Search Results (77)

Millions of puppies are welcomed into the homes of families around the world each year. However, understanding the ways in which puppies are bred and raised by their breeders, as well as the perspectives and perceptions underpinning these practices, is still in its infancy. The current study administered an online survey to 200 Australian dog breeders to investigate their breeding program characteristics, breeding dog selection, understanding of the importance of early experiences in puppyhood, and the extent and diversity of their puppy rearing and socialisation practices. Results indicated that breeders were motivated by breed improvement and producing dogs for themselves rather than providing companion dogs, despite most of their puppies being placed in companionship roles. The participating breeders also acknowledged the important role they play in shaping puppies’ behaviour and temperament, which was reflected in both their breeding dog selection and in their rearing and socialisation practices. The majority of breeders housed their litters within their residence for the initial weeks of life but the socialisation experiences they provided were variable in type and frequency. Longer-term breeders and those with larger, more intensive programs reported providing human-focused socialisation experiences less frequently, though the correlational nature of these findings require cautious interpretation. Whilst future research should endeavor to explore these results more comprehensively among a more diverse sample, these findings provide valuable insight into the breeding, rearing, and socialisation process undertaken by dog breeders in Australia. Full article

Background/Objectives: Chronic kidney disease of unknown etiology (CKDu) disproportionately affects young male agricultural workers who are otherwise healthy. There is a scarcity of biomarkers for early detection of this type of kidney disease. We hypothesized that small extracellular vesicles (sEVs) released into urine may provide novel biomarkers. Methods: We obtained two urine samples at the start and the end of a workday in the fields from a limited set of workers with and without kidney impairment. Isolated sEVs were characterized for size, surface marker expression, and purity and, subsequently, their lipid composition was determined by mass spectrometry. Results: The number of particles per ml of urine normalized to osmolality and the size variance were larger in workers with possible CKDu than in control workers. Surface markers CD9, CD63, and CD81 are characteristic of sEVs and a second set of surface markers suggested the kidney as the origin. Differential expression of CD25 and CD45 suggested early inflammation in CKDu workers. Of the twenty-one lipids differentially expressed, several were bioactive, suggesting that they may have essential functions. Remarkably, fourteen of the lipids showed intermediate expression values in sEVs from healthy individuals with acute creatinine increases after a day of work. Conclusions: We identified twenty-one possible lipid biomarkers in sEVs isolated from urine that may be able to distinguish agricultural workers with early onset of CKDu. Differentially expressed surface proteins in these sEVs suggested early-stage inflammation. This pilot study was limited in the number of workers evaluated, but the approach should be further evaluated in a larger population. Full article

Background: The Malnutrition Screening Tool (MST) is commonly used to identify malnutrition risk; however it has demonstrated poor sensitivity to detect malnutrition in inpatients with chronic kidney disease (CKD) and kidney replacement therapy (KRT) populations. Gastrointestinal symptoms, such as poor appetite, may better detect malnutrition. The accuracy of MST or other nutrition-related parameters to detect malnutrition in ambulatory patients with CKD stages 4–5 without KRT has not been evaluated. Methods: A single site retrospective audit of outpatient records from May 2020 to March 2025 was conducted. Patients with eGFR < 25 mL/min/1.73 m² without KRT who had both MST and a 7-point Subjective Global Assessment (SGA) within 7 days were included. Sensitivity, specificity, and ROC-AUC analyses compared nutritional parameters against SGA-defined malnutrition. Nutritional parameters tested included MST, hand grip strength, upper gastrointestinal symptom burden, poor appetite and a combination of some of these parameters. Results: Among 231 patients (68.8% male, median age 69 years, median eGFR 15), 29.9% were at risk of malnutrition (MST ≥ 2) and 33.8% malnourished (SGA ≤ 5). All potential screening tools had AUC ranging from 0.604 to 0.710, implying a poor-to-moderate discriminator ability to detect malnutrition. Combining HGS ≤ 29.5 kg or MST ≥2 demonstrated high sensitivity (95.5%) and negative predictive value (93.3%), but low specificity (33.3%) for detecting malnutrition, indicating this approach is effective for ruling out malnutrition but may over-identify at-risk individuals. Conclusions: MST and other tested tools showed limited overall accuracy to identify malnutrition. Using combined nutritional markers of HGS or MST score was the most sensitive tool for detecting malnutrition in this advanced CKD without KRT population. Full article

