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The 'evanescent /l/' in Venetan: a preliminary EMA study
Get PDFThis study is the first articulatory investigation of the so-called ‘evanescent /l/’ in Venetan. We propose that this sound be transcribed as a non-syllabic [ɛ̯] or [ə̯] in the variety of interest
Creating, optimising and applying TRANCERS (TRanscriptionally Autonomous enhaNCERS) to drive cell and tissue specific expression
No full textThe process by which a foreign gene is introduced into a cell and translated into a functional protein is referred to as transgene expression. Understanding and optimising transgene expression is crucial for many applications which range from functional genetic studies, recombinant protein production and gene therapy. The overall goal of this project has been to create a flexible system where we can engineer highly tissue- and stage-specific expression patterns. To accomplish this, we have taken advantage of past observations about enhancer function as well as revealing known and novel principles of transcript stability and nuclear export. My thesis has focused on the creation of TRANCERS (TRanscriptionally Autonomous enhaNCERS). To develop TRANCERS, we have shown that cell type specific distal enhancer elements, which normally drive expression from promoters, can also be engineered to themselves act as autonomous, specific, timely and highly compact sources of transcription
The Vulnerability and Resilience of Drinking Water Systems to Extreme Weather Events and Future Climate Change
Get PDFPurpose of Review: We reviewed the evidence on climate resilience of the drinking water sector, focusing on: How are climate hazards affecting drinking water supplies changing? How is resilience measured? What interventions are being used to build resilience? Recent Findings: The frequency and intensity of flooding and drought are increasing, water quality is deteriorating, and wildfire and sea-level rise pose increasing threats. Frameworks to measure resilience are emerging, but none is applied universally. a wide range of actions are required to build resilience but there is limited evidence of uptake and performance. Non-utility water supplies are at particular risk but investment in resilience is limited. Summary: Climate change poses a major threat to drinking water supplies, but current actions to improve resilience are insufficient. More evaluations of the performance of resilience measures are needed. Floods and drought remain the most studied threats, but risks from wildfire, water quality and sea-level need more attention and research. More work is needed to consolidate how resilience is measured. A summary of the detailed findings in provided in Table 1 at the end of the review
Palaeoeconomy of the Eurasian steppe: biomolecular studies
Get PDFThe Bronze and Iron Age inhabitants of the Eurasian steppe region of the former USSR have long been considered dependent upon their domestic stock as the basis for their diet and economy. Research presented by O’Connell et al. (2000) first proposed that freshwater fish played an important and possibly even dominant role in the diets of central Eurasian steppe groups. This set of studies tests the hypothesis that freshwater fish were a major dietary staple for central Eurasian steppe and border-steppe humans during the Bronze and Iron Ages. Evidence for the frequent consumption of freshwater animals is provided by a large-scale palaeodietary study involving the carbon and nitrogen isotope analysis of human and faunal individuals obtained from central Eurasian archaeological sites. The palaeodietary evidence for high-freshwater fish diets is supported by the findings that the frequent consumption of dairy products is unlikely to lead to the highly elevated human δ15N values observed in many Bronze and Iron Age humans. Sulphur isotope analysis of human and faunal remains from two Eurasian steppe sites indicate that δ34S analysis can provide limited information by which to distinguish humans with a mainly freshwater from those with a mainly terrestrial diet. The criteria by which bone collagen may be assessed for sulphur isotope analysis are discussed. The analysis of archaeological food residues demonstrates the potential to identify vessels used to prepare fish in antiquity. Residue analysis of vessels from the archaeological site of Chicha suggest that dairying was a subsistence practice carried out at the site, in addition to fishing and the management of domestic herds for meat. A revision of the dietary and economic profile of central Eurasian steppe peoples is proposed, with added emphasis upon the importance of freshwater fish for many groups
Psychological and Social Impacts of Top-down Conservation Initiatives on Indigenous Communities: Lessons from the Announcement of two Royal Decrees in Thailand
