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Background: Efficient utilisation of allied health workforce may help address the predicted shortfall of 18 million health workers estimated by 2030. Knowledge about allied health professionals' attrition, or intention to leave, and factors influencing attrition can assist in developing evidence-informed strategies to mitigate this issue. The review aimed to map attrition and attrition intention rates, and its attributing factors for allied health professions worldwide. Methods: Adhering to the PRISMA-ScR guidelines, a comprehensive search was conducted across academic databases (PsycINFO, MEDLINE, Embase, Emcare, CINAHL, Scopus, and the Cochrane Library database) and grey literature (Google, Google Scholar, organisational websites). Two reviewers independently undertook a two-stage screening process along with data extraction using customised data extraction forms. A narrative synthesis was used to synthesise the data. Results: Thirty-two studies published between 1990 and 2024 were included. Attrition rates ranged from 0.5% to 41% across allied health disciplines. Pharmacists demonstrated the lowest attrition rates, while audiologists reported the highest. Radiographers reported the lowest intent to leave at 7.6%, while occupational therapists showed highest intent to leave, ranging from 10.7% to 74.1%. The analysis revealed three recurring themes contributing to attrition: profession-centric factors (e.g., career progression, job satisfaction, support, and professional growth), systemic-centric factors (e.g., compensation, staffing challenges, clinical practices, patient care, workload), and individual-centric factors (e.g., recognition, the need for change, and burnout). Conclusion: Attrition in allied health remains a significant challenge. Addressing this issue requires a systemic, nuanced, and evidence-based approach, given the complex, interlinked, and multifaceted factors contributing to attrition. The younger workforce, characterized by changing generational values, necessitates innovative thinking, intersectoral collaboration, and the potential for co-created solutions with, for, and by the allied health workforce. [ABSTRACT FROM AUTHOR]

Host microbial communities (hereafter, the 'microbiome') are recognized as an important aspect of host health and are gaining attention as a useful biomarker to understand the ecology and demographics of wildlife populations. Several studies indicate that the microbiome may contribute to the adaptive capacity of animals to changing environments associated with increasing habitat fragmentation and rapid climate change. To this end, we investigated the gut microbiome of pronghorn (Antilocapra americana), an iconic species in an environment that is undergoing both climatic and anthropogenic change. The bacterial composition of the pronghorn gut microbiome has yet to be described in the literature, and thus our study provides important baseline information about this species. We used 16S rRNA amplicon sequencing of fecal samples to characterize the gut microbiome of pronghorn—a facultative sagebrush (Artemisia spp.) specialist in many regions where they occur in western North America. We collected fecal pellets from 159 captured female pronghorn from four herds in the Red Desert of Wyoming during winters of 2013 and 2014. We found small, but significant differences in diversity of the gut microbiome relative to study area, capture period, and body fat measurements. In addition, we found a difference in gut microbiome composition in pronghorn across two regions separated by Interstate 80. Results indicated that the fecal microbiome may be a potential biomarker for the spatial ecology of free-ranging ungulates. The core gut microbiome of these animals—including bacteria in the phyla Firmicutes (now Bacillota) and Bacteroidota—remained relatively stable across populations and biological metrics. These findings provide a baseline for the gut microbiome of pronghorn that could potentially be used as a target in monitoring health and population structure of pronghorn relative to habitat fragmentation, climate change, and management practices. [ABSTRACT FROM AUTHOR]

Introduction: It is well established that the actions and behaviour of dementia care workers are fundamental to the wellbeing of the people they care for. Not only do they deal with basic healthcare needs, but they also perform a vital psycho-social function by providing–through their regular presence–an underlying continuity for residents. This has been shown to improve well-being, particularly for those in the advanced stages of dementia. It has also been suggested that there are additional psycho-social benefits of such contact which can directly influence the need for anti-psychotic medication. However, unlike most other healthcare and medical settings, the specialised and often difficult interactions that dementia care workers handle every day have not yet been the subject of detailed micro-level analysis. This is particularly significant because much of the impact that care-workers have relates to the way in which they interact with the people they care for. Not having a clear understanding of how their interactions 'work' at the micro-level–particularly ones that are specific to dementia care settings, and that care workers report to be difficult or challenging–means that any training interventions that are developed may not resonate with their real-world experience, and ultimately run the risk of failing. This video-based observational study aims to provide a detailed micro-exploration of problematic and challenging interactions involving care-workers and people living with dementia. Setting and methods: The study is based in the UK and will involve up to 20 dementia care staff and 60 people living with dementia. Fieldwork will be conducted in 5 dementia care home and community-based dementia day care settings using naturalistic observational methods (primarily video-ethnography). Data will be analysed using Conversation Analysis (CA). [ABSTRACT FROM AUTHOR]

