (previously published data), whereas when examined under UV light, 56.3% of the same birds were determined to have oil exposure. Of 705 individuals examined in areas potentially impacted by the spill, we found that fluorescence under UV light assessment identified 259 oiled birds that appeared to be oil-free on visual exam, supporting its utility as a simple tool for improving detection of modestly oiled birds in the field. Further, UV assessment revealed an increase in qualitative severity of oiling (approximate % of body surface oiled) in 40% of birds compared to what was determined on visual exam. Additionally, black skimmers, brown pelicans, and great egrets exposed to oil as determined using UV light experienced oxidative injury to erythrocytes, had decreased numbers of circulating erythrocytes, and showed evidence of a regenerative hematological response in the form of increased reticulocytes. This evidence of adverse effects was similar to changes identified in birds with oil exposure as determined by visual examination without UV light, and is consistent with hemolytic anemia likely caused by oil exposure. Thus, UV assessment proved useful for enhancing detection of birds exposed to oil, but did not increase detection of birds experiencing clinical signs of anemia compared to standard visual oiling assessment. We conclude that UV light evaluation can help identify oil exposure in many birds that would otherwise be identified visually as unexposed during oil spill events. [ABSTRACT FROM AUTHOR]

Adolescence is a critical period in the development of depression. Hence, researching the applicability of cognitive theories in adolescents is crucial. Currently, much remains unknown about how cognitive variables proposed in different theories interplay with one another and whether gender differences in these associations exist. Attempting to integrate Beck's cognitive model and the hopelessness model in adolescents, we conducted a 4-wave study using self-report instruments with 499 adolescents (mean ageTime1 = 15.33 years; SD = 0.75; 63.3% female; 73.7% White, 13.8% Black, 5.4% Latina/o, 4.4% mixed race/ethnicity, and 2.6% other) from a high school where almost one third of the students were eligible for free or reduced lunch. Using AMOS and PROCESS to calculate and compare four different theory-driven models, we found support for an integrated model in which the inferential styles proposed in the hopelessness model are located between cognitive errors and the cognitive triad from Beck's cognitive theory. Further, the individual inferential styles and elements of the cognitive triad are associated differently with each other and other variables in the integrated cognitive model. The gender differences we found were limited and did not form a meaningful pattern. If replicated, the integrated model could be the basis to understand how therapeutic techniques developed to modify cognitive variables proposed in one model can impact cognitive constructs from a different theory. This might make cognitive psychotherapies for depression more effective, as it will allow clinicians to integrate therapeutic techniques based on either of the original theories in one theory-driven treatment approach. [ABSTRACT FROM AUTHOR]

This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual "White Matter and Cognition" workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the "Albert Research Institute for White Matter and Cognition." This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena. [ABSTRACT FROM AUTHOR]

Background: Silent brain infarction (SBI) may be associated with cognitive decline in the general population. We systematically reviewed prior literature on: (1) SBI and cognition cross-sectionally; (2) baseline SBI and future cognitive decline and risk for cognitive disorders including dementia, and (3) incident SBI and the emergence of cognitive decline or cognitive disorders. Methods: The MEDLINE and EMBASE databases were searched for relevant studies. Data were independently extracted by two reviewers. Quality was assessed using the Newcastle Ottawa Scale. Data were pooled using a random effects model when more than two comparable estimates were found. Results: Thirty relevant studies were identified: 17 had a cross-sectional design, 10 evaluated the association of baseline SBI with future cognitive decline, and 5 evaluated the association of incident SBI with cognitive decline. Most cross-sectional studies reported lower cognitive performance in persons with SBI. The pooled risk for incident dementia in persons with SBI was 1.48 (95% CI 1.12–1.97), but there was significant heterogeneity (p = 0.009); removing one outlier eliminated the heterogeneity (p = 0.53), giving a lower but still significant estimate (hazard ratio 1.27, 95% CI 1.06–1.51). The pooled risk for incident MCI was not increased in persons with SBI (hazard ratio 0.83, 95% CI 0.40 to 1.72), but there was significant heterogeneity (p < 0.001). The appearance of new SBI was associated with steeper rate of cognitive decline and the appearance of dementia. Conclusions: SBI are associated with worse cognition and increased risk for dementia. More standardization of cognitive assessment methods would facilitate future cross-study comparisons. [ABSTRACT FROM AUTHOR]