In this paper, a method of estimating the probability of susceptibility of a component on a circuit board to electromagnetic interference (EMI) is presented. The integrated circuit electromagnetic compatibility (IC EMC) standard IEC 62132-4 enables the assessment of the susceptibility of an IC by determining the forward power incident on each pin required to induce a malfunction. Although we focus on IC susceptibility, the method might be applied to other components and sub-circuits where the same information is known. Building upon a previously established numerical model capable of estimating the average coupled forward power at the end of a trace of a lossless PCB trace for a known load in a reverberant environment, this paper updates the model by incorporating PCB losses and utilizes the updated model to estimate the distribution of coupled forward power at the package pin over a number of boundary conditions in a reverberant field. Thus, the probability of failure can be predicted from the known component susceptibility level, the length, transmission line parameters, and the loading of the track to which it is attached. To validate this numerical model, the paper includes measurements obtained with a custom-designed RF IC detector, created for the purpose of measuring RF power coupled into the package pin via test PCB tracks. Full article

Prior research has reported an association between human papillomavirus (HPV) seropositivity and dementia or Alzheimer’s disease. This study aimed to cross-sectionally investigate the association between HPV seropositivity and cognitive function in older adults. The data used for this study were from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) cycles. To account for the complex survey design and missing data, we applied survey-weighted regression models to each imputed dataset, using multiple imputation techniques. Across all cognitive test outcomes, no statistically significant association was observed between HPV status and cognitive performance after controlling for covariates. These findings suggest that there may not be a significant association between HPV infection and cognitive scores in this NHANES sample. Stakeholders, including policymakers and healthcare providers, should consider these findings in their professional decision-making. Future research should investigate the association between HPV seropositivity and cognition using other samples in order to further characterize the association between HPV and cognitive function in older adults. Full article

Space is one of the UK’s fastest-growing industry sectors of the last decade. Recognising this, in 2021 the UK Government’s first National Space Strategy established a new vision to make the nation one of the most innovative and attractive worldwide space economies. As part of the strategic funding programme, in 2023, the UK Space Agency (UKSA) funded a scoping study to assess the potential of satellite data to address issues that the three North East England Local Resilience Forums face at all stages of implementing the UK’s Integrated Emergency Management Framework (IEMF). Through dedicated workshops convened by two North East England universities, regional stakeholders from the emergency domain and related industries identified three case studies ripe for applying satellite data in support of multi-agency IEMF activities. Master’s students in the UK’s Centre for Doctoral Training in Geospatial Systems then undertook a month-long integrated group project to assess the potential for satellite imagery to be applied in the identified application areas. The research reported in this paper demonstrates how satellite imagery may be adopted to help address challenges posed during power outages, for mitigating illegal waste site fires, and during periods of snow and extreme cold. While the maturity levels of satellite applications vary in the three case studies due to data availability and image resolution, all three cases demonstrate that space data, particularly when augmented with additional geospatial information, help to enhance IEMF analysis. It is anticipated that the findings from the study will help stakeholders involved in IEMF management appreciate the added value of integrating satellite data into their current processes and analyses. By empowering key stakeholders to use satellite applications more effectively, it is predicted that better decisions will be achieved, thereby improving emergency risk management. A prototype dashboard, an output of the research to demonstrate the potential of space data for emergency management, is available online. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor prognosis, largely owing to its heterogeneity and the involvement of multiple intracellular signaling pathways that contribute to drug resistance. While recent advancements in targeted drug combination therapies, such as dabrafenib and trametinib, show promise for certain GBM subgroups, identifying effective drug combinations across the broader GBM population remains a challenge. Integrin-mediated signaling, particularly through Focal Adhesion Kinase (FAK), plays a pivotal role in GBM pathogenesis and invasion, making it a potential therapeutic target and component of future drug combination strategies. Methods: In this study, we utilized a chemogenomic screening approach to identify synergistic drug combinations that target FAK in glioblastoma. We initially employed a CRISPR-engineered GBM model to assess the effects of FAK depletion and subsequently discovered that combining FAK inhibitors such as VS4718 with MEK inhibitors, particularly trametinib, demonstrated synergistic effects. This potent combination was validated using various 2D and 3D assays, including cell viability/apoptosis assessment, synergistic analysis, cellular imaging, and target engagement assays. This combination also effectively inhibited spheroid growth and invasion across a diverse panel of patient-derived GBM stem cells. Molecular mechanisms underlying these effects include suppression of multiple kinase signaling pathways and enhanced apoptosis, elucidated using Reverse-Phase Protein Array (RPPA) profiling and Western blot validation. Result: In vivo, combination therapy significantly reduced the tumor volume in orthotopic transplantation models. Conclusions: These findings suggest that the combination of FAK and MEK inhibitors represents a promising therapeutic strategy to overcome the challenges of GBM treatment. Full article

