Observation of an exotic insulator to insulator transition upon electron doping the Mott insulator CeMnAsO.

A promising route to discover exotic electronic states in correlated electron systems is to vary the hole or electron doping away from a Mott insulating state. Important examples include quantum criticality and high-temperature superconductivity in cuprates. Here, we report the surprising discovery of a quantum insulating state upon electron doping the Mott insulator CeMnAsO, which emerges below a distinct critical transition temperature, TII. The insulator-insulator transition is accompanied by a significant reduction in electron mobility as well as a colossal Seebeck effect and slow dynamics due to decoupling of the electrons from the lattice phonons. The origin of the transition is tentatively interpreted in terms of many-body localization, which has not been observed previously in a solid-state material.

Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity.

Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice. Dietary effects are observed in a range of morphological, testicular and spermatozoa traits, although the relative influence of protein, fat, carbohydrate, and their interactions differ depending on the trait being examined. Interestingly, dietary fat has a positive influence on sperm motility and antioxidant capacity, differing to typical high fat diet studies where calorie content is not controlled for. Moreover, body adiposity is not significantly correlated with any of the reproductive traits measured in this study. These results demonstrate the importance of macronutrient balance and calorie intake on reproductive function and support the need to develop specific, targeted, preconception dietary guidelines for males.

Behaviour of mesopredatory coral reef fishes in response to threats from sharks and humans.

Both sharks and humans present a potentially lethal threat to mesopredatory fishes in coral reef systems, with implications for both population dynamics and the role of mesopredatory fishes in reef ecosystems. This study quantifies the antipredator behaviours mesopredatory fishes exhibit towards the presence of large coral reef carnivores and compares these behavioural responses to those elicited by the presence of snorkelers. Here, we used snorkelers and animated life-size models of the blacktip reef shark (Carcharhinus melanopterus) to simulate potential predatory threats to mesopredatory reef fishes (lethrinids, lutjanids, haemulids and serranids). The responses of these reef fishes to the models and the snorkelers were compared to those generated by three non-threatening controls (life-size models of a green turtle [Chelonia mydas], a PVC-pipe [an object control] and a Perspex shape [a second object control]). A Remote Underwater Stereo-Video System (Stereo-RUV) recorded the approach of the different treatments and controls and allowed accurate measurement of Flight Initiation Distance (FID) and categorization of the type of flight response by fishes. We found that mesopredatory reef fishes had greater FIDs in response to the approach of threatening models (1402 ± 402-1533 ± 171 mm; mean ± SE) compared to the controls (706 ± 151-896 ± 8963 mm). There was no significant difference in FID of mesopredatory fishes between the shark model and the snorkeler, suggesting that these treatments provoked similar levels of predator avoidance behaviour. This has implications for researchers monitoring behaviour in situ or using underwater census as a technique to estimate the abundance of reef fishes. Our study suggests that, irrespective of the degree to which sharks actually consume these mesopredatory reef fishes, they still elicit a predictable and consistent antipredator response that has the potential to create risk effects.

A metagenomic-based study of two sites from the Barbadian reef system.

We study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community and their proximity to urban development and runoffs from inland watersheds. The composition of the microbial communities was estimated using whole genome DNA shotgun sequencing with adjuvant measurements of chemical and environmental qualities. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman's Bay) has a strong concentration of phototrophs whereas the more urbanized location (Bellairs reef at Folkstone) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Our results are concordant with previous profiles of warm ocean surface waters, suggesting our approach captures the state of each coral reef site, setting the stage for longitudinal studies of marine microbiome dynamics in Barbados. Supplementary Information: The online version contains supplementary material available at 10.1007/s00338-022-02330-y.

Extreme eutrophication and salinisation in the Coorong estuarine-lagoon ecosystem of Australia's largest river basin (Murray-Darling).

Estuaries in rainfall poor regions are highly susceptible to climatic and hydrological changes. The Coorong, a Ramsar-listed estuarine-coastal lagoon at the end of the Murray-Darling Basin (Australia), has experienced declining ecological health over recent decades. Twenty years of environmental data were analysed to assess patterns and drivers of water quality changes. Large areas of the Coorong are now persistently hyper-saline (salinity >80 psu) and hypereutrophic (total nitrogen, TN > 4 mg L-1, total phosphorus, TP > 0.2 mg L-1, chlorophyll a > 50 µg L-1) which coincided with reduced flushing due to diminished freshwater inflows and increasing evapo-concentration. Sediment quality also was related to flushing, with higher concentrations of organic carbon, TN, TP and sulfides as salinity increased. While total nutrient levels are very high, dissolved inorganic nutrients are generally low. Increased lagoonal flushing would be beneficial to reduce the hypersalinisation and hypereutrophication and improve ecosystem health.