Background: Recognised as essential for high-quality dementia service, person-centred care aims to understand and respect the unique needs of each individual. Self-experience practices may offer caregivers an opportunity to acquire knowledge, empathy, and skills related to person-centred care, especially through recreating experiences similar to dementia. Given the need to enhance the understanding of self-experience practices in dementia care, a more comprehensive investigation of these training interventions for (future) caregivers is needed. Methods: We conducted a scoping review to map the evidence on the use of self-experience practices in dementia training. We systematically searched Cochrane Library, MEDLINE via PubMed, CINAHL, and Web of Science. We also searched for grey literature, as well as registry entries, and conducted backward citation tracking of included reviews. We analysed data on intervention characteristics, factors influencing the implementation, and learning outcomes based on Kirkpatrick's model. Results: We included 44 reports across 30 intervention programmes. The majority of reports (91%) were published from 2016 onwards, with 32% originating from the USA and 25% from the UK. We identified passive, interactive, immersive, and multicomponent self-experience interventions in dementia education and training. Learning outcomes based on Kirkpatrick's model were fairly distributed across all identified modalities. Both consumers and providers emphasised aspects related to the development and implementation of practices, particularly organisational-related considerations such as temporal and spatial planning of trainings. Conclusions: Our review highlights diverse interventions incorporating self-experience practices, with an increasing role for technological tools. While self-experience interventions engage participants, the impact on individuals with dementia and organisational levels remain largely unreported. Our overview, informed by current literature, underscores unique considerations and challenges associated with dementia-related self-experience practices. Implementing and evaluating complex training interventions using self-experience practices should consider ethical aspects. Trial registration: Registry: Registered within the Open Science Framework (available at https://osf.io/fycxa/). [ABSTRACT FROM AUTHOR]

College students with more emotional support experience lower levels of anxiety and other psychosocial and behavioral problems. During the COVID-19 pandemic, the emotional well-being of college students was additionally challenged by an abrupt shift to distance learning followed by a return to face-to-face classes. In this exploratory study, we compared the levels of perceived emotional support and anxiety among incoming first-year undergraduate students, prior to starting classes, which included different learning modes in five semesters of instruction from 2021–2023 (three distance semesters and two face-to-face semesters). Data from 8659 undergraduate students were extracted from a Mexican state university database, corresponding to students' responses collected during new student orientation week. Participants were students in the arts and humanities (9.7%), social and legal sciences (38%), life and health sciences (28.9%), and engineering and architecture (23.4%). Anxiety levels were measured with the GAD-7 scale, and emotional support was measured using a subscale of the PERACT-R (To go through with resilience) inventory. Comparisons of emotional support and anxiety scores among semesters revealed highly significant differences with small effect sizes. Anxiety levels increased significantly with mean average of 6.65 SD(5.52) during the baseline measure to the highest in 2022–2 to 7.53 SD(5.3) and Emotional Support decreased systematically each semester from baseline mean = 8.03 SD(2.0) to the lowest 7.52 SD(1.8) in 2022–2. The results show that a return to face-to-face classes was associated with increased anxiety levels, whereas levels of emotional support systematically decreased across the five semesters. MANOVA analysis revealed significant differences in anxiety and emotional support scores between semesters, with peaks during the learning mode semester that students returned to face-to-face classes after distance learning even after adjusting for gender. Given that the effect of emotional support on anxiety may be related to success in future educational and professional activities, it is important to develop interventions to restore and increase college students' emotional support levels and develop anxiety management strategies. [ABSTRACT FROM AUTHOR]

Purpose: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing. Design: Pilot study using ex vivo human eyes. Methods: Non-vitrectomized, human eyes from nine donors 75–91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors. Results: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 μL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx. Conclusions: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future. [ABSTRACT FROM AUTHOR]

A nanoscale nonvolatile bidirectional reconfigurable field effect transistor (NBRFET) based on source /drain (S/D) self programmable floating gates is proposed. Comparing to the conventional reconfigurable field effect transistor (RFET) which requires two independently powered gates, the proposed NBRFET requires only one control gate. Beside, S/D floating gates are introduced. Reconfigurable function is realized by programming different types of charges into the S/D floating gates through biasing the gate at a positive or negative high voltage. The effective voltages of the S/D floating gates are determined jointly by the quantity of the charge stored in the S/D floating gates and the gate voltage. In addition, the charge stored in the floating gate has an effect of reducing the energy band bending near the source/drain regions when the gate is reversely biased, thereafter, the band to band tunneling (BTBT) leakage current can be largely decreased. The scale of the proposed NBRFET can be reduced to nanometer level. The device performances such as the transfer and output characteristics are verified by device simulation, which proves that the proposed NBRFET has very good performance in the nanometer scale. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the common cancers and the leading cause of death. Tremendous caregiving burden of informal caregivers of lung cancer causes psychological disorders, such as anxiety and depression. Interventions for informal caregivers of patients with lung cancer to improve their psychological health, which ultimately leads to patients' positive health outcomes, are crucial. A systematic review and meta-analysis was conducted to: 1) evaluate the effect of non-pharmacological interventions on the outcomes of depression and anxiety for lung cancer patients' informal caregivers; and 2) compare the effects of interventions with differing characteristics (i.e. intervention types, mode of contact, and group versus individual delivery). Methods: Four databases were searched to identify relevant studies. Inclusion criteria for the articles were peer-reviewed non-pharmacological intervention studies on depression and anxiety in lung cancer patients' informal caregivers published between January 2010 and April 2022. Systematic review procedures were followed. Data analysis of related studies was conducted using the Review Manager Version 5.4 software. Intervention effect sizes and studies' heterogeneity were calculated. Results: Eight studies from our search were eligible for inclusion. Regarding total effect for the caregivers' levels of anxiety and depression, results revealed evidence for significant moderate effects of intervention on anxiety (SMD -0.44; 95% CI, -0.67, -0.21; p = 0.0002) and depression (SMD -0.46; 95% CI, -0.74, -0.18; p = 0.001). Subgroup analyses for both anxiety and depression of informal caregivers revealed moderate to high significant effects for specific intervention types (cognitive behavioral and mindfulness combined with psycho-education interventions), mode of contact (telephone-based interventions), and group versus individual delivery. Conclusion: This review provides evidence that cognitive behavioral and mindfulness-based, telephone-based, individual or group-based interventions were effective for informal caregivers of lung cancer patients. Further research is needed to develop the most effective intervention contents and delivery methods across informal caregivers with larger sample size in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Objective: Japan introduced a financial incentive scheme in April 2016 to improve hospital-based dementia care, but its effectiveness remains unclear. This study aimed to investigate the scheme's impact on medical and long-term care (LTC) expenditures, as well as on changes in care needs levels and daily living independence levels among older persons one year after hospital discharge. Methods: We linked medical and LTC claims databases, and retrospectively identified patients who received LTC needs certification and daily living independence assessments in Fukuoka, Japan. Case patients (received care under the new scheme) were those admitted from April 2016 to March 2018, and control patients were those admitted from April 2014 to March 2016 (before the scheme was implemented). Through propensity score matching, we identified 260 case patients and 260 control patients, and compared using t-tests, and chi-square tests. Results: The analyses found no significant differences between the case and control groups in medical expenditure (US$26,685 vs US$24,823, P = 0.37), LTC expenditure (US$16,870 vs US$14,374, P = 0.08), daily living independence level changes (26.5% vs 20.4%, P = 0.12), or care needs level changes (36.9% vs 30%, P = 0.11). Conclusions: The financial incentive scheme for dementia care did not demonstrate any beneficial effects on patients' healthcare expenditures or health conditions. Further studies are needed to examine the scheme's long-term effects. [ABSTRACT FROM AUTHOR]

