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[This corrects the article DOI: 10.1371/journal.pone.0301032.].

Main objectiveThere is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.Study design and methodsUniversity of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission.Results and significanceThe 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months.ConclusionsMortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

BackgroundA combined vestibular (VI) and cochlear implant (CI) device, also known as the vestibulocochlear implant (VCI), was previously developed to restore both vestibular and auditory function. A new refined prototype is currently being investigated. This prototype allows for concurrent multichannel vestibular and cochlear stimulation. Although recent studies showed that VCI stimulation enables compensatory eye, body and neck movements, the constraints in these acute study designs prevent them from creating more general statements over time. Moreover, the clinical relevance of potential VI and CI interactions is not yet studied. The VertiGO! Trial aims to investigate the safety and efficacy of prolonged daily motion modulated stimulation with a multichannel VCI prototype.MethodsA single-center clinical trial will be carried out to evaluate prolonged VCI stimulation, assess general safety and explore interactions between the CI and VI. A single-blind randomized controlled crossover design will be implemented to evaluate the efficacy of three types of stimulation. Furthermore, this study will provide a proof-of-concept for a VI rehabilitation program. A total of minimum eight, with a maximum of 13, participants suffering from bilateral vestibulopathy and severe sensorineural hearing loss in the ear to implant will be included and followed over a five-year period. Efficacy will be evaluated by collecting functional (i.e. image stabilization) and more fundamental (i.e. vestibulo-ocular reflexes, self-motion perception) outcomes. Hearing performance with a VCI and patient-reported outcomes will be included as well.DiscussionThe proposed schedule of fitting, stimulation and outcome testing allows for a comprehensive evaluation of the feasibility and long-term safety of a multichannel VCI prototype. This design will give insights into vestibular and hearing performance during VCI stimulation. Results will also provide insights into the expected daily benefit of prolonged VCI stimulation, paving the way for cost-effectiveness analyses and a more comprehensive clinical implementation of vestibulocochlear stimulation in the future.Trial registrationClinicalTrials.gov: NCT04918745. Registered 28 April 2021.

This systematic review will identify and synthesize the emerging evidence on older adults with Mild Cognitive Impairment (MCI) utilizing Information and Communication Technology (ICT) to maintain, restore, or augment social networks. The systematic review will consider the evidence on contextual and personal factors of older adults with MCI and their ICT use for social connectedness. The evidence searches will be implemented in PsycINFO, Academic Search Complete, Medline, PubMed, and manual searches. We shall review articles that were published between January 2010 and October 2023 in English and on Information and Communication Technology utility in social networking among older adults with MCI. The process of article selection will be conducted through title screening, abstract screening; and full article screening, following the Population, Intervention, Control, Outcomes (PICO) criteria. Given that all the studies included in this review are publicly accessible and have already obtained ethical approval from their respective institutions, there is no obligation for us to seek additional ethical clearance for our systematic review. We plan to share the outcomes of the systematic review through online presentations and dissemination within the research community. The findings from this review will identify the extent of empirical evidence on older adults with MCI utilizing ICTs to maintain, restore or augment their social networks. This review will provide evidence for contextual and personal factors in older adults with MCI for the social networks with ICT use. This review will propose practical implications for the effective utilization of ICT by older adults with MCI.

Renin-angiotensin system (RAS) modulators, including Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), are effective medications for controlling blood pressure. Cognitive deficits, including lack of concentration, memory loss, and confusion, were reported after COVID-19 infection. ARBs or ACEI increase the expression of angiotensin-converting enzyme-2 (ACE-2), a functional receptor that allows binding of SARS-CoV-2 spike protein for cellular invasion. To date, the association between the use of RAS modulators and the severity of COVID-19 cognitive dysfunction is still controversial.PurposeThis study addressed the following questions: 1) Does prior treatment with RAS modulator worsen COVID-19-induced cerebrovascular and cognitive dysfunction? 2) Can post-treatment with RAS modulator improve cognitive performance and cerebrovascular function following COVID-19? We hypothesize that pre-treatment exacerbates COVID-19-induced detrimental effects while post-treatment displays protective effects.MethodsClinical study: Patients diagnosed with COVID-19 between May 2020 and December 2022 were identified through the electronic medical record system. Inclusion criteria comprised a documented medical history of hypertension treated with at least one antihypertensive medication. Subsequently, patients were categorized into two groups: those who had been prescribed ACEIs or ARBs before admission and those who had not received such treatment before admission. Each patient was evaluated on admission for signs of neurologic dysfunction. Pre-clinical study: Humanized ACE-2 transgenic knock-in mice received the SARS-CoV-2 spike protein via jugular vein injection for 2 weeks. One group had received Losartan (10 mg/kg), an ARB, in their drinking water for two weeks before the injection, while the other group began Losartan treatment after the spike protein injection. Cognitive functions, cerebral blood flow, and cerebrovascular density were determined in all experimental groups. Moreover, vascular inflammation and cell death were assessed.ResultsSigns of neurological dysfunction were observed in 97 out of 177 patients (51%) taking ACEIs/ARBs prior to admission, compared to 32 out of 118 patients (27%) not receiving ACEI or ARBs. In animal studies, spike protein injection increased vascular inflammation, increased endothelial cell apoptosis, and reduced cerebrovascular density. In parallel, spike protein decreased cerebral blood flow and cognitive function. Our results showed that pretreatment with Losartan exacerbated these effects. However, post-treatment with Losartan prevented spike protein-induced vascular and neurological dysfunctions.ConclusionOur clinical data showed that the use of RAS modulators before encountering COVID-19 can initially exacerbate vascular and neurological dysfunctions. Similar findings were demonstrated in the in-vivo experiments; however, the protective effects of targeting the RAS become apparent in the animal model when the treatment is initiated after spike protein injection.

