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Objective This study aimed to (1) examine whether the latent class structure of individuals engaging in self-directed violence and indirect self-harm behaviors (eg, substance use, disordered eating) varied by gender in a sample of US veterans, and (2) test the associations of posttraumatic stress disorder (PTSD) and depressive symptoms with the resulting classes. Study design Cross-sectional data from 3581 veterans, ages 18-50 (51.9% identified as women) were analyzed. Veterans self-reported histories of self-directed violence, substance use, and disordered eating. Latent class analysis and latent class regression were used to explore class structure by gender and examine association of class membership with PTSD and depressive symptoms. Results A 4-class model was supported in the sample. Class 1 (20.0%) was characterized by substance use and self-directed violent thoughts and behaviors. Class 2 (8.3%) was characterized by substance use, disordered eating, and self-directed violent thoughts and behaviors. Class 3 (12.6%) was distinguished by indirect self-harm behaviors (substance use and disordered eating). Class 4 (59.6%) reflected low likelihood of behavioral dysregulation. Classes were partially invariant across gender; endorsement of substance use behaviors was generally higher for men in each class. Comorbid clinically significant depressive and PTSD symptoms were associated with the class characterized by highest behavioral dysregulation. Conclusions Self-directed violent thoughts and behaviors present comorbidly with indirect self-harm in men and women veterans, although patterns of indirect self-harm behaviors differ slightly by gender. Such comorbidity may be associated with more severe presentations of psychiatric concerns.

Introduction. Anorectal malformations (ARM) are complex disorders that often require staged reconstructions. We present a case and imaging findings of a child who developed issues following colostomy closure due to segmental colonic ischemia. Case Presentation. A 3-year-old female with Currarino syndrome presented with abdominal distention, blood-flecked stools, and prolonged cecostomy flush time. For her anorectal malformation, a colostomy was initially placed. A new colostomy was created at posterior sagittal anorectoplasty (PSARP) to allow the distal rectum to reach the anus without tension. Differentials for her presenting symptoms included a mislocation of the anus, stenosis at the anoplasty site, stricture within the colon, or sacral mass from Currarino syndrome, causing obstructive symptoms. Workup at our hospital included an anorectal exam under anesthesia (EUA), which showed a well-located anus with without stenosis at the anoplasty site, and an antegrade contrast study revealed a featureless descending colon with a 3-4 mm stricture in the distal transverse colon at the site of the previous colostomy, without an obstructing presacral mass. To alleviate this obstruction, the child underwent removal of the chronically ischemic descending colon and a redo-PSARP, where the distal transverse colon was brought down to the anus. She is now able to successfully perform antegrade flushes. Conclusion. Patients who have had prior surgeries for ARM repair are at a higher risk of complications, including strictures or ischemic complications at areas of previous surgery or colostomy placement. A thorough preoperative workup, including contrast studies, can alert the surgeon to these potential pitfalls.

Many individuals with lifetime histories of eating disorders (EDs) report exposure to interpersonal trauma and posttraumatic stress disorder (PTSD). However, this relationship is not well-understood, and there are no established, evidence-based therapies for the concurrent treatment of EDs and PTSD. This review focuses on studies of the mechanisms associating trauma exposure and/or PTSD with EDs. Possible mechanisms of the trauma-ED association identified from the literature include self-criticism, low self-worth, guilt, shame, depression, anxiety, emotion dysregulation, anger, and impulsivity/compulsivity. ED behaviors may be used as coping strategies to manage PTSD symptoms and negative affect. Avoidance of hyperarousal symptoms by engaging in binge eating, purging, and/or restriction may serve to maintain both the ED as well as the PTSD. Given the evidence of the bidirectional relationship between EDs and PTSD, we describe an integrated cognitive behavioral theory that may account for the persistence of comorbid PTSD and EDs. The integrated model is based on the theoretical models that underpin existing evidence-based treatments for PTSD and ED and incorporates many of the potential mechanisms highlighted to date. The primary aim of the model is to identify potential treatment targets as well as elucidate future directions for research.

