Publications by authors named "Richard Stevens"

316 Publications

Estimating the effect of moving meat-free products to the meat aisle on sales of meat and meat-free products: A non-randomised controlled intervention study in a large UK supermarket chain.

PLoS Med 2021 Jul 15;18(7):e1003715. Epub 2021 Jul 15.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.

Background: Reducing meat consumption could bring health and environmental benefits, but there is little research to date on effective interventions to achieve this. A non-randomised controlled intervention study was used to evaluate whether prominent positioning of meat-free products in the meat aisle was associated with a change in weekly mean sales of meat and meat-free products.

Methods And Findings: Weekly sales data were obtained from 108 stores: 20 intervention stores that moved a selection of 26 meat-free products into a newly created meat-free bay within the meat aisle and 88 matched control stores. The primary outcome analysis used a hierarchical negative binomial model to compare changes in weekly sales (units) of meat products sold in intervention versus control stores during the main intervention period (Phase I: February 2019 to April 2019). Interrupted time series analysis was also used to evaluate the effects of the Phase I intervention. Moreover, 8 of the 20 stores enhanced the intervention from August 2019 onwards (Phase II intervention) by adding a second bay of meat-free products into the meat aisle, which was evaluated following the same analytical methods. During the Phase I intervention, sales of meat products (units/store/week) decreased in intervention (approximately -6%) and control stores (-5%) without significant differences (incidence rate ratio [IRR] 1.01 [95% CI 0.95-1.07]. Sales of meat-free products increased significantly more in the intervention (+31%) compared to the control stores (+6%; IRR 1.43 [95% CI 1.30-1.57]), mostly due to increased sales of meat-free burgers, mince, and sausages. Consistent results were observed in interrupted time series analyses where the effect of the Phase II intervention was significant in intervention versus control stores.

Conclusions: Prominent positioning of meat-free products into the meat aisle in a supermarket was not effective in reducing sales of meat products, but successfully increased sales of meat-free alternatives in the longer term. A preregistered protocol (https://osf.io/qmz3a/) was completed and fully available before data analysis.
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http://dx.doi.org/10.1371/journal.pmed.1003715DOI Listing
July 2021

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses.

BMJ 2021 07 14;374:n1537. Epub 2021 Jul 14.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK

Objective: To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins.

Design: Systematic review and meta-analysis.

Data Sources: Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020.

Review Methods: Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included.

Main Outcome Measures: Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy.

Data Synthesis: A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10 000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An E model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin.

Results: 62 trials were included, with 120 456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An E dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive.

Conclusions: For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favourable. Evidence to support tailoring the type or dosage of statins to account for safety concerns before starting treatment was limited.

Systematic Review Registration: PROSPERO CRD42020169955.
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http://dx.doi.org/10.1136/bmj.n1537DOI Listing
July 2021

Differential diagnosis of acute traumatic hip pain in the elderly.

Acta Orthop Belg 2021 Mar;87(1):1-7

Elderly patients who present with an inability to weight bear following a fall, with normal radiographs, should be appropriately investigated to rule out an occult hip fracture (OHF). We aim to identify both the range and incidence of the differential diagnosis of acute traumatic hip pain in a large series of patients investigated for OHF. A retrospective analysis of consecutive patients investigated for an OHF with magnetic resonance imaging (MRI) was performed. Dedicated musculo- skeletal radiologists reported the MRI scans. All diagnoses including hip fractures, other fractures and soft tissue injuries were recorded. Case notes were reviewed for all patients to identify subsequent complications, management and outcomes. A total of 157 patients fulfilled the inclusion criteria. 52 (33%) patients had a fracture of the proximal femur. The majority of patients with proximal femoral fractures required surgical intervention. 9 patients who had fractures of the greater trochanter of the femur without fracture extension across the femoral neck were managed non-operatively. 40 (25%) patients had fractures of the pelvis, with a combined pubic rami and sacral fracture occurring frequently. The most common diagnosis was a soft tissue injury alone that was seen in 60 (38%) patients imaged. Injuries to the gluteal muscle group, iliopsaos complex and trochanteric bursa were most prevalent. All patients with soft tissue injuries or fractures of the pelvis were successfully managed non-operatively. This study highlights a wide range of differential diagnoses in elderly patients presenting with acute traumatic hip pain. The proximal femur was fractured in 33% of patients imaged for OHFs in our series. The most common diagnosis was a soft tissue injury around the hip and pelvis ; these injuries can be successfully managed without surgery.
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March 2021

