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The steady increase of chief executives' compensation in both public and private universities has long been at the centre of public debate and has received a lot of criticism in the UK. As higher education is considered as an industry, a pay for performance relationship is expected. This paper differs by demonstrating that UK Vice Chancellors consider incentives other than remuneration in their career progression. By constructing a comprehensive dataset of UK Vice Chancellors covering academic years 2012/2013 to 2016/2017, we demonstrate that UK university chief executives, especially if young, are willing to accept lower salaries when they interpret their role as a springboard for visible high-profile positions in the public arena.

Abstract The COVID-19 pandemic highlighted a pre-existing issue related to healthcare accessibility, especially for comorbid chronic pain and opioid use disorder (OUD) populations. Though researchers and practitioners have relied on telehealth to address barriers to healthcare, telehealth services remain inaccessible for many. This study explored the effectiveness of strategies used to continue a clinical trial for comorbid chronic pain and OUD during the COVID-19 pandemic. This study involved the transition of in-person group psychotherapy (Self-regulation Therapy for Opioid use disorder and Chronic Pain–STOP) to telehealth. We completed a mixed-method data analysis to assess the differences between the telehealth and in-person administrations. Though the telehealth group showed higher retention, the in-person group reached more diverse samples. Participants who completed the telehealth group had higher education and income, longer periods of stability on medication for opioid use disorder (MOUD) and were more likely to be White compared to participants who completed the in-person group. Individuals from minoritized and underserved groups who lack access to in-person services may fall through the gaps of healthcare in the shift to telehealth. There is a clear need for additional research on how to best support those who lack access to current comorbid chronic pain and OUD treatment modalities. ClinicalTrials.gov record number:17–1849, registered November 2017.

Summary: Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by a lack of high-throughput, unbiased, and quantitative methods to identify protein-calcium engagement. To address this, we adapted protein thermostability assays in budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2,884 putative calcium-regulated proteins across human, mouse, and yeast proteomes. These data revealed calcium engagement of signaling hubs and cellular processes, including metabolic enzymes and the spliceosome. Cross-species comparison of calcium-protein engagement and mutagenesis experiments identified residue-specific cation engagement, even within well-known EF-hand domains. Additionally, we found that the dienoyl-coenzyme A (CoA) reductase DECR1 binds calcium at physiologically relevant concentrations with substrate-specific affinity, suggesting direct calcium regulation of mitochondrial fatty acid oxidation. These discovery-based proteomic analyses of calcium effectors establish a key resource to dissect cation engagement and its mechanistic effects across multiple species and diverse biological processes.

ObjectivesThis study aimed to evaluate the agreement between explosive detection dog (EDD) handlers and a team of veterinarians in assessing body condition score (BCS) and muscle condition score (MCS), hypothesizing significant BCS differences between handlers and veterinarians, and no significant MCS differences in healthy active duty EDDs.MethodsThis prospective study analyzed variance and inter-rater intraclass correlation coefficients (ICC) of agreement within BCS and MCS assessments collected from the 43 EDDs by four blinded graders; the EDDs’ respective handler and three veterinarians with varying levels of veterinary expertise.ResultsThe results of the study showed that 74.4% of the EDD population was graded as ideal BCS (4 or 5 out of 9) by the handlers compared to 67.44% by the members of the veterinary team; however, the graders scored different subsets of individual EDDs as ideal. Normal MCS (3 out of 3) was assessed in 86.05% (n = 37) of EDDs by the handlers versus in 70.54% by the veterinary team.ConclusionThis study highlights the importance of standardized training and guidelines for BCS and MCS assessments in working dogs to improve agreement between all members of the healthcare team.

The occupational health-nursing practitioner often becomes involved in ethical dilemmas with regard to the handling of HIV-positive people in the workplace in that the interests of the HIV-positive people conflict with the interests of the employer. Opsomming Die beroepsgesondheidsverpleegkundige raak dikwels in etiese dilemmas betrokke ten opsigte van die hantering van die MIV-positiewe persoon by die werkplek deurdat die belange van die MIV-positiewe persoon botsend is met die belange van die werkgewer. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

Abstract Graphene is a promising material for applications as a channel in graphene field-effect transistors (GFETs) which may be used as a building block for optoelectronics, high-frequency devices and sensors. However, these devices require gate insulators which ideally should form atomically flat interfaces with graphene and at the same time contain small densities of traps to maintain high device stability. Previously used amorphous oxides, such as SiO2 and Al2O3, however, typically suffer from oxide dangling bonds at the interface, high surface roughness and numerous border oxide traps. In order to address these challenges, here we use 2 nm thick epitaxial CaF2 as a gate insulator in GFETs. By analyzing device-to-device variability for about 200 devices fabricated in two batches, we find that tens of them show similar gate transfer characteristics. Our statistical analysis of the hysteresis up to 175oC has revealed that while an ambient-sensitive counterclockwise hysteresis can be present in some devices, the dominant mechanism is thermally activated charge trapping by border defects in CaF2 which results in the conventional clockwise hysteresis. We demonstrate that both the hysteresis and bias-temperature instabilities in our GFETs with CaF2 are comparable to similar devices with SiO2 and Al2O3. In particular, we achieve a small hysteresis below 0.01 V for equivalent oxide thickness (EOT) of about 1 nm at the electric fields up to 15 MV cm−1 and sweep times in the kilosecond range. Thus, our results demonstrate that crystalline CaF2 is a promising insulator for highly-stable GFETs.