Dye sensitized solar cells can be constructed out of inexpensive materials such as titanium dioxide and the anthocyanin dye from raspberries but have shown efficiency issues related to the diffusion of electrons. Intermittent light studies were used to characterize the time-dependent photocurrent decay and growth after a shutter was either closed or opened, respectively, to gain insight on how photoinjected electrons diffuse through these semiconductor films. The data was fit with a biexponential decay or growth model, and significant differences were seen between devices with and without lithium ions in the electrolyte solution as well as a hysteresis depending on how long the device was under illumination or in the dark. We found that for both the photocurrent growths and decays, the faster lifetime component had a larger relative population. For both the decay and growth, the lifetime of the faster component did not have a significant difference when lithium perchlorate was added to the electrolyte solution. However, the presence of the lithium increased the lifetime of the slower component in both the growth curves and the decay curves. When comparing the data for devices that had a 10-second on/off cycle compared to a 1-minute on/off cycle, both the longer and the shorter lifetime components are shorter for the 10-second cycles. These results support the electron hopping model where electrons must diffuse through a dispersive energetic landscape.

The blood–brain barrier (BBB) is a major obstacle for drug delivery to the central nervous system (CNS) such that most therapeutics lack efficacy against brain tumors or neurological disorders due to their inability to cross the BBB. Therefore, developing new drug delivery platforms to facilitate drug transport to the CNS and understanding their mechanism of transport are crucial for the efficacy of therapeutics. Here, we report (i) carbon dots prepared from glucose and conjugated to fluorescein (GluCD-F) cross the BBB in zebrafish and rats without the need of an additional targeting ligand and (ii) uptake mechanism of GluCDs is glucose transporter-dependent in budding yeast. Glucose transporter-negative strain of yeast showed undetectable GluCD accumulation unlike the glucose transporter-positive yeast, suggesting glucose-transporter-dependent GluCD uptake. We tested GluCDs' ability to cross the BBB using both zebrafish and rat models. Following the injection to the heart, wild-type zebrafish showed GluCD-F accumulation in the central canal consistent with the transport of GluCD-F across the BBB. In rats, following intravenous administration, GluCD-F was observed in the CNS. GluCD-F was localized in the gray matter (e.g. ventral horn, dorsal horn, and middle grey) of the cervical spinal cord consistent with neuronal accumulation. Therefore, neuron targeting GluCDs hold tremendous potential as a drug delivery platform in neurodegenerative disease, traumatic injury, and malignancies of the CNS., Glucose-based carbon dots (GluCDs) can cross blood–brain barrier in zebrafish and rat after intravenous injections and accumulate in neurons in rat CNS. Cell uptake of GluCDs involve glucose transporter proteins in a budding yeast model.

Numerous recent assessments indicate that meat and poultry processing facility workers are at increased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-4). Physical proximity to other workers and shared equipment can facilitate disease transmission in these settings (2-4). The disproportionate number of foreign-born workers employed in meat and poultry processing reflects structural, social, and economic inequities that likely contribute to an increased COVID-19 incidence in this population* (5). In May 2020, the Maryland Department of Health and CDC investigated factors that might affect person-to-person SARS-CoV-2 transmission among persons who worked at two poultry processing facilities.† A survey administered to 359 workers identified differences in risk factors for SARS-CoV-2 infection between workers born outside the United States and U.S.-born workers. Compared with U.S.-born workers, foreign-born workers had higher odds of working in fixed locations on the production floor (odds ratio [OR] for cutup and packaging jobs = 4.8), of having shared commutes (OR = 1.9), and of living with other poultry workers (OR = 6.0). They had lower odds of participating in social gatherings (OR for visits to family = 0.2; OR for visits to friends = 0.4), and they visited fewer businesses in the week before the survey than did their U.S.-born coworkers. Some workplace risk factors can be mitigated through engineering and administrative controls focused on the production floor, and this will be of particular benefit to the foreign-born workers concentrated in these areas. Employers and health departments can also partner with local organizations to disseminate culturally and linguistically tailored messages about risk reduction behaviors in community settings, including shared transportation§ and household members dwelling in close quarters.¶.