Once numbering in the tens of millions, bison (Bison bison) have faced a broad range of challenges over the past century, including genetic impacts from the population bottleneck in the 1800s, and significant loss and fragmentation of habitat resulting in little opportunity for population growth on remaining small, geographically isolated reserves. To identify best practices for bison stewardship against this backdrop, managers must understand the genetic composition of existing conservation herds. This study characterized 14 plains bison (Bison bison bison) herds managed by the U.S. Department of Interior and Parks Canada Agency based on complete mtDNA control region sequences. Among 209 bison, we detected 11 major mtDNA control region haplotypes based on nucleotide substitutions and 23 sub-haplotypes where indels are considered. We determined matrilineal relationships between the herds and compared our genetic findings to historic records. The recent common ancestry of modern bison deriving from small, scattered groups combined with gene flow through foundation and translocation events between herds during the last 100 years, is reflected in Fst value (0.21), haplotype (0.48 ± 0.04) and nucleotide (0.004 ± 0.002) diversities, and mean number of pairwise differences (3.38 ± 1.74). Genetic diversity was distributed unevenly among herds, with 21.41% of genetic variation observed between herds. Median joining network, together with trends in the Tajima's D and Fs tests, revealed two patterns in the recent evolution of mtDNA sequences in bison: mutational process has generated diversity with a Hap 1 haplotype epicenter, and missed mtDNA haplotypes exist in the network due to bottleneck, loss through management practices, or incomplete sampling of specimens across conservation herds. This work significantly expands characterization of the genetic diversity among bison conservation herds, providing additional decision support for managers considering restoring gene flow to achieve long-term species viability. [ABSTRACT FROM AUTHOR]

Microalgae and cyanobacteria are considered as important model organisms to investigate the biology of photosynthesis; moreover, they are valuable sources of biomolecules for several biotechnological applications. Understanding the species-specific traits of photosynthetic electron transport is extremely important, because it contributes to the regulation of ATP/NADPH ratio, which has direct/indirect links to carbon fixation and other metabolic pathways and thus overall growth and biomass production. In the present work, a cuvette-based setup is developed, in which a combination of measurements of dissolved oxygen, pH, chlorophyll fluorescence and NADPH kinetics can be performed without disturbing the physiological status of the sample. The suitability of the system is demonstrated using a model cyanobacterium Synechocystis sp. PCC6803, as well as biofuel-candidate microalgae species, such as Chlorella sorokiniana, Dunaliella salina and Nannochloropsis limnetica undergoing inorganic carbon (Ci) limitation. Inorganic carbon limitation, induced by photosynthetic Ci uptake under continuous illumination, caused a decrease in the effective quantum yield of PSII (Y(II)) and loss of oxygen-evolving capacity in all species investigated here; these effects were largely recovered by the addition of NaHCO3. Detailed analysis of the dark-light and light-dark transitions of NADPH production/uptake and changes in chlorophyll fluorescence kinetics revealed species- and condition-specific responses. These responses indicate that the impact of decreased Calvin-Benson cycle activity on photosynthetic electron transport pathways involving several sections of the electron transport chain (such as electron transfer via the QA-QB-plastoquinone pool, the redox state of the plastoquinone pool) can be analyzed with high sensitivity in a comparative manner. Therefore, the integrated system presented here can be applied for screening for specific traits in several significant species at different stages of inorganic carbon limitation, a condition that strongly impacts primary productivity. [ABSTRACT FROM AUTHOR]