Loneliness in young people: a multilevel exploration of social ecological influences and geographic variation.

BACKGROUND: Loneliness is a growing public health concern, yet little is known about loneliness in young people. The current study aimed to identify social ecological factors related to loneliness and examine the extent to which geographic region may account for differences in loneliness. METHODS: The data come from a cross-sectional sample of 6503 young people living in the UK. Loneliness was measured using the UCLA 3-item scale. Bivariate analyses were used to test associations between each predictor and loneliness. Multilevel models were used to identify key social ecological factors related to loneliness, and the extent to which loneliness may vary across geographic regions (local authority districts). RESULTS: Sociodemographic, social, health and well-being, and community factors were found to be associated with loneliness. Geographic region was associated with 5-8% of the variation in loneliness. The effect of gender, sexual orientation and minority ethnic background on loneliness differed across regions. CONCLUSIONS: This is the first study to highlight modifiable social and community factors related to youth loneliness, and individual vulnerabilities, such as poor mental well-being. Results related to geographic differences suggest that local-level initiatives may be most appropriate in tackling loneliness, rather than wider, less contextualized national efforts.

Incidence and type of peripheral intravenous catheter complications documented in hospitalised dogs.

OBJECTIVE: To report the incidence and type of peripheral intravenous catheter complications in hospitalised dogs. METHODS: A prospective, observational trial was performed. Peripheral intravenous catheters were monitored for complications. Complications were documented and classified as extravasation, phlebitis, dislodgement, occlusion and line breakage. If phlebitis was present, the Visual Infusion Phlebitis Scale was used to assign a grade (0 to 5). Fisher's exact test was used to compare the type of complications between the critical care unit and the intermediate care unit. A univariate logistic model was used to compare the incidence of complications between the critical care unit and the intermediate care unit and adjusted odds ratios were used to compare the groups. RESULTS: The incidence of peripheral intravenous catheter complications was 24.2% in the Critical Care Unit and 13.1% in the Intermediate Care Unit, with an overall incidence of 19.9%. Phlebitis was the most common peripheral intravenous catheter complication in the Critical Care Unit, and line breakage was the most common complication in the Intermediate Care Unit. Length of hospitalisation and weight had a significant effect on the likelihood of complication. In a multivariable logistic regression model, the odds of a peripheral intravenous catheter complication was not significantly higher in CCU than IMCU, accounting for length of hospitalisation and weight (adjusted odds ratio, 1.84; 95% confidence interval, 0.98 to 3.48). CLINICAL SIGNIFICANCE: Peripheral intravenous catheter complications are common in hospitalised dogs and may result in an increased expense for owners, failure to deliver prescribed treatments, venous depletion (lack of peripheral vessels for intravenous catheter placement) and pain experienced by the patient. Techniques to reduce peripheral intravenous catheter complications should be further evaluated and may include the use of peripheral intravenous catheter placement and maintenance checklists, use of force-activated separation devices, or patient sedation.

The Scottish Brain Health Service Model: Rationale and Scientific Basis for a National Care Pathway of Brain Health Services in Scotland.

In order to address the oft-cited societal, economic, and health and social care impacts of neurodegenerative diseases, such as Alzheimer's disease, we must move decisively from reactive to proactive clinical practice and to embed evidence-based brain health education throughout society. Most disease processes can be at least partially prevented, slowed, or reversed. We have long neglected to intervene in neurodegenerative disease processes, largely due to a misconception that their predominant symptom - cognitive decline - is a normal, age-related process, but also due to a lack of multi-disciplinary collaboration. We now understand that there are modifiable risk factors for neurodegenerative diseases, that successful management of common comorbidities (such as diabetes and hypertension) can reduce the incidence of neurodegenerative disease, and that disease processes begin (and, crucially, can be detected, reduced, and delayed, prevented, or treated) decades earlier in life than had previously been appreciated. Brain Health Scotland, established by Scottish Government and working in partnership with Alzheimer Scotland, propose far-reaching public health and clinical practice approaches to reduce neurodegenerative disease incidence. Focusing here on Brain Health Scotland's clinical offerings, we present the Scottish Model for Brain Health Services. To our knowledge, the Scottish Model for Brain Health, built on foundations of personalised risk profiling, targeted risk reduction and prevention, early disease detection, equity of access, and harnessing comprehensive data to assist in clinical decision-making, marks the first example of a nationwide approach to overhauling clinical, societal, and political approaches to the prevention, assessment, and treatment of neurodegenerative disease.