The diaphragmatic motor-evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) permits electrophysiological assessment of the cortico-diaphragmatic pathway. Despite the value of TMS for investigating diaphragm motor integrity in health and disease, reliability of the technique has not been established. The study aim was to determine within- and between-session reproducibility of surface electromyogram recordings of TMS-evoked diaphragm potentials. Fifteen healthy young adults participated (6 females, age = 29 ± 7 yr). Diaphragm activation was determined by gradually increasing the stimulus intensity from 60 to 100% of maximal stimulator output (MSO). A minimum of seven stimulations were performed at each intensity. A second block of stimuli was delivered 30 min later for within-day comparisons, and a third block was performed on a separate day for between-day comparisons. Reliability of diaphragm MEPs was assessed at 100% MSO using intraclass correlation coefficients (ICC) and 95% limits of agreement (LOA). MEP latency (ICC = 0.984, P < 0.001), duration (ICC = 0.958, P < 0.001), amplitude (ICC = 0.950, P < 0.001), and area (ICC = 0.956, P < 0.001) were highly reproducible within-day. Between-day reproducibility was good to excellent for all MEP characteristics (latency ICC = 0.953, P < 0.001; duration ICC = 0.879, P = 0.002; amplitude ICC = 0.789, P = 0.019; area ICC = 0.815, P = 0.012). Data revealed less precision between-day versus within-day, as evidenced by wider LOA for all MEP characteristics. Large within- and between-subject variability in MEP amplitude and area was observed. In conclusion, TMS is a reliable means of inducing diaphragm potentials in most healthy individuals. NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS) is a noninvasive technique to assess neural impulse conduction along the cortico-diaphragmatic pathway. The reliability of diaphragm motor-evoked potentials (MEP) induced by TMS is unknown. Notwithstanding large variability in MEP amplitude, we found good-to-excellent reproducibility of all MEP characteristics (latency, duration, amplitude, and area) both within- and between-day in healthy adult men and women. Our findings support the use of TMS and surface EMG to assess diaphragm activation in humans.

Introduction Poor discharge communication is a major contributor to medication-related errors during care transfers. The World Health Organisation 2019 Medication Safety report1 acknowledged this and recommended prioritising collaboration with patients/families/carers, communicating medication changes, and interdisciplinary working. The Care Quality Commission 2020 National Patient Inpatient Survey found that only 28% of participants received information regarding side-effects, 55% given explanations on medicines-use, 48% provided written information and 12% no information.2. Health information systems including Medicines a Patient Profile Summary (MaPPs) provide easy-read leaflets which may improve patient awareness and understanding of their medicines.3 This study explored patients’ experience of DMC at one hospital Trust. Aim To measure patient satisfaction and understanding of DMC offered at Mid Yorkshire Hospitals Trust and establish whether the Trust standards were met of all patients with medication changes (new/stopped/changed) receiving verbal DMC and being offered a MaPPs leaflets/charts documenting the changes. Method Ethics approval was not required for this service evaluation. Baseline data was collected from the Trust Medicines Information department to establish which ward had the most discharge enquiries in October 2021. Inpatients from this ward were included if they were elderly, had a previous admission within the last 2 months, usually lived at home and managed their own medications or had help from relatives/friends. Inpatients were excluded if they were care-homes residents, had carers who visited to administer medicines, used a compliance aid or had no medication changes. A 13-item questionnaire was designed for qualitative/quantitative data collection over a 4-week period in December 2021. Questions concerned discharge medicines information provided (written/verbal), patient/relative satisfaction and patient/relative understanding of medicines indicated and changes. Quantitative data underwent descriptive statistical analysis, whilst qualitative data were grouped by similarity and frequency counted. Results A total of 20 elderly patients/relatives were included: 11 were female and 9 were male. Eight respondents (40%) reported not receiving written information. Twelve respondents (60%) reported received a SystmOne discharge letter, of whom 7 received additional written information that included a discharge medication list. This was provided by nurses on all occasions. No respondents reported being offered a MaPPs leaflet/chart, but 17 respondents indicated that they thought that a MaPPs leaflets/chart would have been beneficial. Eleven respondents reported receiving verbal DMC, of whom 4 rated themselves as being “not very satisfied” with it. Key themes were: ‘rushed discharges’, ‘limited patient/relative involvement’. No respondents reported being informed about side-effects. Eleven and 14 respondents respectively reported partially/not fully understanding why medications were indicated or changes made. Discussion/Conclusion Overall, DMC was below the Trust standards. Poor explanation of changes and no information on side-effects was common practice. The findings are limited by the small sample size and limited generalisability to ethnic minorities. Future study plans include involving underrepresented patient groups in a larger sample. Nevertheless, the following recommendations were made: Offer all patients MaPPs leaflets/reminder charts and verbal DMC; Offer all elderly ward nurses pharmacy-led MaPPs training; add monthly reminders during morning handovers to use MaPPs; Document on the electronic prescribing system when MaPPs leaflets are provided. References 1. Medication Without Harm [online]. World Health Organisation.2019 [accessed:07/04/22]. Available from: https://www.who.int/initiatives/medication-without-harm 2. Adult inpatient survey | Care Quality Commission [online].2020 [accessed:07/04/22]. Available from: https://www.cqc.org.uk/publications/surveys/adult-inpatient-survey-2020 3. Introducing MaPPs Patient-Friendly, Personalised Medicines Information [online]. Medicines: a Patient Profile Summary. [accessed:07/04/22]. Available from: https://www.mappsorg.com/

