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To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel. We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004–12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually). A simulation was performed; outcomes of interest were driving distance and time between the centroid of the patient's residence zip code and the treating facility zip code. Overall, 60,493 patients met inclusion criteria. Between 2004 and 2018, 210 facilities were performing cytoreductive surgery for OC in New York; 159 facilities (75.7%) met low-volume and 51 (24.3%) met high-volume criteria. Overall, 10,514 patients (17.4%) were treated at low-volume and 49,979 (82.6%) at high-volume facilities. In 2004, 78.2% of patients were treated at high-volume facilities, which increased to 84.6% in 2018 (P <.0001). Median travel distance and time for patients treated at high-volume centers was 12.2 miles (IQR, 5.6–25.5) and 23.0 min (IQR, 15.2–37.0), and 8.2 miles (IQR, 3.7–15.9) and 16.8 min (IQR, 12.4–26.0) for patients treated at low-volume centers. If cytoreductive surgery was centralized to high-volume centers, median distance and time traveled for patients originally treated at low-volume centers would be 11.2 miles (IQR, 3.8–32.3; P <.001) and 20.2 min (IQR, 13.6–43.0; P <.001). Centralizing cytoreductive surgery for OC to high-volume centers in New York would increase patient travel burden by negligible amounts of distance and time for most patients. • The impact on patient travel from ovarian cancer surgery regionalization to high-volume centers has not been studied. • Centralizing ovarian cancer surgery in New York State would increase patient travel by negligible distance and time. • These findings could have future implications for patient education and health policy on the regionalization of care. [ABSTRACT FROM AUTHOR]

To define molecular features of ovarian cancer (OC) with germline pathogenic variants (PVs) in non-BRCA homologous recombination (HR) genes and analyze survival compared to BRCA1/2 and wildtype (WT) OC. We included patients with OC undergoing tumor-normal sequencing (MSK-IMPACT) from 07/01/2015–12/31/2020, including germline assessment of BRCA1/2 and other HR genes ATM, BARD1, BRIP1, FANCA, FANCC, NBN, PALB2, RAD50, RAD51B, RAD51C, and RAD51D. Biallelic inactivation was assessed within tumors. Progression-free (PFS) and overall survival (OS) were calculated from pathologic diagnosis using the Kaplan-Meier method with left truncation. Whole-exome sequencing (WES) was performed in a subset. Of 882 patients with OC, 56 (6.3%) had germline PVs in non-BRCA HR genes; 95 (11%) had BRCA1 -associated OC (58 germline, 37 somatic); and 59 (6.7%) had BRCA2 -associated OC (40 germline, 19 somatic). High rates of biallelic alterations were observed among germline PVs in BRIP1 (11/13), PALB2 (3/4), RAD51B (3/4), RAD51C (3/4), and RAD51D (8/10). In cases with WES (27/35), there was higher tumor mutational burden (TMB; median 2.5 [1.1–6.0] vs. 1.2 mut/Mb [0.6–2.6]) and enrichment of HR-deficient (HRD) mutational signatures in tumors associated with germline PALB2 and RAD51B/C/D compared with BRIP1 PVs (p < 0.01). Other features of HRD, including telomeric-allelic imbalance (TAI) and large-scale state transitions (LSTs), were similar. Although there was heterogeneity in PFS/OS by gene group, only BRCA1/2 -associated OC had improved survival compared to WT OC (p < 0.01). OCs associated with germline PVs in non-BRCA HR genes represent a heterogenous group, with PALB2 and RAD51B/C/D associated with an HRD phenotype. • Those with germline pathogenic variants (PV) in non- BRCA1/2 homologous recombination (HR) genes were a heterogeneous group. • There was enrichment of HR-deficient (HRD) phenotype in those with germline PVs in PALB2 and RAD51B/C/D compared to BRIP1. • Patients with BRCA1/2- associated ovarian cancer (OC) had improved survival compared to those with wildtype OC. • Survival was variable among those with germline PVs in other HR genes. • OC associated with germline PVs in PALB2 and RAD51B/C/D may have similar features to BRCA1/2 -associated OC. [ABSTRACT FROM AUTHOR]

Depression is disproportionately high in patients with coronary artery disease and has been associated with adverse outcomes following coronary artery bypass graft (CABG). One quality metric, non-home discharge (NHD), can have substantial implications for patients and health care resource utilization. Depression increases the risk of NHD after many operations, but it has not been studied after CABG. We hypothesized that a history of depression would be associated with an increased risk of NHD following CABG. CABG cases were identified from the 2018 National Inpatient Sample using ICD-10 codes. Depression, demographic data, comorbidities, length of stay (LOS), rate of NHD were analyzed using appropriate statistical tests where a P -value < 0.05 was defined as statistically significant. Adjusted multivariable logistic regression models were used to assess independent association between depression and NHD as well as LOS while controlling for confounders. There were 31,309 patients, of which 2743 (8.8%) had depression. Depressed patients were younger, females, in a lower income quartile, and more medically complex. They also demonstrated more frequent NHD and prolonged LOS. After adjusted multivariable analysis, depressed patients had a 70% increased odds of NHD (adjusted odds ratio: 1.70 [1.52-1.89] P < 0.001) and a 24% increased odds of prolonged LOS (AOR: 1.24 [1.12-1.38] P < 0.001). From a national sample, depressed patients were associated with more frequent NHD following CABG. To our knowledge, this is the first study to demonstrate this, and it highlights the need for improved preoperative identification in order to improve risk stratification and timely allocation of discharge services. [ABSTRACT FROM AUTHOR]

We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer. We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006–9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded. Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7–61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%–56.2%). Median OS was 81.3 months (95% CI: 68.9–103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P <.001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P =.003). Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS. • Intrathoracic surgery for advanced ovarian cancer is both safe and feasible. • Complete gross resection of ovarian cancer can be obtained in patients with intrathoracic disease. • Primary cytoreductive surgery with intrathoracic procedures can offer excellent survival outcomes in select patients. [ABSTRACT FROM AUTHOR]

To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%–81.7% for patients meeting GOG-249 inclusion criteria, 40.2%–81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%–75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results. • Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogenous cohorts of patients. • 5-year survival was 60–82% for patients meeting GOG-249 criteria, 40–82% for PORTEC-3, and 18–75% for GOG-258 criteria. • The variation in expected survival for subsets of patients may result in underpowered studies or misleading results. [ABSTRACT FROM AUTHOR]

Delirium is associated with adverse post-operative outcomes, long-term cognitive dysfunction, and prolonged hospitalization. Risk factors for its development include longer surgical duration, increased operative complexity and invasiveness, and medical comorbidities. This study aims to further evaluate the incidence of delirium and its impact on outcomes among patients undergoing both elective and emergency bowel resections. This is a retrospective cohort study using an institutional patient registry. All patients undergoing bowel resection over a 3.5-year period were included. The study measured the incidence of post-operative delirium via the nursing confusion assessment method. This incidence was then compared to patient age, emergency versus elective admission, length of stay, mortality, discharge disposition, and hospital cost. A total of 1934 patients were included with an overall delirium incidence of 8.8%. Compared to patients without delirium, patients with delirium were more likely to have undergone emergency surgery, be greater than 70 y of age, have a longer length of stay, be discharged to a skilled nursing facility, and have a more expensive hospitalization. In addition, the overall mortality was 14% in patients experiencing delirium versus 0.1% in those that did not. Importantly, when broken down between elective and emergency groups, the mortality of those experiencing delirium was similar (11 versus 13%). The development of delirium following bowel resection is an important risk factor for worsened outcomes and mortality. Although the incidence of delirium is higher in the emergency surgery population, the development of delirium in the elective population infers a similar risk of mortality. [ABSTRACT FROM AUTHOR]