MuRF1 [muscle RING (Really Interesting New Gene)-finger protein-1] is an ubiquitin-protein ligase (E3), which encode by TRIM63 (tripartite motif containing 63) gene, playing a crucial role in regulating cardiac muscle size and function through ubiquitylation. Among hypertrophic cardiomyopathy (HCM) patients, 24 TRIM63 variants have been identified, with 1 additional variant linked to restrictive cardiomyopathy. However, only three variants have been previously investigated for their functional effects. The structural impacts of the 25 variants remain unexplored. This study investigated the effects of 25 MuRF1 variants on ubiquitylation activity using in vitro ubiquitylation assays and structural predictions using computational approaches. The variants were generated using site-directed PCR (Polymerase Chain Reaction) mutagenesis and subsequently purified with amylose affinity chromatography. In vitro ubiquitylation assays demonstrated that all 25 variants compromised the ability of MuRF1 to monoubiquitylate a titin fragment (A168-A170), while 17 variants significantly impaired or completely abolished auto-monoubiquitylation. Structural modelling predicted that 10 MuRF1 variants disrupted zinc binding or key stabilising interactions, compromising structural integrity. In contrast, three variants were predicted to enhance the structural stability of MuRF1, while six others were predicted to have no discernible impact on the structure. This study underscores the importance of functional assays and structural predictions in evaluating MuRF1 variant pathogenicity and provides novel insights into mechanisms by which these variants contribute to HCM and related cardiomyopathies. Full article

Flood incident management involves taking actions to save lives and reduce damages during a flood. Agent-based modelling tools have recently been developed to simulate the dynamic interactions between people and floodwater as a flood event unfolds. To date, these have only been applied in locations with a wealth of data, relying upon bespoke local or national datasets. Although informal settlements have a concentration of vulnerable people and are often more exposed to natural hazards, data availability is often limited, posing challenges for planning and implementing flood incident management actions. In this study, a model that was first applied in the UK is adapted and applied to simulate flood evacuations in Kibera, a densely populated informal settlement in Nairobi. Although data quality limits some of the model’s potential, the results reproduce patterns of observed behaviour. Evacuation shelters in the Northwest, North, and Northeast are shown to perform best. A major exit route to the South, a bridge crossing, and a river path are shown to be especially prone to congestion during evacuations. This paper reports on the first application of an agent-based model to an informal settlement, Kibera. The demonstration is an important step towards an operational tool for flood incident management planning in informal settlements around the world. Full article

This narrative review examines infectious diseases as modifiable risk factors for dementia, particularly in the context of an aging global population. As the prevalence of Alzheimer’s disease and related dementias is expected to rise, prevention has become increasingly important due to the limited efficacy of current treatments. Emerging evidence links specific infectious diseases to increased dementia risk, possibly through mechanisms like neuroinflammation and disruption to normal cell function. Here, we review findings on how viral and bacterial infections contribute to dementia and explore potentially preventive measures, including vaccinations and antiviral treatments. Studies indicate that vaccinations against influenza, herpes zoster, and hepatitis, as well as antiviral treatments targeting human herpesvirus, could reduce the incidence of dementia. Additionally, non-pharmaceutical interventions during pandemics and in long-term care settings are highlighted as effective strategies for reducing the spread of infectious diseases, potentially lowering dementia risk. Putative mechanisms underlying the protective effects of these interventions suggest that reducing systemic inflammation may be important to their efficacy. While the currently available evidence suggests at best an association between some infectious diseases and dementia, this narrative review emphasizes the need to incorporate infectious disease prevention into broader public health strategies to potentially mitigate the growing burden of dementia. Further research is required to explore these preventive measures across diverse populations and to deepen our understanding of the biological mechanisms involved. Full article