Frequency of Renal Monitoring - Creatinine and Cystatin C (FORM-2C): an observational cohort study of patients with reduced eGFR in primary care.

Br J Gen Pract 2021 May 27. Epub 2021 May 27.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK; NIHR Oxford and Thames Valley Applied Research Collaborative, Oxford, UK.

Background: Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this.

Aim: To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m.

Design And Setting: Observational cohort study in UK primary care.

Method: Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged ≥18 years with an eGFR of 30-89 ml/min/1.73 m within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months.

Results: Average change in eGFR was 0.51 ml/min/1.73 m/year when estimated by serum creatinine and -2.35 ml/min/1.73 m/year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged ≥75 or <75 years, or with eGFR ≥60 ml/min/1.73 m. In those with eGFR <60 ml/min/1.73 m, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function.

Conclusion: In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m.
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http://dx.doi.org/10.3399/BJGP.2020.0940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279657PMC
May 2021

Recommendations for accurate genotyping of SARS-CoV-2 using amplicon-based sequencing of clinical samples.

Clin Microbiol Infect 2021 Jul 2;27(7):1036.e1-1036.e8. Epub 2021 Apr 2.

SOPHiA GENETICS, Rue Du Centre 172, CH-1025 Saint Sulpice, Switzerland. Electronic address:

Objectives: Genotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in monitoring viral evolution and transmission during the pandemic. The quality of the sequence data obtained from these genotyping efforts depends on several factors, including the quantity/integrity of the input material, the technology, and laboratory-specific implementation. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in genomic epidemiology studies. We aimed to establish clear and broadly applicable recommendations for reliable virus genotyping.

Methods: We established and used a sequencing data analysis workflow that reliably identifies and removes technical artefacts; such artefacts can result in miscalls when using alternative pipelines to process clinical samples and synthetic viral genomes with an amplicon-based genotyping approach. We evaluated the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination.

Results: We found that at least 1000 viral genomes are necessary to confidently detect variants in the SARS-CoV-2 genome at frequencies of ≥10%. The broad applicability of our recommendations was validated in over 200 clinical samples from six independent laboratories. The genotypes we determined for clinical isolates with sufficient quality cluster by sampling location and period. Our analysis also supports the rise in frequencies of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was facilitated by travel during the summer of 2020.

Conclusions: We present much-needed recommendations for the reliable determination of SARS-CoV-2 genome sequences and demonstrate their broad applicability in a large cohort of clinical samples.
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http://dx.doi.org/10.1016/j.cmi.2021.03.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016543PMC
July 2021

Universal Wind Profile for Conventionally Neutral Atmospheric Boundary Layers.

Phys Rev Lett 2021 Mar;126(10):104502

Physics of Fluids Group, Max Planck Center Twente for Complex Fluid Dynamics, University of Twente, 7500 AE Enschede, Netherlands.

Conventionally neutral atmospheric boundary layers (CNBLs), which are characterized with zero surface potential temperature flux and capped by an inversion of potential temperature, are frequently encountered in nature. Therefore, predicting the wind speed profiles of CNBLs is relevant for weather forecasting, climate modeling, and wind energy applications. However, previous attempts to predict the velocity profiles in CNBLs have had limited success due to the complicated interplay between buoyancy, shear, and Coriolis effects. Here, we utilize ideas from the classical Monin-Obukhov similarity theory in combination with a local scaling hypothesis to derive an analytic expression for the stability correction function ψ=-c_{ψ}(z/L)^{1/2}, where c_{ψ}=4.2 is an empirical constant, z is the height above ground, and L is the local Obukhov length based on potential temperature flux at that height, for CNBLs. An analytic expression for this flux is also derived using dimensional analysis and a perturbation method approach. We find that the derived profile agrees excellently with the velocity profile in the entire boundary layer obtained from high-fidelity large eddy simulations of typical CNBLs.
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http://dx.doi.org/10.1103/PhysRevLett.126.104502DOI Listing
March 2021