Genetic variation of macronutrient tolerance in Drosophila melanogaster.

Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.

Gut-derived acetate promotes B10 cells with antiinflammatory effects.

Autoimmune diseases are characterized by a breakdown of immune tolerance partly due to environmental factors. The short-chain fatty acid acetate, derived mostly from gut microbial fermentation of dietary fiber, promotes antiinflammatory Tregs and protects mice from type 1 diabetes, colitis, and allergies. Here, we show that the effects of acetate extend to another important immune subset involved in tolerance, the IL-10-producing regulatory B cells (B10 cells). Acetate directly promoted B10 cell differentiation from mouse B1a cells both in vivo and in vitro. These effects were linked to metabolic changes through the increased production of acetyl-coenzyme A, which fueled the TCA cycle and promoted posttranslational lysine acetylation. Acetate also promoted B10 cells from human blood cells through similar mechanisms. Finally, we identified that dietary fiber supplementation in healthy individuals was associated with increased blood-derived B10 cells. Direct delivery of acetate or indirect delivery via diets or bacteria that produce acetate might be a promising approach to restore B10 cells in noncommunicable diseases.

Genome-wide surveillance of transcription errors in response to genotoxic stress.

Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.

Hall technique: is it superior in success and savings to conventional restorations?

Design A cost-effectiveness analysis of caries management in primary molars using Hall technique (HT) versus conventional restoration (CR) from a pre-existing dataset from a randomised split-mouth trial, within primary care in Scotland, with a five-year follow-up.Case selection Computer-generated block randomisation was used to match asymptomatic primary molars of 3-10-year-old children recruited from primary care, to either HT or CR arms.Economic evaluation A cost-effectiveness analysis was undertaken. A five-year horizon was chosen. A societal perspective was adopted. Estimation of direct, indirect and opportunity costs were presented. Costs were discounted at 1.5%. Molar survival was chosen as the effectiveness measure.Data analysis Statistical significance of primary outcome (survival) was examined using the log-rank test. Bootstrapping produced a sampling distribution of mean cost and effectiveness with a 95% confidence interval around a mean value. An incremental cost-effectiveness ratio (ICER) was provided.Results HT molars had superior survival of 99% (95% CI: 98-100%) compared to CR at 92% (95% CI: 87-97%). Initials costs indicated HT to be more expensive than CR; however, direct costs, including retreatments, were cheaper for HT when using both NHS Scotland and NHS England cost data. Indirect/opportunity costs, including time and travel of parents, were significantly less for HT. Total cumulative costs were significantly lower in HT (32 GBP; 95% CI: 31-34) than CR (49 GBP; 34-69). HT dominated CR, being less costly and more effective with a mean ICER of 2.38 GBP spent additionally while losing 1% of molar survival with CR over HT.Conclusions HT molars are cost-effective, compared to CR, when managing asymptomatic carious primary molars after five years' follow-up.

Condition-dependent responses of fish to motorboats.

Anthropogenic noise is a pollutant of global concern that has been shown to have a wide range of detrimental effects on multiple taxa. However, most noise studies to-date consider only overall population means, ignoring the potential for intraspecific variation in responses. Here, we used field experiments on Australia's Great Barrier Reef to assess condition-dependent responses of blue-green damselfish (Chromis viridis) to real motorboats. Despite finding no effect of motorboats on a physiological measure (opercular beat rate; OBR), we found a condition-dependent effect on anti-predator behaviour. In ambient conditions, startle responses to a looming stimulus were equivalent for relatively poor- and good-condition fish, but when motorboats were passing, poorer-condition fish startled at significantly shorter distances to the looming stimulus than better-condition fish. This greater susceptibility to motorboats in poorer-condition fish may be the result of generally more elevated stress levels, as poorer-condition fish had a higher pre-testing OBR than those in better condition. Considering intraspecific variation in responses is important to avoid misrepresenting potential effects of anthropogenic noise and to ensure the best management and mitigation of this pervasive pollutant.

Animal and translational models of SARS-CoV-2 infection and COVID-19.

COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.

Hypothermia - an unusual initial presentation of human immunodeficiency virus infection.