IntroductionAutologous split thickness skin grafting is the standard-of-care for most deep dermal and full thickness skin defects. Historically, mesh grafting is used to expand skin grafts for smaller defects and other techniques such as Meek micrografting is used to enable expansion for larger skin defects. Yet, Meek micrografting is increasingly used for smaller skin defects as well. Both techniques are frequently used, especially in burn centers, but evidence on which one is preferable for relative smaller skin defects is lacking. Therefore, an intra-patient randomized controlled trial was designed to adequately compare multiple outcomes of the Meek micrografting and mesh grafting techniques.Materials and methodsA multicenter intra-patient controlled randomized trial is being performed in two burn centers (the Netherlands and Belgium) to compare multiple outcomes of Meek micrografting and mesh grafting burns or skin defects. Study registration number (NL74274.029.20). Adult patients with a (burn) wound and an indication for surgical excision and skin grafting were screened for inclusion. In total 70 patients will be included and the primary outcome is scar quality twelve months post-surgery assessed by the Patient and Observer Scar Assessment Scale. Moreover, graft take, re-epithelialization, infection rate, donor site size and patients' preference are also measured within hospital admission, on 3 months and 12 months post-surgery.DiscussionThis is the first randomized trial that is intra-patient controlled, which enables a proper comparison between both skin expansion techniques. The results of this study will contribute to the clarification of the indications of both techniques and ample attention is paid for the patients' opinion on the surgical treatment options.

Objective During certain phases of the COVID-19 pandemic, a decrease was observed in emergency department (ED) utilization. Although this phenomenon has been thoroughly characterized for the first wave (FW), second wave (SW) studies are limited. We examined the changes in ED utilization between the FW and SW, compared to 2019 reference periods. Study design and methods We performed a retrospective analysis of ED utilization in 3 Dutch hospitals in 2020. The FW and SW (March-June and September–December, respectively) were compared to the reference periods in 2019. ED visits were labeled as (non-)COVID-suspected. Results During the FW and SW ED visits decreased by 20.3% and 15.3%, respectively, when compared to reference periods in 2019. During both waves high urgency visits significantly increased with 3.1% and 2.1%, and admission rates (ARs) increased with 5.0% and 10.4%. Trauma related visits decreased by 5.2% and 3.4%. During the SW we observed less COVID-related visits compared to the FW (4,407 vs 3,102 patients). COVID-related visits were significantly more often in higher need of urgent care and ARs were at least 24.0% higher compared to non-COVID visits. Conclusion During both COVID-19 waves, ED visits were significantly reduced. ED patients were more often triaged as high urgent, the ED length of stay was longer and ARs were increased compared to the reference period in 2019, reflecting a high burden on ED resources. During the FW, the reduction in ED visits was most pronounced. Here, ARs were also higher and patient were more often triaged as high urgency. These findings stress the need to gain better insight into the motives of patients to delay or avoid emergency care during pandemics, as well as to better prepare EDs for future outbreaks.

The COVID-19-pandemic forced many countries to close schools abruptly in the spring of 2020. These school closures and the subsequent period of distance learning has led to concerns about increasing inequality in education, as children from lower-educated and poorer families have less access to (additional) resources at home. This study analyzes differences in declines in learning gains in primary education in the Netherlands for reading, spelling and math, using rich data on standardized test scores and register data on student and parental background for almost 300,000 unique students. The results show large inequalities in the learning loss based on parental education and parental income, on top of already existing inequalities. The results call for a national focus on interventions specifically targeting vulnerable students.

There is significant regulatory and economic need to distinguish analytically between tobacco-derived nicotine (TDN) and synthetic nicotine (SyN) in commercial products. Currently, commercial e-liquid and oral pouch products are available that contain tobacco-free nicotine, which could be either extracted from tobacco or synthesized. While tobacco products that contain TDN are regulated by FDA Center for Tobacco Products, those with SyN are currently not in the domain of any regulatory authority. This regulatory difference provides an economic incentive to use or claim the use of SyN to remain on the market without submitting a Premarket Tobacco Product Application. TDN is ~99.3% (S)-nicotine, whereas SyN can vary from racemic (50/50 (R)/(S)) to ≥ 99% (S)-nicotine, i.e., chemically identical to the tobacco-derived compound. Here we report efforts to distinguish between TDN and SyN in various samples by characterizing impurities, (R)/(S)-nicotine enantiomer ratio, (R)/(S)-nornicotine enantiomer ratio, and carbon-14 (14C) content. Only 14C analysis accurately and precisely differentiated TDN (100% 14C) from SyN (35-38% 14C) in all samples tested. 14C quantitation of nicotine samples by accelerator mass spectrometry is a reliable determinate of nicotine source and can be used to identify misbranded product labelled as containing SyN. This is the first report to distinguish natural, bio-based nicotine from synthetic, petroleum-based nicotine across a range of pure nicotine samples and commercial e-liquid products.

Tyrosine-protein kinase receptor Tie2, also known as Tunica interna Endothelial cell Kinase or TEK plays a prominent role in endothelial responses to angiogenic and inflammatory stimuli. Here we generated a novel inducible Tie2 knockout mouse model, which targets mature (micro)vascular endothelium, enabling the study of the organ-specific contribution of Tie2 to these responses. Mice with floxed Tie2 exon 9 alleles (Tie2floxed/floxed) were crossed with end-SCL-Cre-ERT transgenic mice, generating offspring in which Tie2 exon 9 is deleted in the endothelial compartment upon tamoxifen-induced activation of Cre-recombinase (Tie2ΔE9). Successful deletion of Tie2 exon 9 in kidney, lung, heart, aorta, and liver, was accompanied by a heterogeneous, organ-dependent reduction in Tie2 mRNA and protein expression. Microvascular compartment-specific reduction in Tie2 mRNA and protein occurred in arterioles of all studied organs, in renal glomeruli, and in lung capillaries. In kidney, lung, and heart, reduced Tie2 expression was accompanied by a reduction in Tie1 mRNA expression. The heterogeneous, organ- and microvascular compartment-dependent knockout pattern of Tie2 in the Tie2floxed/floxed;end-SCL-Cre-ERT mouse model suggests that future studies using similar knockout strategies should include a meticulous analysis of the knockout extent of the gene of interest, prior to studying its role in pathological conditions, so that proper conclusions can be drawn.