IntroductionCurrent high demand for effective odor detection dogs calls for the development of reliable methods for measuring performance-related behavioral phenotypes in these highly specialized working animals. The Canine Behavioral Assessment & Research Questionnaire (C-BARQ) is a widely used behavioral assessment tool among working dog organizations with a demonstrated ability to predict success/failure of dogs in training. However, this instrument was developed originally to study the prevalence of behavior problems in the pet dog population, and it therefore lacks the capacity to measure specific behavioral propensities that may also be important predictors of working dog success. The current paper examines the factor structure, internal reliability, and content validity of a modified version of the C-BARQ designed to evaluate four new domains of canine behavior in addition to those encompassed by the original C-BARQ. These domains, labeled Playfulness, Impulsivity, Distractibility, and Basophobia (fear of falling), respectively, describe aspects of canine behavior or temperament which are believed to contribute substantially to working dog performance.MethodsExploratory factor analysis (EFA) of owner/handler questionnaire responses based on a sample of 1,117 working odor detection dogs.ResultsA total of 15 factors were extracted by EFA, 10 of which correspond to original C-BARQ factors. The remaining 5 comprise the four new domains– Playfulness, Impulsivity, Distractibility, and Basophobia– as well as a fifth new factor labeled Food focus.DiscussionThe resulting Working Dog Canine Behavioral Assessment & Research Questionnaire (WDC-BARQ) successfully expands the measurement capacities of the original C-BARQ to include dimensions of behavior/temperament of particular relevance to many working dog populations.

To maintain a global zero-emission policy and a high standard of living, new energy systems with higher system efficiency and net zero-emission productions need to be designed and deployed. This paper describes a novel integrated system between a direct-fired supercritical carbon dioxide (sCO2) power system with hydrogen and oxygen for zero-emission power generation and storage. sCO2 power cycles offer higher thermodynamic efficiencies than conventional gas-fired Brayton cycles. Heat is added to the system from the combustion of hydrogen and oxygen. The system consists of an electrolyzer unit and two cryogenic storage systems for hydrogen and oxygen. The proposed system is designed as a medium/long-term battery that can use excess electricity from the grid to produce hydrogen (electrolyzer) and supply to the grid (hydrogen combustion) in times of higher demand. Nitrous oxide emissions are mitigated by oxy-combustion and water separation from the post-combustion products allows for a closed-loop water cycle. The optimization of cycle parameters suggests a turbine inlet temperature of 1473 K and a pressure of 30 MPa for a specific net power output of 348 kJ/kg electrical. This results in an H2-sCO2 direct-fired power cycle efficiency of around 53 % with an overall system round-trip efficiency of up to 35 %.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

ABSTRACTChronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy that affects both free-ranging and farmed cervid species, including mule deer, white-tailed deer, and elk (Odocoileus hemionus, Odocoileus virginianus, and Cervus canadensis). Due to the long incubation period and variability of clinical signs, CWD can expand and spread to new areas before they reach diagnostically detectable levels. Antemortem testing methods currently available can be difficult to obtain and to be applied to the large numbers required for adequate surveillance. However, key volatile biomarkers could be harnessed for non-invasive antemortem surveillance. Detection dogs are the most effective tool currently available for volatile detection; dogs can effectively complete wildlife surveys at rates surpassing that of humans. This study is the first to demonstrate that trained detection dogs can be used as an antemortem test for CWD. First, we trained three dogs to differentiate between CWD-positive and CWD-negative white-tailed deer faeces in a laboratory setting. Dogs spent significantly more time at the positive sample than the negative samples, suggesting that they differentiated between the positive and negative volatile signatures. We then trained the same dogs to search for CWD-positive faecal samples in a more naturalistic field setting. In the field, dogs found 8/11 CWD-positive samples and had an average false detection rate of 13%. These results suggest that dogs can be trained to differentiate CWD-positive faeces from CWD-negative faeces in both laboratory and field settings. Future studies will compare canine accuracy to other antemortem methods, as well as improved canine training methods.