We report an unusual case of human immunodeficiency virus (HIV) infection initially presenting with hypothermia and bradycardia associated with an HIV encephalitis. Searches reveal only five reported cases of spontaneous episodic hypothermia in the context of HIV infection. In our case, magnetic resonance imaging revealed the presence of a persistent cavum septum pellucidum (CSP), an anatomical and functional neuro-developmental abnormality, as well as changes compatible with an HIV encephalitis. Episodic hypothermia can occur in association with agenesis of the corpus callosum, known as Shapiro's syndrome, and the presence of a persistent CSP in our case suggests it may have contributed to the clinical presentation.

Characterization of intentional lurasidone ingestions using the United States National Poison Data System.

Introduction: The ziprasidone analogue lurasidone is approved for the treatment of schizophrenia and bipolar disorder for adults and children older than 10 years. Small studies and case reports suggest lurasidone overdose is not generally associated with major adverse effects, but no large sample has been published.Objective: To describe intentional lurasidone overdoses reported to poison centers.Methods: Retrospective analysis of single-substance intentional lurasidone ingestions from the National Poison Data System (NPDS) from 2011 to 2018.Results: There were 1753 single-substance intentional overdoses. Average age was 28.6 years (SD = 13.3 years) and 1199 (68.4%) of patients were female. Most cases (86.6%) were coded as suspected suicide. Regarding final management site, 1143 (65.2%) were discharged or admitted to psychiatric facilities; 328 (18.8%) were admitted, half of whom were admitted to critical care units (CCUs). Major effect was coded in 12 (0.7%), moderate effect in 259 (14.8%), minor effect in 531 (30%), and no effect in 614 (35%). There were no deaths. For cases for which dose information was available, there was not a statistically significant difference between median doses when analyzed by clinical effect. Most common adverse effects were drowsiness (449, 25.6%), tachycardia (254, 14.5%), vomiting (121, 6.9%), and hypertension (115, 6.6%). Most cases had either no therapy reported, or therapy was recommended by the poison center but confirmed not to have been administered (1010, 57.6%). Of the 164 patients admitted to CCUs, 80 (48.8%) received either no therapy or intravenous fluids alone.Discussion: These data suggest major effects are uncommon from lurasidone overdose. Despite a high rate of admission to CCUs, a substantial proportion received no critical therapies.Conclusions: This report demonstrates intentional lurasidone overdoses reported to poison centers generally have a favorable clinical course.

Mixed Reality Anatomy Using Microsoft HoloLens and Cadaveric Dissection: A Comparative Effectiveness Study.

PURPOSE: As the amount of curricular material required of medical students increases, less time is available for anatomy; thus, methods to teach anatomy more efficiently and effectively are necessary. In this randomized controlled trial, we looked at the effectiveness of a mixed reality (MR) device to teach musculoskeletal anatomy to medical students compared with traditional cadaveric dissection. METHOD: Participating students were divided into three cohorts. Cohort 1 first studied upper limb anatomy in MR followed by lower limb anatomy through cadaveric dissection. Cohort 2 studied upper limb anatomy with cadaveric dissection followed by lower limb anatomy in MR. After the six sessions, a third cohort of 33 students who never received any teaching in MR was recruited to participate in the final practical exams as a control group. All 64 students completed two practical exams with equivalent content, one in the cadaver lab and one using MR. RESULTS: The average scores were 73.8% + 12.3 on the cadaver exam and 74.2% + 13.0 in MR. There is no statistical difference between these scores (p > 0.05). A correlation was found between the MR practical exam and cadaver practical exam scores (r = 0.74, p < 0.01) across all students. CONCLUSIONS: To our knowledge, this study marks the first time that MR was compared with traditional anatomy learning modalities in a multi-session, group course. Our results clearly indicate that medical students, regardless of the study modality, performed similarly on the MR and the cadaver practical exams.

Mastery is associated with greater physical and mental health-related quality of life in two international cohorts of people with multiple sclerosis.

