4500-Year Paleohurricane Record From The Western Gulf of Mexico, Coastal Central TX, USA

Texas receives the second-highest number of tropical cyclone (TC) landfalls per year in the United States. At present, long-term TC projections from climate models remain uncertain due to the short and biased nature of Atlantic TC observations. Sediment archives of past storms can help extend the observational record of TC strikes over the past few millennia. When a TC makes landfall along the central Texas coast, coastal downwelling channels and storm currents transport and deposit coarse sediment to a zone of rapid accumulation along the shelf, known as the Texas Mud Blanket (TMB). This “backwash” process results in expansive storm deposits along the shelf, making this region ideal for paleotempestological reconstructions. Here, we present two sediment cores, located approximately 6 km southeast of Matagorda Island (TX), that collectively yield a ∼4500-year paleohurricane record. 210Pb and 137Cs are utilized in conjunction with radiocarbon ages to produce high-resolution Bayesian age models. One-centimeter interval grain size analyses are used to identify TC deposits. Two-centimeter interval X-Ray Fluorescence (XRF) is used as an additional measure to verify depositional mechanisms in this shelf environment. We define an intense paleohurricane event threshold through statistical analysis of mean grain size data. The sediment-derived TC record is correlated to Palmer Drought Severity Index (PDSI) data from Paleo Hydrodynamics Data Assimilation (PHYDA) to bolster our interpretation of the TC record, revealing a coupled relationship between PDSI and TCs since ∼300 yr BP. Over the ∼4500-year period, 24 intense TCs were recorded in the sediment record, yielding a long-term annual landfall probability of ∼0.53%. Additionally, comparisons between other TC records within the Atlantic establish a relationship between enhanced TC activity in the Western Gulf of Mexico (GOM) and TCs formed in the Caribbean Sea

Beyond Nanopore Sequencing in Space: Identifying the Unknown

Astronaut Kate Rubins sequenced DNA on the International Space Station (ISS) for the first time in August 2016 (Figure 1A). A 2D sequencing library containing an equal mixture of lambda bacteriophage, Escherichia coli, and Mus musculus was prepared on the ground with a SQK_MAP006 kit and sent to the ISS frozen and loaded into R7.3 flow cells. After a total of 9 on-orbit sequencing runs over 6 months, it was determined that there was no decrease in sequencing performance on-orbit compared to ground controls (1). A total of ~280,000 and ~130,000 reads generated on-orbit and on the ground, respectively, identified 90% of reads that were attributed to 30% lambda bacteriophage, 30% Escherichia coli, and 30% M. musculus (Figure 1B). Extensive bioinformatics analysis determined comparable 2D and 1D read accuracies between flight and ground runs (Figure 1C), and data collected from the ISS were able to construct directed assemblies of E.coli and lambda genomes at 100% and M. musculus mitochondrial genome at 96.7%. These findings validate sequencing as a viable option for potential on-orbit applications such as environmental microbial monitoring and disease diagnosis. Current microbial monitoring of the ISS applies culture-based techniques that provide colony forming unit (CFU) data for air, water, and surface samples. The identity of the cultured microorganisms in unknown until sample return and ground-based analysis, a process that can take up to 60 days. For sequencing to benefit ISS applications, spaceflight-compatible sample preparation techniques are required. Subsequent to the testing of the MinION on-orbit, a sample-to-sequence method was developed using miniPCR and basic pipetting, which was only recently proven to be effective in microgravity. The work presented here details the in- flight sample preparation process and the first application of DNA sequencing on the ISS to identify unknown ISS-derived microorganisms

Atomically Thin Resonant Tunnel Diodes built from Synthetic van der Waals Heterostructures

Vertical integration of two-dimensional van der Waals materials is predicted to lead to novel electronic and optical properties not found in the constituent layers. Here, we present the direct synthesis of two unique, atomically thin, multi-junction heterostructures by combining graphene with the monolayer transition-metal dichalocogenides: MoS2, MoSe2, and WSe2.The realization of MoS2-WSe2-Graphene and WSe2-MoSe2-Graphene heterostructures leads toresonant tunneling in an atomically thin stack with spectrally narrow room temperature negative differential resistance characteristics

The Effect of Glucagon-Like Peptide-2 Receptor Agonists on Colonic Anastomotic Wound Healing

Background. Glucagon-like peptide 2 (GLP-2) is an intestinal specific trophic hormone, with therapeutic potential; the effects on intestinal healing are unknown. We used a rat model of colonic healing, under normoxic, and stress (hypoxic) conditions to examine the effect of GLP-2 on intestinal healing. Methods. Following colonic transection and reanastomosis, animals were randomized to one of six groups (n = 8/group): controls, native GLP-2, long-acting GLP-2 (GLP-2- MIMETIBODY, GLP-2-MMB), animals were housed under normoxic or hypoxic (11%  O2) conditions. Animals were studied five days post-operation for anastomotic strength and wound characteristics. Results. Anastomotic bursting pressure was unchanged by GLP-2 or GLP-2-MMB in normoxic or hypoxic animals; both treatments increased crypt cell proliferation. Wound IL-1β increased with GLP-2; IFNγ with GLP-2 and GLP-2-MMB. IL-10 and TGF-β were decreased; Type I collagen mRNA expression increased in hypoxic animals while Type III collagen was reduced with both GLP-2 agonists. GLP-2 MMB, but not native GLP-2 increased TIMP 1-3 mRNA levels in hypoxia. Conclusions. The effects on CCP, cytokines and wound healing were similar for both GLP-2 agonists under normoxic and hypoxic conditions; anastomotic strength was not affected. This suggests that GLP-2 (or agonists) could be safely used peri-operatively; direct studies will be required