Abstract Background Working dogs exposed to narcotics might require reversal in the field. Objective To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. Animals Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg. Methods In this randomized, controlled cross‐over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120 minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. Results There was a significant increase in sedation score from baseline (0.25 [−4 to 1] IM; 0 [−2 to 1] IN) after fentanyl administration (11 [5‐12] IM; 9.25 [4‐11] IN), followed by a significant reduction at 5 (0.5 [−0.5 to 1.5] IM; 1.25 [−1.5 to 4.5] IN) through 120 minutes (−0.5 [−2 to 1] IM; 0 [−4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8‐18.8] ng/mL IN, 36.7 [22.1‐56.4] ng/mL IM, P

Abstract There is growing interest in canine behavioral research specifically for working dogs. Here we take advantage of a dataset of a Transportation Safety Administration olfactory detection cohort of 628 Labrador Retrievers to perform Machine Learning (ML) prediction and classification studies of behavioral traits and environmental effects. Data were available for four time points over a 12 month foster period after which dogs were accepted into a training program or eliminated. Three supervised ML algorithms had robust performance in correctly predicting which dogs would be accepted into the training program, but poor performance in distinguishing those that were eliminated (~ 25% of the cohort). The 12 month testing time point yielded the best ability to distinguish accepted and eliminated dogs (AUC = 0.68). Classification studies using Principal Components Analysis and Recursive Feature Elimination using Cross-Validation revealed the importance of olfaction and possession-related traits for an airport terminal search and retrieve test, and possession, confidence, and initiative traits for an environmental test. Our findings suggest which tests, environments, behavioral traits, and time course are most important for olfactory detection dog selection. We discuss how this approach can guide further research that encompasses cognitive and emotional, and social and environmental effects.

Abstract Background Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. Methods A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb])

IntroductionThe study investigated the utilization of odor detection dogs to identify the odor profile of Staphylococcus aureus (S. aureus) biofilms in pure in vitro samples and in in vivo biosamples from animals and humans with S. aureus periprosthetic joint infection (PJI). Biofilms form when bacterial communities aggregate on orthopedic implants leading to recalcitrant infections that are difficult to treat. Identifying PJI biofilm infections is challenging, and traditional microbiological cultures may yield negative results even in the presence of clinical signs.MethodsDogs were trained on pure in vitro S. aureus biofilms and tested on lacrimal fluid samples from an in vivo animal model (rabbits) and human patients with confirmed S. aureus PJI.ResultsThe results demonstrated that dogs achieved a high degree of sensitivity and specificity in detecting the odor profile associated with S. aureus biofilms in rabbit samples. Preliminary results suggest that dogs can recognize S. aureus volatile organic compounds (VOCs) in human lacrimal fluid samples.DiscussionTraining odor detection dogs on in vitro S. aureus, may provide an alternative to obtaining clinical samples for training and mitigates biosecurity hazards. The findings hold promise for culture-independent diagnostics, enabling early disease detection, and improved antimicrobial stewardship. In conclusion, this research demonstrates that dogs trained on in vitro S. aureus samples can identify the consistent VOC profile of PJI S. aureus biofilm infections. The study opens avenues for further investigations into a retained VOC profile of S. aureus biofilm infection. These advancements could revolutionize infectious disease diagnosis and treatment, leading to better patient outcomes and addressing the global challenge of antimicrobial resistance.

Abstract Background Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure. Methods We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PEmax). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure. Results We analyzed 385 lung function tests from 38 patients with SMA types 1c–3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2–30.1) and median standardized FVC, FEV1 and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PEmax was 35.3 cmH2O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV1, PEF and PEmax were lower in patients who electively started mechanical ventilation (p

Landing kinetics and kinematics have historically been correlated with potential injury. A factor that requires more attention associated with its correlation to injury risk includes the impact of physiological fatigue. Fatigue is a multifaceted phenomenon involving central and peripheral factors resulting in a slowing or cessation of motor unit firing and a decrease in maximal force and power. Sports participation rarely results in momentary muscular failure occurring, as many sports consist of intermittent periods of activity that are interspersed with short rest periods that allow for recovery to take place. However, over the course of the competition, fatigue can still accumulate and can result in impaired performance. Current literature on the topic struggles to replicate the peripheral and central metabolic stresses required to induce a state of fatigue that would be equivalent to athletic exposure. Furthermore, the current literature fails to demonstrate consistency regarding the kinetic implications associated with fatigue, which may be secondary to the inconsistencies associated with fatigue protocols utilized. This article focuses on providing an overview of the current literature associated with fatigue’s impact on the kinetics associated with landing from a jump. The article will provide a prospective methodology utilizing repeat bouts of the Wingate Anaerobic Power Test. The proposed protocol may help further our understanding of the relationship between fatigue and lower extremity biomechanics.