Objective Vascular patients suffer some of the highest complications rates. Surprisingly, there is no uniformly accepted medical therapy to reduce complications in these patients. Time restricted feeding (TRF) is an approach that emphasizes energy intake limited to certain windows of time within the 24-hour cycle, without restrictions on any calories or macronutrients. In healthy young human, TRF improves cardio-metabolic fitness. However, there is a lack of research on TRF in patient undergoing surgery, and suffering from cardiovascular diseases. This study aims to investigate the feasibility and efficacy of a pre-operative 2-week, 10-hour TRF in patient undergoing vascular surgery. Methods The OptiSurg Study is a randomized open-label clinical trial, that plan to enroll 40 patients, undergoing elective femoral endarterectomy. Only Fontaine stage II peripheral artery disease, and a BMI ≥ 20 kg/m2 are included. Patients are randomized with a 1:1 ratio to either the control or intervention group. The control group receives diet nutritional counselling (standard of care, SOC). The intervention group receives the same SOC and a self-selected 10-hour TRE window. After the surgery, patients will be on SOC only, and followed every 3 months up to 1 year. Primary endpoint is a composite of death, myocardial infarction, stroke, and surgical re-intervention at 1 month post-operative. Blood glucose, body weight, body composition, biomarkers (neuroendocrine, inflammatory and metabolic), sleep and quality of life will also be examined. Temporal calorie intake is monitored with the smartphone application myCircadianClock preoperatively. VascuQoL-6 is used to monitor quality of life. Results 9 participants were enrolled since the start of the recruitment in February 2021, 4 were randomized in the 8 hours TRF intervention, and 5 to SOC. They all completed the study: 7 men and 2 women, age 73, 53–87 (median, min-max) years. Using the myCircadianClock app, adherence to the TRF was >90% (Figure 1). Conclusion Our preliminary experience seems to demonstrate that a 2-week TRF regimen before vascular surgery is feasible. The complete results will be disseminated through future peer-reviewed manuscripts, reports and presentations.

The Pd-Cu catalysed Sonogashira coupling of terminal alkynes and aryl halides is a cornerstone synthetic strategy for C-C bond formation. Homogeneous organometallic systems conventionally applied are typically not reusable and require efficient downstream Pd removal steps for product purification, making it challenging to fully recover the precious metal. A holistic cradle-to-gate life cycle assessment (LCA) unveils that process footprint can be improved up to two orders of magnitude from repeated catalyst reuse. New classes of heterogeneous catalysts based on isolated metal atoms (single-atom catalysts, SACs) demonstrate promising potential to synergise the benefits of solid and molecular catalysts for efficient Pd utilisation. Here we show that using Pd atoms anchored on nitrogen-doped carbon permits full recovery of the metal and reuse of the catalyst over multiple cycles. A hybrid process using the Pd-SAC with a homogeneous CuI cocatalyst is more effective than a fully heterogeneous analogue based on a bimetallic Pd-Cu SAC, which deactivates severely due to copper leaching. In some scenarios, the LCA-based metrics demonstrate the footprint of the hybrid homogeneous-heterogeneous catalytic process is leaner than the purely homogeneous counterpart already upon single reuse. Combining LCA with experimental evaluation will be a useful guide to the implementation of solid, reusable catalysts for sustainable organic transformations., Green Chemistry, 24 (18), ISSN:1463-9262, ISSN:1463-9270