Multiple arguments for or against the presence of 'urban' settlements in the Early Bronze Age of the southern Levant have identified the need to compare these settlements against their rural hinterlands through multiple lines of evidence. This meta-analysis of zooarchaeological data from the region compares and identifies patterns of animal production, provisioning and consumption between the supposed "urban" and rural sites of the southern Levant from the Early Bronze (EB) against the (more widely recognised urban) Middle Bronze (MB) Ages. It also identifies distinct and regionally specific patterns in animal production and consumption that can be detected between urban and rural sites of the southern Levant. The taxonomic and age profiles from EB Ia and Ib sites do not demonstrate any urban versus rural differentiation patterning, even though fortifications appear in the EB Ib. Beginning in the EB II and clearly visible in the EB III, there is differentiation between rural and urban sites in the taxonomic and age proportions. Differentiation is repeated in the MB II. The clear differentiation between "urban" and rural zooarchaeological assemblages from the EB II-III and MB suggest that rural sites are provisioning the larger fortified settlements. This pattern indicates that these sites are indeed urban in nature, and these societies are organized at the state-level. From the EB II onwards, there is a clear bias in the large centres towards the consumption of cattle and of subadult sheep and goats with a corresponding bias in smaller rural sites towards the consumption of adult sheep and goats and a reduced presence of cattle. After the emergence of this differential pattern, it disappears with the decline in social complexity at the end of the Early Bronze Age, only to come 'back again' with the re-emergence of urban settlement systems in the Middle Bronze Age. [ABSTRACT FROM AUTHOR]

Introduction: The number of cancer survivors is projected to increase to 22.1 million by 2030. Late effects incorporate the full domains of cancer survivorship (e.g., physiologic, psychosocial, economic). They are numerous, complex, and potentially alter the life trajectories of cancer survivors. Currently, research is missing on the impact of late effects (e.g., cardiomyopathy, fertility, lymphedema, anxiety) on cancer survivors. Objective: The goal of this study is to present a systematic review of existing instruments for identifying, diagnosing, and managing late effects within cancer survivors. Methods: Using PRISMA guidelines, a systematic search was conducted using the electronic databases of PubMed and Web of Science to identify relevant papers. Articles considered eligible for this review met the following criteria: 1) written in English, 2) published until September 30, 2019, and 3) containing instruments with questions on late effects. Hypothesis, study design, study sample, questionnaire domains, details of late effects, results, conclusions, and advantages/disadvantages of each article were assessed using a modified version of the NHLBI quality assessment tool. Results: An exhaustive literature review revealed 576 publications in PubMed, 628 in Web of Science, and 260 from additional sources. After removing duplicates, articles without late-effects questionnaires, and publications using identical questionnaires, 11 studies fulfilled the eligibility criteria. Study quality assessment was measured on a scale of 0–6 (0 = poor quality; 6 = highest quality). Only one study was rated with a score of 5 (Rocque). Conclusions: Taken in totality, none of the studies adequately addressed the prevalence, etiology, characteristics, management, and prevention of late effects. There is currently no comprehensive questionnaire that captures all of the relevant details of late effects across the cancer survivorship continuum nor that tracks the interrelatedness of multiple late effects. Hence, it is difficult to identify, diagnose, manage, and ultimately prevent late effects. [ABSTRACT FROM AUTHOR]

Quantitative models describing environmentally-mediated disease transmission rarely focus on the independent contribution of recruitment and the environment on the force of infection driving outbreaks. In this study we attempt to investigate the interaction between external factors and host’s population dynamics in determining the outbreaks of some indirectly transmitted diseases. We first built deterministic and stochastic compartmental models based on anthrax which were parameterized using information from literature and complemented with field observations. Our force of infection function was derived modeling the number of successful transmission encounters as a pure birth process that depends on the pathogen’s dispersion effort. After accounting for individual heterogeneity in pathogen’s dispersion effort, we allowed the force of infection to vary seasonally according to external factors recreating a scenario in which disease transmission increases in response to an environmental variable. Using simulations we demonstrate that anthrax disease dynamics in mid-latitude grasslands is decoupled from hosts population dynamics. When seasonal forcing was ignored, outbreaks matched hosts reproductive events, a scenario that is not realistic in nature. Instead, when allowing the force of infection to vary seasonally, outbreaks were only present in years were environmental variables were appropriate for the outbreaks to develop. We used the stochastic formulation of the force of infection to derive R0 under scenarios with different assumptions. The derivation of R0 allowed us to conclude that during epizootic years, pathogen contribution to disease persistence is nearly independent of dispersion. In endemic years, only pathogens with high dispersion significantly prevent disease extinction. Finally, we used our model in a maximum likelihood framework to estimate the parameters that determined a significant anthrax outbreak in Montana in 2008. Our study highlights the importance of the environment in determining anthrax outbreak intensity and could be useful to predict future events that could result in significant wildlife and domestic livestock losses. [ABSTRACT FROM AUTHOR]

