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Higher intakes of Na may contribute to weight gain. The primary aim of this systematic review and meta-analysis was to examine the relationship between dietary Na intake and measures of adiposity in children and adults. Given the previous link between Na intake and the consumption of sugar-sweetened beverages (SSB), which are a known risk factor for obesity, a secondary aim examining the relationship between Na intake and SSB consumption was assessed. A systematic literature search identified cross-sectional and longitudinal studies and randomised controlled trials (RCT) which reduced dietary Na (≥3 months). Meta-analysis was performed for outcomes with ≥3 studies. Cross-sectionally higher Na intakes were associated with overweight/obesity in adults (five studies; n 11 067; OR 1·74; 95 % CI 1·43, 2·13) and in children (three studies; n 3625, OR 3·29; 95 % CI 2·25, 4·80), and abdominal obesity (five studies; n 19 744; OR 2·04; 95 % CI 1·72, 2·42) in adults. Overall, associations remained in sensitivity analyses which adjusted for energy. Findings from longitudinal studies were inconsistent. RCT in adults indicated a trend for lower body weight on reduced-Na compared with control diets (fifteen studies; n 5274; −0·29 kg; 95 % CI −0·59, 0·01; P = 0·06); however, it is unclear if energy intakes were also altered on reduced-Na diets. Among children higher Na intakes were associated with higher intake of SSB (four studies, n 10 329, b = 22, 16 and 26 g/d); no studies were retrieved for adults. Overall, there was a lack of high-quality studies retrieved. While cross-sectional evidence indicates Na intake was positively associated with adiposity, these findings have not been clearly confirmed by longitudinal studies or RCT.

The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.

Of 350 patients who were referred to the National Amyloidosis Centre in London with biopsy-proved amyloidosis and a presumed diagnosis of immunoglobulin light-chain amyloidosis, almost 10 percent actually had hereditary amyloidosis due to genetic variants of transthyretin, apolipoprotein A-I, lysozyme, or fibrinogen A α-chain. Some of these patients had an incidental monoclonal gammopathy. Of 350 patients referred with light-chain disease, almost 10 percent had hereditary amyloidosis. Systemic amyloidosis is the diagnosis in 2.5 percent of all native renal biopsies, 1 and the cause of death in more than 1 in 1500 people in the United Kingdom annually. Acquired monoclonal immunoglobulin light-chain (AL) amyloidosis, formerly known as primary amyloidosis, is the most common form of systemic amyloidosis and can respond to chemotherapy directed at the underlying plasma-cell dyscrasia. 2 – 5 Scintigraphy with labeled serum amyloid P component (SAP), a technique for quantitatively imaging amyloid deposits in vivo, 6 has shown that deposits frequently regress after a reduction in monoclonal light-chain production. 7 The chief consideration in the differential diagnosis of AL . . .

In 2018 the first subglacial lake in the Canadian Arctic was proposed to exist beneath the Devon Ice Cap, based on the analysis of airborne radar data. Here, we report a new interpretation of the subglacial material beneath the Devon Ice Cap, supported by data acquired from multiple surface-based geophysical methods in 2022. The geophysical data recorded included 9 km of active-source seismic-reflection profiles, seven transient electromagnetic (TEM) soundings, and 17 magnetotellurics (MT) stations. These surface-based geophysical datasets were collected above the inferred locations of the subglacial lakes and show no evidence for the presence of subglacial water. The acoustic impedance of the subglacial material, estimated from the seismic data, is 9.49 ± 1.92 × 106 kg m−2 s−1, comparable to consolidated or frozen sediment. The resistivity models obtained by inversion of both the TEM and MT measurements show the presence of highly resistive rock layers (1000–100 000 Ω m) directly beneath the ice. Re-evaluation of the airborne reflectivity data shows that the radar attenuation rates were likely overestimated, leading to an overestimation of the basal reflectivity in the original radar studies. Here, we derive new radar attenuation rates using the temperature- and chemistry-dependent Arrhenius equation, and when applied to correct the returned bed power, the bed power does not meet the basal reflectivity threshold expected over subglacial water. Thus, the radar interpretation is now consistent with the seismic and electromagnetic observations of dry or frozen, non-conductive basal material.