The Whitehorse Group and Quartermaster Formation are extensive red-bed terrestrial sequences representing the final episode of sedimentation in the Palo Duro Basin in north-central Texas, U.S.A. Regionally, these strata record the culmination of a long-term regression sequence beginning in the middle to late Permian. The Whitehorse Group includes beds of abundant laminated to massive red quartz siltstone to fine sandstone and rare dolomite, laminated to massive gypsum, and claystones, as well as diagenetic gypsum. The Quartermaster Formation exhibits a change from nearly equal amounts of thin planar and lenticular fine sandstone and laminated to massive mudstone in its lower half to overlying strata with coarser-grained, cross-bedded sandstones indicative of meandering channels up to 7 m deep and rare overbank mudstones. Paleosols are absent in the Upper Whitehorse Group and only poorly developed in the Quartermaster Formation. Volcanic ash-fall deposits (tuffs) present in uppermost Whitehorse Group and lower Quartermaster Formation strata permit correlation among five stratigraphic sections distributed over ∼150 km and provide geochronologic age information for these rocks. Both the Whitehorse Group and Quartermaster Formation have traditionally been assigned to the late Permian Ochoan (Changhsingian) stage, and workers assumed that the Permian-Triassic boundary is characterized by a regionally significant unconformity. Chemostratigraphic or biostratigraphic evidence for this age assignment, however, have been lacking to date. Single zircon U-Pb CA-TIMS analyses from at least two distinct volcanic ash fall layers in the lower Quartermaster Formation, which were identified and collected from five different localities across the Palo Duro Basin, yield interpreted depositional ages ranging from 252.19 ± 0.30 to 251.74 ± 0.28 Ma. Single zircon U-Pb CA-TIMS analyses of detrital zircons from sandstones located only a few meters beneath the top of the Quartermaster Formation yield a range of dates from Mesoproterozoic (1418 Ma) to Middle Triassic (244.5 Ma; Anisian), the latter of which is interpreted as a maximum depositional age, which is no older than Anisian, thus indicating the Permian-Triassic boundary to lie somewhere within the lower Quartermaster Formation/upper Whitehorse Group succession. Stable carbon isotope data from 180 samples of early-burial dolomicrite cements preserve a chemostratigraphic signal that is similar among sections, with a large ∼−8‰ negative isotope excursion ∼20 m beneath the Whitehorse Group-Quartermaster Formation boundary. This large negative carbon isotope excursion is interpreted to be the same excursion associated with the end-Permian extinction and this is in concert with the new high precision radioisotopic age data presented and the fact that the excursion lies within a normal polarity stratigraphic magnetozone. Dolomite cement δ13C values remain less negative (between about −5 and −8 permil) into the lower part of the Quartermaster Formation before becoming more positive toward the top of the section. This long interval of negative δ13C values in the Quartermaster Formation is interpreted to represent the earliest Triassic (Induan) inception of biotic and ecosystem “recovery.” Oxygen isotope values of dolomicrite cements show a progressive trend toward more positive values through the boundary interval, suggesting substantially warmer conditions around the end-Permian extinction event and a trend toward cooler conditions after the earliest Triassic. Our observations on these strata show that the paleoenvironment and paleoclimate across the Permian-Triassic boundary in western, sub-equatorial Pangea was characterized by depositional systems that were not conducive to plant preservation.