Recent work on augmented reality (AR) has explored the use of adaptive agents to overcome attentional issues that negatively impact task performance. However, despite positive technical evaluations, adaptive agents have shown no significant improvements to user task performance in AR. Furthermore, previous works have primarily evaluated such agents using abstract tasks. In this paper, we develop an agent that observes user behaviour and performs appropriate actions to mitigate attentional issues in a realistic sense-making task in AR. We employ mixed methods to evaluate our agent in a between-subject experiment (N=60) to understand the agent's effect on user task performance and behaviour. While we find no significant improvements in task performance, our analysis revealed that users' preferences and trust in the agent affected their receptiveness of the agent's recommendations. We discuss the pitfalls of autonomous agents and highlight the need to shift from designing better Human–AI interactions to better Human–AI collaborations. • We develop an adaptive agent to mitigate attentional issues in augmented reality. • We assess our agent via a technical evaluation and user study. • We discuss user preference and trust in relation to the agent's performance. • We highlight the need for human-centred approaches in designing adaptive agents. [ABSTRACT FROM AUTHOR]

Do people judge those who overcome temptation as more virtuous than those who don't feel tempted in the first place? Because prior research provides conflicting answers to this question, the current paper uses an expanded set of methodological and statistical tools to solve this puzzle. First, we replicated results of prior research showing that agents who overcome temptation are seen as less virtuous than non-tempted agents, with 74–78% of people making this judgment. Second, we used participant-generated stimuli and one measure from each of two published papers to rule out stimulus and measurement sampling as explanations for the previous opposite effects. We replicated our original results: 72–75% of people judged agents who overcame temptation as less virtuous than non-tempted agents. Third, we investigated whether judgments were moderated by relationship context. Again, the majority of people judged agents who overcame temptation–that would harm strangers or close others–as less virtuous than non-tempted agents. Additionally, the following interaction effect was the most common (modal) pattern: While judging tempted agents as less virtuous than non-tempted agents within each relationship context, 39% of people judged agents who were tempted to act in a way that would harm close others as even less virtuous than those agents whose temptations would harm strangers. Together, these results provide a detailed moral psychological account of temptation by: resolving a puzzle in the literature, revealing moderation by relationship context, and documenting the pervasiveness of this effect across stimuli, measures, and persons. [ABSTRACT FROM AUTHOR]

Nitric oxide synthase (NOS) inhibition with N(G)-monomethyl- l -arginine (L-NMMA) is often used to assess the role of NO in human cardiovascular function. However, the window of effect for L-NMMA on human vascular function is unknown, which is critical for designing and interpreting human-based studies. This study utilized the passive leg movement (PLM) assessment of vascular function, which is predominantly NO-mediated, in 7 young male subjects under control conditions, immediately following intra-arterial L-NMMA infusion (0.24 mg⋅dl−1⋅min−1), and at 45–60 and 90–105 min post L-NMMA infusion. The leg blood flow (LBF) and leg vascular conductance (LVC) responses to PLM, measured with Doppler ultrasound and expressed as the change from baseline to peak (ΔLBF peak and ΔLVC peak) and area under the curve (LBF AUC and LVC ACU), were assessed. PLM-induced robust control ΔLBF peak (1135 ± 324 ml⋅min−1) and ΔLVC peak (10.7 ± 3.6 ml⋅min−1⋅mmHg−1) responses that were significantly attenuated (704 ± 196 ml⋅min−1 and 6.7 ± 2 ml⋅min−1⋅mmHg−1) immediately following L-NMMA infusion. Likewise, control condition PLM ΔLBF AUC (455 ± 202 ml) and ΔLVC AUC (4.0 ± 1.4 ml⋅mmHg−1) were significantly attenuated (141 ± 130 ml and 1.3 ± 1.2 ml⋅mmHg−1) immediately following L-NMMA infusion. However, by 45–60 min post L-NMMA infusion all PLM variables were not significantly different from control, and this was still the case at 90–105 min post L-NMMA infusion. These findings reveal that the potent reduction in NO bioavailability afforded by NOS inhibition with L-NMMA has a window of effect of less than 45–60 min in the human vasculature. These data are particularly important for the commonly employed approach of pharmacologically inhibiting NOS with L-NMMA in the human vasculature. • The nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) is presumed to have long-lasting effects.ITh • The current data demonstrate that the window of effect for L-NMMA inhibition in the human vasculature is <45–60 min. • Experiments using intra-arterial L-NMMA infusion in humans can be strengthened by a more flexible infusion order. [ABSTRACT FROM AUTHOR]

Although widely used in the detection and characterization of protein–protein interactions, Y2H screening has been under-used for the engineering of new optogenetic tools or the improvement of existing tools. Here we explore the feasibility of using Y2H selection and screening to evaluate libraries of photoswitchable protein–protein interactions. We targeted the interaction between circularly permuted photoactive yellow protein (cPYP) and its binding partner binder of PYP dark-state (BoPD) by mutating a set of four surface residues of cPYP that contribute to the binding interface. A library of ~ 10,000 variants was expressed in yeast together with BoPD in a Y2H format. An initial selection for the cPYP/BoPD interaction was performed using a range of concentrations of the cPYP chromophore. As expected, the majority (> 90% of cPYP variants) no longer bound to BoPD. Replica plating was then used to evaluate the photoswitchability of the surviving clones. Photoswitchable cPYP variants with BoPD affinities equal to, or higher than, native cPYP were recovered in addition to variants with altered photocycles and binders that interacted with BoPD as apo-proteins. Y2H results reflected protein–protein interaction affinity, expression, photoswitchability, and chromophore uptake, and correlated well with results obtained both in vitro and in mammalian cells. Thus, by systematic variation of selection parameters, Y2H screens can be effectively used to generate new optogenetic tools for controlling protein–protein interactions for use in diverse settings. Unlabelled Image • A library of ~ 10,000 variants of photoactive yellow protein (PYP) was evaluated for binding to a partner protein Binder of PYP-Dark (BoPD) using a yeast two-hybrid approach. • By varying parameters of the two-hybrid selection, distinct photoswitchable behaviors were recovered including PYP variants with altered affinity, kinetics, and apo-state binding. • Phenotypes observed in yeast two-hybrid assays correlate well with results obtained in vitro and in mammalian cells. [ABSTRACT FROM AUTHOR]