Chronic wasting disease (CWD) is a highly infectious, fatal prion disease that affects cervid species. One promising method for CWD surveillance is the use of detection dog–handler teams wherein dogs are trained on the volatile organic compound signature of CWD fecal matter. However, using fecal matter from CWD-positive deer poses a biohazard risk; CWD prions can bind to soil particles and remain infectious in contaminated areas for extended periods of time, and it is very difficult to decontaminate the affected areas. One solution is to use noninfectious training aids that can replicate the odor of fecal matter from CWD-positive and CWD-negative deer and are safe to use in the environment. Trained CWD detection dogs’ sensitivity and specificity for different training aid materials (cotton, GetXent tubes, and polydimethylsiloxane, or PDMS) incubated with fecal matter from CWD-positive and CWD-negative deer at two different temperatures (21 °C and 37 °C) for three different lengths of time (6 h, 24 h, and 48 h) were evaluated. Cotton incubated at 21 °C for 24 h was identified as the best aid for CWD based on the dogs’ performance and practical needs for training aid creation. Implications for CWD detection training and for training aid selection in general are discussed.

Abstract Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration’s (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed for family studies, we performed a case-control genome wide association study (GWAS) of elimination due to behavioral observation and testing results in a cohort of 528 Labrador Retrievers (2002–2013). We accounted for relatedness by including the pedigree as a covariate and maximized power by including individuals with phenotype, but not genotype, data (approximately half of this cohort). We determined genome wide significance based on Bonferroni adjustment of two quasi-likelihood score tests optimized for either small or nearly-fully penetrant effect sizes. Six loci were significant and five suggestive, with approximately equal numbers of loci for the two tests and frequencies of loci with single versus multiple mapped markers. Several loci implicate a single gene, including CHD2, NRG3 and PDE1A which have strong relevance to behavior in humans and other species. We briefly discuss how expanded studies of canine breeding programs could advance understanding of learning and performance in the mammalian life course. Although human interactions and other environmental conditions will remain critical, our findings suggest genomic breeding selection could help improve working dog populations.

Abstract Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes—SLC39A8, GRK4 and HGFAC—within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder. The role of these genes was assessed using the two-bottle choice addiction paradigm in transgenic mice for each of the genes. We found significant decreases in chronic alcohol consumption and preference in female Hgfac knockout (KO) mice, and decreased nicotine preference in male Hgfac KO compared with wild-type (WT) mice. Additionally, male Slc39a8 hypomorph mice showed greater overall nicotine preference compared with WT mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and preference in either sex. Thus, this study implicates Hgfac and Slc39a8 in alcohol and tobacco use in a sex-specific manner.

Working dogs are at a high risk of canine non-pyrogenic hyperthermia, a life-threatening condition that can occur due to physical exertion or environmental factors that inhibit dogs’ ability to cool themselves. Two frequently recommended cooling methods to reduce body temperature are water immersion and the application of isopropyl alcohol to paw pads. This cross-over study compared the relative efficacy of these methods in 12 working-dogs-in-training with post-exertional heat stress. On each study day, dogs had a physical exam and performed a warm-up exercise followed by sequential recalls in which dogs ran approximately 25 m between two designated handlers for 10 min until they showed multiple signs of heat stress or their core temperature reached 105 °F (40.6 °C). Dogs’ temperature and heart rate were collected after each recall. Dogs completed three study days, and each day, randomly received one of three interventions: passive cooling (no intervention), partial water immersion, or isopropyl alcohol. Post-intervention dogs rested for 20 min. Partial water immersion and isopropyl alcohol both cooled dogs more than no intervention, and water immersion cooled dogs more efficiently than isopropyl alcohol. Additionally, the application of isopropyl alcohol raised dogs’ heart rates more than water immersion or no intervention, suggesting that the process of applying isopropyl alcohol is potentially stressful to dogs. Thus, partial water immersion is preferred to cool dogs post-exertion due to its more efficient cooling and better tolerance of use.

Abstract Background Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life. Methods We measured maximal expiratory and inspiratory pressure (PEmax and PImax), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns. Results We included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1–2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PEmax and PImax were severely lowered in most patients throughout life, with PEmax values abnormally low (i.e.

In adults with severe aortic stenosis, sex and age differences in symptoms and diagnosis may lead to delays in intervention. Choice of intervention partly depends on expected longevity because bioprosthetic valves have limited durability, particularly in younger patients. Current guidelines recommend the following: a mechanical valve in younger adults (aged 80 years based on lower mortality and morbidity compared to SAVR and adequate valve durability. For patients aged 65–80 years, the choice between TAVI and a bioprosthetic SAVR depends on expected longevity, which is greater in women than men, as well as associated cardiac and noncardiac conditions, valvular and vascular anatomy, estimated risk of SAVR versus TAVI and expected complications and patient preferences.