Get PDFIn November 2024, the Thai government approved two Royal Decrees for ecosystem conservation that would severely threaten the livelihoods, living prospects, and continued residence of Indigenous communities in protected areas. Protests with 10,000 participants prompted a review of the decrees in May 2025. This research report investigates the psychological and social implications of the announcement of the Royal Decrees and argues that it undermined community social capital and intrinsic engagement with everyday environmental heritage. We drew on qualitative and survey data collected from 09/2024 to 05/2025 in two Pga K’Nyau and two Hmong communities in the northern Thai highlands, comprising community consultations with 73 participants, 101 semi-structured interviews, and two survey rounds, for a total of 384 observations. We used qualitative thematic analysis and descriptive statistics to explore how community members experienced, interpreted, and responded to the announcement of the decrees. We found that Indigenous villagers experienced anxiety and unease, and that the decrees undermined community efforts to conserve and engage with local ecosystems. The continued uncertainty surrounding communities’ future sparked a strong activist sentiment to resist the decrees. Disruptions to community social capital and everyday environmental heritage also had plausible, potentially significant ecological downstream effects. We therefore call for an urgent correction to the conservation initiative to embrace inclusive, bottom-up natural resource governance
Development of Superfluid Helium-3 Bolometry Using Nanowire Resonators with SQUID Readout for the QUEST-DMC Experiment
Get PDFSuperfluid helium-3 bolometers can be utilised for dark matter direct detection searches. The extremely low heat capacity of the B phase of the superfluid helium-3 at ultra-low temperatures offers the potential to reach world leading sensitivity to spin-dependent interactions of dark matter in the sub-GeV/c2 mass range. Here, we describe the development of bolometry using both micron scale and sub-micron diameter vibrating wire resonators, with a SQUID amplifier-based readout scheme. Characterisation of the resonators and bolometer measurements are shown, including the use of nonlinear operation and the corresponding corrections. The bolometer contains two vibrating wire resonators, enabling heat injection calibration and simultaneous bolometer tracking measurements. Coincident events measured on both vibrating wire resonators verify their response. We also demonstrate proof of concept frequency multiplexed readout. Development of these measurement techniques lays the foundations for the use of superfluid helium-3 bolometers, instrumented with vibrating nanomechanical resonators, for future low-threshold dark matter searches
Outcomes from the English National Lynch Syndrome transformation project
Get PDFThe English National Health Service (NHS) Lynch Syndrome Transformation Project was established to deliver universal testing for Lynch syndrome (LS) of newly diagnosed colorectal (CRC) and endometrial cancer (EC). A central aim was to integrate ‘mainstreamed’ genetic testing into routine care by cancer multidisciplinary teams in England. In June 2021 national and regional LS project teams were established to support ‘LS champions’ within local cancer multidisciplinary teams (MDTs). A comprehensive retrospective genomic dataset and dashboard was compiled by the National Disease Registration Service (NDRS), complimented with prospective local MDT audit (2022–2023). A robust national registry of people diagnosed with LS was developed to ascertain individuals for targeted interventions, including for a new national LS Bowel Cancer Screening Programme (LS‐BCSP). In total 276 LS champions were appointed and trained across 248 CRC and EC MDTs (>95% coverage nationally). Tumour Mismatch repair (MMR) tumour testing rates increased for CRC (43 >94%) and EC (19 >94%). MDT‐led mainstreaming services were developed in 46% of all CRC and 41% EC teams in England. In subgroup data, the time to germline genetic testing was 21 days in ‘mainstreamed’ patients, versus 180 days referred to regional clinical genetics services. New diagnoses of LS have consistently increased each year from a total of 545 in 2020 to a total of 1394 in 2024 (an increase of 255% vs. a target of >50%). The NHS England LS Transformation project has driven equitable nationwide delivery of diagnosis testing for Lynch syndrome, with integration of ‘mainstreamed’ genetic testing into routine cancer care
Withdrawal of antihypertensive drugs in older people
Get PDFBackground
Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, and heart failure, as well as chronic kidney disease, cognitive decline, and premature death. Overall, the use of antihypertensive medications has led to a reduction in cardiovascular disease, morbidity rates, and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions and drug‐drug interactions, and can contribute to increasing medication‐related burden. As such, discontinuation of antihypertensives may be considered appropriate in some older people.
Objectives
To evaluate the effects of withdrawal of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults.
Search methods
For this update, we searched the Cochrane Hypertension Specialised Register, CENTRAL (2022, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO ICTRP, and ClinicalTrials.gov up to October 2022. We also conducted reference checking and citation searches, and contacted study authors to identify any additional studies when appropriate. There were no language restrictions on the searches.