Professional development has been identified as an effective way to increase college STEM instructors' use of research-based instructional strategies (RBIS) known to benefit student learning and persistence in STEM. Yet only a few studies relate professional development experiences to later teaching behaviors of higher education instructors. This study of 361 undergraduate mathematics instructors, all of whom participated in multi-day, discipline-based workshops on teaching held in 2010-2019, examined the relationship between such participation and later use of RBIS. We found that instructors' RBIS attitudes, knowledge, and skills strengthened after participating in professional development, and their self-reported use of RBIS became more frequent in the first year after the workshop. Applying the Theory of Planned Behavior as a conceptual framework, we used a structural equation model to test whether this theory could explain the roles of workshop participation and other personal, professional and contextual factors in fostering RBIS use. Findings indicated that, along with workshop participation, prior RBIS experience, class size, and course coordination affected RBIS use. That is, both targeted professional development and elements of the local context for implementation were important in supporting instructors' uptake of RBIS-but, remarkably, both immediate and longer-term outcomes of professional development did not depend on other individual or institutional characteristics. In this study, the large sample size, longitudinal measurement approach, and consistency of the form and quality of professional development make it possible to distinguish the importance of multiple possible influences on instructors' uptake of RBIS. We discuss implications for professional development and for institutional structures that support instructors as they apply what they learned, and we offer suggestions for the use of theory in future research on this topic.

Main objective There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Currently early diagnosis of malignant lesions at the periphery of lung parenchyma requires guidance of the biopsy needle catheter from the bronchoscope into the smaller peripheral airways via harmful X-ray radiation. Previously, we developed an image-guided system, iMTECH which uses electromagnetic tracking and although it increases the precision of biopsy collection and minimizes the use of harmful X-ray radiation during the interventional procedures, it only traces the tip of the biopsy catheter leaving the remaining catheter untraceable in real time and therefore increasing image registration error. To address this issue, we developed a shape sensing guidance system containing a fiber-Bragg grating (FBG) catheter and an artificial intelligence (AI) software, AIrShape to track and guide the entire biopsy instrument inside the lung airways, without radiation or electromagnetic navigation. We used a FBG fiber with one central and three peripheral cores positioned at 120° from each other, an array of 25 draw tower gratings with 1cm/3nm spacing, 2 mm grating length, Ormocer-T coating, and a total outer diameter of 0.2 mm. The FBG fiber was placed in the working channel of a custom made three-lumen catheter with a tip bending mechanism (FBG catheter). The AIrShape software determines the position of the FBG catheter by superimposing its position to the lung airway center lines using an AI algorithm. The feasibility of the FBG system was tested in an anatomically accurate lung airway model and validated visually and with the iMTECH platform. The results prove a viable shape-sensing hardware and software navigation solution for flexible medical instruments to reach the peripheral airways. During future studies, the feasibility of FBG catheter will be tested in pre-clinical animal models.

BackgroundWe aimed to improve mental health referral quality of young people by helping educators build capacity for early identification of youth at risk of mental illness and facilitate referrals between the education and health systems.MethodsWe applied the Go-To Educator mental health literacy training for early identification, triage and support in 208 schools in Calgary, Alberta between 2013 and 2016. Students presenting to mental health services during this time were compared on a number of clinical, system, and demographic variables, based on the training status of the school (untrained schools; before and after training schools), using retrospective cohort design. Based on clinical and system data, bivariate and multivariable logistic regression analysis were employed to compare the three school status domains.ResultsAfter training, referrals differed significantly from control and pre-training schools. Students presenting to services from these schools were younger, from single parent families; were referred more because of adjustment and learning/attention problems; had complex social/family issues; thought disturbances, and harmful behavior/thoughts towards others. While they waited longer to be admitted they stayed longer in services; had more provisional comorbid diagnoses and demonstrated positive treatment outcomes.ConclusionsThe Go-To Educator training may be an effective intervention helping educators identify students at risk of mental disorders and in substantial need of mental health services, demonstrating improved linkages between education and health sectors.

Renin-angiotensin system (RAS) modulators, including Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), are effective medications for controlling blood pressure. Cognitive deficits, including lack of concentration, memory loss, and confusion, were reported after COVID-19 infection. ARBs or ACEI increase the expression of angiotensin-converting enzyme-2 (ACE-2), a functional receptor that allows binding of SARS-CoV-2 spike protein for cellular invasion. To date, the association between the use of RAS modulators and the severity of COVID-19 cognitive dysfunction is still controversial. Purpose: This study addressed the following questions: 1) Does prior treatment with RAS modulator worsen COVID-19-induced cerebrovascular and cognitive dysfunction? 2) Can post-treatment with RAS modulator improve cognitive performance and cerebrovascular function following COVID-19? We hypothesize that pre-treatment exacerbates COVID-19-induced detrimental effects while post-treatment displays protective effects. Methods: Clinical study: Patients diagnosed with COVID-19 between May 2020 and December 2022 were identified through the electronic medical record system. Inclusion criteria comprised a documented medical history of hypertension treated with at least one antihypertensive medication. Subsequently, patients were categorized into two groups: those who had been prescribed ACEIs or ARBs before admission and those who had not received such treatment before admission. Each patient was evaluated on admission for signs of neurologic dysfunction. Pre-clinical study: Humanized ACE-2 transgenic knock-in mice received the SARS-CoV-2 spike protein via jugular vein injection for 2 weeks. One group had received Losartan (10 mg/kg), an ARB, in their drinking water for two weeks before the injection, while the other group began Losartan treatment after the spike protein injection. Cognitive functions, cerebral blood flow, and cerebrovascular density were determined in all experimental groups. Moreover, vascular inflammation and cell death were assessed. Results: Signs of neurological dysfunction were observed in 97 out of 177 patients (51%) taking ACEIs/ARBs prior to admission, compared to 32 out of 118 patients (27%) not receiving ACEI or ARBs. In animal studies, spike protein injection increased vascular inflammation, increased endothelial cell apoptosis, and reduced cerebrovascular density. In parallel, spike protein decreased cerebral blood flow and cognitive function. Our results showed that pretreatment with Losartan exacerbated these effects. However, post-treatment with Losartan prevented spike protein-induced vascular and neurological dysfunctions. Conclusion: Our clinical data showed that the use of RAS modulators before encountering COVID-19 can initially exacerbate vascular and neurological dysfunctions. Similar findings were demonstrated in the in-vivo experiments; however, the protective effects of targeting the RAS become apparent in the animal model when the treatment is initiated after spike protein injection. [ABSTRACT FROM AUTHOR]

Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed.

Biodiversity data derive from myriad sources stored in various formats on many distinct hardware and software platforms. An essential step towards understanding global patterns of biodiversity is to provide a standardized view of these heterogeneous data sources to improve interoperability. Fundamental to this advance are definitions of common terms. This paper describes the evolution and development of Darwin Core, a data standard for publishing and integrating biodiversity information. We focus on the categories of terms that define the standard, differences between simple and relational Darwin Core, how the standard has been implemented, and the community processes that are essential for maintenance and growth of the standard. We present case-study extensions of the Darwin Core into new research communities, including metagenomics and genetic resources. We close by showing how Darwin Core records are integrated to create new knowledge products documenting species distributions and changes due to environmental perturbations.