• We present the first empirical investigation into the ability to crowdfund community-led projects in the context of digital civics. • Working with four community projects we determine that crowdfunding can: • Provide an alternative funding mechanism suitable for financing some community-led projects. • Create a sense of empowerment and ownership. • Increase community awareness. • We identify and discuss four key challenges to using crowdfunding to support community-led projects, specifically: • The time/benefit analysis. • A reliance on existing social networks. • The need for glamorous projects. • Exclusiveness and marginalisation. • We outline four key pieces of advice to community groups, namely: • Lesson 1: Select your platform carefully. • Lesson 2: Prepare your business model. • Lesson 3: Work with other organisations. • Lesson 4: Focus your messaging on benefits. Digital technology is increasingly being used to bring citizens and communities together to address local concerns. While a variety of approaches have been developed that allow citizens and communities to improve their local communities, these approaches are often financially unsustainable. In this paper, we describe our exploration of crowdfunding as an alternative approach to funding community-led projects in the context of digital civics. Through our analysis of four community-led crowdfunding projects, we demonstrate that crowdfunding can a) provide an alternative funding mechanism suitable for financing community-led projects, b) create a sense of empowerment and ownership for project leaders, and c) increase community awareness of a project. By reflecting on our experiences, we identify four key challenges to utilising crowdfunding to support community-led projects in the context digital civics, namely 1) the benefits gained versus the time invested, 2) a reliance on existing social networks, 3) the need for glamorous projects and 4) issues of exclusiveness and marginalisation. We also provide advice specific to crowdfunding in the context of digital civics, before discussing the role of crowdfunding within digital civics. By addressing these challenges, we will be able to better support community groups crowdfund for the public good. [ABSTRACT FROM AUTHOR]

On a daily basis, we constantly deal with changing environmental cues and perceptual conflicts and as such, our brains must flexibly adapt to current demands in order to act appropriately. Brains become more efficient and are able to switch states more readily by increasing the complexity of their neural networks. However, it is unclear how brain signal complexity relates to behavior in young adults performing cognitively demanding executive function tasks. Here we used multiscale entropy analysis and multivariate statistics on EEG data while participants performed a bivalency effect task-switching paradigm to show that brain signal complexity in young adults increases as task demands increase, that increases in brain signal complexity are associated with both speed gains and losses depending on scalp location, and that more difficult tasks are associated with more circumscribed complexity across the scalp. Overall, these findings highlight a critical role for brain signal complexity in predicting behavior on an executive function task among young adults. • Brain signal complexity was measured in young adults during an executive function task. • Brain signal complexity predicted both speed gains and losses across the scalp. • More difficult tasks were associated with more circumscribed complexity across the scalp. [ABSTRACT FROM AUTHOR]

Bilingualism is associated with enhancement of executive control (EC) across the lifespan. Working memory and non-verbal emotion regulation both draw upon EC mechanisms so may also be affected by bilingualism, but these relationships are not fully understood. These relationships were explored using an n-back task with distracting emotional stimuli administered to young adults while continuous EEG was recorded. Monolinguals were faster but less accurate on the 2-back than bilinguals, and monolingual accuracy was more impeded by the presence of emotional stimuli than was that of bilinguals. The P300 event-related potential, a neural signature of working memory processing in the n-back, had smaller amplitudes in both groups on the 2-back than the 1-back, but attenuation in response to distracting emotional stimuli was greater for bilinguals than monolinguals. P300 latencies were also differentially affected by emotional stimuli in each group: Bilingual latencies were constant across emotions but monolingual latencies increased from neutral to angry conditions. In general, bilingual performance was less impacted by the emotional distraction than was that of the monolinguals. Additionally, bilinguals adjusted to the changing demands of the 1-back and 2-back conditions by recruiting neural networks to support different behavioral outcomes than monolinguals. [ABSTRACT FROM AUTHOR]

Humidity control is an important factor affecting the overall sustainability, productivity, and energy efficiency of controlled environment agriculture. Liquid desiccants offer the potential for pinpoint control of humidity levels in controlled environments. In the present work, a dehumidification processes utilizing liquid desiccants pumped through the lumens of triple-bore PVDF hollow fibre membranes is implemented in a bench scale controlled environment agriculture system. Hydrophobic hollow fibre membranes were combined into an array and placed near the crops. Concentrated magnesium chloride liquid desiccant solution with a low vapour pressure was pumped through the hollow fibre lumens. The dehumidification permeance rate responded dynamically to the changing transpiration rate of the plants, as influenced by changes in environmental factors such as light, temperature, and vapour pressure. The dehumidification permeance rate increased from an average of 0.26–0.31 g m−2 h−1 Pa−1 as the velocity of the liquid desiccant through the hollow fibres increased from 0.023 to 0.081 m s−1. Humidity levels were targeted to be maintained within a range of 70–90% relative humidity at 23 °C. The membrane-based liquid desiccant system was demonstrated to successfully control humidity within a bench-scale controlled environment agricultural setup. Water and liquid desiccant cycles when utilizing the proposed hollow fibre membrane-based liquid desiccant humidity control system for controlled environment agriculture. Image 1 • Liquid desiccant in triple bore hollow fibre membrane. • Humidity successfully controlled at levels desirable for plant cultivation. • Dehumidification rate varies dynamically in response to plant transpiration rate. • Average membrane dehumidification permeance of 0.26–0.31 g m−2 h−1 Pa−1. [ABSTRACT FROM AUTHOR]

Abstract Commensal microorganisms present at mucosal surfaces play a vital role in protecting the host organism from bacterial infection. There are multiple factors that contribute to selecting for the microbiome, including host genetics. Flavobacterium psychrophilum, the causative agent of Bacterial Cold Water Disease in salmonids, accounts for acute losses in wild and farmed rainbow trout (Oncorhynchus mykiss). The U.S. National Center for Cool and Cold Water Aquaculture has used family-based selective breeding to generate a line of rainbow trout with enhanced resistance to F. psychrophilum. The goal of this study is to determine whether selective breeding impacts the gut and gill microbiome of the F. psychrophilum -resistant as compared to a background matched susceptible trout line. Mid-gut and gill samples were collected from juvenile fish maintained at high or low stocking densities and microbial diversity assessed by 16S rDNA amplicon sequencing. Results indicate that alpha diversity was significantly higher in the mid-gut of the susceptible line compared to the resistant line, while no significant differences in alpha diversity were observed in the gills. Mycoplasma sp. was the dominant taxon in the mid-gut of both groups, although it was present at a decreased abundance in the susceptible line. We also observed an increased abundance of the potential opportunistic pathogen Brevinema andersonii in the susceptible line. Within the gills, both lines exhibited similar microbial profiles, with Candidatus Branchiomonas being the dominant taxon. Together, these results suggest that selectively bred F. psychrophilum -resistant trout may harness a more resilient gut microbiome, attributing to the disease resistant phenotype. Importantly, interactions between host genetics and environmental factors such as stocking density have a significant impact in shaping trout microbial communities. Highlights • Selective breeding results in enhanced resistance (ARS-Fp-R) or susceptibility (ARS-Fp-S) to F. psychrophilum infection. • The gut microbiome of the ARS-Fp-R line is less diverse than that of the ARS-Fp-S. line. • Mycoplasma sp. constituted a majority of the gut microbiome in both lines, although it was more abundant in ARS-Fp-R. • An increased abundance of potential opportunistic pathogens was observed in the ARS-Fp-S line. • Stocking density had an impact on the trout microbial communities. [ABSTRACT FROM AUTHOR]