Impact of changes to national guidelines on hypertension-related workload: an interrupted time series analysis in English primary care.

Br J Gen Pract 2021 04 26;71(705):e296-e302. Epub 2021 Mar 26.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Background: In 2011, National Institute for Health and Care Excellence (NICE) guidelines recommended the routine use of out-of-office blood pressure (BP) monitoring for the diagnosis of hypertension. These changes were predicted to reduce unnecessary treatment costs and workload associated with misdiagnosis.

Aim: To assess the impact of guideline change on rates of hypertension-related consultation in general practice.

Design And Setting: A retrospective open cohort study in adults registered with English general practices contributing to the Clinical Practice Research Datalink between 1 April 2006 and 31 March 2017.

Method: The primary outcome was the rate of face-to-face, telephone, and home visit consultations related to hypertension with a GP or nurse. Age- and sex-standardised rates were analysed using interrupted time-series analysis.

Results: In 3 937 191 adults (median follow-up 4.2 years) there were 12 253 836 hypertension-related consultations. The rate of hypertension-related consultation was 71.0 per 100 person-years (95% confidence interval [CI] = 67.8 to 74.2) in April 2006, which remained flat before 2011. The introduction of the NICE hypertension guideline in 2011 was associated with a change in yearly trend (change in trend -3.60 per 100 person-years, 95% CI = -5.12 to -2.09). The rate of consultation subsequently decreased to 59.2 per 100 person-years (95% CI = 56.5 to 61.8) in March 2017. These changes occurred around the time of diagnosis, and persisted when accounting for wider trends in all consultations.

Conclusion: Hypertension-related workload has declined in the last decade, in association with guideline changes. This is due to changes in workload at the time of diagnosis, rather than reductions in misdiagnosis.
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http://dx.doi.org/10.3399/bjgp21X714281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997675PMC
April 2021

Is current body temperature measurement practice fit-for-purpose?

J Med Eng Technol 2021 Feb 26;45(2):136-144. Epub 2021 Feb 26.

Office of the Chief Scientific Officer, Medical Directorate, London, UK.

There has been a marked rise in the number of avoidable deaths in health services around the world. At the same time there has been a growing increase in antibiotic resistant so-called "superbugs." We examine here the potential role of body temperature measurement in these adverse trends. Electronic based thermometers have replaced traditional mercury (and other liquid-in-glass type) thermometers for reasons of safety rather than superiority. Electronic thermometers are in general less robust from a measurement perspective than their predecessors. We illustrate the implications of unreliable temperature measurement on the diagnosis and management of disease, including COVID-19, through statistical calculations. Since a return to mercury thermometers is both undesirable and impractical, we call for better governance in the current practice of clinical thermometry to ensure the traceability and long-term accuracy of electronic thermometers and discuss how this could be achieved.
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http://dx.doi.org/10.1080/03091902.2021.1873441DOI Listing
February 2021

Association between antihypertensive treatment and adverse events: systematic review and meta-analysis.

BMJ 2021 02 10;372:n189. Epub 2021 Feb 10.

Nuffield Department of Primary Care Health Sciences, Radcliffe Primary Care Building, University of Oxford, Oxford, OX2 6GG, UK

Objective: To examine the association between antihypertensive treatment and specific adverse events.

Design: Systematic review and meta-analysis.

Eligibility Criteria: Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up.

Information Sources: Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020.

Main Outcome Measures: The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (τ).