Selection criteria
We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years of age and over). Eligible participants were living in the community, residential aged care facilities, or based in hospital settings. We included trials evaluating the complete withdrawal of all antihypertensive medication, as well as those focusing on a dose reduction of antihypertensive medication.
Data collection and analysis
We compared the intervention of discontinuing or reducing the dose of antihypertensive medication to continuing antihypertensive medication using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables, and Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes were mortality, myocardial infarction, and the development of adverse drug reactions or adverse drug withdrawal reactions. Secondary outcomes included hospitalisation, stroke, blood pressure (systolic and diastolic), falls, quality of life, and success in withdrawing from antihypertensives. Two review authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment.
Main results
We identified no new studies in this update. Six RCTs from the original review met the inclusion criteria and were included in the review (1073 participants). Study duration and follow‐up ranged from 4 weeks to 56 weeks. Meta‐analysis of studies showed that discontinuing antihypertensives, compared to continuing, may result in little to no difference in all‐cause mortality (OR 2.08, 95% CI 0.79 to 5.46; P = 0.14, I2 = 0%; 4 studies, 630 participants; low certainty of evidence), and that the evidence is very uncertain about the effect on myocardial infarction (OR 1.86, 95% CI 0.19 to 17.98; P = 0.59, I2 = 0%; 2 studies, 447 participants; very low certainty of evidence). Meta‐analysis was not possible for the development of adverse drug reactions and withdrawal reactions; the evidence is very uncertain about the effect of antihypertensive discontinuation on the risk of adverse drug reactions (very low certainty of evidence), and the included studies did not assess adverse drug withdrawal reactions specifically. One study reported on hospitalisations; discontinuing antihypertensives may result in little to no difference in hospitalisation (OR 0.83, 95% CI 0.33 to 2.10; P = 0.70; 1 study, 385 participants; low certainty of evidence). Meta‐analysis showed that discontinuing antihypertensives may result in little to no difference in stroke (OR 1.44, 95% CI 0.25 to 8.35; P = 0.68, I2 = 6%; 3 studies, 524 participants; low certainty of evidence). Blood pressure may be higher in the discontinuation group than the continuation group (systolic blood pressure: MD 9.75 mmHg, 95% CI 7.33 to 12.18; P < 0.001, I2 = 67%; 5 studies, 767 participants; low certainty of evidence; and diastolic blood pressure: MD 3.5 mmHg, 95% CI 1.82 to 5.18; P < 0.001, I2 = 47%; 5 studies, 768 participants; low certainty of evidence). No studies reported falls. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias).
Authors' conclusions
The main conclusions from the 2020 review still apply. Discontinuing antihypertensives may result in little to no difference in mortality, hospitalisation, and stroke. The evidence is very uncertain about the effect of discontinuing antihypertensives on myocardial infarction and adverse drug reactions and adverse drug withdrawal reactions. Discontinuing antihypertensives may result in an increase in blood pressure. There was no information about the effect on falls. The evidence was of low to very low certainty, mainly due to small studies and low event rates. These limitations mean that we cannot draw any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for the use of antihypertensive medications, such as those with frailty, older age groups, and those taking polypharmacy, and measure clinically important outcomes such as adverse drug events, falls, and quality of life
On the Importance of Correct Snake Identification. Comment on Chippaux et al. Snakebites in Cameroon by Species Whose Effects Are Poorly Described. <i>Trop. Med. Infect. Dis.</i> 2024, <i>9</i>, 300
Get PDFOne of the major obstacles to improving the management of snakebite envenoming is the lack of accurate identification of species responsible for clinical cases, which prevent the improvement of definitions of species-specific syndromes [...]
Taking care of ageing futures: reflections on a care-full, response-able praxis of co-design with older adults
No full textThis article contributes to the Responsible Research and Innovation (RRI) literature by drawing on feminist posthuman care approaches to discuss experiences of researching and co-designing with older minoritised adults. It responds to calls in RRI for a focus on new conceptualisations of ‘care’ and ‘response-ability’ for the future of the field. We focus on the praxis of care-full and response-able design adopted on the Connecting Through Culture As We Age project. In so doing we respond to the need for empirical accounts of how these RRI concepts take shape in grounded practices of research and innovation. We highlight a set of practices that aim to embed care and response-ability in digital design processes involving older adults, researchers and designers, to deeply consider our roles in ‘taking care of the future’ in RRI. In the context of ageing populations and increasing inequalities we hope these practices may be useful to others