Multisite phosphorylation of guanylyl cyclase (GC)-A, also known as NPR-A or NPR1, is required for receptor activation by natriuretic peptides (NPs) because alanine substitutions for the first four GC-A phosphorylation sites produce an enzyme that cannot be stimulated by NPs. In contrast, single Glu substitutions for the first six chemically identified GC-A phosphorylation sites to mimic the negative charge of phosphate produced an enzyme that is activated by NPs but had an elevated Michaelis constant (Km), resulting in low activity. Here, we show that vicinal (double adjacent) Glu substitutions for the same sites to mimic the two negative charges of phosphate produced a near wild type (WT) enzyme with a low Km. Unlike the enzyme with single glutamate substitutions, the vicinally substituted enzyme did not require the functionally identified Ser-473-Glu substitution to achieve WT-like activity. Importantly, the negative charge associated with either phosphorylation or glutamate substitutions was required for allosteric activation of GC-A by ATP. We conclude that vicinal Glu substitutions are better phosphomimetics than single Glu substitutions and that phosphorylation is required for allosteric activation of GC-A in the absence and presence of NP. Finally, we suggest that the putative functionally identified phosphorylation sites, Ser-473 in GC-A and Ser-489 in GC-B, are not phosphorylation sites at all.

Exercise training is recommended for patients with idiopathic pulmonary fibrosis (IPF); however, the mechanism(s) underlying its physiological benefits remain unclear. We investigated the effects of an individualised aerobic interval training programme on exercise capacity and redox status in IPF patients. IPF patients were recruited prospectively to an 8-week, twice-weekly cardiopulmonary exercise test (CPET)-derived structured responsive exercise training programme (SRETP). Systemic redox status was assessed pre- and post-CPET at baseline and following SRETP completion. An age- and sex-matched non-IPF control cohort was recruited for baseline comparison only. At baseline, IPF patients (n = 15) had evidence of increased oxidative stress compared with the controls as judged by; the plasma reduced/oxidised glutathione ratio (median, control 1856 vs. IPF 736 p = 0.046). Eleven IPF patients completed the SRETP (median adherence 88%). Following SRETP completion, there was a significant improvement in exercise capacity assessed via the constant work-rate endurance time (+82%, p = 0.003). This was accompanied by an improvement in post-exercise redox status (in favour of antioxidants) assessed via serum total free thiols (median increase, +0.26 μmol/g protein p = 0.005) and total glutathione concentration (+0.73 μM p = 0.03), as well as a decrease in post-exercise lipid peroxidation products (−1.20 μM p = 0.02). Following SRETP completion, post-exercise circulating nitrite concentrations were significantly lower compared with baseline (−0.39 μM p = 0.04), suggestive of exercise-induced nitrite utilisation. The SRETP increased both endurance time and systemic antioxidant capacity in IPF patients. The observed reduction in nitrite concentrations provides a mechanistic rationale to investigate nitrite/nitrate supplementation in IPF patients.

Phlegmasia cerulea dolens is a rare presentation of deep venous thrombus treated with catheter directed thrombolysis and pharmacomechanical thrombectomy. This is the case of a 78-year-old woman who underwent catheter directed thrombolysis to treat phlegmasia cerulea dolens and subsequently developed left-sided hemiplegia and expressive aphasia in the setting of an international normalized ratio of 2.0. Further imaging revealed a lacunar infarct in the right thalamus with a middle cerebral artery distribution. Further workup revealed a patent foramen ovale. We highlight the unexpected enigmatic consequence from multimodal endovascular intervention, the consequence of long-term inferior vena cava filters.

Landslide is a major natural hazard in Kyrgyzstan and Tajikistan. Knowledge about atmospheric triggering conditions and climatic disposition of landslides in Kyrgyzstan and Tajikistan is limited even though this topic has already been investigated thoroughly in other parts of the world. In this study, the newly developed, high-resolution High Asia Refined analysis version 2 (HAR v2) data set generated by dynamical downscaling was combined with historical landslide inventories to analyze the atmospheric conditions that initialized landslides in Kyrgyzstan and Tajikistan. The results indicate the crucial role of snowmelt in landslide-triggering processes since it contributes to the initialization of 40 % of landslide events. Objective thresholds for rainfall, snowmelt, and the sum of rainfall and snowmelt (rainfall + snowmelt) were defined. Thresholds defined by rainfall + snowmelt have the best predictive performance. Mean intensity, peak intensity, and the accumulated amount of rainfall + snowmelt events show similar predictive performance. Using the entire period of rainfall + snowmelt events results in better predictive performance than just considering the period up to landslide occurrence. Mean annual exceedance maps were derived from defined regional thresholds for rainfall + snowmelt. Mean annual exceedance maps depict climatic disposition and have added value in landslide susceptibility mapping. The results reported in this study highlight the potential of dynamical downscaling products generated by regional climate models in landslide prediction.