The objective of this study was to report post-operative complications and outcomes in canines undergoing elbow arthrodesis (EA) with fixation techniques including bone plate fixation with a non-locking dynamic compression plate (DCP), bone plate fixation with a locking plate (LCP), and external skeletal fixator (ESF). Medical records of twenty-two cases that underwent EA between January 2009-December 2019 from 8 referral hospitals including both private practice and academic institutions were reviewed. Post-operative complications were classified as either minor or major, surgical evaluations were performed 8 weeks post operatively, and a follow-up questionnaire was sent to owners. Of the total 22 cases that met inclusion criteria, a total of 19/22 cases had complications, 12 major and 7 minor. Complications reported in 8/9, 7/9, and 4/4, for the DCP, LCP, and ESF fixation groups, respectively. Mild to moderate mechanical lameness was identified at surgical evaluation in 16/22 cases. Complete radiographic bone healing was achieved after 9 weeks in 19/22 cases. Long term owner follow up was available in 14/22 cases. Owners reported a good to normal quality of life in 13/14 cases and poor in one case. The majority of owners (11/14) reported good to excellent satisfaction with the outcome irrespective of persistent lameness. This study demonstrates that successful EA can be achieved using a variety of fixation methods, but persistent lameness is expected and complication rate is high.

Tillering and secondary branching are two plastic traits with high agronomic importance, especially in terms of the ability of plants to adapt to changing environments. We describe a quantitative trait analysis of tillering and secondary branching in two novel BC1F2 populations totaling 246 genotypes derived from backcrossing two Sorghum bicolor x S. halepense F1 plants to a tetraploidized S. bicolor. A two-year, two-environment phenotypic evaluation in Bogart, GA and Salina, KS permitted us to identify major effect and environment specific QTLs. Significant correlation between tillering and secondary branching followed by discovery of overlapping sets of QTLs continue to support the developmental relationship between these two organs and suggest the possibility of pleiotropy. Comparisons with two other populations sharing S. bicolor BTx623 as a common parent but sampling the breadth of the Sorghum genus, increase confidence in QTL detected for these two plastic traits and provide insight into the evolution of morphological diversity in the Eusorghum clade. Correspondence between flowering time and vegetative branching supports other evidence in suggesting a pleiotropic effect of flowering genes. We propose a model to predict biomass weight from plant architecture related traits, quantifying contribution of each trait to biomass and providing guidance for future breeding experiments.

BackgroundWe evaluated measures to protect healthcare workers (HCWs) in Vancouver, Canada, where variants of concern (VOC) went from 92% in mid-May. Canada has amongst the longest periods between vaccine doses worldwide, despite Vancouver having the highest P.1 variant rate outside Brazil.MethodsWith surveillance data since the pandemic began, we tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in all 25,558 HCWs in Vancouver Coastal Health, by occupation and subsector, and compared to the general population. Cox regression modelling adjusted for age and calendar-time calculated vaccine effectiveness (VE) against SARS-CoV-2 in fully vaccinated (≥ 7 days post-second dose), partially vaccinated infection (after 14 days) and unvaccinated HCWs; we also compared with unvaccinated community members of the same age-range.FindingsOnly 3.3% of our HCWs became infected, mirroring community rates, with peak positivity of 9.1%, compared to 11.8% in the community. As vaccine coverage increased, SARS-CoV-2 infections declined significantly in HCWs, despite a surge with predominantly VOC; unvaccinated HCWs had an infection rate of 1.3/10,000 person-days compared to 0.89 for HCWs post first dose, and 0.30 for fully vaccinated HCWs. VE compared to unvaccinated HCWs was 37.2% (95% CI: 16.6-52.7%) 14 days post-first dose, 79.2% (CI: 64.6-87.8%) 7 days post-second dose; one dose provided significant protection against infection until at least day 42. Compared with community infection rates, VE after one dose was 54.7% (CI: 44.8-62.9%); and 84.8% (CI: 75.2-90.7%) when fully vaccinated.InterpretationRigorous droplet-contact precautions with N95s for aerosol-generating procedures are effective in preventing occupational infection in HCWs, with one dose of mRNA vaccination further reducing infection risk despite VOC and transmissibility concerns. Delaying second doses to allow more widespread vaccination against severe disease, with strict public health, occupational health and infection control measures, has been effective in protecting the healthcare workforce.

In-situ resource utilization (ISRU) is increasingly acknowledged as an essential requirement for the construction of sustainable extra-terrestrial colonies. Even with decreasing launch costs, the ultimate goal of establishing colonies must be the usage of resources found at the destination of interest. Typical approaches towards ISRU are often constrained by the mass and energy requirements of transporting processing machineries, such as rovers and massive reactors, and the vast amount of consumables needed. Application of self-reproducing bacteria for the extraction of resources is a promising approach to reduce these pitfalls. In this work, the bacterium Shewanella oneidensis was used to reduce three different types of Lunar and Martian regolith simulants, allowing for the magnetic extraction of iron-rich materials. The combination of bacterial treatment and magnetic extraction resulted in a 5.8-times higher quantity of iron and 43.6% higher iron concentration compared to solely magnetic extraction. The materials were 3D printed into cylinders and the mechanical properties were tested, resulting in a 400% improvement in compressive strength in the bacterially treated samples. This work demonstrates a proof of concept for the on-demand production of construction and replacement parts in space exploration.