Results: Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, τ=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, τ=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, τ=0.122, n=26), hypotension (1.97, 1.67 to 2.32, τ=0.132, n=35), and syncope (1.28, 1.03 to 1.59, τ=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction.

Conclusions: This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.

Registration: PROSPERO CRD42018116860.
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http://dx.doi.org/10.1136/bmj.n189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873715PMC
February 2021

Design, methods, and reporting of impact studies of cardiovascular clinical prediction rules are suboptimal: a systematic review.

J Clin Epidemiol 2021 May 27;133:111-120. Epub 2021 Jan 27.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, United Kingdom.

Objectives: To evaluate design, methods, and reporting of impact studies of cardiovascular clinical prediction rules (CPRs).

Study Design And Setting: We conducted a systematic review. Impact studies of cardiovascular CPRs were identified by forward citation and electronic database searches. We categorized the design of impact studies as appropriate for randomized and nonrandomized experiments, excluding uncontrolled before-after study. For impact studies with appropriate study design, we assessed the quality of methods and reporting. We compared the quality of methods and reporting between impact and matched control studies.

Results: We found 110 impact studies of cardiovascular CPRs. Of these, 65 (59.1%) used inappropriate designs. Of 45 impact studies with appropriate design, 31 (68.9%) had substantial risk of bias. Mean number of reporting domains that impact studies with appropriate study design adhered to was 10.2 of 21 domains (95% confidence interval, 9.3 and 11.1). The quality of methods and reporting was not clearly different between impact and matched control studies.

Conclusion: We found most impact studies either used inappropriate study design, had substantial risk of bias, or poorly complied with reporting guidelines. This appears to be a common feature of complex interventions. Users of CPRs should critically evaluate evidence showing the effectiveness of CPRs.
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http://dx.doi.org/10.1016/j.jclinepi.2021.01.016DOI Listing
May 2021

Current prevalence of self-monitoring of blood pressure during pregnancy: the BUMP Survey.

J Hypertens 2021 05;39(5):994-1001

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Objective: To understand the current prevalence of, and attitudes to, self-monitoring of blood pressure (BP) during pregnancy.

Methods: Five thousand, five hundred and fifty-five pregnant women from antenatal clinics in 16 hospitals in England were invited to complete a survey.

Main Outcome Measures: The primary outcome was the proportion of women currently BP self-monitoring. Secondary outcomes included self-monitoring schedules and women's interactions with clinicians regarding self-monitoring. Population characteristics including risk factors for preeclampsia, ethnicity and deprivation level were considered.

Results: Completed surveys were received and analysed from 5181 pregnant women (93% response rate). Comparison to hospital demographic data suggests that respondents were representative of the UK population. Nine hundred and eighty-three of 5181 (19%) women were currently self-monitoring their BP, constituting 189 of 389 (49%) hypertensive women and 794 of 4792 (17%) normotensive women. However, only 482 of 983 (49%) reported ever sharing this information with antenatal care teams. Of those who self-monitored, 68% (668/983) were able to provide a previous BP reading, compared with 1% (67/5181) of those who did not self-monitor.

Conclusion: Many women are now choosing to self-monitor their BP during pregnancy and clinicians should enquire about this proactively and consider providing better information on BP monitoring. Those who self-monitor appear to have better knowledge about their blood pressure. If these findings were replicated nationwide, around 125 000 pregnant women would be currently self-monitoring BP in the UK, yet only half of these women may communicate their readings to their antenatal care teams, suggesting a missed opportunity for enhanced care. Current trials will make the place of self-monitoring in pregnancy clearer.
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http://dx.doi.org/10.1097/HJH.0000000000002734DOI Listing
May 2021

Novel CRISPR-based sequence specific enrichment methods for target loci and single base mutations.

PLoS One 2020 23;15(12):e0243781. Epub 2020 Dec 23.

Genetics Research LLC, Waltham, Massachusetts, United States of America.