Telomeres are protein–DNA complexes that protect chromosome ends from illicit ligation and resection. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA to counter telomere shortening. Human telomeres are composed of complexes between telomeric DNA and a six-protein complex known as shelterin. The shelterin proteins TRF1 and TRF2 provide the binding affinity and specificity for double-stranded telomeric DNA, while the POT1-TPP1 shelterin subcomplex coats the single-stranded telomeric G-rich overhang that is characteristic of all our chromosome ends. By capping chromosome ends, shelterin protects telomeric DNA from unwanted degradation and end-to-end fusion events. Structures of the human shelterin proteins reveal a network of constitutive and context-specific interactions. The shelterin protein–DNA structures reveal the basis for both the high affinity and DNA sequence specificity of these interactions, and explain how shelterin efficiently protects chromosome ends from genome instability. Several protein–protein interactions, many provided by the shelterin component TIN2, are critical for upholding the end-protection function of shelterin. A survey of these protein–protein interfaces within shelterin reveals a series of "domain–peptide" interactions that allow for efficient binding and adaptability towards new functions. While the modular nature of shelterin has facilitated its part-by-part structural characterization, the interdependence of subunits within telomerase has made its structural solution more challenging. However, the exploitation of several homologs in combination with recent advancements in cryo-EM capabilities has led to an exponential increase in our knowledge of the structural biology underlying telomerase function. Telomerase homologs from a wide range of eukaryotes show a typical retroviral reverse transcriptase-like protein core reinforced with elements that deliver telomerase-specific functions including recruitment to telomeres and high telomere-repeat addition processivity. In addition to providing the template for reverse transcription, the RNA component of telomerase provides a scaffold for the catalytic and accessory protein subunits, defines the limits of the telomeric repeat sequence, and plays a critical role in RNP assembly, stability, and trafficking. While a high-resolution definition of the human telomerase structure is only beginning to emerge, the quick pace of technical progress forecasts imminent breakthroughs in this area. Here, we review the structural biology surrounding telomeres and telomerase to provide a molecular description of mammalian chromosome end protection and end replication. [ABSTRACT FROM AUTHOR]

Physical differences between youth and adults, which include incomplete myelination, limited neck muscle development, and a higher head-body ratio in the youth population, likely contribute towards the increased susceptibility of youth to concussion. Previous research efforts have considered the biomechanics of concussion for adult populations, but these known age-related differences highlight the necessity of quantifying the risk of concussion for a youth population. This study adapted the previously developed Generalized Acceleration Model for Brian Injury Threshold (GAMBIT) that combines linear and rotational head acceleration to model the risk of concussion for a youth population with the Generalized Acceleration Model for Concussion in Youth (GAM-CY). Survival analysis was used in conjunction with head impact data collected during participation in youth football to model risk between individuals who sustained medically-diagnosed concussions (n = 15). Receiver operator characteristic curves were generated for peak linear acceleration, peak rotational acceleration, and GAM-CY, all of which were observed to be better injury predictors than random guessing. GAM-CY was associated with an area under the curve of 0.89 (95% confidence interval: 0.82–0.95) when all head impacts experienced by the concussed players were considered. Concussion tolerance was observed to be lower for youth athletes, with average peak linear head acceleration of 62.4 ± 29.7 g compared to 102.5 ± 32.7 g for adults and average peak rotational head acceleration of 2609 ± 1591 rad/s2 compared to 4412 ± 2326 rad/s2. These data provide further evidence of age-related differences in concussion tolerance and may be used for the development of youth-specific protective designs. [ABSTRACT FROM AUTHOR]

Recently, there has been much discussion about the role of the p-value in scientific research. The American Statistical Association has published an editorial that presents guidelines for the use and interpretation of p-values. Numerous authors have commented and criticized its use as a means to identify scientific importance of results and have called for an end to using the term "statistical significance." Recent articles in Estuaries and Coasts were evaluated for reliance on the use of statistical significance and reporting errors were identified. Suggestions are made for improving what is reported related to statistical testing. Focus should be on scientific importance of estimates, estimation of the size of the effect and the certainty in the size of the effect instead of simply reporting a p-value and relying on hypothesis tests. [ABSTRACT FROM AUTHOR]