BackgroundEmerging evidence suggests that individuals use mHealth apps in multiple disjointed ways in the real-world—individuals, for example, may engage, take breaks, and re-engage with these apps. To our knowledge, very few studies have adopted this ‘multiple-live’ perspective to analyze long-term usage of a physical activity (PA) app. This study aimed to examine the duration of use, as well as the frequency, length, and timing of streaks (uninterrupted periods of use) and breaks (uninterrupted periods of non-use) within a popular commercial PA app called Carrot Rewards over 12 months. We also examined sociodemographic correlates of usage.MethodThis retrospective observational study analyzed data from 41,207 Carrot Rewards users participating in the “Steps” walking program from June/July 2016 to June/July 2017. We measured four usage indicators: duration of use, frequency and length of streaks and breaks, time to first break, and time to resume second streak. We also extracted information regarding participants' age, gender, province, and proxy indicators of socioeconomic status derived from census data. We used descriptive statistics to summarize usage patterns, Kaplan-Meier curves to illustrate the time to first break and time to resume second streak. We used linear regressions and Cox Proportional Hazard regression models to examine sociodemographic correlates of usage.ResultsOver 60% of the participants used Carrot Rewards for ≥6 months and 29% used it for 12 months (mean = 32.59 ± 18.435 weeks). The frequency of streaks and breaks ranged from 1 to 9 (mean = 1.61 ± 1.04 times). The mean streak and break length were 20.22 ± 18.26 and 16.14 ± 15.74 weeks, respectively. The median time to first break was 18 weeks across gender groups and provinces; the median time for participants to resume the second streak was between 12 and 32 weeks. Being female, older, and living in a community with greater post-secondary education levels were associated with increased usage.ConclusionThis study provides empirical evidence that long-term mHealth app usage is possible. In this context, it was common for users to take breaks and re-engage with Carrot Rewards. When designing and evaluating PA apps, therefore, interventionists should consider the 'multiple-lives' perspective described here, as well as the impact of gender and age.

Ethical frameworks are the foundation for any research with humans or nonhuman animals. Human research is guided by overarching international ethical principles, such as those defined in the Helsinki Declaration by the World Medical Association. However, for nonhuman animal research, because there are several sets of ethical principles and national frameworks, it is commonly thought that there is substantial variability in animal research approaches internationally and a lack of an animal research 'Helsinki Declaration', or the basis for one. We first overview several prominent sets of ethical principles, including the 3Rs, 3Ss, 3Vs, 4Fs and 6Ps. Then using the 3Rs principles, originally proposed by Russell & Burch, we critically assess them, asking if they can be Replaced, Reduced or Refined. We find that the 3Rs principles have survived several replacement challenges, and the different sets of principles (3Ss, 3Vs, 4Fs and 6Ps) are complementary, a natural refinement of the 3Rs and are ripe for integration into a unified set of principles, as proposed here. We also overview international frameworks and documents, many of which incorporate the 3Rs, including the Basel Declaration on animal research. Finally, we propose that the available animal research guidance documents across countries can be consolidated, to provide a similar structure as seen in the Helsinki Declaration, potentially as part of an amended Basel Declaration on animal research. In summary, we observe substantially greater agreement on and the possibility for unification of the sets of ethical principles and documents that can guide animal research internationally.

We have designed and implemented an experimental module in the 2014 Health and Retirement Study to measure older persons' willingness to defer claiming of Social Security benefits. Under the current system’ status quo where delaying claiming boosts eventual benefits, we show that 46% of the respondents would delay claiming and work longer. If respondents were instead offered an actuarially fair lump sum payment instead of higher lifelong benefits, about 56% indicate they would delay claiming. Without a work requirement, the average amount needed to induce delayed claiming is only $60,400, while when part-time work is stipulated, the amount is slightly higher, $66,700. This small difference implies a low utility value of leisure foregone, of under 20% of average household income.

INTRODUCTION: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children

Science engagement can be a daunting prospect. This is especially true for scientists whose work involves animal models, and particularly nonhuman primates. Here, we show that openly explaining our rationale for our neuroscience work involving nonhuman primates — and the legal and ethical regulations that govern animal experimentation — increased public support and understanding, which is crucial for this essential research to continue.

Literature-based discovery (LBD) summarizes information and generates insight from large text corpuses. The SemNet framework utilizes a large heterogeneous information network or “knowledge graph” of nodes and edges to compute relatedness and rank concepts pertinent to a user-specified target. SemNet provides a way to perform multi-factorial and multi-scalar analysis of complex disease etiology and therapeutic identification using the 33+ million articles in PubMed. The present work improves the efficacy and efficiency of LBD for end users by augmenting SemNet to create SemNet 2.0. A custom Python data structure replaced reliance on Neo4j to improve knowledge graph query times by several orders of magnitude. Additionally, two randomized algorithms were built to optimize the HeteSim metric calculation for computing metapath similarity. The unsupervised learning algorithm for rank aggregation (ULARA), which ranks concepts with respect to the user-specified target, was reconstructed using derived mathematical proofs of correctness and probabilistic performance guarantees for optimization. The upgraded ULARA is generalizable to other rank aggregation problems outside of SemNet. In summary, SemNet 2.0 is a comprehensive open-source software for significantly faster, more effective, and user-friendly means of automated biomedical LBD. An example case is performed to rank relationships between Alzheimer’s disease and metabolic co-morbidities.