Abstract Background Despite a proven record of identifying injuries missed during clinical evaluation, the effect of autopsy on injury severity score (ISS) calculation is unknown. We hypothesized that autopsy data would alter final ISS and improve the accuracy of outcome data analyses. Materials and methods All trauma deaths from January 2010 through June 2014 were reviewed. Trauma registrars calculated Abbreviated Injury Scale and ISS from clinical documentation alone. The most detailed available autopsy report then was reviewed, and AIS/ISS recalculated. Predictors of ISS change were identified using multivariate logistic regression. Results Seven hundred thirty-nine deaths occurred, of which 682 (92.3%) underwent autopsy (31% view-only, 3% with preliminary report, and 66% with full report). Patients undergoing full autopsy had a lower median age (39 versus 74 years, P < 0.01), a higher rate of penetrating injury (41.7% versus 0%, P < 0.01), and a higher emergency department mortality rate (30.8% versus 0%, P < 0.01) than those receiving view-only autopsy. Incorporating autopsy findings increased mean ISS (21.3 to 29.6, P < 0.001) and the percentage of patients with ISS ≥ 25 (49.9% to 69.2%, P < 0.001). Multivariate analysis identified length of stay, death in the emergency department, full rather than view-only autopsy, and presenting heart rate as variables associated with ISS increase. Conclusions Autopsy data significantly increased ISS values for trauma deaths. This effect was greatest in patients who died early in their course. Targeting this group, rather than all trauma patients, for full autopsy may improve risk-adjustment accuracy while minimizing costs. [ABSTRACT FROM AUTHOR]

Abstract Background Tranexamic acid (TXA) has been shown to reduce mortality in the treatment of traumatic hemorrhage. This effect seems most profound when given early after injury. We hypothesized that extending a protocol for TXA administration into the prehospital aeromedical setting would improve outcomes while maintaining a similar safety profile to TXA dosed in the emergency department (ED). Materials and methods We identified all trauma patients who received TXA during prehospital aeromedical transport or in the ED at our urban level I trauma center over an 18-mo period. These patients had been selected prospectively for TXA administration using a protocol that selected adult trauma patients with high-risk mechanism and concern for severe hemorrhage to receive TXA. Patient demographics, vital signs, lab values including thromboelastography, blood administration, mortality, and complications were reviewed retrospectively and analyzed. Results One hundred sixteen patients were identified (62 prehospital versus 54 ED). Prehospital TXA patients were more likely to have sustained blunt injury (76% prehospital versus 46% ED, P = 0.002). There were no differences between groups in injury severity score or initial vital signs. There were no differences in complication rates or mortality. Patients receiving TXA had higher rates of venous thromboembolic events (8.1% in prehospital and 18.5% in ED) than the overall trauma population (2.1%, P < 0.001). Conclusions Prehospital administration of TXA during aeromedical transport did not improve survival compared with ED administration. Treatment with TXA was associated with increased risk of venous thromboembolic events. Prehospital TXA protocols should be refined to identify patients with severe hemorrhagic shock or traumatic brain injury. [ABSTRACT FROM AUTHOR]

Dietary adaptations specific to the premolar row remain largely undocumented across primates. This study examines how relative premolar size varies among broad dietary groups (i.e., folivores, frugivores, insectivores, hard-object feeders) using a phylogenetically and ecologically diverse sample of species. We quantified relative premolar size with shape ratios computed using mandibular length, body mass, palate area, and M 1 area to evaluate hypotheses that link variation in relative premolar size to differences in tooth loading, energy requirements, the probability of tooth-food-tooth contact during mastication, and shifts in preferred bite point. Our results revealed the following dietary signals. First, primate folivores have large premolar rows relative to palate area in comparison to frugivores and insectivores. This contrast is consistent with the hypothesis that folivores require large postcanine teeth relative to the size of the oral cavity to increase the probability of particle fracture during mastication. Second, hard-object feeders are distinct from other groups in having P 4 s that are large relative to their M 1 s. This morphology is not associated with an increase in the size of the premolar row relative to mandibular length. This combination challenges the idea that hard-object feeders have large premolars as an adaptive response to resisting the loads incurred when processing mechanically challenging foods. We therefore interpret the large P 4 /M 1 ratios of hard-object feeders as indicating greater functional integration across the premolar-molar boundary owing to a mesial shift in preferred bite point. Finally, in a restricted subset of anthropoids, we found that, relative to mandibular length, premolar area increases with dietary elastic modulus ( E ) and toughness ( R ), indicating that relative premolar size is evolutionarily sensitive to food mechanical properties. Thus, our results show that relative premolar size is correlated with diet, highlighting the importance of this region for understanding the evolutionary history of primate dietary adaptations. [ABSTRACT FROM AUTHOR]

Following Williams' (2014) call for a more thoughtful approach to the study of place meaning , the present study employs a phenomenological research paradigm to elicit deeply personal meanings formed through conservation volunteerism. A photovoice protocol (n = 18) and life history interviews (n = 53) explore meaningful places for volunteer “stewards” in Scottsdale, Arizona's McDowell Sonoran Conservancy. Inductive thematic text analysis reveals how these volunteers form identity-expressive meanings that transcend and traverse geographic place scales. Results suggest that the concept of place identity is more than a sub-construct of place attachment , and requires further theorizing as a phenomenologically-embodied experience. Nonprofits and municipalities can learn from the organization's success in fostering an environmental steward identity as a means of community building. [ABSTRACT FROM AUTHOR]

Technology now enables killing from remote locations. Killing remotely might be psychologically easier than killing face to face, which could promote more killing behavior and incur less severe emotional consequences. The current study manipulated the medium via which participants completed an ostensible ladybug-killing task. Participants who were in the same room as the insects killed fewer of them than participants who killed remotely via videoconference. Remoteness exerted an indirect effect on self-reported emotional consequences of killing. There was no additional effect of varying the ostensible location of the remote targets (same building vs. different state). This research emphasizes the importance of considering the psychological consequences of the remoteness technology affords. [ABSTRACT FROM AUTHOR]

Background Canine osteosarcoma (OSA) is the most common cancer of the appendicular skeleton and is associated with high metastatic rate to the lungs and poor prognosis. Recent studies have shown the impact of malignant-derived exosomes on immune cells and the facilitation of immune evasion. In the current study, we have characterized the proteomic profile of exosomes derived from healthy osteoblasts and osteosarcoma cell lines. We investigated the direct impact of these exosomes on healthy T cells. Results Proteomic cargo of the malignant exosomes was markedly different from osteoblastic exosomes and contained immunosuppressive proteins including TGF-β, α fetoprotein and heat shock proteins. OSA exosomes directly attenuated the rate of T cell proliferation, increased a regulatory (FoxP3+) CD4+ phenotype and diminished the expression of the activation marker CD25+ on CD8+ cells. Exosomes of osteoblasts also demonstrated a direct impact on T cells, but to a lesser degree. Conclusions Osteosarcoma-derived exosomes compared to normal osteoblasts contain an immunomodulatory cargo, which reduced the rate of T cell proliferation and promoted T regulatory phenotype. Osteoblast-derived exosomes can also reduce T cell activity, but to lesser degree compared to OSA exosomes and without promoting a T regulatory phenotype. [ABSTRACT FROM AUTHOR]

One may measure the kinetic rate constants associated with biochemical reactions using an optical biosensor: an instrument in which ligand molecules are convected through a flow cell over a surface to which receptors are immobilized. If there are multiple reactants, one is faced with the problem of fitting multiple kinetic rate constants to one signal, since data from all of the reacting species is lumped together. Even in the presence of ambiguous data, one may use a series of experiments to accurately determine the rate constants. Moreover, the true set of rate constants may be identified by either postprocessing the signals or adjusting the ligand inflow concentrations. [ABSTRACT FROM AUTHOR]