Background: Post-stroke care delivery may be affected by provider participation in Medicare Shared Savings Program (MSSP) Accountable Care Organizations (ACOs) through systematic changes to discharge planning, care coordination, and transitional care.Objective: To evaluate the association of MSSP with patient outcomes in the year following hospitalization for ischemic stroke.Design: Retrospective cohort SETTING: Get With The Guidelines (GWTG)-Stroke (2010-2014) PARTICIPANTS: Hospitalizations for mild to moderate incident ischemic stroke were linked with Medicare claims for fee-for-service beneficiaries ≥ 65 years (N = 251,605).Main Measures: Outcomes included discharge to home, 30-day all-cause readmission, length of index hospital stay, days in the community (home-time) at 1 year, and 1-year recurrent stroke and mortality. A difference-in-differences design was used to compare outcomes before and after hospital MSSP implementation for patients (1) discharged from hospitals that chose to participate versus not participate in MSSP or (2) assigned to an MSSP ACO versus not or both. Unique estimates for 2013 and 2014 ACOs were generated.Key Results: For hospitals joining MSSP in 2013 or 2014, the probability of discharge to home decreased by 2.57 (95% confidence intervals (CI) = - 4.43, - 0.71) percentage points (pp) and 1.84 pp (CI = - 3.31, - 0.37), respectively, among beneficiaries not assigned to an MSSP ACO. Among discharges from hospitals joining MSSP in 2013, beneficiary ACO alignment versus not was associated with increased home discharge, reduced length of stay, and increased home-time. For patients discharged from hospitals joining MSSP in 2014, ACO alignment was not associated with changes in utilization. No association between MSSP and recurrent stroke or mortality was observed.Conclusions: Among patients with mild to moderate ischemic stroke, meaningful reductions in acute care utilization were observed only for ACO-aligned beneficiaries who were also discharged from a hospital initiating MSSP in 2013. Only 1 year of data was available for the 2014 MSSP cohort, and these early results suggest further study is warranted.Registration: None. [ABSTRACT FROM AUTHOR]

Introduction: Despite recent developments in the diagnosis and treatment of prostate cancer, the advanced stages still have poor survival rates. This warrants further exploration of related molecular targets for patient screening, detection of metastatic disease, and treatment/treatment monitoring. Recent studies have indicated that neurotensin receptors (NTSRs) and their ligand neurotensin (NTS) critically affect the progression of prostate cancers. In this study, we evaluated the expression of neurotensin receptor1 (NTSR1) in patient tissues and performed NTSR1 PET imaging in a prostate cancer animal model. Methods: The NTSR1 expression was evaluated in 97 cases of prostate cancer and 100 cases of benign prostatic hyperplasia (BPH) of clinical patients by immunohistochemistry staining. The expression profile of PSMA and GRPR was also performed for comparison. The mRNA expression of NTSR1 in LnCap and PC-3 cells was measured by PCR. NTSR1 PET, and biodistribution studies were performed in PC-3 xenografts using 18F-DEG-VS-NT. Results: NTSR1 showed high or moderate expression in 91.8% of prostate cancer tissue, compared with PSMA (86.7%) and GRPR (65.3%). All examined PSMA-negative tissues showed positive NTSR1 expression, suggesting the potential complementary role of NTSR1 targeted imaging or therapy. Only 8% of BPH shows strong or moderate expression of NTSR1, which is significantly lower than that in prostate cancer (91.8%). PCR results indicated LNCap (an androgen-dependent prostate cancer cell) showed negative NTSR1 expression while PC-3 demonstrated positive expression (an androgen-independent prostate cancer cell), which correlated well with previously reported western blot results. In a preclinical animal model, NTSR1 targeted PET probe 18F-DEG-VS-NT demonstrated prominent tumor accumulation and low background. Conclusion: We have demonstrated that NTSR1 is a promising molecular marker for prostate cancer based on patient tissue staining. The NTSR targeted probe 18F-DEG-VS-NT demonstrated high tumor to background contrast in animal models, which could be valuable in selecting patients for therapies targeting NTSR1 as well as monitoring therapeutic efficacy during treatment accordingly. [ABSTRACT FROM AUTHOR]