COS-PPA: protocol to develop a core outcome set for primary progressive aphasia

Introduction: The term primary progressive aphasia (PPA) describes a group of language-led dementias. Disease-modifying treatments that delay, slow or reverse progression of PPA are currently lacking, though a number of interventions to manage the symptoms of PPA have been developed in recent years. Unfortunately, studies exploring the effectiveness of these interventions have used a variety of different outcome measures, limiting comparability. There are more constructs, apart from word retrieval, that are important for people with PPA that have not received much attention in the research literature. Existing core outcome sets (COS) for dementia and non-progressive aphasia do not meet the needs of people with PPA, highlighting a need to develop a specific COS for PPA. // Methods and analysis: This protocol describes a three-stage study to identify a COS for PPA interventions in research and clinical practice. The stage 1 systematic review will identify existing speech, language and communication measures used to examine the effectiveness of interventions for PPA in the research literature. Employing a nominal group technique, stage 2 will identify the most important outcomes for people with PPA and their families. The data collected in stages 1 and 2 will be jointly analysed with the project PPI group and will inform the stage 2 modified Delphi consensus study to identify a core outcome measurement set for PPA among a range of research disciplines undertaking intervention studies for people with PPA. // Ethics and dissemination: Ethical approval for stage 2 of the study has been sought individually in each country at collaborating institutions and is stated in detail in the manuscript. Stage 3 has been granted ethical approval by the Chairs of UCL Language and Cognition Department Ethics, Project ID LCD-2023-06. Work undertaken at stages 1, 2 and 3 will be published in open-access peer-reviewed journal articles and presented at international scientific conferences. // PROSPERO registration number: CRD42022367565

Defining County-Level Terrestrial Rabies Freedom Using the US National Rabies Surveillance System: Surveillance Data Analysis

Background: Rabies is a deadly zoonotic disease with nearly 100% fatality rate. In the United States, rabies virus persists in wildlife reservoirs, with occasional spillover into humans and domestic animals. The distribution of reservoir hosts in US counties plays an important role in public health decision-making, including the recommendation of lifesaving postexposure prophylaxis upon suspected rabies exposures. Furthermore, in surveillance data, it is difficult to discern whether counties have no cases reported because rabies was not present or because counties have an unreported rabies presence. These epizootics are monitored by the National Rabies Surveillance System (NRSS), to which approximately 130 state public health, agriculture, and academic laboratories report animal rabies testing statistics. Historically, the NRSS classifies US counties as free from terrestrial rabies if, over the previous 5 years, they and any adjacent counties did not report any rabies cases and they tested ≥15 reservoir animals or 30 domestic animals. Objective: This study aimed to describe and evaluate the historical NRSS rabies-free county definition, review possibilities for improving this definition, and develop a model to achieve more precise estimates of the probability of terrestrial rabies freedom and the number of reported county-level terrestrial rabies cases. Methods: Data submitted to the NRSS by state and territorial public health departments and the US Department of Agriculture Wildlife Services were analyzed to evaluate the historical rabies-free definition. A zero-inflated negative binomial model created county-level predictions of the probability of rabies freedom and the expected number of rabies cases reported. Data analyzed were from all animals submitted for laboratory diagnosis of rabies in the United States from 1995 to 2020 in skunk and raccoon reservoir territories, excluding bats and bat variants. Results: We analyzed data from 14,642 and 30,120 county-years in the raccoon and skunk reservoir territories, respectively. Only 0.85% (9/1065) raccoon county-years and 0.79% (27/3411) skunk county-years that met the historical rabies-free criteria reported a case in the following year (99.2% negative predictive value for each), of which 2 were attributed to unreported bat variants. County-level model predictions displayed excellent discrimination for detecting zero cases and good estimates of reported cases in the following year. Counties classified as rabies free rarely (36/4476, 0.8%) detected cases in the following year. Conclusions: This study concludes that the historical rabies freedom definition is a reasonable approach for identifying counties that are truly free from terrestrial raccoon and skunk rabies virus transmission. Gradations of risk can be measured using the rabies prediction model presented in this study. However, even counties with a high probability of rabies freedom should maintain rabies testing capacity, as there are numerous examples of translocations of rabies-infected animals that can cause major changes in the epidemiology of rabies

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography

Women from breast cancer families without a demonstrable BRCA1/2 mutation were subjected to annual mammography from age 30 years onwards. One-hundred and ninety-eight patients were diagnosed prospectively with invasive breast cancer and followed for a total of 1513 years. Overall 10-year survival was 88 %. Together with our previous report that women in such kindreds had about twice the population risk of breast cancer, the combined conclusion was that the overall chances of developing breast cancer causing death within 10 years before 50 years of age was 1 % or less when subjected to annual mammography and current treatment. These are empirical prospective observations which may be used for genetic counselling. The majority (160/194 = 84 %) of patients had ER+ and/or low grade tumours with 92 % 10-year survival. One minor group of the patients had ER- tumours, another small group had high grade tumours with nodal spread, both groups were associated with worse prognosis, but the two groups were not mutually associated

Clinicians’ perspectives and experiences of providing cervical ripening at home or in-hospital in the United Kingdom

Acknowledgements We are grateful to those who gave their time for interviews and focus groups despite the severe workload pressures and ongoing COVID-19 pandemic. CHOICE is funded by the National Institute of Healthcare Research Health Technology and Assessment (NIHR HTA) NIHR 127569. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the National Institute of Healthcare Research or the Department of Health and Social Care.Peer reviewedPublisher PD