An essential first step to elucidating the ecology and life histories of Metarhizium anisopliae -group species as entomopathogens, endophytes and soil-adapted fungi is the ability to define species limits and confidently infer a species phylogeny. In a multilocus phylogeny of the core Metarhizium anisopliae species complex, the majority of isolates sampled herein group within the currently defined limits of M. pingshaense , M. anisopliae , M. robertsii and M. brunneum , designated informally as the “PARB” clade. Multilocus phylogenetic analyses reveal pervasive congruent hierarchical structure among the genomic regions analyzed, which suggest that current PARB species delimitations likely encompass additional cryptic complexes. Further, the interpolation of isolates from different continents throughout each species lineage indicates periodic inter-continental dispersals. Although no PARB species has yet been confirmed to produce a sexual state, we demonstrate the mutually exclusive incidence of the MAT1 and MAT2 mating type idiomorphs among individuals in all PARB species. This configuration of mating type is diagnostic of a heterothallic, obligately outcrossing mating system, indicating the conservation of and ongoing potential for sexual reproduction in all PARB species. As one example of the utility of IGS markers, the commercially registered M. anisopliae strain F52, which is widely used for pest control in North America, Canada and Europe, is shown to be a member of the M. brunneum complex. While current PARB species delimitations evidently encompass cryptic partitions, formal recognition of segregate species should be approached cautiously until further evidence of their phylogenetic exclusivity, ecological distinctiveness or other unique attributes is demonstrated. Nevertheless, acknowledgment of these intraspecific partitions will provide a useful conceptual framework to guide future investigations of the community structure, phylogeography, population genetics, ecology and reproductive biology of this recent species radiation. [ABSTRACT FROM AUTHOR]

The current study aims to overcome methodological constraints of previous goal pursuit research by exploring how people simultaneously rely upon person-level characteristic adaptations and unique goal-level attributes to pursue their personal projects. Undergraduate participants identified 10 projects they would pursue over an academic quarter and rated project meaningfulness, effort exerted, patience employed, and progress satisfaction at five time points. Multilevel structural equation models revealed the relative influence of person-level and project-level attributes on project appraisals. Person-level adaptations accounted for a large portion of variance in project pursuit appraisals, though significant project-specific trends were found over time as well, including mutual positive cross-lag influences between meaning, patience, and effort, and a negative predictive effect of progress satisfaction on meaning. [ABSTRACT FROM AUTHOR]

Background Posttraumatic coagulopathy and inflammation can exacerbate secondary cerebral damage after traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown clinically to reduce mortality in hemorrhaging and head-injured trauma patients and has the potential to mitigate secondary brain injury with its reported antifibrinolytic and antiinflammatory properties. We hypothesized that TXA would improve posttraumatic coagulation and inflammation in a murine model of TBI alone and in a combined injury model of TBI and hemorrhage (TBI/H). Methods An established murine weight drop model was used to induce a moderate TBI. Mice were administered intraperitoneal injections of 10 mg/kg TXA or equivalent volume of saline 10 min after injury. An additional group of mice was subjected to TBI followed by hemorrhagic shock using a pressure-controlled model. TBI/H mice were given intraperitoneal injections of TXA or saline during resuscitation. Blood was collected at intervals after injury to assess coagulation by rotational thromboelastometry (ROTEM) and inflammation by Multiplex cytokine analysis. Soluble P-selectin, a biomarker of platelet activation, and serum neuron-specific enolase, a biomarker of cerebral injury, were measured at intervals. Brain homogenates were analyzed for inflammatory changes by Multiplex enzyme-linked immunosorbent assay, and splenic tissue was collected for splenic cell population assessment by flow cytometry. Results There were no coagulation, serum or cerebral cytokine, P-selectin, or neuron-specific enolase differences between mice treated with TXA or saline after TBI. After the addition of hemorrhagic shock and resuscitation to TBI, TXA administration still did not affect coagulation parameters, systemic or cerebral inflammation, or platelet activation, as compared with saline alone. At 24 hours after TBI, mice given TXA demonstrated lower splenic total cell counts central memory CD8, effector CD8, B cell, and increased naive CD4 cell populations. By contrast, TXA did not affect splenic leukocyte populations after combined TBI/H. Conclusions Despite clinical data suggesting a mortality benefit, TXA did not modulate coagulation, inflammation, or biomarker generation in either the TBI or TBI/H murine models. Administration of TXA after TBI altered splenic leukocyte populations, which may contribute to a change in posttraumatic immune status. Future studies should be done to investigate the role of TXA in the development of posttraumatic immunosuppression and risk of nosocomial infections. [ABSTRACT FROM AUTHOR]

Given any Banach space X and any weak ⁎ -compact subset K of X ⁎ , we compute the Szlenk index of the weak ⁎ -closed, convex hull of K as a function of the Szlenk index of K . Also as an application, we compute the Szlenk index of any injective tensor product of two operators. In particular, we compute the Szlenk index of an injective tensor product X ⊗ ˆ ε Y in terms of S z ( X ) and S z ( Y ) . As another application, we give a complete characterization of those ordinals which occur as the Szlenk index of a Banach space, as well as those ordinals which occur as the Bourgain ℓ 1 or c 0 index of a Banach space. [ABSTRACT FROM AUTHOR]

This review aimed to determine the most popular physical activities performed by children, adolescents, and adults globally. Statistic bureau websites and article databases Scopus, ProQuest, SPORTDiscus, and Science Direct were searched between November 17th, 2014 and April 31st, 2015. Eligible studies were published in the last 10years with participation rates for specific physical activities among individuals five years or older. Data extraction for included articles (n=64) was assessed independently and agreed upon by two authors. A random-effects model was used to calculate participation rates in specific activities for each age group and region. In total 73,304 articles were retrieved and 64 articles representing 47 countries were included in the final meta-analysis. Among adults, walking was the most popular activity in the Americas (18.9%; 95% CI 10.2 to 32.5), Eastern Mediterranean (15.0%; 95% CI 5.8 to 33.6), Southeast Asia (39.3%; 95% CI 0.9 to 98.0) and Western Pacific (41.8%; 95% CI 25.2 to 60.6). In Europe and Africa, soccer (10.0%; 95% CI 6.5 to 15.1) and running (9.3%; 95% CI 0.9 to 53.9), respectively, were top activities. Child and adolescent participation results were highly dependent upon region. American youth team sport participation was high, while youth from the Eastern Mediterranean and Western Pacific were more likely to report participation in lifelong physical activities. Global data for adults reflects a consistent pattern of participation in running and walking. Among all age groups and regions soccer was popular. In children and adolescents, preferences were variable between regions. [ABSTRACT FROM AUTHOR]

The assembly of the Escherichia coli ribosome has been widely studied and characterized in vitro . Despite this, ribosome biogenesis in living cells is only partly understood because assembly is coupled with transcription, modification and processing of the pre-ribosomal RNA. We present a method for footprinting and isolating pre-rRNA as it is synthesized in E. coli cells. Pre-rRNA synthesis is synchronized by starvation, followed by nutrient upshift. RNA synthesized during outgrowth is metabolically labeled to facilitate isolation of recent transcripts. Combining this technique with two in vivo RNA probing methods, hydroxyl radical and DMS footprinting, allows the structure of nascent RNA to be probed over time. Together, these can be used to determine changes in the structures of ribosome assembly intermediates as they fold in vivo . [ABSTRACT FROM AUTHOR]