Secondary cavity-nesting birds depend on tree cavities for nesting and roosting, but many studies of these birds are conducted using nest boxes. Implementation of effective conservation strategies for cavity-nesting species such as nest-site supplementation requires careful comparisons of fecundity and other vital rates for birds using both natural and artificial nest site types. We compared breeding phenology, clutch and brood sizes, and fledging success of Tree Swallows (Tachycineta bicolor) nesting in tree cavities and nest boxes during 2001–2003 in British Columbia, Canada. Swallows using nest boxes initiated egg-laying and hatched young at approximately the same time as those in tree cavities (2 June, 23 June, respectively). Female Tree Swallows in boxes laid larger clutches (5.9 ± 0.9 eggs, N = 76) than those in tree cavities (4.2 ± 1.6 eggs, N = 67). The mean number of nestlings hatched was greater in nest boxes (5.2 ± 1.1 nestlings, N = 67) than in tree cavities (2.6 ± 2.0 nestlings, N = 58). Pairs in boxes were over twice as successful in producing fledglings (93.4%; 57 of 61 pairs fledged > 1 young) than those in tree cavities (35.8%; 19 of 53 pairs). Of those successful nests, pairs nesting in boxes fledged 5.1 ± 1.1 young (N = 57), whereas those in tree cavities fledged 3.5 ± 1.2 young (N = 18). Because cavities in nest boxes averaged 60% larger in volume and 1.8 cm wider internally than tree cavities, we suggest that increased reproductive output was correlated with boxes enabling a larger clutch size. In previous research, we found that Tree Swallows were a poor competitor with other cavity-nesting passerines for tree cavities. The addition of nest boxes may serve as an effective way to supplement local reproduction for secondary cavity-nesting bird populations by reducing competition for limited nest sites. This is especially true in regions where the availability of natural nesting sites is highly variable, and where species compete with many other cavity-nesting passerines using a similar ecological niche and nesting cavities. [ABSTRACT FROM AUTHOR]

Frequently, port scans are early indicators of more serious attacks. Unfortunately, the detection of slow port scans in company networks is challenging due to the massive amount of network data. This paper proposes an innovative approach for preprocessing flow-based data which is specifically tailored to the detection of slow port scans. The preprocessing chain generates new objects based on flow-based data aggregated over time windows while taking domain knowledge as well as additional knowledge about the network structure into account. The computed objects are used as input for the further analysis. Based on these objects, we propose two different approaches for detection of slow port scans. One approach is unsupervised and uses sequential hypothesis testing whereas the other approach is supervised and uses classification algorithms. We compare both approaches with existing port scan detection algorithms on the flow-based CIDDS-001 data set. Experiments indicate that the proposed approaches achieve better detection rates and exhibit less false alarms than similar algorithms. [ABSTRACT FROM AUTHOR]

In order to improve animal welfare it is recommended that dairy farmers move calving cows from the herd to individual pens when calving is imminent. However, the practicality of moving cows has proven a challenge and may lead to disturbance of the cows rather than easing the process of calving. One solution may be to allow the cow to seek isolation prior to calving. This study examined whether pre-parturient dairy cows will isolate in an individual calving pen placed in a group calving setting and whether a closing gate in this individual calving pen will cause more cows to isolate prior to calving. Danish Holstein cows (n = 66) were housed in groups of six in a group pen with access to six individual calving pens connected to the group area. Cows were trained to use one of two isolation opportunities i.e. individual calving pens with functional closing gates (n = 35) allowing only one cow access at a time, or individual calving pens with permanently open gates allowing free cow traffic between group area and individual pen (n = 31). The response variables were calving site, calving behaviour and social behaviour. Unexpectedly, a functional gate did not facilitate isolation seeking, perhaps because the cows were not able to combine a learnt response with the motivation to isolate. Dominant cows had the highest chance of calving in an individual calving pen. If an alien calf was present in the group pen or any of the individual pens, cows were less likely to calve in an individual calving pen. Future studies should allow cows easy access to an individual calving pen and explore what motivates pre-parturient cows to seek isolation in order to facilitate voluntary use of individual calving pens. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that autophagy dysfunction is involved in exfoliation syndrome (XFS), a systemic disorder of extracellular elastic matrices that causes a distinct form of human glaucoma. Methods: Fibroblasts derived from tenon tissue discards (TFs) from filtration surgery to relieve intraocular pressure in XFS patients were compared against age-matched TFs derived from surgery in primary open-angle glaucoma (POAG) patients or from strabismus surgery. Differential interference contrast light, and electron microscopy were used to examine structural cell features. Immunocytochemistry was used to visualize LOXL1 and Fibulin-5, lysosomes, endosomes, Golgi, and microtubules. Light scatter, Cyto-IDTM and JC1 flow cytometry were used to measure relative cell size, autophagic flux rate and mitochondrial membrane potential (MMPT), respectively. Enhanced autophagy was induced by serum withdrawal. Results: In culture, XFS-TFs were 1.38-fold larger (by light scatter ratio, p = 0.05), proliferated 42% slower (p = 0.026), and were morphologically distinct in 2D and 3D culture compared to their POAG counterparts. In extended 3D cultures, XFS-TFs accumulated 8–10 times more Fibulin-5 than the POAG-TFs, and upon serum withdrawal, there were marked deficiencies in relocation of endosomes and lysosomes to the perinuclear area. Correspondingly, the XFS-TFs displayed significant accumulation of the autophagasome marker LC3 II (3.9 fold increase compared to POAG levels, p = 0.0001) and autophagic flux rate as measured by Cyto-ID dye was 53% lower in XFS-TFs than in POAG-TFs (p = 0.01), indicating reduced clearance of autophagasomes. Finally the percent of cells with diminished MMPT was 3–8 times larger in the XFS-TFs than in POAG-TFs (p = 0.02). Conclusions: Our results provide for the first time a link between XFS pathology to autophagy dysfunction, a major contributor to multiple age related diseases systemically throughout the body, in the brain and in the retina. A diminished capacity for degradation of denatured protein and aging cellular organelles may underpin the development of extracellular protein aggregates in XFS. [ABSTRACT FROM AUTHOR]