ObjectivesPreoperative anaemia is associated with increased risks of postoperative complications, blood transfusion and mortality. This meta-analysis aims to review the best available evidence on the clinical effectiveness of preoperative iron in anaemic patients undergoing elective total hip (THR) or total knee replacement (TKR).DesignElectronic databases and handsearching were used to identify randomised and non-randomised studies of interventions (NRSI) reporting perioperative blood transfusion rates for anaemic participants receiving iron before elective THR or TKR. Searches of CENTRAL, MEDLINE, Embase, PubMed and other databases were conducted on 17 April 2019 and updated on 15 July 2020. Two investigators independently reviewed studies for eligibility and evaluated risk of bias using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and a modified Newcastle-Ottawa scale for NRSIs. Data extraction was performed by ABS and checked by AB. Meta-analysis used the Mantel-Haenszel method and random-effects models.Results807 records were identified: 12 studies met the inclusion criteria, of which 10 were eligible for meta-analyses (one RCT and nine NRSIs). Five of the NRSIs were of high-quality while there were some concerns of bias in the RCT. Meta-analysis of 10 studies (n=2178 participants) showed a 39% reduction in risk of receiving a perioperative blood transfusion with iron compared with no iron (risk ratio 0.61, 95% CI 0.50 to 0.73, p<0.001, I2=0%). There was a significant reduction in the number of red blood cell units transfused with iron compared with no iron (mean difference −0.37units, 95% CI −0.47 to -0.27, p<0.001, I2=40%); six studies (n=1496). Length of stay was significantly reduced with iron, by an average of 2.08 days (95% CI −2.64 to −1.51, p<0.001, I2=40%); five studies (n=1140).ConclusionsPreoperative iron in anaemic, elective THR or TKR patients, significantly reduces the number of patients and number of units transfused and length of stay. However, high-quality, randomised trials are lacking.PROSPERO registration numberCRD42019129035.

Background Measures shown to improve outcomes for patients often fail to be adopted into routine practice in the NHS. The Institute for Health Improvement Breakthrough Series Collaborative (BSC) model is designed to support implementation at scale. This trial aims to assess the effectiveness and cost-effectiveness of quality improvement collaboratives (QICs) based on the BSC method for introducing service improvements at scale in the NHS. Methods Forty Trusts will be randomised (1:1) to introduce one of two protocols already shown to improve outcomes in patients undergoing elective total hip and knee replacement surgery. The intervention is improvement collaboratives based on the BSC model, a learning system that brings together a large number of teams to seek improvement focussed on a proven intervention. Collaboratives aim to deliver at scale, maximise local engagement and leadership and are designed to build capacity, enable learning and prepare for sustainability. Collaboratives involve Learning Sessions, Action Periods, and a summative congress. Trusts will be supported to introduce either: decolonisation for Methicillin Sensitive Staphylococcus aureus (MSSA) to reduce post-operative infection (QIST: Infection), or an anaemia optimisation programme to reduce peri-operative blood transfusions (QIST: Anaemia). Trusts will continue with their usual practice for whichever protocol they are not introducing. Anonymised data related to both infection and anaemia outcomes for patients undergoing hip or knee arthroplasty at all sites will mean that the two groups act as controls for each other. The primary outcome for the QIST: Infection collaborative is deep MSSA surgical site infection within 90 days of surgery, and for the QIST: Anaemia collaborative is blood transfusion within 7 days of surgery. Patient-level secondary outcomes include length of hospital stay and readmission, which will also inform the economic costings. Qualitative interviews will evaluate the support provided to teams. Discussion The scale of this trial brings considerable challenges and potential barriers to delivery. Anticipated challenges relate to recruiting and sustaining up to 40 organisations, each with its own culture and context. This complex project with multiple stakeholders across a large geographical area will be managed by experienced senior-level project leaders with a proven track record in advanced project management. The team should ensure effective project governance and communications. Trial registration ISRCTN, ISRCTN11085475 . Prospectively registered on 15 February 2018.

