Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

The Paisley Cave archeological site in the Northern Great Basin has provided a rich archaeological record from 13,000 to 6000 cal yr BP, including abundant mammalian coprolites preserved in a well-dated stratigraphy. Here we analyze and contrast pollen from within coprolites and pollen in associated sediments to examine vegetation history and assess whether coprolite pollen provides unique information with respect to the coprolite producer, such as the use of specific habitats, foods, or water sources. We found that the dissimilarity of pollen assemblages between coprolites and associated sediments was greater than the serial dissimilarity between stratigraphically adjacent samples within either group. Serial dissimilarity within types was not greater for coprolites than sediments, as would be expected if there were unique pollen signatures derived from the short period (1–2 days) represented by each coprolite. Compared with sediment pollen assemblages, the coprolites had higher abundances of lighter pollen types, and some individual samples were high in wetland taxa (especially Typha). Our results are consistent with coprolite pollen representing short time periods collected as a mammal moves on the landscape, whereas sediment pollen reflects longer time periods and more regional vegetation indicators.

Across South Africa, Lesotho, and Eswatini, long-term citizen science atlas data have suggested concerning declines in the population of Black Stork Ciconia nigra. Unlike the Asian and European populations, the southern African Black Stork population is described as resident and is listed as “Vulnerable” in South Africa, Lesotho, and Eswatini. Here we report on surveys of historical nesting locations across northern South Africa, finding evidence for nest site abandonment and limited evidence of recent breeding. We undertook detailed species distribution modelling within a maximum entropy framework, using occurrence records from the BirdLasser mobile app. We cross-validated the models against information in the Southern African Bird Atlas Project (SABAP2) database, highlighting Lesotho as an important potential breeding area. Additionally, we used SABAP2 to assess population trends by investigating interannual patterns in reporting rate. Comparing current reporting rates with those from SABAP1 (1987–1992), we found that there has been a dramatic decrease. We noted that a large proportion of the population occurs outside the breeding range during the breeding season, suggesting a considerable non-breeding population, especially in the extensive wildlife refuge of the Kruger National Park. The slow declines observed might be indicative of a population which is not losing many adults but is failing to recruit significant numbers of juveniles due to limited breeding. Using densities derived from transect surveys, we used predictive models to derive estimates of breeding range carrying capacity and a population estimate, which suggested declines to numbers around 600 for this subregion. Minimising disturbance at breeding sites of this cliff-nesting species and improving water quality at key population strongholds are pathways to improving the status of the species in the subregion.

In 1929, Congress passed a law capping the US House of Representatives at 435 seats, delegating the power to reapportion to the Executive Branch, and empowering state legislatures to redistrict with few federal limitations. The 1929 law was a compromise after nearly ten years of squabbling over how to apportion pursuant to the 1920 Census. In this article, we consider the apportionment debates of the 1920s both to better understand the politics of the era and to draw lessons that might apply to a potential reapportionment debate today. Throughout the decade, partisanship and political self-interest structured members’ votes on reapportionment. The legislation that eventually passed resulted from a compromise that greatly empowered state legislatures to redistrict freely by removing federal requirements that had been in effect since the 1870s, effectively shifting the battle over congressional representation from one over reapportionment in Congress to one over redistricting in the states.

The EG95 recombinant vaccine is protective against cystic echinococcus in animal intermediate hosts. Preparation of the existing, registered EG95 vaccines involves semi-purification of the vaccine protein, adding to the cost of production. Truncation of the EG95 cDNA, shortening both the amino and carboxy-termini of the protein, leads to high levels of recombinant protein expression. The recombinant EG95 protein was prepared as a bacterin from clarified, whole bacterial lysate, and used in a vaccine trial in sheep against an experimental challenge infection with Echinococcus granulosus eggs. The EG95 bacterin was found to induce 98% protection. Use of this in a new generation EG95 vaccine would simplify production, facilitate new sources of the vaccine and potentially enhance uptake of vaccination in control of E. granulosus transmission.

Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF – a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.

The Wilkes Subglacial Basin in East Antarctica contains ice equivalent to 3–4 m of global mean sea level rise and is primarily drained by Cook Glacier. Of concern is that recent observations (since the 1970s) show an acceleration in ice speed over the grounding line of both the Eastern and Western portions of Cook Glacier. Here, we use a numerical ice-flow model (Úa) to simulate the instantaneous effects of observed changes at the terminus of Cook Glacier in order to understand the link between these changes and recently observed ice acceleration. Simulations suggest that the acceleration of Cook West was caused by a retreat in calving-front position in the 1970s, potentially enhanced by grounding-line retreat, while acceleration of Cook East was likely caused by ice-shelf thinning and grounding-line retreat in the mid-1990s. Moreover, we show that the instantaneous ice discharge at Cook East would increase by up to 85% if the whole ice shelf is removed and it ungrounds from a pinning point; and that the discharge at Cook West could increase by ~300% if its grounding line retreated by 10 km.