Purpose: Flexion contracture after total knee arthroplasty (TKA) can cause significant dissatisfaction. Botulinum toxin A has shown improved extension in patients with spastic flexion contractures after TKA. The purpose of this study was to evaluate whether Botulinum toxin A improves knee extension for any patient with flexion contractures following TKA.Methods: A prospective, double-blinded, randomized controlled trial was conducted. Fourteen patients (15 knees), with a flexion contracture (≥10°) one month postoperatively, were randomized to receive either Botulinum toxin A or saline placebo to the affected hamstrings. The subject, surgeon, and administering physiatrist were blinded to the treatment group throughout the study. Subject range of motion (ROM) was evaluated at 1, 6, and 12 months following injection. Differences were tested using mixed-effects regression to control for multiple measurements.Results: The initial post-operative flexion contracture averaged 19° ± 6° in the Botulinum toxin A group and 13° ± 3° in the saline group. Injections were performed 53 and 57 days after TKA in the Botulinum toxin A and saline groups, respectively. Post-injection extension improved to an average of 8, 5, and 1 degrees for BTX and 4, 2, and 1 degrees for SAL, at 1, 6, and 12 months, respectively, compared to pre-injection extension (p < 0.0001). Improvement in knee extension at 1 year improved 18° ± 7.5° for Botulinum toxin A and 12° ± 2° for saline (p = 0.04). No complications resulted from either injection.Conclusion: Patients who received Botulinum toxin A or placebo were able to achieve near full extension one year after surgery. There was a statistically significant improvement in the amount of extension achieved at 1 year with Botulinum toxin A, but this may be of little clinical significance. Since achieving full extension is important for patient function and satisfaction, novel techniques to address this issue deserve special attention.Level Of Evidence: I. [ABSTRACT FROM AUTHOR]

Information theory, introduced by Shannon in the context of information transfer in communication channels, is used as a foundation for research in many diverse fields. The concept Entropy in terms of information theory is seen as the average amount of information or the rate of information produced when forming a message, element by element. Entropy has found broad application in many research fields and can also be applied in software engineering for quantifying the uncertainty associated with a software code. In this paper, information entropy and its application towards measuring software complexity are explored, along with the formulation of an information entropy based complexity measure that considers logical decision-making, processes, and software statement interaction patterns in control flow graphs mapped from actual software code. To broaden the application of the proposed metric, the execution times of nodes in the control flow graphs are also incorporated. Further, the metric is evaluated against eight different axioms that a software complexity measure should satisfy. [ABSTRACT FROM AUTHOR]

Background: We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer.Aim: To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro.Methods and Results: In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation.Conclusions: This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC. [ABSTRACT FROM AUTHOR]

Purpose of Review: The treatment landscape of multiple myeloma is rapidly changing; however, despite improvement in patients' survival, it still remains a largely incurable disease. One hallmark of myeloma is substantial immune dysfunction leading to an increased infection rate and the inability of immune surveillance to detect neoplastic cells. Here, we critically analyze clinical approaches to harness the immune system to overcome this defect with a focus on antibody based and adoptive cellular therapies. Recent Findings: Clinical trials exploring these immunotherapies to treat myeloma are now well underway and show promising results. In relapsed myeloma, monoclonal antibodies directed against plasma cell antigens and immune checkpoints have already shown substantial efficacy. In parallel, trials of adoptive cellular therapy have exciting promise in myeloma, having induced dramatic responses in a handful of early study participants. Summary: Taken together, immunotherapeutic approaches hold enormous potential in the field of multiple myeloma and in the near future can be combined with or even replace the current standard of care. [ABSTRACT FROM AUTHOR]

Introduction: In the developing world, occupation has been identified as a risk factor for snake bite. Such an association has not been described in the USA. The objective of this study was to describe the epidemiology and clinical manifestations of occupational snake bite in patients reported to the ToxIC North American Snakebite Registry (NASBR). Methods: This was a prospective case series of patients reported to the ToxIC NASBR between January 1, 2014 and November 5, 2015. Variables collected included snake species, patient demographics, date and location of exposure, occupation, bite location, clinical manifestations, and management. Results: Of 180 adult snake bites reported, 25 (13.9 %; 95 % CI 9.2-19.8 %) were occupational in nature. Rattlesnake envenomations were common (80 %). Most snake bites (96 %) occurred in men. Occupations most associated with snake bite were landscaping (28 %) and working directly with snakes (24 %). Fifty-six percent of bites occurred in an outdoor work environment. Seventy-six percent of envenomations were to the upper extremities. Intentional interaction occurred in 40 % of cases, all of which sustained finger envenomations. No cases presented with apparent acute ethanol intoxication. Conclusions: The majority of occupational snake bites occurred in men working outdoors and were unintentional injuries. Bites involving the upper extremity tended to result from intentional interactions. Acute ethanol intoxication did not appear to be involved with occupational envenomations. [ABSTRACT FROM AUTHOR]