Invasion by exotic grasses is a severe threat to the integrity of grassland ecosystems all over the world. Because grasslands are typically grazed by livestock and wildlife, the invasion is a community process modulated by herbivory. We hypothesized that the invasion of native South American grasslands by Eragrostis plana Nees, an exotic tussock-forming grass from Africa, could be deterred by grazing if grazers switched dietary preferences and included the invasive grass as a large proportion of their diets. Bos taurus (heifers) and Ovis aries (ewes) grazed plots with varying degrees of invasion by E. plana in a replicated manipulative experiment. Animal positions and species grazed were observed every minute in 45-min grazing session. Proportion of bites and steps in and out of E. plana tussocks were measured and used to calculate several indices of selectivity. Both heifers and ewes exhibited increasing probability of grazing E. plana as the proportion of area covered by tussocks increased, but they behaved differently. In agreement with expectations based on the allometry of dietary preferences and morphology, ewes consumed a low proportion of E. plana, except in areas that had more than 90% E. plana cover. Heifers consumed proportionally more E. plana than ewes. Contrary to our hypothesis, herbivores did not exhibit dietary switching towards the invasive grass. Moreover, they exhibited avoidance of the invasive grass and preference for short-statured native species, both of which should tend to enhance invasion. Unless invasive plants are highly palatable to livestock, the effect of grazing to deter the invasion is limited, due to the inherent avoidance of the invasive grass by the main grazers in the ecosystem, particularly sheep. [ABSTRACT FROM AUTHOR]

Wild American plains bison (Bison bison) populations virtually disappeared in the late 1800s, with some remnant animals retained in what would become Yellowstone National Park and on private ranches. Some of these private bison were intentionally crossbred with cattle for commercial purposes. This forced hybridization resulted in both mitochondrial and nuclear introgression of cattle genes into some of the extant bison genome. As the private populations grew, excess animals, along with their history of cattle genetics, provided founders for newly established public bison populations. Of the US public bison herds, only those in Yellowstone and Wind Cave National Parks (YNP and WCNP) appear to be free of detectable levels of cattle introgression. However, a small free-ranging population (~350 animals) exists on public land, along with domestic cattle, in the Henry Mountains (HM) of southern Utah. This isolated bison herd originated from a founder group translocated from YNP in the 1940s. Using genetic samples from 129 individuals, we examined the genetic status of the HM population and found no evidence of mitochondrial or nuclear introgression of cattle genes. This new information confirms it is highly unlikely for free-living bison to crossbreed with cattle, and this disease-free HM bison herd is valuable for the long-term conservation of the species. This bison herd is a subpopulation of the YNP/WCNP/HM metapopulation, within which it can contribute significantly to national efforts to restore the American plains bison to more of its native range. [ABSTRACT FROM AUTHOR]

CD4 T cells are required to fight malaria infection by promoting both phagocytic activity and B cell responses for parasite clearance. In Plasmodium chabaudi infection, one specific CD4 T cell subset generates anti-parasitic IFN-γ and the antibody-promoting cytokine, IL-21. To determine the lineage of these multifunctional T cells, we followed IFN-γ+ effector T cells (Teff) into the memory phase using Ifng-reporter mice. While Ifng+ Teff expanded, the level of the Th1 lineage-determining transcription factor T-bet only peaked briefly. Ifng+ Teff also co-express ICOS, the B cell area homing molecule CXCR5, and other Tfh lineage-associated molecules including Bcl6, the transcription factor required for germinal center (GC) T follicular helper cells (Tfh) differentiation. Because Bcl6 and T-bet co-localize to the nucleus of Ifng+ Teff, we hypothesized that Bcl6 controls the Tfh-like phenotype of Ifng+ Teff cells in P. chabaudi infection. We first transferred Bcl6-deficient T cells into wildtype hosts. Bcl6-deficient T cells did not develop into GC Tfh, but they still generated CXCR5+IFN-γ+IL-21+IL-10+ Teff, suggesting that this predominant population is not of the Tfh-lineage. IL-10 deficient mice, which have increased IFN-γ and T-bet expression, demonstrated expansion of both IFN-γ+IL-21+CXCR5+ cells and IFN-γ+ GC Tfh cells, suggesting a Th1 lineage for the former. In the memory phase, all Ifng+ T cells produced IL-21, but only a small percentage of highly proliferative Ifng+ T cells maintained a T-bethi phenotype. In chronic malaria infection, serum IFN-γ correlates with increased protection, and our observation suggests Ifng+ T cells are maintained by cellular division. In summary, we found that Ifng+ T cells are not strictly Tfh derived during malaria infection. T cells provide the host with a survival advantage when facing this well-equipped pathogen, therefore, understanding the lineage of pivotal T cell players will aid in the rational design of an effective malaria vaccine. [ABSTRACT FROM AUTHOR]