The programmable sequence specificity of CRISPR has found uses in gene editing and diagnostics. This manuscript describes an additional application of CRISPR through a family of novel DNA enrichment technologies. CAMP (CRISPR Associated Multiplexed PCR) and cCAMP (chimeric CRISPR Associated Multiplexed PCR) utilize the sequence specificity of the Cas9/sgRNA complex to target loci for the ligation of a universal adapter that is used for subsequent amplification. cTRACE (chimeric Targeting Rare Alleles with CRISPR-based Enrichment) also applies this method to use Cas9/sgRNA to target loci for the addition of universal adapters, however it has an additional selection for specific mutations through the use of an allele-specific primer. These three methods can produce multiplex PCR that significantly reduces the optimization required for every target. The methods are also not specific to any downstream analytical platform. We additionally will present a mutation specific enrichment technology that is non-amplification based and leaves the DNA in its native state: TRACE (Targeting Rare Alleles with CRISPR-based Enrichment). TRACE utilizes the Cas9/sgRNA complex to sterically protect the ends of targeted sequences from exonuclease activity which digests both the normal variant as well as any off-target sequences.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757808PMC
January 2021

Long-term health outcomes of people with reduced kidney function in the UK: A modelling study using population health data.

PLoS Med 2020 12 16;17(12):e1003478. Epub 2020 Dec 16.

Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: People with reduced kidney function have increased cardiovascular disease (CVD) risk. We present a policy model that simulates individuals' long-term health outcomes and costs to inform strategies to reduce risks of kidney and CVDs in this population.

Methods And Findings: We used a United Kingdom primary healthcare database, the Clinical Practice Research Datalink (CPRD), linked with secondary healthcare and mortality data, to derive an open 2005-2013 cohort of adults (≥18 years of age) with reduced kidney function (≥2 measures of estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 ≥90 days apart). Data on individuals' sociodemographic and clinical characteristics at entry and outcomes (first occurrences of stroke, myocardial infarction (MI), and hospitalisation for heart failure; annual kidney disease stages; and cardiovascular and nonvascular deaths) during follow-up were extracted. The cohort was used to estimate risk equations for outcomes and develop a chronic kidney disease-cardiovascular disease (CKD-CVD) health outcomes model, a Markov state transition model simulating individuals' long-term outcomes, healthcare costs, and quality of life based on their characteristics at entry. Model-simulated cumulative risks of outcomes were compared with respective observed risks using a split-sample approach. To illustrate model value, we assess the benefits of partial (i.e., at 2013 levels) and optimal (i.e., fully compliant with clinical guidelines in 2019) use of cardioprotective medications. The cohort included 1.1 million individuals with reduced kidney function (median follow-up 4.9 years, 45% men, 19% with CVD, and 74% with only mildly decreased eGFR of 60-89 mL/min/1.73 m2 at entry). Age, kidney function status, and CVD events were the key determinants of subsequent morbidity and mortality. The model-simulated cumulative disease risks corresponded well to observed risks in participant categories by eGFR level. Without the use of cardioprotective medications, for 60- to 69-year-old individuals with mildly decreased eGFR (60-89 mL/min/1.73 m2), the model projected a further 22.1 (95% confidence interval [CI] 21.8-22.3) years of life if without previous CVD and 18.6 (18.2-18.9) years if with CVD. Cardioprotective medication use at 2013 levels (29%-44% of indicated individuals without CVD; 64%-76% of those with CVD) was projected to increase their life expectancy by 0.19 (0.14-0.23) and 0.90 (0.50-1.21) years, respectively. At optimal cardioprotective medication use, the projected health gains in these individuals increased by further 0.33 (0.25-0.40) and 0.37 (0.20-0.50) years, respectively. Limitations include risk factor measurements from the UK routine primary care database and limited albuminuria measurements.

Conclusions: The CKD-CVD policy model is a novel resource for projecting long-term health outcomes and assessing treatment strategies in people with reduced kidney function. The model indicates clear survival benefits with cardioprotective treatments in this population and scope for further benefits if use of these treatments is optimised.
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http://dx.doi.org/10.1371/journal.pmed.1003478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769604PMC
December 2020

The effects of a UK lockdown on orthopaedic trauma admissions and surgical cases: A multicentre comparative study.