Similar to other organizations that encourage positive youth development, the American Kennel Club (AKC) created the Junior Showmanship program to develop skills and pave a path for the next generation of competitors in canine conformation. Although participants age out of the Junior Showmanship Program when they turn eighteen, the hope is that Juniors will continue to be active in dog sports into adulthood. Females are overly represented in all age groups in this survey and in current participation. Although both males and females most commonly stopped participating at age 17 or 18, males had a significantly higher drop out at age 15. Further study is warranted to investigate factors specifically pertaining to male participation. A strong Belief System Model which accounted for positive responses associated with camaraderie and mentoring during the showmanship program was significantly (p=0.01) associated with commitment, member interest and active participation as an adult. In addition, success in the show ring was associated with future involvement in conformation or dog sports. Thus, both perceived achievement and mentorship by adult “volunteers” were associated with continued participation.

Abstract Surface plasmons have found a wide range of applications in plasmonic and nanophotonic devices. The combination of plasmonics with three-dimensional photonic crystals has enormous potential for the efficient localization of light in high surface area photoelectrodes. However, the metals traditionally used for plasmonics are difficult to form into three-dimensional periodic structures and have limited optical penetration depth at operational frequencies, which limits their use in nanofabricated photonic crystal devices. The recent decade has seen an expansion of the plasmonic material portfolio into conducting ceramics, driven by their potential for improved stability, and their conformal growth via atomic layer deposition has been established. In this work, we have created three-dimensional photonic crystals with an ultrathin plasmonic titanium nitride coating that preserves photonic activity. Plasmonic titanium nitride enhances optical fields within the photonic electrode while maintaining sufficient light penetration. Additionally, we show that post-growth annealing can tune the plasmonic resonance of titanium nitride to overlap with the photonic resonance, potentially enabling coupled-phenomena applications for these three-dimensional nanophotonic systems. Through characterization of the tuning knobs of bead size, deposition temperature and cycle count, and annealing conditions, we can create an electrically- and plasmonically-active photonic crystal as-desired for a particular application of choice.

ObjectiveSeptic peritonitis is associated with significant morbidity and mortality. As a potential therapeutic agent in the treatment of sepsis, 2-O, 3-O desulfated heparin (ODSH) reduces histones and platelet factor 4 (PF4) in mouse sepsis models. This pilot clinical trial evaluated the safety and effect of ODSH in client-owned dogs with septic peritonitis.InterventionsIn an IACUC-approved, open-label, prospective, dose-escalation clinical trial in 6 dogs with spontaneous septic peritonitis, ODSH administration was initiated following surgical explore to achieve source control. Acute patient physiology and laboratory evaluation (APPLEfast and APPLEfull) scores on admission, source of septic peritonitis, requirement for vasopressors, the administration of blood products, and survival to discharge were recorded. Platelet count, cell free DNA (cfDNA) concentration, and platelet factor 4 (PF4) concentrations were measured at the time of each ODSH dosage. A dose of ODSH was administered every 8 hs for a total of 4 doses (maximum total dosage 75 mg/kg) based on a pre-determined escalation protocol. Patients were monitored in the ICU following administration for evidence of clinical hemorrhage.Main ResultsThe mean APPLEfast and APPLEfull scores on admission were 22 +/- 6 and 32 +/-10, respectively. Four dogs received 4 total dosages of ODSH and 2 dogs received 3 total dosages of ODSH intravenously. The mean total dosage of ODSH administered during the study period was 48.3 +/- 21.6 mg/kg. No dog required dose de-escalation or had any evidence of bleeding. Four dogs survived to discharge.ConclusionsNo adverse effects of ODSH administration were documented in dogs with septic peritonitis. A randomized controlled trial is necessary to evaluate ODSH as a novel therapeutic in the treatment of septic peritonitis.

COVID-19 has revealed how challenging it is to manage global, systemic and compounding crises. Like COVID-19, climate change impacts, and maladaptive responses to them, have potential to disrupt societies at multiple scales via networks of trade, finance, mobility and communication, and to impact hardest on the most vulnerable. However, these complex systems can also facilitate resilience if managed effectively. This review aims to distil lessons related to the transboundary management of systemic risks from the COVID-19 experience, to inform climate change policy and resilience building. Evidence from diverse fields is synthesised to illustrate the nature of systemic risks and our evolving understanding of resilience. We describe research methods that aim to capture systemic complexity to inform better management practices and increase resilience to crises. Finally, we recommend specific, practical actions for improving transboundary climate risk management and resilience building. These include mapping the direct, cross-border and cross-sectoral impacts of potential climate extremes, adopting adaptive risk management strategies that embrace heterogenous decision-making and uncertainty, and taking a broader approach to resilience which elevates human wellbeing, including societal and ecological resilience.