As global climate change progresses, wildlife management will benefit from knowledge of demographic responses to climatic variation, particularly for species already endangered by other stressors. In Canada, climate change is expected to increasingly impact populations of threatened woodland caribou (Rangifer tarandus caribou) and much focus has been placed on how a warming climate has potentially facilitated the northward expansion of apparent competitors and novel predators. Climate change, however, may also exert more direct effects on caribou populations that are not mediated by predation. These effects include meteorological changes that influence resource availability and energy expenditure. Research on other ungulates suggests that climatic variation may have minimal impact on low-density populations such as woodland caribou because per-capita resources may remain sufficient even in "bad" years. We evaluated this prediction using demographic data from 21 populations in western Canada that were monitored for various intervals between 1994 and 2015. We specifically assessed whether juvenile recruitment and adult female survival were correlated with annual variation in meteorological metrics and plant phenology. Against expectations, we found that both vital rates appeared to be influenced by annual climatic variation. Juvenile recruitment was primarily correlated with variation in phenological conditions in the year prior to birth. Adult female survival was more strongly correlated with meteorological conditions and declined during colder, more variable winters. These responses may be influenced by the life history of woodland caribou, which reside in low-productivity refugia where small climatic changes may result in changes to resources that are sufficient to elicit strong demographic effects. Across all models, explained variation in vital rates was low, suggesting that other factors had greater influence on caribou demography. Nonetheless, given the declining trajectories of many woodland caribou populations, our results highlight the increased relevance of recovery actions when adverse climatic conditions are likely to negatively affect caribou demography.

rfaRm is an R package providing a client-side interface for the Rfam database of non-coding RNA and other structured RNA elements. The package facilitates the search of the Rfam database by keywords or sequences, as well as the retrieval of all available information about specific Rfam families, such as member sequences, multiple sequence alignments, secondary structures and covariance models. By providing such programmatic access to the Rfam database, rfaRm enables genomic workflows to incorporate information about non-coding RNA, whose potential cannot be fully exploited just through interactive access to the database. The features of rfaRm are demonstrated by using it to analyze the SARS-CoV-2 genome as an example case.

BackgroundHuman central nervous system-stem cells grown as neurospheres (hCNS-SCns) self-renew, are multipotent, and have potential therapeutic applications following trauma to the spinal cord. We have previously shown locomotor recovery in immunodeficient mice that received a moderate contusion spinal cord injury (SCI) and hCNS-SCns transplantation 9 days post-injury (dpi). Engrafted hCNS-SCns exhibited terminal differentiation to myelinating oligodendrocytes and synapse-forming neurons. Further, selective ablation of human cells using Diphtheria toxin (DT) abolished locomotor recovery in this paradigm, suggesting integration of human cells within the mouse host as a possible mechanism for the locomotor improvement. However, the hypothesis that hCNS-SCns could alter the host microenvironment as an additional or alternative mechanism of recovery remained unexplored; we tested that hypothesis in the present study.Methods and FindingsStereological quantification of human cells using a human-specific cytoplasmic marker demonstrated successful cell engraftment, survival, migration and limited proliferation in all hCNS-SCns transplanted animals. DT administration at 16 weeks post-transplant ablated 80.5% of hCNS-SCns. Stereological quantification for lesion volume, tissue sparing, descending serotonergic host fiber sprouting, chondroitin sulfate proteoglycan deposition, glial scarring, and angiogenesis demonstrated no evidence of host modification within the mouse spinal cord as a result of hCNS-SCns transplantation. Biochemical analyses supplemented stereological data supporting the absence of neural stem-cell mediated host repair. However, linear regression analysis of the number of engrafted hCNS-SCns vs. the number of errors on a horizontal ladder beam task revealed a strong correlation between these variables (r = −0.78, p

This systematic review will identify and synthesize the emerging evidence on older adults with Mild Cognitive Impairment (MCI) utilizing Information and Communication Technology (ICT) to maintain, restore, or augment social networks. The systematic review will consider the evidence on contextual and personal factors of older adults with MCI and their ICT use for social connectedness. The evidence searches will be implemented in PsycINFO, Academic Search Complete, Medline, PubMed, and manual searches. We shall review articles that were published between January 2010 and October 2023 in English and on Information and Communication Technology utility in social networking among older adults with MCI. The process of article selection will be conducted through title screening, abstract screening; and full article screening, following the Population, Intervention, Control, Outcomes (PICO) criteria. Given that all the studies included in this review are publicly accessible and have already obtained ethical approval from their respective institutions, there is no obligation for us to seek additional ethical clearance for our systematic review. We plan to share the outcomes of the systematic review through online presentations and dissemination within the research community. The findings from this review will identify the extent of empirical evidence on older adults with MCI utilizing ICTs to maintain, restore or augment their social networks. This review will provide evidence for contextual and personal factors in older adults with MCI for the social networks with ICT use. This review will propose practical implications for the effective utilization of ICT by older adults with MCI. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) accelerates coronary artery disease (CAD) and atherosclerosis, the causes of most heart attacks. The biomolecules involved in these inter-related disease processes are not well understood. This study analyzes biomolecules in the sera of patients with CAD, with and without type (T) 2DM, who are about to undergo coronary artery bypass graft (CABG) surgery. The goal is to develop methodology to help identify and monitor CAD patients with and without T2DM, in order to better understand these phenotypes and to glean relationships through analysis of serum biomolecules. Aorta, fat, muscle, and vein tissues from CAD T2DM patients display diabetic-related histologic changes (e.g., lipid accumulation, fibrosis, loss of cellularity) when compared to non-diabetic CAD patients. The patient discriminatory methodology utilized is serum biomolecule mass profiling. This mass spectrometry (MS) approach is able to distinguish the sera of a group of CAD patients from controls (p value 10-15), with the CAD group containing both T2DM and non-diabetic patients. This result indicates the T2DM phenotype does not interfere appreciably with the CAD determination versus control individuals. Sera from a group of T2DM CAD patients however are distinguishable from non-T2DM CAD patients (p value 10-8), indicating it may be possible to examine the T2DM phenotype within the CAD disease state with this MS methodology. The same serum samples used in the CAD T2DM versus non-T2DM binary group comparison were subjected to MS/MS peptide structure analysis to help identify potential biochemical and phenotypic changes associated with CAD and T2DM. Such peptide/protein identifications could lead to improved understanding of underlying mechanisms, additional biomarkers for discriminating and monitoring these disease conditions, and potential therapeutic targets. Bioinformatics/systems biology analysis of the peptide/protein changes associated with CAD and T2DM suggested cell pathways/systems affected include atherosclerosis, DM, fibrosis, lipogenesis, loss of cellularity (apoptosis), and inflammation.