The thapsigargins are a family of complex guaianolides with potent and selective Ca2+-modulating properties. This article documents the evolution of a synthetic route through several iterations to a final practical and scaleable synthetic route capable of generating both unnatural and natural products based around the guaianolide skeleton.

Background The aim of this trial was to assess the effectiveness of quality improvement collaboratives to implement large-scale change in the National Health Service (NHS) in the UK, specifically for improving outcomes in patients undergoing primary, elective total hip or knee replacement. Methods We undertook a two-arm, cluster randomised controlled trial comparing the roll-out of two preoperative pathways: methicillin-sensitive Staphylococcus aureus (MSSA) decolonisation (infection arm) and anaemia screening and treatment (anaemia arm). NHS Trusts are public sector organisations that provide healthcare within a geographical area. NHS Trusts ( n = 41) in England providing primary, elective total hip and knee replacements, but that did not have a preoperative anaemia screening or MSSA decolonisation pathway in place, were randomised to one of the two parallel collaboratives. Collaboratives took place from May 2018 to November 2019. Twenty-seven Trusts completed the trial (11 anaemia, 16 infection). Outcome data were collected for procedures performed between November 2018 and November 2019. Co-primary outcomes were perioperative blood transfusion (within 7 days of surgery) and deep surgical site infection (SSI) caused by MSSA (within 90 days post-surgery) for the anaemia and infection trial arms, respectively. Secondary outcomes were deep and superficial SSIs (any organism), length of hospital stay, critical care admissions and unplanned readmissions. Process measures included the proportion of eligible patients receiving each preoperative initiative. Results There were 19,254 procedures from 27 NHS Trusts included in the results (6324 from 11 Trusts in the anaemia arm, 12,930 from 16 Trusts in the infection arm). There were no improvements observed for blood transfusion (anaemia arm 183 (2.9%); infection arm 302 (2.3%) transfusions; adjusted odds ratio 1.20, 95% CI 0.52–2.75, p = 0.67) or MSSA deep SSI (anaemia arm 8 (0.13%); infection arm 18 (0.14%); adjusted odds ratio 1.01, 95% CI 0.42–2.46, p = 0.98). There were no significant improvements in any secondary outcome. This is despite process measures showing the preoperative pathways were implemented for 73.7% and 61.1% of eligible procedures in the infection and anaemia arms, respectively. Conclusions Quality improvement collaboratives did not result in improved patient outcomes in this trial; however, there was some evidence they may support successful implementation of new preoperative pathways in the NHS. Trial registration Prospectively registered on 15 February 2018, ISRCTN11085475

We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

Background A thoracolumbar fracture is the most common fracture of the spinal column. Where the fracture is not obviously stable or unstable, the optimal management is uncertain. There are variations between surgeons, treating centres and within the evidence base as to whether surgical or non-surgical approaches should be used. In addition, the boundaries of this zone of uncertainty for stability are unclear. This study has been designed in response to an NIHR HTA commissioning brief to assess the feasibility of undertaking a large-scale trial to evaluate the effectiveness of surgical and non-surgical treatments for thoracolumbar fractures without neurological deficit. Methods Assessment of feasibility will be addressed through three elements: a randomised external feasibility study, a national survey of surgeons and a qualitative study. The external feasibility study is a pragmatic, parallel-group, randomised controlled trial comparing surgical fixation (intervention) versus non-surgical management (control). Recruitment will take place in three secondary care centres in the UK. The primary outcome is recruitment rate, defined as the proportion of eligible participants who are randomised. Further outcomes related to recruitment, randomisation, drop-out, cross-over, loss to follow-up, completeness of outcome data, study processes and details of the interventions delivered will be collected. The survey of surgeons and qualitative study of clinicians, recruiting staff and patients will enhance the feasibility study, enabling a broad overview of current practice in the field in addition to perceived facilitators and barriers to running a full-scale trial. Discussion PRESTO is a feasibility study which aims to inform methodology for a definitive trial comparing surgical fixation with non-surgical management for patients with stable thoracolumbar fractures. Trial registration The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN12094890). Date of registration was 22/02/2018 ( http://www.isrctn.com/ISRCTN12094890 ).