North American bison (Bison bison) are becoming increasingly important to both grassland management and commercial ranching. However, a lack of quantitative data on their diet constrains conservation efforts and the ability to predict bison effects on grasslands. In particular, we know little about the seasonality of the bison diet, the degree to which bison supplement their diet with eudicots, and how changes in diet influence gut microbial communities, all of which play important roles in ungulate performance. To address these knowledge gaps, we quantified seasonal patterns in bison diet and gut microbial community composition for a bison herd in Kansas using DNA sequencing-based analyses of both chloroplast and microbial DNA contained in fecal matter. Across the 11 sampling dates that spanned 166 days, we found that diet shifted continuously over the growing season, allowing bison to take advantage of the seasonal availability of high-protein plant species. Bison consumed more woody shrubs in spring and fall than in summer, when forb and grass intake predominated. In examining gut microbiota, the bacterial phylum Tenericutes shifted significantly in relative abundance over the growing season. This work suggests that North American bison can continuously adjust their diet with a high reliance on non-grasses throughout the year. In addition, we find evidence for seasonal patterns in gut community composition that are likely driven by the observed dietary changes. [ABSTRACT FROM AUTHOR]

Diatoms and other phytoplankton in coastal waters experience rapid pH changes in milieu due to high biological activities and/or upwelled CO2-rich waters. While CO2 concentrating mechanisms (CCMs) are employed by all diatoms tested to counter low CO2 availability in seawater, little is known how this mechanism responds to fast pH changes. In the present study, the model diatom Thalassiosira pseudonana was acclimated for 20 generations to low pH (7.81) at an elevated CO2 of 1000 μatm (HC) or to high pH (8.18) at ambient CO2 levels of 390 μatm (LC), then its physiological characteristics were investigated as cells were shifted from HC to LC or vice versa. The maximal electron transport rate (ETRmax) in the HC-acclimated cells was immediately reduced by decreased CO2 availability, showing much lower values compared to that of the LC-acclimated cells. However, the cells showed a high capacity to regain their photochemical performance regardless of the growth CO2 levels, with their ETRmax values recovering to initial levels in about 100 min. This result indicates that this diatom might modulate its CCMs quickly to maintain a steady state supply of CO2, which is required for sustaining photosynthesis. In addition, active uptake of CO2 could play a fundamental role during the induction of CCMs under CO2 limitation, since the cells maintained high ETR even when both intracellular and periplasmic carbonic anhydrases were inhibited. It is concluded that efficient regulation of the CCM is one of the key strategies for diatoms to survive in fast changing pH environment, e.g. for the tested species, which is a dominant species in coastal waters where highly fluctuating pH is observed. [ABSTRACT FROM AUTHOR]

This study aims to compare the suicide risk over the past decade following recent onset psychosis to findings from the eighties and nineties in the same catchment area and to identify predictors of suicide in the context of the Psychosis Recent Onset Groningen-Survey (PROGR-S). A medical file search was carried out to determine the current status of all patients admitted between 2000 and 2009. The suicide rate was compared with a study executed in 1973–1988 in the same catchment area. Predictors of suicide were investigated using Cox regression. The status of 424 of the 614 patients was known in July 2014. Suicide occurred in 2.4% of patients with psychosis disorders (n = 10; mean follow-up 5.6 years); 6 out of 10 suicides took place within two years. Within two decades, the suicide rate dropped from 11% (follow-up 15 years, 8.5% after 5 years) to 2.4%. The Standardized Mortality Rate (SMR) of suicides compared with the general population was 41.6. A higher age was the only significant predictor for suicide. Neuroticism, living situation, disorganized and negative symptoms, and passive coping style all showed a trend for significance. A significant reduction in the suicide rate was found for people with psychosis over the past decades. Given the high SMR, suicide research should be given the highest priority. Identifying predictors may contribute to further reduction of suicide among patients with psychosis. [ABSTRACT FROM AUTHOR]

The discrete data structure and large sequencing depth of RNA sequencing (RNA-seq) experiments can often generate outlier read counts in one or more RNA samples within a homogeneous group. Thus, how to identify and manage outlier observations in RNA-seq data is an emerging topic of interest. One of the main objectives in these research efforts is to develop statistical methodology that effectively balances the impact of outlier observations and achieves maximal power for statistical testing. To reach that goal, strengthening the accuracy of outlier detection is an important precursor. Current outlier detection algorithms for RNA-seq data are executed within a testing framework and may be sensitive to sparse data and heavy-tailed distributions. Therefore, we propose a univariate algorithm that utilizes a probabilistic approach to measure the deviation between an observation and the distribution generating the remaining data and implement it within in an iterative leave-one-out design strategy. Analyses of real and simulated RNA-seq data show that the proposed methodology has higher outlier detection rates for both non-normalized and normalized negative binomial distributed data. [ABSTRACT FROM AUTHOR]

Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules) specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1) known biochemical pathways associated with liver injuries and 2) clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20%) genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects. [ABSTRACT FROM AUTHOR]

Hybridization and introgression can impact the evolution of natural populations. Several wild canid species hybridize in nature, sometimes originating new taxa. However, hybridization with free-ranging dogs is threatening the genetic integrity of grey wolf populations (Canis lupus), or even the survival of endangered species (e.g., the Ethiopian wolf C. simensis). Efficient molecular tools to assess hybridization rates are essential in wolf conservation strategies. We evaluated the power of biparental and uniparental markers (39 autosomal and 4 Y-linked microsatellites, a melanistic deletion at the β-defensin CBD103 gene, the hypervariable domain of the mtDNA control-region) to identify the multilocus admixture patterns in wolf x dog hybrids. We used empirical data from 2 hybrid groups with different histories: 30 presumptive natural hybrids from Italy and 73 Czechoslovakian wolfdogs of known hybrid origin, as well as simulated data. We assessed the efficiency of various marker combinations and reference samples in admixture analyses using 69 dogs of different breeds and 99 wolves from Italy, Balkans and Carpathian Mountains. Results confirmed the occurrence of hybrids in Italy, some of them showing anomalous phenotypic traits and exogenous mtDNA or Y-chromosome introgression. Hybridization was mostly attributable to village dogs and not strictly patrilineal. The melanistic β-defensin deletion was found only in Italian dogs and in putative hybrids. The 24 most divergent microsatellites (largest wolf-dog FST values) were equally or more informative than the entire panel of 39 loci. A smaller panel of 12 microsatellites increased risks to identify false admixed individuals. The frequency of F1 and F2 was lower than backcrosses or introgressed individuals, suggesting hybridization already occurred some generations in the past, during early phases of wolf expansion from their historical core areas. Empirical and simulated data indicated the identification of the past generation backcrosses is always uncertain, and a larger number of ancestry-informative markers is needed. [ABSTRACT FROM AUTHOR]