BackgroundThe Health Resources and Services Administration's (HRSA), HIV/AIDS Bureau (HAB) is responsible for leading the nation's efforts to provide health care, medications, and support services to low-income people living with HIV through the Ryan White HIV/AIDS Program (RWHAP). The RWHAP funds and coordinates with cities, states, and local community-based organizations to deliver efficient and effective HIV care, treatment, and support services for over half a million vulnerable people living with HIV (PLWH) and their families in the United States. The annual RWHAP Services Report (RSR) is an important source of information for monitoring RWHAP's progress towards National HIV/AIDS Strategy goals. Since 2010, HRSA HAB has used the annual client-level RSR data to monitor program-related outcomes, conduct program evaluations, understand service provision, and conduct extensive analysis on disparities in viral suppression and retention in HIV care. HRSA HAB receives annual RSR submissions from RWHAP recipients and sub-recipients. However, the de-identified nature of the data limits HRSA HAB's ability to expand beyond year-to-year analyses and conduct additional analyses to evaluate outcomes for clients who are seen in multiple years. The current paper describes the development and validation of a method to link RSR client-level records across multiple data years.Methods and findingsUsing seven RSR reporting years of data (2010 to 2016), we applied a Fellegi-Sunter (F-S) linkage model that used client demographic characteristics and their providers' geographic locations to calculate matching weights for each record pair based on estimated agreement and disagreement conditional probabilities across RSR years. To validate our methodology, we conducted an internal sample review and external validation to assess the level of accuracy of the linkage, and the extent to which the linked data set corresponds accurately to clinical records of individual clients. The linkage result yielded 70 to 80 percent year-to-year client carry-over rate over seven years of the RSR data; 96 percent linkage ratio from the internal sample review and 79.9 to 94.2 percent of provider network client carry- over rate per year from the external validation.ConclusionsThis methodology addresses a gap in data analysis capabilities by allowing HRSA HAB to link RWHAP clients across reporting years. Despite weak identifying information and lack of continuity of service reporting, the longitudinal linkage improves HRSA HAB's ability to evaluate the patterns of viral suppression and monitor service utilization over time for individuals who receive services in multiple years. These analyses will support future analytic activities in understanding the impact and outcomes of the RWHAP, and will assist HRSA HAB in monitoring progress toward meeting National HIV/AIDS Strategy goals. For those looking for ways to assess health services data, the F-S unsupervised method combining weak identifying attributes and geographic proximity offers practical solutions to the problem of linking de-identified information about individuals across multiple years and improving longitudinal research.

Emergency department triage is the first point in time when a patient's acuity level is determined. The time to assign a priority at triage is short and it is vital to accurately stratify patients at this stage, since under-triage can lead to increased morbidity, mortality and costs. Our aim was to present a model that can assist healthcare professionals in triage decision making, namely in the stratification of patients through the risk prediction of a composite critical outcome-mortality and cardiopulmonary arrest. Our study cohort consisted of 235826 adult patients triaged at a Portuguese Emergency Department from 2012 to 2016. Patients were assigned to emergent, very urgent or urgent priorities of the Manchester Triage System (MTS). Demographics, clinical variables routinely collected at triage and the patients' chief complaint were used. Logistic regression, random forests and extreme gradient boosting were developed using all available variables. The term frequency-inverse document frequency (TF-IDF) natural language processing weighting factor was applied to vectorize the chief complaint. Stratified random sampling was used to split the data into train (70%) and test (30%) data sets. Ten-fold cross validation was performed in train to optimize model hyper-parameters. The performance obtained with the best model was compared against the reference model-a regularized logistic regression trained using only triage priorities. Extreme gradient boosting exhibited good calibration properties and yielded areas under the receiver operating characteristic and precision-recall curves of 0.96 (95% CI 0.95-0.97) and 0.31 (95% CI 0.26-0.36), respectively. The predictors ranked with higher importance by this model were the Glasgow coma score, the patients' age, pulse oximetry and arrival mode. Compared to the reference, the extreme gradient boosting model using clinical variables and the chief complaint presented higher recall for patients assigned MTS-3 and can identify those who are at risk of the composite outcome.

The risk stratification of patients in the emergency department begins at triage. It is vital to stratify patients early based on their severity, since undertriage can lead to increased morbidity, mortality and costs. Our aim was to present a new approach to assist healthcare professionals at triage in the stratification of patients and in identifying those with higher risk of ICU admission. Adult patients assigned Manchester Triage System (MTS) or Emergency Severity Index (ESI) 1 to 3 from a Portuguese and a United States Emergency Departments were analyzed. Variables routinely collected at triage were used and natural language processing was applied to the patient chief complaint. Stratified random sampling was applied to split the data in train (70%) and test (30%) sets and 10-fold cross validation was performed for model training. Logistic regression, random forests, and a random undersampling boosting algorithm were used. We compared the performance obtained with the reference model-using only triage priorities-with the models using additional variables. For both hospitals, a logistic regression model achieved higher overall performance, yielding areas under the receiver operating characteristic and precision-recall curves of 0.91 (95% CI 0.90-0.92) and 0.30 (95% CI 0.27-0.33) for the United States hospital and of 0.85 (95% CI 0.83-0.86) and 0.06 (95% CI 0.05-0.07) for the Portuguese hospital. Heart rate, pulse oximetry, respiratory rate and systolic blood pressure were the most important predictors of ICU admission. Compared to the reference models, the models using clinical variables and the chief complaint presented higher recall for patients assigned MTS/ESI 3 and can identify patients assigned MTS/ESI 3 who are at risk for ICU admission.