The transition from DSM-IV to DSM-5 relaxed diagnostic criteria for anorexia nervosa and bulimia nervosa, and recognised a third eating disorder, binge eating disorder. However, a large proportion of cases remain in the ill-defined category of ‘other specified feeding and eating disorders’. We sought to investigate the utility of a proposed solution to classify this group further, subdividing based on the dominant clinical feature: binge eating/purging or restraint. Cluster analysis failed to identify clusters in a treatment-seeking sample based on symptoms of restraint, binge eating, purging and over-evaluation of shape and weight. Further investigation of this highly heterogeneous group is required.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.

A survey of acute-care hospitals found that rapid molecular diagnostic tests (RMDTs) have been widely adopted. Although many hospitals use their antimicrobial stewardship team and/or guidelines to help clinicians interpret results and optimize treatment, opportunities to more fully achieve the potential benefits of RMDTs remain.

The studied seep carbonates from Tsushima, Japan, are embedded within marine siliciclastics of the lower Miocene Taishu Group and represent the earliest evidence of hydrocarbon seepage in the Sea of Japan. In contrast to Miocene and Pliocene examples from Honshu, which are often found above anticlines, the seeps from Tsushima formed within a pull-apart basin before major anticlines had formed. The three carbonates from Fukuzaki, Kanoura and Tanohama are composed chiefly of calcite, with significant admixture of ankerite only at Kanoura. The stable carbon isotope composition of calcites (δ13C as low as −40.2 ‰ VPDB for Fukuzaki, −41.8 ‰ VPDB for Kanoura, and −52.8 ‰ VPDB for Tanohama) indicate methanogenic origin of the carbonates. Textures of these deposits, including radiaxial and yellow cements, are indicative of formation at a methane seep. The stable oxygen isotope composition of calcites (δ18O values as low as −14.4 ‰ VPDB for Fukuzaki, −14.5 ‰ VPDB for Kanoura and −13.9 ‰ VPDB for Tanohama) indicate that they were influenced by burial fluids. Burial diagenesis is also indicated by the stable isotopic compositions of ankerite (δ13C ranging from −19.1 ‰ to −7.1 ‰ VPDB, δ18O from −11.1 ‰ to −9.7 ‰ VPDB). Molecular fossils from Tanohama comprise n-alkanes with short-chain predominance, interpreted to have formed due to thermal cracking of organic matter. The carbonates yield a chemosynthesis-based community comprising vesicomyids Pleurophopsis chitanii, P. cf. hamuroi, the bathymodiolin ‘Bathymodiolus’ akanudaensis, the lucinid Lucinoma sp. and the provannid Provanna? sp., which have never been hitherto identified. ‘Bathymodiolus’ akanudaensis, Lucinoma sp. and Provanna? sp. are the oldest records of these taxa in the Sea of Japan.

Public mental health incorporates a number of strategies from mental well-being promotion to primary prevention and other forms of prevention. There is considerable evidence in the literature to suggest that early interventions and public education can work well for reducing psychiatric morbidity and resulting burden of disease. Educational strategies need to focus on individual, societal and environmental aspects. Targeted interventions at individuals will also need to focus on the whole population. A nested approach with the individual at the heart of it surrounded by family surrounded by society at large is the most suitable way to approach this. This Guidance should be read along with the European Psychiatric Association (EPA) Guidance on Prevention. Those at risk of developing psychiatric disorders also require adequate interventions as well as those who may have already developed illness. However, on the model of triage, mental health and well-being promotion need to be prioritized to ensure that, with the limited resources available, these activities do not get forgotten. One possibility is to have separate programmes for addressing concerns of a particular population group, another that is relevant for the broader general population. Mental health promotion as a concept is important and this will allow prevention of some psychiatric disorders and, by improving coping strategies, is likely to reduce the burden and stress induced by mental illness.

Evolving conditions at the terminus of Thwaites Glacier will be important in determining the rate of its future sea-level contribution over the coming decades. Here, we use remote-sensing observations to investigate recent changes (2000–2018) in the structure and velocity of Thwaites Glacier and its floating tongue. We show that the main trunk of Thwaites Glacier has accelerated by 38% over this period, while its previously intact floating tongue has transitioned to a weaker mélange of fractured icebergs bounded by sea ice. However, the rate of structural weakening and acceleration was not uniform across the observational period and we identify two periods of rapid acceleration and structural weakening (2006–2012; 2016–2018), separated by a period of deceleration and re-advance of the structurally-intact shear margin boundary (2012–2015). The timing of these accelerations/decelerations strongly suggests a link to variable ocean forcing. The weakened tongue now has some dependency on landfast sea ice for structural integrity and is vulnerable to changes in landfast ice persistency. Future reductions in landfast sea ice could manifest from changes in climate and/or the imminent removal of the B-22A iceberg from the Thwaites embayment. Such changes could have important implications for the integrity of the ice tongue and future glacier discharge.