There is insufficient evidence to recommend a specific protocol for treatment of infantile spasms (IS) and a lack of standardization among, and even within, institutions. Twice-daily dosing (for the first two weeks) of high-dose natural ACTH for IS is used by many centers and recommended by the National Infantile Spasms Consortium (NISC). Conversely, it is our practice to use once-daily dosing of high-dose natural ACTH for IS. In order to determine the effectiveness of our center's practice, we retrospectively reviewed 57 cases over the past four years at Boston Children's Hospital (BCH). We found that 70% of infants were spasm-free at 14 days from ACTH initiation and 54% continued to be spasm-free at 3-month follow-up. Electroencephalogram showed resolution of hypsarrhythmia (when present on the pretreatment EEG) in all responders. Additionally, once-daily dosing of ACTH was well tolerated. We performed a meta-analysis to compare our results against the reports of published literature using twice-daily high-dose ACTH for treatment of IS. The meta-analysis revealed that our results were comparable to previously published outcomes using twice-daily ACTH administration for IS treatment. Our experience shows that once-daily dosing of ACTH is effective for treatment of IS. If larger prospective trials can confirm our findings, it would obviate the need for additional painful injections, simplify the schedule, and support a universal standardized protocol. [ABSTRACT FROM AUTHOR]

The ability to manipulate transcription in human pluripotent stem cells (hPSCs) is fundamental for the discovery of key genes and mechanisms governing cellular state and differentiation. Recently developed CRISPR-effector systems provide a systematic approach to rapidly test gene function in mammalian cells, including hPSCs. In this review, we discuss recent advances in CRISPR-effector technologies that have been employed to control transcription through gene activation, gene repression, and epigenome engineering. We describe an application of CRISPR-effector mediated transcriptional regulation in hPSCs by targeting a synthetic promoter driving a GFP transgene, demonstrating the ease and effectiveness of CRISPR-effector mediated transcriptional regulation in hPSCs. [ABSTRACT FROM AUTHOR]

We construct a class of minimal trees and use these trees to establish a number of coloring theorems on general trees. Among the applications of these trees and coloring theorems are quantification of the Bourgain ℓ p and c 0 indices, dualization of the Bourgain c 0 index, establishing sharp positive and negative results for constant reduction, and estimating the Bourgain ℓ p index of an arbitrary Banach space X in terms of a subspace Y and the quotient X / Y . [ABSTRACT FROM AUTHOR]

• Highly standardised biological models obscure effects in sub-populations. • Adding sex or age to analysis causes a large explosion in samples needed. • Statistical power differs for males and females in high throughput data sets such as RNAsequencing. • female/male gene dispersions vary enough to warrant different biological replicates between sexes. One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward. [ABSTRACT FROM AUTHOR]

Recent archaeological investigations indicate that coastal Fort Walton cultures in the St. Joseph Bay region of northwest Florida emphasized marine and estuarine foraging. These late prehistoric, Mississippi-period (A.D. 1000–1500) peoples collected fish, shellfish, and other aquatic resources. At the Richardson's Hammock site (8Gu10), radiocarbon-dated to about A.D. 1300, large, predatory gastropods were a major subsistence component. This adaptation is in sharp contrast with that of contemporaneous inland Fort Walton societies, who relied on maize agriculture, and raises the question whether coastal groups were separate hunter–gatherer–fisher populations or migrated seasonally from inland farming villages. We perform stable oxygen and carbon isotope sclerochronology on lightning whelks ( Busycon sinistrum ) to determine the seasonality of Fort Walton foraging and to compare the environment of prehistoric St. Joseph Bay with that of the modern bay. Oxygen isotope profiles suggest that shellfish collecting was relegated primarily to the summer months, producing a scheduling conflict with the primary growing season for maize in northwest Florida. Thus, coastal and inland Fort Walton sites probably represent separate culture groups. The relationship between δ 18 O shell and δ 13 C shell indicates similar environmental and climatic conditions between prehistoric St. Joseph Bay and today. However, modern whelks are depleted in 13 C compared to Fort Walton whelks, which reflects both twentieth century CO 2 emissions and years of dredging and wastewater pollution entering the bay. [ABSTRACT FROM AUTHOR]

Mnemonic representations vary in fidelity, sharpness, and strength—qualities that can be examined using both introspective judgements of mental states and objective measures of brain activity. Subjective and objective measures are both valid ways of "reading out" the content of someone's internal mnemonic states, each with different strengths and weaknesses. St-Laurent and colleagues (2015) compared the neural correlates of memory vividness ratings with patterns of neural reactivation evoked during memory recall and found considerable overlap between the two, suggesting a common neural basis underlying these different markers of representational quality. Here we extended this work with meta-analytic methods by pooling together four neuroimaging datasets in order to contrast the neural substrates of neural reactivation and those of vividness judgements. While reactivation and vividness judgements correlated positively with one another and were associated with common univariate activity in the dorsal attention network and anterior hippocampus, some notable differences were also observed. Vividness judgments were tied to stronger activation in the striatum and dorsal attention network, together with activity suppression in default mode network nodes. We also observed a trend for reactivation to be more closely associated with early visual cortex activity. A mediation analysis found support for the hypothesis that neural reactivation is necessary for memory vividness, with activity in the anterior hippocampus associated with greater reactivation. Our results suggest that neural reactivation and vividness judgements reflect common mnemonic processes but differ in the extent to which they engage effortful, attentional processes. Additionally, the similarity between reactivation and vividness appears to arise, partly, through hippocampal engagement during memory retrieval. [ABSTRACT FROM AUTHOR]

Alpha 1 -proteinase inhibitor (A1PI) augmentation is the only specific treatment targeting the underlying deficiency in alpha 1 -antitrypsin deficiency (AATD). The demonstration of efficacy has been based on maintaining the biochemical surrogate endpoints of plasma antigenic and functional A1PI levels above >11 μM. Here we report a biochemical comparability analysis based on data from a phase 2/3, randomized, double-blind, two-arm study with partial crossover of Glassia® (Baxalta US Inc. Westlake Village, CA, USA) and Prolastin® (Grifols Therapeutics LLC, Research Triangle Park, NC, USA) in patients with AATD (NCT00460096). Patients (N = 50) were randomly assigned in a 2:1 ratio to receive either Glassia (n = 33) or Prolastin (n = 17), respectively. In the present study, data from patients in the per-protocol population (n = 29, Glassia; n = 12, Prolastin) were analyzed. We compared the biochemical efficacy of these two A1PI products at steady state of A1PI in plasma after weekly intravenous administration of A1PI at a dose of 60 mg/kg body weight. For both antigenic and functional A1PI levels, with or without baseline correction, the geometric mean ratios (GMRs) of plasma trough levels (Glassia/Prolastin) over a 6-week period at steady state (Weeks 7–12 post-randomization) were near or above 100%, with the 90% confidence intervals (CIs) contained within the 80%–125% interval. For antigenic A1PI, the GMR (90% CI) was 115.8% (108.1–124.2) for baseline corrected and 114.2% (109.2–119.5) for uncorrected concentrations. For functional A1PI, the GMR (90% CI) was 98.7 (92.5–105.4) for baseline corrected and 107.8% (102.3–113.5) for uncorrected concentrations. In conclusion, the biochemical efficacy of Glassia using the endpoints of plasma antigenic and functional A1PI trough concentrations at steady state was comparable with Prolastin in patients with AATD. [ABSTRACT FROM AUTHOR]