Analyzed endometrial cancer (EC) genomes have allowed for the identification of molecular signatures, which enable the classification, and sometimes prognostication, of these cancers. Artificial intelligence algorithms have facilitated the partitioning of mutations into driver and passenger based on a variety of parameters, including gene function and frequency of mutation. Here, we undertook an evaluation of EC cancer genomes deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC), with the goal to classify all mutations as either driver or passenger. Our analysis showed that approximately 2.5% of all mutations are driver and cause cellular transformation and immortalization. We also characterized nucleotide level mutation signatures, gross chromosomal re-arrangements, and gene expression profiles. We observed that endometrial cancers show distinct nucleotide substitution and chromosomal re-arrangement signatures compared to other cancers. We also identified high expression levels of the CLDN18 claudin gene, which is involved in growth, survival, metastasis and proliferation. We then used in silico protein structure analysis to examine the effect of certain previously uncharacterized driver mutations on protein structure. We found that certain mutations in CTNNB1 and TP53 increase protein stability, which may contribute to cellular transformation. While our analysis retrieved previously classified mutations and genomic alterations, which is to be expected, this study also identified new signatures. Additionally, we show that artificial intelligence algorithms can be effectively leveraged to accurately predict key drivers of cancer. This analysis will expand our understanding of ECs and improve the molecular toolbox for classification, diagnosis, or potential treatment of these cancers. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a well-established risk factor for cardiovascular diseases. Although, advances in genome-wide technologies have enabled the discovery of hundreds of genes associated with blood lipid phenotypes, most of the heritability remains unexplained. Here we performed targeted resequencing of 13 bona fide candidate genes of dyslipidemia to identify the underlying biological functions. We sequenced 940 Sikh subjects with extreme serum levels of hypertriglyceridemia (HTG) and 2,355 subjects were used for replication studies; all 3,295 participants were part of the Asian Indians Diabetic Heart Study. Gene-centric analysis revealed burden of variants for increasing HTG risk in GCKR (p = 2.1x10-5), LPL (p = 1.6x10-3) and MLXIPL (p = 1.6x10-2) genes. Of these, three missense and damaging variants within GCKR were further examined for functional consequences in vivo using a transgenic zebrafish model. All three mutations were South Asian population-specific and were largely absent in other multiethnic populations of Exome Aggregation Consortium. We built different transgenic models of human GCKR with and without mutations and analyzed the effects of dietary changes in vivo. Despite the short-term of feeding, profound phenotypic changes were apparent in hepatocyte histology and fat deposition associated with increased expression of GCKR in response to a high fat diet (HFD). Liver histology of the GCKRmut showed severe fatty metamorphosis which correlated with ~7 fold increase in the mRNA expression in the GCKRmut fish even in the absence of a high fat diet. These findings suggest that functionally disruptive GCKR variants not only increase the risk of HTG but may enhance ectopic lipid/fat storage defects in absence of obesity and HFD. To our knowledge, this is the first transgenic zebrafish model of a putative human disease gene built to accurately assess the influence of genetic changes and their phenotypic consequences in vivo.

BACKGROUND:The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (VMHD) obtained from electrocardiogram (ECG) recordings performed inside MRI's static magnetic field (B0). Integrating the regional VMHD over the Swave-Twave segment of the cardiac cycle (Vsegment) provides a non-invasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost. METHODS:VMHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B0's strength at specified distances from isocenter. Vsegment mapping was performed in six subjects and validated against MR angiograms (MRA). RESULTS:Fluctuations in Vsegment, which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B0. The smallest fluctuations corresponded to areas of vasculature that were parallel to B0. Significant correlations (specifically, Spearman's ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and Vsegment maps (p < 0.001). CONCLUSIONS:A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes.

With the help of the method of Lagrange multipliers and KKT theory, we investigate the structure and existence of optimal solutions of the continuous-time model of consumption with satiation. We show that the differential equations have no solutions in the C1 class but that solutions exist in a wider space of functions, namely, the space of functions of bounded variation with non-negative Borel measures as controls. We prove our theorems with no additional assumptions about the structure of the control Borel measures. We prove the conjecture made in the earlier literature, that there are only three types of solutions: I-shaped solutions, with a gulp of consumption at the end of the interval and no consumption at the beginning or in the interior; U-shaped solutions, with consumption in the entire interior of the interval and gulps at the beginning and the end; and intermediate (J-shaped) solutions, with an initial interval of abstinence followed by a terminal interval of distributed consumption at rates and a gulp at the end. We also establish the criteria that permit determination of the solution type using the problem's parameters. When the solution structure is known, we reduce the problem of the existence of a solution to algebraic equations and discuss the solvability of these equations. We construct explicit solutions for logarithmic utility and CRRA utility.

RationaleWe propose renin angiotensin system (RAS) peptides are critical in wound reparative processes such as in acute respiratory distress syndrome (ARDS). Their role in predicting clinical outcomes in ARDS has been unexplored; thus, we used a targeted metabolomics approach to investigate them as potential predictors of outcomes.MethodsThirty-nine ARDS patients were enrolled within 24 hours of ARDS diagnosis. Plasma RAS peptide levels were quantified at study entry and 24, 48 and 72 hours using a liquid chromatography-mass spectrometry based metabolomics assay. RAS peptide concentrations were compared between survivors and non-survivors, and were correlated with clinical and pulmonary measures.Measurements and main resultsAngiotensin I (Ang-I or A(1-10)) levels were significantly higher in non-survivors at study entry and 72 hours. ARDS survival was associated with lower A(1-10) concentration (OR 0.36, 95% CI 0.18-0.72, p = 0.004) but higher A(1-9) concentration (OR 2.24, 95% CI 1.15-4.39, p = 0.018), a biologically active metabolite of A(1-10) and an agonist of angiotensin II receptor type 2. Survivors had significantly higher median A(1-9)/A(1-10) and A(1-7)/A(1-10) ratios than the non-survivors (p = 0.001). Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors.ConclusionA(1-10) accumulation and reduced A(1-9) concentration in the non-survivor group suggest that ACE2 activities may be reduced in patients succumbing to ARDS. Plasma levels of both A(1-10) and A(1-9) and their ratio may serve as useful biomarkers for prognosis in ARDS patients.

Mammalian predators encounter unique hunting challenges during the winter as snow increases the cost of locomotion and influences predator-prey interactions. Winter precipitation may also affect predators' ability to detect and pursue prey. We investigated the effects of snowfall events on grey wolves (Canis lupus) in a boreal forest ecosystem in northeastern Alberta, Canada. We predicted that wolves would respond to snowfall events by reducing their travel speed and the time they spent travelling. Over the course of two winters, we used remote cameras to identify localized snowfall events and estimate snow depth. We used telemetry data from 17 wolves to calculate travel speed and time spent travelling versus resting. Data were categorized by time of day (night versus day) and time since snowfall events, and analyzed using linear and logistic regression mixed-effects models. We found that wolves were less likely to travel on dates of snowfall events than any date prior to or after an event. Wolves also travelled slower during snowfall events, but only when compared to their travel speed 24 hours before. Effects were most pronounced at night, when movements appeared to be consistent with hunting behavior, and activity levels resumed within 24 hours of a snowfall event. Including snow depth as a variable did not improve model fit. Collectively, our findings suggest that wolves' response is not driven by increased hunting success or by energetic considerations resulting from increased snow depth. Instead, we propose that wolves reduce their activity levels because precipitation dampens hunting success. Snowfall events may impact wolves' ability to detect prey and changes in prey behavior could also lead to decreased encounter rates. We encourage scientists to further investigate the effects of short-term weather events on movement rates and predator-prey interactions.