Working dogs are prevalent throughout our societies, assisting people in diverse contexts, from explosives detection and livestock herding, to therapy partners. Our scientific exploration and understanding of animal welfare have grown dramatically over the last decade. As community attitudes toward the use of animals continue to change, applying this new knowledge of welfare to improve the everyday lives of working dogs will underpin the sustainability of working with dogs in these roles. The aim of this report was to consider the scientific studies of working dogs from the last decade (2011–2021) in relation to modern ethics, human interaction, and the five domains of animal welfare: nutrition, environment, behavioral interaction, physical health, and mental state. Using this framework, we were able to analyze the concept and contribution of working dog welfare science. Noting some key advances across the full working dog life cycle, we identify future directions and opportunities for interdisciplinary research to optimize dog welfare. Prioritizing animal welfare in research and practice will be critical to assure the ongoing relationship between dogs and people as co-workers.

The spread of SARS-CoV-2, which causes the disease COVID-19, is difficult to control as some positive individuals, capable of transmitting the disease, can be asymptomatic. Thus, it remains critical to generate noninvasive, inexpensive COVID-19 screening systems. Two such methods include detection canines and analytical instrumentation, both of which detect volatile organic compounds associated with SARS-CoV-2. In this study, the performance of trained detection dogs is compared to a noninvasive headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) approach to identifying COVID-19 positive individuals. Five dogs were trained to detect the odor signature associated with COVID-19. They varied in performance, with the two highest-performing dogs averaging 88% sensitivity and 95% specificity over five double-blind tests. The three lowest-performing dogs averaged 46% sensitivity and 87% specificity. The optimized linear discriminant analysis (LDA) model, developed using HS-SPME-GC-MS, displayed a 100% true positive rate and a 100% true negative rate using leave-one-out cross-validation. However, the non-optimized LDA model displayed difficulty in categorizing animal hair-contaminated samples, while animal hair did not impact the dogs’ performance. In conclusion, the HS-SPME-GC-MS approach for noninvasive COVID-19 detection more accurately discriminated between COVID-19 positive and COVID-19 negative samples; however, dogs performed better than the computational model when non-ideal samples were presented.

Disaster search dogs traverse diverse and unstable surfaces found in collapsed buildings. It is unknown if the physical conditioning on a treadmill involves the same muscle groups that are involved in rubble search. This 14-week prospective cohort study was conducted to investigate changes within the thermal gradients of specific dog muscles following treadmill compared to rubble search. Nine dogs, ranging in age from 6 months to 4 years, were randomly assigned to one of two groups. Each week the two groups would participate in either 20 min of treadmill or rubble searches. Prior to exercise, the dogs were weighed and then kenneled in a temperature-controlled study room for 20 min at 21°C. Pre-exercise thermal images were then captured of the standing dog from the dorsal, left and right lateral, and caudal perspectives, and of the sitting dog from the rostral perspective. Following a 10-min warm-up period of stretches, dogs proceeded to either treadmill or search. Upon completion, dogs were kenneled in the study room for 20 min prior to post-exercise thermal images. Images were sectioned into 22 muscle regions, the pre-exercise images were subtracted from the post-exercise images to determine the temperature difference (ΔT) for that dog, on that day, for that activity. Thermography measures radiant energy, temperature, and converts this information into an image. This study looked at ΔT within a region pre and post-exercise. The study failed to find a statistically significant difference in the ΔT within each muscle group between treadmill and search activities. There was a decrease in ΔT within all muscle regions over the of the study except for the right cranial shoulder, right caudal shoulder, and right hamstring for the treadmill activity only. The decrease was significant in the pelvis, left longissimus, right cranial shoulder for the search activity, left oblique, left caudal shoulder, and left quadricep muscular regions. These findings suggest that ΔT in muscle groups are similar between treadmill exercise and rubble search. Regardless of the exercise type, 14 weeks of structured Search and Rescue training and treadmill exercise resulted in less ΔT associated with a structured weekly exercise.

This paper takes a new look on transition processes in social-ecological systems, identified based on household use of direct ecosystem services in a case study in KwaZulu-Natal, South Africa. We build on the assumption that high dependence on local ecosystems for basic needs satisfaction corresponds to a “green loop” type of system, with direct feedbacks between environmental degradation and human well-being. Increasing use of distant ecosystems marks a regime shift and with that, the transition to “red loops” in which feedbacks between environmental degradation and human well-being are only indirect. These systems are characterized by a fundamentally different set of sustainability problems as well as distinct human-nature connections. The analysis of a case study in KwaZulu-Natal, South Africa, shows that social-ecological systems identified as green loops in 1993, the average share of households using a characteristic bundle of direct ecosystem services drops consistently (animal production, crop production, natural building materials, freshwater, wood). Conversely, in systems identified as red loops, mixed tendencies occur which underpins non-linearities in changing human-nature relationships. We propose to apply the green to red loop transition model to other geographical contexts with regards to studying the use of local ecosystem services as integral part of transformative change in the Anthropocene.