Magnetoencephalography (MEG) has been revolutionised by optically pumped magnetometers (OPMs). "OPM-MEG" offers higher sensitivity, better spatial resolution, and lower cost than conventional instrumentation based on superconducting quantum interference devices (SQUIDs). Moreover, because OPMs are small, lightweight, and portable they offer the possibility of lifespan compliance and (with control of background field) motion robustness, dramatically expanding the range of MEG applications. However, OPM-MEG remains nascent technology; it places stringent requirements on magnetic shielding, and whilst a number of viable systems exist, most are custom made and there have been no cross-site investigations showing the reliability of data. In this paper, we undertake the first cross-site OPM-MEG comparison, using near identical commercial systems scanning the same participant. The two sites are deliberately contrasting, with different magnetic environments: a "green field" campus university site with an OPM-optimised shielded room (low interference) and a city centre hospital site with a "standard" (non-optimised) MSR (higher interference). We show that despite a 20-fold difference in background field, and a 30-fold difference in low frequency interference, using dynamic field control and software-based suppression of interference we can generate comparable noise floors at both sites. In human data recorded during a visuo-motor task and a face processing paradigm, we were able to generate similar data, with source localisation showing that brain regions could be pinpointed with just ∼10 mm spatial discrepancy and temporal correlations of > 80%. Overall, our study demonstrates that, with appropriate field control, OPM-MEG systems can be sited even in city centre hospital locations. The methods presented pave the way for wider deployment of OPM-MEG. [ABSTRACT FROM AUTHOR]

The bulk of aqueous humor passing through the conventional outflow pathway must cross the inner wall endothelium of Schlemm's canal (SC), likely through micron-sized transendothelial pores. SC pore density is reduced in glaucoma, possibly contributing to obstructed aqueous humor outflow and elevated intraocular pressure (IOP). Little is known about the mechanisms of pore formation; however, pores are often observed near dome-like cellular outpouchings known as giant vacuoles (GVs) where significant biomechanical strain acts on SC cells. We hypothesize that biomechanical strain triggers pore formation in SC cells. To test this hypothesis, primary human SC cells were isolated from three non-glaucomatous donors (aged 34, 44 and 68), and seeded on collagen-coated elastic membranes held within a membrane stretching device. Membranes were then exposed to 0%, 10% or 20% equibiaxial strain, and the cells were aldehyde-fixed 5 min after the onset of strain. Each membrane contained 3-4 separate monolayers of SC cells as replicates ( N = 34 total monolayers), and pores were assessed by scanning electron microscopy in 12 randomly selected regions (∼65,000 μm 2 per monolayer). Pores were identified and counted by four independent masked observers. Pore density increased with strain in all three cell lines ( p < 0.010), increasing from 87 ± 36 pores/mm 2 at 0% strain to 342 ± 71 at 10% strain; two of the three cell lines showed no additional increase in pore density beyond 10% strain. Transcellular “I-pores” and paracellular “B-pores” both increased with strain ( p < 0.038), however B-pores represented the majority (76%) of pores. Pore diameter, in contrast, appeared unaffected by strain ( p = 0.25), having a mean diameter of 0.40 μm for I-pores ( N = 79 pores) and 0.67 μm for B-pores ( N = 350 pores). Pore formation appears to be a mechanosensitive process that is triggered by biomechanical strain, suggesting that SC cells have the ability to modulate local pore density and filtration characteristics of the inner wall endothelium based on local biomechanical cues. The molecular mechanisms of pore formation and how they become altered in glaucoma may be studied in vitro using stretched SC cells. [ABSTRACT FROM AUTHOR]

Felis catus gammaherpesvirus 1 (FcaGHV1), recently discovered in the USA, was detected in domestic cats in Australia (11.4%, 95% confidence interval 5.9-19.1, n=110) and Singapore (9.6%, 95% confidence interval 5.9-14.6, n=176) using qPCR. FcaGHV1 qPCR positive cats were 2.8 times more likely to be sick than healthy. Risk factors for FcaGHV1 detection included being male, increasing age and coinfection with pathogenic retroviruses, feline immunodeficiency virus (FIV) or feline leukaemia virus. FcaGHV1 DNA was detected in multiple tissues from infected cats with consistently high virus loads in the small intestine. FcaGHV1 viral load was significantly higher in FIV-infected cats compared with matched controls, mimicking increased Epstein-Barr virus loads in human immunodeficiency virus-infected humans. FcaGHV1 is endemic in distant geographic regions and is associated with being sick and with coinfections. Horizontal transmission of FcaGHV1 is supported, with biting being a plausible route. A pathogenic role for FcaGHV1 in domestic cats is supported. [ABSTRACT FROM AUTHOR]

Abstract: Applications of fluorescence based imaging techniques for detection in cellular and tissue environments are severely limited by autofluorescence of endogenous components of cells, tissue, and the fixatives used in sample processing. To achieve sufficient signal-to-background ratio, a high concentration of the probe needs to be used which is not always feasible. Since typically autofluorescence is in the nanosecond range, long-lived fluorescence probes in combination with time-gated detection can be used for suppression of unwanted autofluorescence. Unfortunately, this requires the sacrifice of the large portion the probe signal in order to sufficiently filter the background. We report a simple and practical approach to achieve a many-fold increase in the intensity of a long-lived probe without increasing the background fluorescence. Using controllable, well separated bursts of closely spaced laser excitation pulses, we are able to highly increase the fluorescence signal of a long-lived marker over the endogenous fluorescent background and scattering, thereby greatly increasing detection sensitivity. Using a commercially available confocal microscopy system equipped with a laser diode and time correlated single photon counting (TCSPC) detection, we are able to enhance the signal of a long-lived Ruthenium (Ru)-based probe by nearly an order of magnitude. We used 80MHz bursts of pulses (12.5ns pulse separation) repeated with a 320kHz repetition rate as needed to adequately image a dye with a 380ns lifetime. Just using 10 pulses in the burst increases the Ru signal almost 10-fold without any increase in the background signal. [Copyright &y& Elsevier]

Abstract: The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies. [Copyright &y& Elsevier]

This cross-sectional study examined the associations between serum interleukin-6 (IL-6) and muscle, bone, and fat parameters in recreationally active women. One-hundred forty-five women (48.7 ± 17.8 years; 164.4 ± 7.1 cm; 66.8 ± 10.7 kg; and 24.7 ± 3.9 kg/m2) underwent dual energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) assessments to determine total and regional muscle, bone, and fat parameters. Muscle performance of the knee extensors was examined via isometric, isotonic, and isokinetic dynamometry assessments, and serum IL-6 was measured via enzyme linked immunosorbent assay. Serum IL-6 was inversely associated with thigh muscle cross-sectional area (mCSA, r = -0.28, p < 0.01); isometric strength (r = -0.19, p < 0.05); hip areal bone mineral density [aBMD] (r = -0.18, p < 0.05); trochanter aBMD (r = -0.23, p < 0.01); total body aBMD (r = -0.20, p < 0.05); cortical volumetric bone density at 38 and 66% tibia (r = -0.18 and r = -0.19, respectively, both p < 0.05), and 66% cortical thickness (r = -0.17, p < 0.05). These associations were present after adjusting for age, BMI, and physical activity. Thigh mCSA was significantly lower in the tertile possessing the greatest IL-6 compared to the lowest tertile (p < 0.01); after adjusting for age, body mass index, and physical activity. Collectively, these observations indicate that IL-6 is inversely associated with skeletal muscle and bone parameters independent of relevant confounders. These observations bolster the prognostic value of serum IL-6. [ABSTRACT FROM AUTHOR]

