In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing Escherichia coli (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case–control study was conducted to investigate exposure to these products. Case food history information was collected by telephone. Controls were recruited using a market research panel and self-completed an online questionnaire. Univariable and multivariable analyses were undertaken using Firth Logistic Regression. Eleven cases and 24 controls were included in the analysis. Consumption of the brie-style cheese of interest was associated with illness (OR 57.5, 95% confidence interval: 3.10–1,060). Concurrently, the production of the brie-style cheese was investigated. Microbiological sample results for the cheese products and implicated dairy herd did not identify the outbreak strain, but did identify the presence of stx genes and STEC, respectively. Together, epidemiological, microbiological, and environmental investigations provided evidence that the brie-style cheese was the vehicle for this outbreak. Production of unpasteurized dairy products was suspended by the business operator, and a review of practices was performed.

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

While it is commonly understood that the poll tax and literacy tests, among other measures, were used effectively in the South to disenfranchise Black voters from the late nineteenth through the mid-twentieth century, what is not well known is how much those disenfranchising laws mattered. Specifically, how much did the enactment of poll taxes or literacy tests affect turnout in federal and state elections? And how much did those disenfranchising provisions dampen vote totals for Republican candidates in the South? Using the staggered implementation and removal of several disenfranchising policies over a 101-year period, we answer these questions and provide some precision to our collective knowledge of the “disenfranchising era” in American electoral politics. Overall, we find that the poll tax was the main driver of disenfranchisement in Southern elections, with literacy tests and the Australian ballot providing some secondary effects. We also find that ex-felon disenfranchisement laws were considerably more important—both in reducing turnout as well as Republican vote share in Southern elections—than has been traditionally understood. Finally, we unpack the “South” and unsurprisingly find that racial politics drove these results: the disenfranchising institutions were more impactful in states with a larger Black population share. Our results show the powerful effects of disenfranchising policies on electorates and electoral outcomes. We discuss these results in both their historical context as well as with a mind to the continuing use of disenfranchising provisions in law today.

NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

Hydrothermal synthesis experiments were conducted to study the transition from smectite to corrensite. A mixture of oxides with the bulk composition of corrensite—Na0.4(Si6.4Al1.6)(Mg7.8Al1.2)-O20(OH)10—was sealed in platinum capsules with 29–37 wt. % water. One set of samples was treated in cold-seal vessels at 500°C and 2 kbar for durations of 2, 3, 6, 12, and 24 h; the other set was treated at 350°C and 2 kbar for periods of 12 to 89 d. X-ray diffraction patterns (XRD) of oriented aggregates from treated products were obtained from ethylene glycol-solvated and air-dried preparations. Samples were also heated to 350°C either in a calibrated muffle furnace, removed and quickly placed in a nitrogen filled chamber on the diffractometer, or were heated at 350°C by using a calibrated heating stage mounted on the diffractometer.

Initial mineral assemblages at both temperatures contained only saponite and serpentine. In experiments at 500°C, saponite transformed to corrensite within 6 h; in experiments at 350°C, the transformation occurred as early as 22 d. Increased experiment times at both temperatures produced increasing amounts of well-crystallized corrensite, as indicated by several well-defined XRD peaks. No evidence of a randomly interstratified chlorite-smectite (C-S) precursor to corrensite was found. The identification of pure smectite, as opposed to highly-expanded randomly interstratified C-S, was possible only when clays were dehydrated on a heating stage on the diffractometer.

These results call for a new examination of hydrothermally-altered basalt that has been reported to contain randomly interstratified C-S as an intermediate step in the reaction of smectite to corrensite or chlorite. These results also strengthen the view held by increasing numbers of investigators that corrensite should be regarded as a single phase, not as a mixed-layered phyllosilicate.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

The Taita Falcon Falco fasciinucha is known to occur and breed at only a few locations in eastern and southern Africa and is currently listed as globally “Vulnerable” and “Critically Endangered” in South Africa. An accurate estimation of its conservation status is however hampered by a lack of data and understanding of the species’ habitat requirements and competitive interactions with congeners. Our aim was to address some of these knowledge gaps. We conducted cliff-nesting raptor surveys across a substantial area of the Mpumalanga/Limpopo escarpment in north-eastern South Africa and modelled habitat suitability for nesting Taita Falcons in relation to the proximity of conspecifics and a community of five other sympatric cliff-nesting raptor species, and in relation to a suite of biotic and abiotic environmental variables. Results suggested the location of Taita Falcon nest sites was negatively associated with distance to the nearest pair of conspecifics and the nearest pair of Lanner Falcons Falco biarmicus, and positively associated with tracts of intact, unfragmented forest and woodland around the base of the cliffs. Our results indicated that Taita Falcon and Lanner Falcon appeared to be responding in opposite ways to a directional change in environmental conditions. This response appeared to be detrimental to Taita Falcon and beneficial to Lanner Falcon. Furthermore, the degradation and destruction of Afrotropical woodland and forest is a documented and ongoing reality, both locally and across much of the Taita Falcon’s global distribution. We argue that our findings are sufficient to justify uplisting Taita Falcon to globally “Endangered”.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Faecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 region). General linear models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: β=−0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.

