Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western U.S. National Park Fish: Concentrations and Consumption Guidelines

Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western U.S. National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit, -18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1% relative standard deviation (RSD)), and accurate (7% deviation from standard reference material (SRM)) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs, and chlordanes in western U.S. fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western U.S. fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, lake average contaminant concentrations in fish exceeded subsistence fishing cancer thresholds in 8 of 14 lakes and wildlife contaminant health thresholds for piscivorous birds in 1 of 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health

The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.

BackgroundStudies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinson's disease (PD).MethodsWe included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinson's study. Group comparisons of data were made using Welch's t-test and Kruskal-Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (≤55 years) in the Queen Square Brain Bank PSP case series.ResultsWe identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z-score, 0.59) and LOPSP (mean z-score, 0.48) groups was significantly higher (P ConclusionsThe initial clinical profile of EOPSP is often PD-like. At the group level, a PSP GRS was able to differentiate EOPSP from PD, and this may be helpful in future diagnostic algorithms. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Clonal differences in Staphylococcus aureus bacteraemia-associated mortality.

The bacterium Staphylococcus aureus is a major human pathogen for which the emergence of antibiotic resistance is a global public health concern. Infection severity, and in particular bacteraemia-associated mortality, has been attributed to several host-related factors, such as age and the presence of comorbidities. The role of the bacterium in infection severity is less well understood, as it is complicated by the multifaceted nature of bacterial virulence, which has so far prevented a robust mapping between genotype, phenotype and infection outcome. To investigate the role of bacterial factors in contributing to bacteraemia-associated mortality, we phenotyped a collection of sequenced clinical S. aureus isolates from patients with bloodstream infections, representing two globally important clonal types, CC22 and CC30. By adopting a genome-wide association study approach we identified and functionally verified several genetic loci that affect the expression of cytolytic toxicity and biofilm formation. By analysing the pooled data comprising bacterial genotype and phenotype together with clinical metadata within a machine-learning framework, we found significant clonal differences in the determinants most predictive of poor infection outcome. Whereas elevated cytolytic toxicity in combination with low levels of biofilm formation was predictive of an increased risk of mortality in infections by strains of a CC22 background, these virulence-specific factors had little influence on mortality rates associated with CC30 infections. Our results therefore suggest that different clones may have adopted different strategies to overcome host responses and cause severe pathology. Our study further demonstrates the use of a combined genomics and data analytic approach to enhance our understanding of bacterial pathogenesis at the individual level, which will be an important step towards personalized medicine and infectious disease management

TESS spots a mini-neptune interior to a hot saturn in the TOI-2000 system

Hot jupiters (P 60 $\mathrm{M}_\oplus$) are almost always found alone around their stars, but four out of hundreds known have inner companion planets. These rare companions allow us to constrain the hot jupiter's formation history by ruling out high-eccentricity tidal migration. Less is known about inner companions to hot Saturn-mass planets. We report here the discovery of the TOI-2000 system, which features a hot Saturn-mass planet with a smaller inner companion. The mini-neptune TOI-2000 b ($2.70 \pm 0.15 \,\mathrm{R}_\oplus$, $11.0 \pm 2.4 \,\mathrm{M}_\oplus$) is in a 3.10-day orbit, and the hot saturn TOI-2000 c ($8.14^{+0.31}_{-0.30} \,\mathrm{R}_\oplus$, $81.7^{+4.7}_{-4.6} \,\mathrm{M}_\oplus$) is in a 9.13-day orbit. Both planets transit their host star TOI-2000 (TIC 371188886, V = 10.98, TESS magnitude = 10.36), a metal-rich ([Fe/H] = $0.439^{+0.041}_{-0.043}$) G dwarf 174 pc away. TESS observed the two planets in sectors 9-11 and 36-38, and we followed up with ground-based photometry, spectroscopy, and speckle imaging. Radial velocities from CHIRON, FEROS, and HARPS allowed us to confirm both planets by direct mass measurement. In addition, we demonstrate constraining planetary and stellar parameters with MIST stellar evolutionary tracks through Hamiltonian Monte Carlo under the PyMC framework, achieving higher sampling efficiency and shorter run time compared to traditional Markov chain Monte Carlo. Having the brightest host star in the V band among similar systems, TOI-2000 b and c are superb candidates for atmospheric characterization by the JWST, which can potentially distinguish whether they formed together or TOI-2000 c swept along material during migration to form TOI-2000 b.Comment: v3 adds RV frequency analysis; 25 pages, 11 figures, 14 tables; revision submitted to MNRAS; machine-readable tables available as ancillary files; posterior samples available from Zenodo at https://doi.org/10.5281/zenodo.7683293 and source code at https://doi.org/10.5281/zenodo.798826

Infertility and the provision of infertility medical services in developing countries

developing countrie

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

The TESS Grand Unified Hot Jupiter Survey. II. Twenty New Giant Planets

NASA's Transiting Exoplanet Survey Satellite (TESS) mission promises to improve our understanding of hot Jupiters by providing an all-sky, magnitude-limited sample of transiting hot Jupiters suitable for population studies. Assembling such a sample requires confirming hundreds of planet candidates with additional follow-up observations. Here, we present twenty hot Jupiters that were detected using TESS data and confirmed to be planets through photometric, spectroscopic, and imaging observations coordinated by the TESS Follow-up Observing Program (TFOP). These twenty planets have orbital periods shorter than 7 days and orbit relatively bright FGK stars ($10.9 < G < 13.0$). Most of the planets are comparable in mass to Jupiter, although there are four planets with masses less than that of Saturn. TOI-3976 b, the longest period planet in our sample ($P = 6.6$ days), may be on a moderately eccentric orbit ($e = 0.18\pm0.06$), while observations of the other targets are consistent with them being on circular orbits. We measured the projected stellar obliquity of TOI-1937A b, a hot Jupiter on a 22.4 hour orbit with the Rossiter-McLaughlin effect, finding the planet's orbit to be well-aligned with the stellar spin axis ($|\lambda| = 4.0\pm3.5^\circ$). We also investigated the possibility that TOI-1937 is a member of the NGC 2516 open cluster, but ultimately found the evidence for cluster membership to be ambiguous. These objects are part of a larger effort to build a complete sample of hot Jupiters to be used for future demographic and detailed characterization work.Comment: 67 pages, 11 tables, 13 figures, 2 figure sets. Resubmitted to ApJS after revision

Improving Conversations about Parkinson's Dementia

Background: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that “nothing can be done about it”. However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. Objectives: To co‐produce information resources for patients and healthcare professionals to improve conversations about PD dementia. Methods: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. Results: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co‐develop two open‐access resources: one for people with PD and their families, and one for healthcare professionals. Conclusion: Using artistic and creative workshops, co‐learning and striving for diverse voices, we co‐produced relevant resources for a wider audience to improve conversations about PD dementia