Bone Jt Open 2020 May 21;1(5):137-143. Epub 2020 Jul 21.

Trauma and Orthopaedics, Rotherham General Hospitals NHS Trust, Rotherham, UK.

Aims: The current global pandemic due to COVID-19 is generating significant burden on the health service in the UK. On 23 March 2020, the UK government issued requirements for a national lockdown. The aim of this multicentre study is to gain a greater understanding of the impact lockdown has had on the rates, mechanisms and types of injuries together with their management across a regional trauma service.

Methods: Data was collected from an adult major trauma centre, paediatric major trauma centre, district general hospital, and a regional hand trauma unit. Data collection included patient demographics, injury mechanism, injury type and treatment required. Time periods studied corresponded with the two weeks leading up to lockdown in the UK, two weeks during lockdown, and the same two-week period in 2019.

Results: There was a 55.7% (12,935 vs 5,733) reduction in total accident and emergency (A&E) attendances with a 53.7% (354 vs 164) reduction in trauma admissions during lockdown compared to 2019. The number of patients with fragility fractures requiring admission remained constant (32 patients in 2019 vs 31 patients during lockdown; p > 0.05). Road traffic collisions (57.1%, n = 8) were the commonest cause of major trauma admissions during lockdown. There was a significant increase in DIY related-hand injuries (26% (n = 13)) lockdown vs 8% (n = 11 in 2019, p = 0.006) during lockdown, which resulted in an increase in nerve injuries (12% (n = 6 in lockdown) vs 2.5% (n = 3 in 2019, p = 0.015) and hand infections (24% (n = 12) in lockdown vs 6.2% (n = 8) in 2019, p = 0.002).

Conclusion: The national lockdown has dramatically reduced orthopaedic trauma admissions. The incidence of fragility fractures requiring surgery has not changed. Appropriate provision in theatres should remain in place to ensure these patients can be managed as a surgical priority. DIY-related hand injuries have increased which has led to an increased in nerve injuries requiring intervention.
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http://dx.doi.org/10.1302/2633-1462.15.BJO-2020-0028.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684391PMC
May 2020

Orthodontists' preference on type of rigid fixed functional appliance for skeletal Class II correction: A survey study.

J Clin Exp Dent 2020 Oct 1;12(10):e958-e963. Epub 2020 Oct 1.

Roseman University of Health Sciences, College of Dental Medicine, Henderson, NV, USA.

Background: Rigid fixed functional appliances are most commonly used to correct skeletal Class II malocclusions. The objective of this study was to assess orthodontists' preference of different rigid fixed functional appliances used in the U.S.A for correction of skeletal Class II malocclusions.

Material And Methods: A survey on use and preference of rigid fixed functional appliances for skeletal Class II correction was emailed to 2,227 members of the American Association of Orthodontists (AAO) in the U.S.A. Frequency distribution of different responses and their association with demographic factors was assessed.

Results: Out of 140 orthodontists completing the survey, 110 responded as using rigid fixed functional appliances. Eight incomplete responses were eliminated from data analysis. 51.5% (68/132) orthodontists used rigid fixed functional appliances. The most preferred rigid fixed functional appliance was the Herbst appliance with 72% response followed by Mandibular Anterior Repositioning Appliance (24%) and AdvanSync (4%). There was no statistically significant difference in use of rigid fixed functional appliances between different age groups (=0.284). However, the 40-54 age group used the most rigid fixed functional appliances in practice, followed by the 25-39 year age group and the 55-69 age group using these appliances the least. There was statistical significance between the type of practice setting one works in and the use of rigid fixed functional appliances in practice (=0.022).