Prion diseases are fatal neurodegenerative disorders, epitomized by the recent bovine spongiform encephalopathy (BSE) epidemic in cattle and the emergence of a novel variant of Creutzfeldt-Jacob disease (vCJD) in humans. In prion disease, the agent of infection is believed to be composed of proteinaceous particles, termed prions, which are converted from a normal isoform into a pathogenic isoform during pathogenesis. A bioassay to detect pathogenic prions of BSE in bovine products consumed by humans was unattainable until the development of transgenic mice, due to the significantly lower susceptibility of wild-type mice to BSE. Transgenic mice have now been generated which express the bovine prion protein and are susceptible to BSE. Following an intracerebral injection with brain homogenate of BSE-infected cattle, transgenic mice develop numerous clinical signs of prion disease, including truncal ataxia (inability to coordinate the torso's muscular activity), increased tone of the tail, generalized tremor, and lack of a forelimb extensor response.

In this study, the ethical score system devised by Porter (1992) was applied to the BSE bioassay as a tool for identifying welfare issues affecting animals used in the bioassay. We acknowledge that there are limitations to the use of the information arising from the application of the Porter scoring scheme for assessing the justification to proceed with any animal experiment; notwithstanding these problems, however, our application of the Porter model to the BSE bioassay enabled us to identify potential targets for refinement: pain involved, duration of distress and the duration of the experiment. This was despite lenient scoring for the duration of distress and pain experienced by the mice, and optimal scoring for the quality of animal care. The targets identified for refinement are discussed in relation to the method of inoculation, the duration of the bioassay, and the duration of the clinical phase, with the objective of exploring ways of reducing the severity of the bioassay.

Across many real-world domains, men engage in more risky behaviors than do women.To examine some of the beliefs and preferences that underlie this difference,657 participants assessed their likelihood of engaging in various riskyactivities relating to four different domains (gambling, health, recreation, andsocial), and reported their perceptions of (1) probability of negative outcomes,(2) severity of potential negative outcomes, and (3) enjoyment expected from therisky activities. Women’s greater perceived likelihood of negativeoutcomes and lesser expectation of enjoyment partially mediated their lowerpropensity toward risky choices in gambling, recreation, and health domains.Perceptions of severity of potential outcomes was a partial mediator in thegambling and health domains. The genders did not differ in their propensitytowards taking social risks. A fifth domain of activities associated with highpotential payoffs and fixed minor costs was also assessed. In contrast to otherdomains, women reported being more likely to engage in behaviors in this domain.This gender difference was partially mediated by women’s more optimisticjudgments of the probability of good outcomes and of outcomes being moreintensely positive.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

A multidisciplinary team collaborated to develop and validate a process to electronically capture patient and device denominator data at 6 hospitals in the same healthcare system. Validation was completed within 4–16 months. Manual count errors were identified as the main driver of electronic versus manual discrepancies.

Background: Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA) are neurodegenerative disorders with disabling morbidities and premature death. Variable illness trajectories make the timing for initiating neuropalliative care unclear. This scoping review aims to identify milestones relevant to survival and neuropalliative care in PSP and MSA. Methods: A systematic literature search was performed in Medline and EMBASE databases to identify publications investigating predictors of survival in PSP and MSA. Titles and abstracts of 2091 articles were independently screened by two reviewers and 22 research studies published after 2010 were included. Results were qualitatively combined to suggest triggers for targeted palliative care throughout the disease trajectory. Results: ‘Milestones’ are well documented, clinically relevant disease points prompting further care. Important milestones include frequent falls, cognitive impairment, severe dysarthria, severe dysphagia, wheelchair dependence, urinary catheterisation, and institutionalization. Early disease milestones include falls and cognitive impairment in PSP, and urinary catherization and falls in MSA. Time from milestone to death is variable. Conclusions: Milestones can be used to follow disease progression and help predict survival. We propose a framework in which milestones are used as triggers for targeted neuropalliative care interventions including the early initiation of a primary palliative care or referral to specialised palliative care services.

In November 2019, an outbreak of Shiga toxin-producing Escherichia coli O157:H7 was detected in South Yorkshire, England. Initial investigations established consumption of milk from a local dairy as a common exposure. A sample of pasteurised milk tested the next day failed the phosphatase test, indicating contamination of the pasteurised milk by unpasteurised (raw) milk. The dairy owner agreed to immediately cease production and initiate a recall. Inspection of the pasteuriser revealed a damaged seal on the flow divert valve. Ultimately, there were 21 confirmed cases linked to the outbreak, of which 11 (52%) were female, and 12/21 (57%) were either <15 or >65 years of age. Twelve (57%) patients were treated in hospital, and three cases developed haemolytic uraemic syndrome. Although the outbreak strain was not detected in the milk samples, it was detected in faecal samples from the cattle on the farm. Outbreaks of gastrointestinal disease caused by milk pasteurisation failures are rare in the UK. However, such outbreaks are a major public health concern as, unlike unpasteurised milk, pasteurised milk is marketed as ‘safe to drink’ and sold to a larger, and more dispersed, population. The rapid, co-ordinated multi-agency investigation initiated in response to this outbreak undoubtedly prevented further cases.

Many recorded roll calls in Congress each year are votes on bills that have no chance of becoming law, or are purely symbolic, or are procedural without policy content. Yet models of voting and measurement models of member preferences make assumptions that vote choices are largely about utility derived from policies. We consider the possibility that votes plausibly connected to policy and votes not plausibly connected to policy may have different data-generating processes and rely on different utility functions. Substantively, similarity across different contexts for policy change implies an importance of messaging over policy. Methodologically, similarity across these contexts is necessary to avoid biasing estimates of member preferences. We find that members’ voting patterns are highly stable across contexts in which policy change is credible and not credible. This indicates that existing measures of ideal points are likely not dramatically biased by the inclusion of policy-irrelevant votes.