BACKGROUND: Mastery is the sense of being in control of one's life and improvement in mastery may help to enhance quality of life. Little research has explored mastery in people with multiple sclerosis (MS), including its association with quality of life. OBJECTIVE: To explore the association between mastery and health-related quality of life (HRQOL) in people with MS. METHOD: Two cross-sectional cohorts of adults with MS (n = 1401 and n = 573), recruited through convenience sampling, completed an online survey which measured mastery using the Pearlin Mastery Scale, physical and mental HRQOL via physical and mental health composite scores of MSQOL-54, along with other covariates, including demographics, clinical characteristics and lifestyle factors. Linear regression assessed associations between mastery and physical HRQOL adjusting for age, sex, education, disability and depression, and between mastery and mental HRQOL adjusting for age, sex, education, disability and clinically significant fatigue. RESULTS: Greater mastery score was associated with higher physical and mental HRQOL in both cohorts, such that a one-point increase in the PMS was associated with an increase of 2.9 (95% Confidence Interval (CI): 2.6, 3.1) and 2.8 points (95% CI: 2.4, 3.2) in the means of physical HRQOL score in the first and second cohorts respectively, and a 2.9-point (95% CI: 2.7, 3.1) and 3.1-point (95% CI: 2.7, 3.4) increase in the means of mental HRQOL score. A dose-dependent relationship was demonstrated between a quartile categorical mastery variable and both physical and mental HRQOL in both cohorts. Mastery was associated with all subscores of both physical and mental HRQOL. CONCLUSIONS: Greater mastery is associated with better physical and mental quality of life. Efforts to improve the sense of self control and agency of people with MS may have benefits for their quality of life, even despite clinical features of the illness.

Factors associated with pneumococcal vaccination in 2040 people with type 2 diabetes: A cross-sectional study.

AIMS: Pneumococcal vaccination is recommended in diabetes because of the high risk for invasive pneumococcal disease and mortality; however, vaccination rates are below recommended targets. This study was conducted to identify possible reasons behind the low rate of vaccine uptake. METHODS: We examined baseline information from the Alberta Caring for Diabetes study, a prospective cohort study of 2040 adults with type 2 diabetes. Patients were recruited between December 2011 and December 2013. The baseline survey collected information on a wide range of socio-demographic characteristics, disease and management information, as well as health status measurements and health service utilization. Multivariable logistic regression analyses were conducted to identify factors associated with self-reported pneumococcal vaccination status. RESULTS: Mean age was 64 (SD 11) years, 45% were women, mean duration of diabetes was 12 (SD 10) years, and 1090 (53%) were vaccinated. Age≥65 years (adjusted odds ratio [aOR] 2.52; 95% CI: 1.98-3.20), respiratory disease (aOR 1.50; 95% CI: 1.17-1.93), and cancer (aOR 1.45; 95% CI: 1.08-1.94) were independently associated with pneumococcal vaccination. In addition, women, retirees, people with diabetes≥10 years, people using antihypertensive medications or insulin, and those who had their HbA1c, kidney function, or their weight or waist circumference measured by a healthcare professional in the past year were more likely to have been vaccinated. CONCLUSION: Based on this information, future programs aimed at people aged<65 years old, men, those who are currently working, those recently diagnosed with diabetes, and those with few comorbidities could have the most potential for improving pneumococcal vaccine uptake in people with diabetes.

Costarting sitagliptin with metformin is associated with a lower likelihood of disease progression in newly treated people with type 2 diabetes: a cohort study.

AIM: To examine whether early addition of sitagliptin to metformin is associated with a delay in type 2 diabetes progression. METHODS: Administrative health records from Alberta, Canada, for the period April 2008 to March 2015, were used to conduct a retrospective cohort study in new metformin users. People who started sitagliptin on the same day they initiated metformin therapy were compared with those who added sitagliptin later. Insulin initiation served as a surrogate marker for diabetes progression, and multivariable logistic regression models were used to evaluate the association with sitagliptin addition (costart vs later use). A mixed-effects linear regression model was used to examine the effect of timing of sitagliptin addition on HbA1c change over 1 year. RESULTS: The mean (sd) age of the 8764 people who used sitagliptin was 52.1 (11.1) years, 5665 (64.6%) were men, and 1153 (13.2%) started sitagliptin on the same day as metformin. Insulin was added to the therapy of 173 (15.0%) costarters and 1453 (19.1%) later sitagliptin users. The adjusted odds ratio for adding insulin was 0.76 (95% CI 0.64 to 0.90) in favour of costarting sitagliptin. HbA1c levels decreased in both groups 1 year after starting sitagliptin, with costarters having a significantly greater reduction [absolute between-group difference of 0.5% (95% CI 0.3 to 0.7)] compared with later sitagliptin users. CONCLUSION: Costarting drug therapy with sitagliptin and metformin was associated with a lower likelihood of disease progression in people with type 2 diabetes compared with adding sitagliptin later.