We test whether probability weighting affects household portfolio choice in a representative survey. On average, people display inverse-S-shaped probability weighting, overweighting low probability events. As theory predicts, probability weighting is positively associated with portfolio underdiversification and significant Sharpe ratio losses. Analyzing respondents’ individual stock holdings, we find higher probability weighting is associated with owning lottery-type stocks and positively skewed equity portfolios. People with higher probability weighting are less likely to own mutual funds and more likely to either avoid equities or hold individual stocks. We are the first to empirically link individuals’ elicited probability weighting and real-world decisions under risk.

Human activity causes major changes in natural landscapes via introduction of non-native species, development on natural habitat, and alteration of local weather patterns. These factors contribute to global change and may interact to affect local populations of plants and animals. We studied a viable, non-native lizard population (Anolis sagrei) in southeast Alabama, USA that has depended upon thermal conditions inside a greenhouse nursery during the winter for at least 10 years. Using Capture-Mark-Recapture surveys, we compared population parameters and movement patterns of this introduced A. sagrei population to a native lizard population (Sceloporus undulatus) that also inhabits our study site. The population size of both species fluctuated over time, but that of A. sagrei was considerably larger than S. undulatus. Anolis sagrei was relatively philopatric and confined within the greenhouse and its immediate vicinity, whereas the S. undulatus population extended into the surrounding forest habitat. The thermal landscape within the greenhouse was substantially altered after the roof was removed due to winds from a tropical storm. Indeed, temperatures of all microhabitats commonly used by lizards frequently dropped below the critical thermal minimum for A. sagrei and below freezing during winter. Post-winter surveys revealed that no A. sagrei individuals survived, indicating that the temperature change in the greenhouse resulted in extinction. The native S. undulatus population, however, was still present after winter. Our study provides rare documentation of an extinction of an established introduced population and illustrates the role that human-made structures and natural weather events play in the process of biological invasion.

Optimal ex vivo expansion protocols of tumor-specific T cells followed by adoptive cell therapy must yield T cells able to home to tumors and effectively kill them. Our previous study demonstrated ex vivo activation in the presence of IL-12–induced optimal CD8+ T cell expansion and melanoma regression; however, adverse side effects, including autoimmunity, can occur. This may be due to transfer of high-avidity self-specific T cells. In this study, we compared mouse low- and high-avidity T cells targeting the tumor Ag tyrosinase-related protein 2 (TRP2). Not surprisingly, high-avidity T cells provide superior tumor control, yet low-avidity T cells can promote tumor regression. The addition of IL-12 during in vitro expansion boosts low-avidity T cell responsiveness, tumor regression, and prevents T cell exhaustion. In this study, we demonstrate that IL-12–primed T cells are resistant to PD-1/PD-L1–mediated suppression and retain effector function. Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while simultaneously increasing KLRG1. Using intravital imaging, we also determined that high-avidity T cells have sustained contacts with intratumoral dendritic cells and tumor targets compared with low-avidity T cells. However, with Ag overexpression, this defect is overcome, and low-avidity T cells control tumor growth. Taken together, these data illustrate that low-avidity T cells can be therapeutically beneficial if cocultured with IL-12 cytokine during in vitro expansion and highly effective in vivo if Ag is not limiting. Clinically, low-avidity T cells provide a safer alternative to high-avidity, TCR-engineered T cells, as IL-12–primed, low-avidity T cells cause less autoimmune vitiligo.