Dogs are trained for a variety of working roles including assistance, protection, and detection work. Many canine working roles, in their modern iterations, were developed at the turn of the 20th century and training practices have since largely been passed down from trainer to trainer. In parallel, research in psychology has advanced our understanding of animal behavior, and specifically canine learning and cognition, over the last 20 years; however, this field has had little focus or practical impact on working dog training. The aims of this narrative review are to (1) orient the reader to key advances in animal behavior that we view as having important implications for working dog training, (2) highlight where such information is already implemented, and (3) indicate areas for future collaborative research bridging the gap between research and practice. Through a selective review of research on canine learning and behavior and training of working dogs, we hope to combine advances from scientists and practitioners to lead to better, more targeted, and functional research for working dogs.

Dogs perform a variety of integral roles in our society, engaging in work ranging from assistance (e.g., service dogs, guide dogs) and therapy to detection (e.g., search-and-rescue dogs, explosive detection dogs) and protection (e.g., military and law enforcement dogs). However, success in these roles, which requires dogs to meet challenging behavioral criteria and to undergo extensive training, is far from guaranteed. Therefore, enhancing the selection process is critical for the effectiveness and efficiency of working dog programs and has the potential to optimize how resources are invested in these programs, increase the number of available working dogs, and improve working dog welfare. In this paper, we review two main approaches for achieving this goal: (1) developing selection tests and criteria that can efficiently and effectively identify ideal candidates from the overall pool of candidate dogs, and (2) developing approaches to enhance performance, both at the individual and population level, via improvements in rearing, training, and breeding. We summarize key findings from the empirical literature regarding best practices for assessing, selecting, and improving working dogs, and conclude with future steps and recommendations for working dog organizations, breeders, trainers, and researchers.

The spotted lanternfly (Lycorma delicatula) is an invasive species first detected in 2014. The insect feeds on plants causing severe damage in vineyards such as the occurrence of sooty mold fungus that impairs leaf photosynthesis. Currently, there is extensive research on how to track and ultimately prevent the spread of this species. It lays eggs that persist through the winter, while the adults die out, which presents a unique opportunity to enter infested or suspected infested areas to begin quarantine and management of the spread while the species is dormant. Detection dogs may be a tool that can be used to search out the spotted lanternfly egg masses during this overwintering period, however it is not known whether dogs can detect any specific odor from the spotted lanternfly eggs. Moreover, as the eggs are only available during certain times of the year, and hatch based on temperature, finding training aids for the dogs could prove difficult. In this study, we investigated whether three detection dogs could learn the odor from dead spotted lanternfly egg masses and if so, whether that would allow them to recognize live spotted lanternfly egg masses. We found that dogs could be trained to find dead spotted lanternfly egg masses, and could learn to ignore relevant controls, with high levels of sensitivity and specificity (up to 94.6% and 92.8%, respectively). Further, we found that after the training, dogs could find live spotted lanternfly egg masses without additional training and returned to previous levels of sensitivity and specificity within a few sessions. Coded videos of training and testing sessions showed that dogs spent more time at the egg masses than at controls, as expected from training. These results suggest that dead spotted lanternfly egg masses could be a useful training aid for spotted lanternfly detection dogs.

While the world awaits a widely available COVID-19 vaccine, availability of testing is limited in many regions and can be further compounded by shortages of reagents, prolonged processing time and delayed results. One approach to rapid testing is to leverage the volatile organic compound (VOC) signature of SARS-CoV-2 infection. Detection dogs, a biological sensor of VOCs, were utilized to investigate whether SARS-CoV-2 positive urine and saliva patient samples had a unique odor signature. The virus was inactivated in all training samples with either detergent or heat treatment. Using detergent-inactivated urine samples, dogs were initially trained to find samples collected from hospitalized patients confirmed with SARS-CoV-2 infection, while ignoring samples collected from controls. Dogs were then tested on their ability to spontaneously recognize heat-treated urine samples as well as heat-treated saliva from hospitalized SARS-CoV-2 positive patients. Dogs successfully discriminated between infected and uninfected urine samples, regardless of the inactivation protocol, as well as heat-treated saliva samples. Generalization to novel samples was limited, particularly after intensive training with a restricted sample set. A unique odor associated with SARS-CoV-2 infection present in human urine as well as saliva, provides impetus for the development of odor-based screening, either by electronic, chemical, or biological sensing methods. The use of dogs for screening in an operational setting will require training with a large number of novel SARS-CoV-2 positive and confirmed negative samples.