This study focused on the value of quantitatively analyzed and qualitatively graded renal scintigraphy in relation to the expected duration of delayed graft function after kidney transplantation. A more reliable prediction of delayed graft function duration may result in a more tailored and patient-specific treatment regimen post-transplantation.From 2000 to 2014, patients with early transplant dysfunction and a Tc-99m MAG3 renal scintigraphy, within 3 days post-transplantation, were included in a dual center retrospective study. Time-activity curves of renal scintigraphy procedures were qualitatively graded and various quantitative indices (R20/3, TFS, cTER, MUC10) were combined with a new index (Average upslope). The delayed graft function duration was defined as the number of days of dialysis-based/functional delayed graft function.A total of 377 patients were included, with a mean age (± SD) of 52 ± 14 years, and 58% were male. A total of 274 (73%) patients experienced delayed graft function≥ 7 days. Qualitative grading for the prediction of delayed graft function≥ 7 days had a sensitivity and specificity of respectively 87% and 65%. The quantitative indices with the most optimal results were cTER (76% sensitivity, 72% specificity), and Average upslope (75% sensitivity, 73% specificity).Qualitative renal scintigraphy grading and the quantitative indices cTER and Average upslope predict delayed graft function ≥ 7 days with a high sensitivity. This finding may help to support both clinicians and patients in managing early post-operative expectations. However, the specificity is limited and thus renal scintigraphy does not reliably help to identify patients in whom the course of delayed graft function is longer than anticipated.

Phonotraumatic vocal hyperfunction (PVH) is associated with chronic misuse and/or abuse of voice that can result in lesions such as vocal fold nodules. The clinical aerodynamic assessment of vocal function has been recently shown to differentiate between patients with PVH and healthy controls to provide meaningful insight into pathophysiological mechanisms associated with these disorders. However, all current clinical assessment of PVH is incomplete because of its inability to objectively identify the type and extent of detrimental phonatory function that is associated with PVH during daily voice use. The current study sought to address this issue by incorporating, for the first time in a comprehensive ambulatory assessment, glottal airflow parameters estimated from a neck-mounted accelerometer and recorded to a smartphone-based voice monitor. We tested this approach on 48 patients with vocal fold nodules and 48 matched healthy-control subjects who each wore the voice monitor for a week. Seven glottal airflow features were estimated every 50 ms using an impedance-based inverse filtering scheme, and seven high-order summary statistics of each feature were computed every 5 minutes over voiced segments. Based on a univariate hypothesis testing, eight glottal airflow summary statistics were found to be statistically different between patient and healthy-control groups. L1-regularized logistic regression for a supervised classification task yielded a mean (standard deviation) area under the ROC curve of 0.82 (0.25) and an accuracy of 0.83 (0.14). These results outperform the state-of-the-art classification for the same classification task and provide a new avenue to improve the assessment and treatment of hyperfunctional voice disorders.

COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

Marine turtles are caught and slaughtered for consumption as part of traditional indigenous community harvest in Australia as well as in many countries in which marine turtles can be found. However, changes to the Animal Care and Protection Act 2001 in 2012 resulted in Australian indigenous hunters becoming potentially liable to prosecution for using traditional practices to slaughter marine turtles. To provide indigenous hunters with an alternative scientifically tested method to hunt, we developed and tested a humane method as an option to use in indigenous communities. Between 2012 and 2015, a device was developed, tested on 11 carcasses to determine effectiveness and repeatability, used on 5 anaesthetised animals independently diagnosed as candidates for euthanasia, and ultimately used on 2 healthy, conscious animals as part of normal indigenous community subsistence harvesting under observation before being left with the communities for use. Feedback was sought from the communities on the suitability and potential adoption of the device. The device effectively ablated the hind brain and severed the spinal cord when deployed in 81% (9/11) of the tested carcasses, with death in 100% (5/5) of turtles, on average, within 78 seconds of deployment on anaesthetised turtles and death in 100% (2/2) of turtles, on average, within 144 seconds when deployed on healthy turtles within community. Failure to ablate the hindbrain and sever the spinal cord in the cadaver cases was due to incorrect deployment of the device. This device showed promise as an alternative euthanasia method available to indigenous communities of the Torres Straits. Further work is required to encourage acceptance by hunters.

The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety.

Olfactory responses are intensely enhanced with the addition of endogenous and engineered primarily-elemental small zinc nanoparticles (NPs). With aging, oxidation of these Zn nanoparticles eliminated the observed enhancement. The design of a polyethylene glycol coating to meet storage requirements of engineered zinc nanoparticles is evaluated to achieve maximal olfactory benefit. The zinc nanoparticles were covered with 1000 g/mol or 400 g/mol molecular weight polyethylene glycol (PEG). Non-PEGylated and PEGylated zinc nanoparticles were tested by electroolfactogram with isolated rat olfactory epithelium and odorant responses evoked by the mixture of eugenol, ethyl butyrate and (±) carvone after storage at 278 K (5 oC), 303 K (30 oC) and 323 K (50 oC). The particles were analyzed by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and laser Doppler velocimetry. Our data indicate that stored ZnPEG400 nanoparticles maintain physiologically-consistent olfactory enhancement for over 300 days. These engineered Nanoparticles support future applications in olfactory research, sensitive detection, and medicine.

Brown bears are known to use rubbing behavior as a means of chemical communication, but the function of this signaling is unclear. One hypothesis that has gained support is that male bears rub to communicate dominance to other males. We tested the communication of dominance hypothesis in a low-density brown bear population in southeast British Columbia. We contrasted rubbing rates for male and female bears during and after the breeding season using ten years of DNA-mark-recapture data for 643 individuals. Here we demonstrate that male brown bears rub 60% more during the breeding than the non-breeding season, while female rubbing had no seasonal trends. Per capita rub rates by males were, on average, 2.7 times higher than females. Our results suggest that the function of rubbing in the Rocky Mountains may not only be to communicate dominance, but also to self-advertise for mate attraction. We propose that the role of chemical communication in this species may be density-dependent, where the need to self-advertise for mating is inversely related to population density and communicating for dominance increases with population density. We suggest that future endeavors to elucidate the function of rubbing should sample the behavior across a range of population densities using camera trap and genotypic data.