Circadian rhythms are endogenous and entrainable daily patterns of physiology and behavior. Molecular mechanisms underlie circadian rhythms, characterized by an ~24-h pattern of gene expression of core clock genes. Although it has long been known that breathing exhibits circadian rhythms, little is known concerning clock gene expression in any element of the neuromuscular system controlling breathing. Furthermore, we know little concerning gene expression necessary for specific respiratory functions, such as phrenic motor plasticity. Thus, we tested the hypotheses that transcripts for clock genes ( Bmal1, Clock, Per1, and Per2) and molecules necessary for phrenic motor plasticity ( Htr2a, Htr2b, Bdnf, and Ntrk2) oscillate in regions critical for phrenic/diaphragm motor function via RT-PCR. Tissues were collected from male Sprague-Dawley rats entrained to a 12-h light-dark cycle at 4 zeitgeber times (ZT; n = 8 rats/group): ZT5, ZT11, ZT17, and ZT23; ZT0 = lights on. Here, we demonstrate that 1) circadian clock genes ( Bmal1, Clock, Per1, and Per2) oscillate in regions critical for phrenic/diaphragm function, including the caudal medulla, ventral C3–C5 cervical spinal cord, and diaphragm; 2) the clock protein BMAL1 is localized within CtB-labeled phrenic motor neurons; 3) genes necessary for intermittent hypoxia-induced phrenic/diaphragm motor plasticity ( Htr2b and Bdnf) oscillate in the caudal medulla and ventral C3–C5 spinal cord; and 4) there is higher intensity of immunofluorescent BDNF protein within phrenic motor neurons at ZT23 compared with ZT11 ( n = 11 rats/group). These results suggest local circadian clocks exist in the phrenic motor system and confirm the potential for local circadian regulation of neuroplasticity and other elements of the neural network controlling breathing.

Eating disorders (EDs) and overweight/obesity (OW/OB) have a significant impact on veterans. This review highlights current research on EDs and OW/OB in this population. Prevalence estimates for both EDs and OW/OB among veterans remain consistent with and possibly higher than those in the general population. Both diagnoses share multiple risk factors, including trauma history, and mental health comorbidities. Although weight loss treatments have been fairly well studied among veteran samples, there are no published investigations on psychotherapies for EDs in this population. The Veterans Healthcare Administration is working to train providers in ED treatments. VHA treatments for OW/OB show some benefits and areas for improvement. Areas for future research include structured assessments for EDs and disordered eating behaviors in veterans to clarify prevalence estimates. There is a need for interventions that consider common mechanisms for ED and OW/OB, and there is a need for more research on the associations between different types of trauma and ED/OW/OB in veterans.

Acute intermittent hypoxia (AIH) elicits phrenic motor plasticity via multiple distinct cellular mechanisms. With moderate AIH, phrenic motor facilitation (pMF) requires Gq protein-coupled serotonin type 2 receptor activation, ERK MAP kinase activity, and new synthesis of brain-derived neurotrophic factor. In contrast, severe AIH elicits pMF by an adenosine-dependent mechanism that requires exchange protein activated by cAMP, Akt, and mammalian target of rapamycin (mTOR) activity, followed by new tyrosine receptor kinase B protein synthesis; this same pathway is also initiated by Gs protein-coupled serotonin 7 receptors (5-HT7). Because the metabolic sensor AMP-activated protein kinase (AMPK) inhibits mTOR-dependent protein synthesis, and mTOR signaling is necessary for 5-HT7 but not 5-HT2 receptor-induced pMF, we hypothesized that spinal AMPK activity differentially regulates pMF elicited by these distinct receptor subtypes. Serotonin type 2A receptor [5-HT2A; (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride] or 5-HT7 (AS-19) receptor agonists were administered intrathecally at C4 (3 injections, 5-min intervals) while recording integrated phrenic nerve activity in anesthetized, vagotomized, paralyzed, and ventilated rats. Consistent with our hypothesis, spinal AMPK activation with 2-deoxyglucose or metformin blocked 5-HT7, but not 5-HT2A receptor-induced pMF; in both cases, pMF inhibition was reversed by spinal administration of the AMPK inhibitor compound C. Thus, AMPK differentially regulates cellular mechanisms of serotonin-induced phrenic motor plasticity. NEW & NOTEWORTHY Spinal AMP-activated protein kinase (AMPK) overactivity, induced by local 2-deoxyglucose or metformin administration, constrains serotonin 7 (5-HT7) receptor-induced (but not serotonin type 2A receptor-induced) respiratory motor facilitation, indicating that metabolic challenges might regulate specific forms of respiratory motor plasticity. Pharmacological blockade of spinal AMPK activity restores 5-HT7 receptor-induced respiratory motor facilitation in the presence of either 2-deoxyglucose or metformin, showing that AMPK is an important regulator of 5-HT7 receptor-induced respiratory motor plasticity.