Abstract: SR proteins are essential splicing factors whose biological function is regulated through phosphorylation of their C-terminal RS domains. Prior studies have shown that cytoplasmic–nuclear translocalization of the SR protein SRSF1 is regulated by multisite phosphorylation of a long Arg-Ser repeat in the N-terminus of the RS domain while subnuclear localization is controlled by phosphorylation of a shorter Arg-Ser repeat along with several Ser-Pro dipeptides in the C-terminus of the RS domain. To better understand how these two kinases partition Arg-Ser versus Ser-Pro specificities, we monitored the phosphorylation of SRSF1 by CLK1 and SRPK1. Although SRPK1 initially binds at the center of the RS domain phosphorylating in an orderly, N-terminal direction, CLK1 makes widespread contacts in the RS domain and generates multiple enzyme–substrate complexes that induce a random addition mechanism. While SRPK1 rapidly phosphorylates N-terminal serines, SRPK1 and CLK1 display similar activities toward Arg-Ser repeats in the C-terminus, suggesting that these kinases may not separate function in a strict linear manner along the RS domain. CLK1 induces a unique gel shift in SRSF1 that is not the result of enhanced Arg-Ser phosphorylation but rather is the direct result of the phosphorylation of several Ser-Pro dipeptides. These prolines are important for binding and phosphorylation of the SR protein by CLK1 but not for the SRPK1-dependent reaction. The data establish a new view of SR protein regulation in which SRPK1 and CLK1 partition activities based on Ser-Pro versus Arg-Ser placement rather than on N- and C-terminal preferences along the RS domain. [Copyright &y& Elsevier]

Highlights: [•] Three genes sequenced from nematodes parasitizing Sirex spp. in North America. [•] Evidence found for nematode host switching between S. noctilio and S. nigricornis. [•] Each Sirex species included had its own associated nematode parasite. [ABSTRACT FROM AUTHOR]

Abstract: Most of the current EEG-based workload classifiers are subject-specific; that is, a new classifier is built and trained for each human subject. In this paper we introduce a cross-subject workload classifier based on a hierarchical Bayes model. The cross-subject classifier is trained and tested with data from a group of subjects. In our work, it was trained and tested on EEG data collected from 8 subjects as they performed the Multi-Attribute Task Battery across three levels of difficulty. The accuracy of this cross-subject classifier is stable across the three levels of workload and comparable to a benchmark subject-specific neural network classifier. [Copyright &y& Elsevier]

Abstract: The septo-hippocampal system in birds resembles that of mammals, motivating research into the function of the avian hippocampus while surprisingly little attention has been given to the septum. To investigate a possible role of the avian septum in memory, the effects of septal area lesions on a spatial working memory (SpWM) task was tested in homing pigeons. After preoperative training on an analogue eight-arm (feeders) radial maze, now sham-operated control and septal lesioned pigeons were then trained again on the same task of locating the four feeders on the test phase of a trial that were not baited during the sample phase of a trial. During the test phase of a working memory trial, septal lesioned pigeons, compared to both their own preoperative performance and the performance of the controls, required significantly more choices to locate the four baited feeders not baited during the sample phase of a trial, and they made significantly fewer correct responses to the now baited feeders on their first four choices. The results demonstrate that, like its mammalian counterpart, the avian septum plays an important role in SpWM, suggesting that at least some functional properties of the septum are evolutionarily conserved in birds and mammals. [Copyright &y& Elsevier]

Abstract: The Drosophila Suppressor of Hairy wing [Su(Hw)] insulator protein has an essential role in the development of the female germline. Here we investigate the function of Su(Hw) in the ovary. We show that Su(Hw) is universally expressed in somatic cells, while germ cell expression is dynamic. Robust levels accumulate in post-mitotic germ cells, where Su(Hw) localization is limited to chromosomes within nurse cells, the specialized cells that support oocyte growth. Although loss of Su(Hw) causes global defects in nurse cell chromosome structure, we demonstrate that these architectural changes are not responsible for the block in oogenesis. Connections between the fertility and insulator functions of Su(Hw) were investigated through studies of the two gypsy insulator proteins, Modifier of (mdg4)67.2 (Mod67.2) and Centrosomal Protein of 190kDa (CP190). Accumulation of these proteins is distinct from Su(Hw), with Mod67.2 and CP190 showing uniform expression in all cells during early stages of oogenesis that diminishes in later stages. Although Mod67.2 and CP190 extensively co-localize with Su(Hw) on nurse cell chromosomes, neither protein is required for nurse cell chromosome development or oocyte production. These data indicate that while the gypsy insulator function requires both Mod67.2 and CP190, these proteins are not essential for oogenesis. These studies represent the first molecular investigations of Su(Hw) function in the germline, which uncover distinct requirements for Su(Hw) insulator and ovary functions. [Copyright &y& Elsevier]

Abstract: SR proteins (splicing factors containing arginine–serine repeats) are essential splicing factors whose phosphorylation by the SR-specific protein kinase (SRPK) family regulates nuclear localization and mRNA processing activity. In addition to an N-terminal extension with unknown function, SRPKs contain a large, nonhomologous spacer insert domain (SID) that bifurcates the kinase domain and anchors the kinase in the cytoplasm through interactions with chaperones. While structures for the kinase domain are now available, constructs that include regions outside this domain have been resistant to crystallographic elucidation. To investigate the conformation of the full-length kinase and the functional role of noncatalytic regions, we performed hydrogen–deuterium exchange and steady-state kinetic experiments on SRPK1. Unlike the kinase core, the large SID lacks stable, hydrogen-bonded structure and may provide an intrinsically disordered region for chaperone interactions. Conversely, the N-terminus, which positively regulates SR protein binding, adopts a stable structure when the insert domain is present and stabilizes a docking groove in the large lobe of the kinase domain. The N-terminus and SID equally enhance SR protein turnover by altering the stability of several catalytic loop segments. These studies reveal that SRPK1 uses an N-terminal extension and a large, intrinsically disordered region juxtaposed to a stable structure to facilitate high-affinity SR protein interactions and phosphorylation rates. [Copyright &y& Elsevier]

Abstract: Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity. [Copyright &y& Elsevier]

Abstract: We report characterization of pH-dependent behavior in polyelectrolyte multilayers (PEMs) fabricated from poly(allylamine) (PAH) and low molecular weight poly(acrylic acid) (PAA) synthesized by living/controlled polymerization. Exposure of these films to solutions of low pH (e.g. pH 2.0–3.2) resulted in transformations from films that were smooth and uniform to films with porous morphologies, as characterized by scanning electron microscopy (SEM). We observed large differences in both the extent of this transformation and the sizes of the pores that resulted compared to films fabricated using higher molecular weight PAA used in past studies. Whereas transformations reported in past studies generally lead to pores with sizes in the range of 0.3–2μm, we observed larger-scale transformations and films with cell-like internal structures comprised of networks of closed pores, interconnected pores, and through-pores with sizes as large as 10–15μm depending on pH and the manner in which the films were incubated. Films fabricated using fluorescently end-labeled samples of PAA permitted real-time imaging of changes in internal structure using confocal microscopy (LSCM). The results of these studies also revealed large differences in the nature of these transformations when films were placed in contact with surfaces as opposed to when dipped into aqueous solutions. Our results reveal approaches that can be used to fabricate films with large pores (e.g., pores with sizes on the order of 10–15μm) and suggest methods that could potentially be used to generate PEMs having controlled gradients in pore size. [Copyright &y& Elsevier]