Understanding the impact that human memory B-cells (MBC), primed by previous infections or vaccination, exert on neutralizing antibody responses against drifted influenza hemagglutinin (HA) is key to design best protective vaccines. A major obstacle to these studies is the lack of practical tools to analyze HA-specific MBCs in human PBMCs ex vivo. We report here an efficient method to identify MBCs carrying HA-specific BCR in frozen PBMC samples. By using fluorochrome-tagged recombinant HA baits, and vaccine antigens from mismatched influenza strains to block BCR-independent binding, we developed a protocol suitable for quantitative, functional and molecular analysis of single MBCs specific for HA from up to two different influenza strains in the same tube. This approach will permit to identify the naive and MBC precursors of plasmablasts and novel MBCs appearing in the blood following infection or vaccination, thus clarifying the actual contribution of pre-existing MBCs in antibody responses against novel influenza viruses. Finally, this protocol can allow applying high throughput deep sequencing to analyze changes in the repertoire of HA+ B-cells in longitudinal samples from large cohorts of vaccinees and infected subjects with the ultimate goal of understanding the in vivo B-cell dynamics driving the evolution of broadly cross-protective antibody responses. [ABSTRACT FROM AUTHOR]

Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables individual monitoring of the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment. [ABSTRACT FROM AUTHOR]

Background: Despite the initial promise of myoblast transfer therapy to restore dystrophin in Duchenne muscular dystrophy patients, clinical efficacy has been limited, primarily by poor cell survival post-transplantation. Murine muscle derived stem cells (MDSCs) isolated from slowly adhering cells (SACs) via the preplate technique, induce greater muscle regeneration than murine myoblasts, primarily due to improved post-transplantation survival, which is conferred by their increased stress resistance capacity. Aldehyde dehydrogenase (ALDH) represents a family of enzymes with important morphogenic as well as oxidative damage mitigating roles and has been found to be a marker of stem cells in both normal and malignant tissue. In this study, we hypothesized that elevated ALDH levels could identify murine and human muscle derived cell (hMDC) progenitors, endowed with enhanced stress resistance and muscle regeneration capacity. Methodology/Principal Findings: Skeletal muscle progenitors were isolated from murine and human skeletal muscle by a modified preplate technique and unfractionated enzymatic digestion, respectively. ALDHhi subpopulations isolated by fluorescence activate cell sorting demonstrated increased proliferation and myogenic differentiation capacities compared to their ALDHlo counterparts when cultivated in oxidative and inflammatory stress media conditions. This behavior correlated with increased intracellular levels of reduced glutathione and superoxide dismutase. ALDHhi murine myoblasts were observed to exhibit an increased muscle regenerative potential compared to ALDHlo myoblasts, undergo multipotent differentiation (osteogenic and chondrogenic), and were found predominately in the SAC fraction, characteristics that are also observed in murine MDSCs. Likewise, human ALDHhi hMDCs demonstrated superior muscle regenerative capacity compared to ALDHlo hMDCs. Conclusions: The methodology of isolating myogenic cells on the basis of elevated ALDH activity yielded cells with increased stress resistance, a behavior that conferred increased regenerative capacity of dystrophic murine skeletal muscle. This result demonstrates the critical role of stress resistance in myogenic cell therapy as well as confirms the role of ALDH as a marker for rapid isolation of murine and human myogenic progenitors for cell therapy. [ABSTRACT FROM AUTHOR]

The liver possesses distinct tolerogenic properties because of continuous exposure to bacterial constituents and nonpathogenic food antigen. The central immune mediators required for the generation of effective immune responses in the liver environment have not been fully elucidated. In this report, we demonstrate that the liver can indeed support effector CD8+ T cells during adenovirus infection when the T cells are primed in secondary lymphoid tissues. In contrast, when viral antigen is delivered predominantly to the liver via intravenous (IV) adenovirus infection, intrahepatic CD8+ T cells are significantly impaired in their ability to produce inflammatory cytokines and lyse target cells. Additionally, intrahepatic CD8+ T cells generated during IV adenovirus infection express elevated levels of PD-1. Notably, lower doses of adenovirus infection do not rescue the impaired effector function of intrahepatic CD8+ T cell responses. Instead, intrahepatic antigen recognition limits the generation of potent anti-viral responses at both priming and effector stages of the CD8+ T cell response and accounts for the dysfunctional CD8+ T cell response observed during IV adenovirus infection. These results also implicate that manipulation of antigen delivery will facilitate the design of improved vaccination strategies to persistent viral infection. [ABSTRACT FROM AUTHOR]