Background: Approximately 11.3% of the US population has diabetes. The burden of diabetes is higher in older adults and African Americans (AAs), such that 40% of adults aged 50 years and older have diabetes; African Americans are 60% more likely to be diagnosed with diabetes compared to non-Hispanic Whites (NHWs). Structural racism has resulted in fewer economic and educational opportunities for AAs, higher social risks, and unmet basic needs, which result in financial instability, housing instability, food insecurity, and a lack of transportation compared to NHWs. The presence of these unmet basic needs is a driver of poor adherence to diabetes self-management in older AAs. Aim: To test the preliminary efficacy of a nurse case-manager, telephone-delivered intervention that provides foundational diabetes self-management education and skills training, while also addressing and resolving the unmet social needs of older AAs with poorly controlled type 2 diabetes mellitus (T2DM). The primary hypothesis is that older AAs with T2DM randomized to the DM Social Needs intervention will have significantly lower hemoglobin A1C (HbA1C), blood pressure, and LDL levels compared to the usual care arm at 6 months post randomization. Methods: This is a three-year prospective, randomized clinical trial that will enroll 100 AAs aged 50 and older with type 2 diabetes (T2DM) and HbA1C ≥ 8% into one of the following two groups: (1) a nurse case-manager, telephone-delivered intervention that provides foundational diabetes self-management education and skills training, but also addresses and resolves unmet social needs; or (2) an enhanced usual care group that will receive mailed diabetes education materials. Participants will be followed for 6 months to determine the effect of the intervention on HbA1C, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. Results: Baseline characteristics will be presented by study group, and within- and between-group changes in primary outcomes from baseline to 6 months will be reported. Conclusion: The results from this study will provide insights into the efficacy of a combined diabetes education and skills training and social needs resolution intervention for older African Americans with poorly controlled type 2 diabetes and will inform strategies to improve diabetes outcomes for this vulnerable population. Full article

Mechanical bowel preparation (MBP) is essential for visualisation of the colon during colonoscopy. Previous studies have identified changes in gut microbiota composition after MBP and colonoscopy. Considering the gut microbiota is increasingly implicated in psychiatry, we explored the potential impact of this intervention on mood and the microbiota–gut–brain axis. We conducted a pre–post intervention study in adults, with timepoints of one week before and one month after MBP and colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores. We examined changes in average anxiety, stress, and quality of life scores and gut microbiota composition using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and gut microbiota and conducted post hoc analyses to explore potential effect modifiers. Average depressive symptom scores decreased one month post-procedure compared to baseline (n = 59; adjusted β = −0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (β = 1.78; 95%CI: 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Reduced alpha diversity, modest effects on beta-diversity, and increases in health-associated genera were observed one month post-procedure. Increases in the CLR-transformed abundances of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. There is preliminary evidence of a potential mental health effect of MBP and colonoscopy, particularly for those with IBS, which may be associated with changes to the gut microbiota. Further research is required to confirm these findings and their clinical relevance. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n = 59) exploring re-establishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n = 45) and without (n = 13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential re-establishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house. Full article

Neurodegenerative disease is a major global health problem with 150 million people predicted to have dementia by 2050. Genetic factors, environmental factors, demographics, and some diseases have been associated with dementia. In addition to associations between diseases such as hypertension and cerebrovascular disease and dementia, emerging findings associate some psychiatric disorders with incident dementia. Because of the high and increasing global prevalence of dementia and the high worldwide prevalence of psychiatric disorders, the primary objective of this narrative review was to evaluate published findings that evaluate the association between bipolar disorder, depression, anxiety, post-traumatic stress disorder, obsessive–compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, schizophrenia and other psychosis syndromes, and personality disorders and personality traits and incident dementia. Here, we highlight findings indicating possible associations between these psychiatric disorders and subsequent dementia and suggest that some psychiatric disorders may be risk factors for incident dementia. Further research, including more large longitudinal studies and additional meta-analyses, however, is needed to better characterize the associations between psychiatric disorders and incident dementia, to identify possible mechanisms for these putative associations, and to identify risk factors within psychiatric disorders that predispose some people with a psychiatric disorder but not others to subsequent dementia. Additional important questions concern how the treatment of psychiatric disorders might affect the risk of incident dementia. Full article