Conclusions: About 52% of orthodontists use rigid fixed functional appliances to correct skeletal Class II malocclusions. The Herbst appliance is the most commonly used and most preferred amongst all rigid fixed functional appliances with a 72% preferred rate. Orthodontic, Rigid fixed functional appliance, Skeletal Class II, Class II Malocclusion, Mandibular retrognathism, Herbst, Mandibular Anterior Repositioning Appliance (MARA), AdvanSync, Molar to molar, M2M.
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http://dx.doi.org/10.4317/jced.57461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600212PMC
October 2020

GPs' familiarity with and use of cardiovascular clinical prediction rules: a UK survey study.

BJGP Open 2020 Dec 15;4(5). Epub 2020 Dec 15.

Nuffield Department of Primary Care Health Sciences, Medical Science Division, University of Oxford, Oxford, UK.

Background: Clinical prediction rules (CPRs) can help general practitioners (GPs) address challenges in cardiovascular disease. A survey published in 2014 evaluated GPs' awareness and use of CPRs in the UK. However, many new CPRs have been published since and it is unknown which cardiovascular CPRs are currently recognised and used.

Aim: To identify cardiovascular CPRs recognised and used by GPs, and to assess how GPs' familiarity and use have changed over time.

Design & Setting: An online survey of GPs in the UK was undertaken.

Method: Using comparable methods to the 2014 survey, GPs were recruited from a network of doctors in the UK. They were asked how familiar they were with cardiovascular CPRs, how frequently they used them, and why they used them. The results were compared with the 2014 survey.

Results: Most of 401 GPs were familiar with QRISK scores, ABCD scores, CHADS scores, HAS-BLED score, Wells scores for deep vein thrombosis, and Wells scores for pulmonary embolism. The proportions of GPs using these CPRs were 96.3%, 65.1%, 97.3%, 93.0%, 92.5%, and 82.0%, respectively. GPs' use increased by 31.2% for QRISK scores, by 13.5% for ABCD scores, by 54.6% for CHADS scores, by 33.2% for Wells scores for deep vein thrombosis, and by 43.6% for Wells scores for pulmonary embolism; and decreased by 45.9% for the Joint British Societies (JBS) risk calculator, by 38.7% for Framingham risk scores, and by 8.7% for New Zealand tables. GPs most commonly used cardiovascular CPRs to guide therapy and referral.

Conclusion: The study found GPs' familiarity and use of cardiovascular CPRs changed substantially. Integrating CPRs into guidelines and practice software might increase familiarity and use.
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http://dx.doi.org/10.3399/bjgpopen20X101081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880194PMC
December 2020

Survey on awareness and preference of ceramic bracket debonding techniques among orthodontists.

J Clin Exp Dent 2020 Jul 1;12(7):e656-e662. Epub 2020 Jul 1.

Roseman University of Health Sciences, College of Dental Medicine, Henderson, NV, USA.

Background: The objectives of this study was to evaluate the awareness of different ceramic bracket debonding techniques among orthodontists in the USA and the most commonly used debonding technique for ceramic bracket removal.

Material And Methods: A survey on preference for debonding and awareness of debonding techniques was emailed to 2,227 members of the American Association of Orthodontists (AAO).

Results: 119 orthodontists completed the survey. 111 responses were included in the study analysis of ceramic bracket users. The most common technique used was mechanical debonding. 86.5% used a specially designed bracket removing plier from the manufacturer. Overall, there were 59.5% of surveyed orthodontists who were aware of electrothermal debonding, 73% were unaware of ultrasonic debonding and 83.8% were unaware of laser debonding. There were more orthodontists with an affiliation with an academic institution aware of electrothermal debonding (=0.002). There also was a trend of orthodontists having no affiliation with an institution who were unaware of laser debonding (=0.015).

Conclusions: This survey showed that the majority of orthodontists who responded to the questionnaire were unaware of alternative debonding techniques of ceramic brackets. All orthodontists who use ceramic brackets utilized mechanical debonding technique. Orthodontic ceramic brackets, mechanical, electrothermal, ultrasonic, laser debonding.
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http://dx.doi.org/10.4317/jced.56976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462376PMC
July 2020

Flow organization and heat transfer in turbulent wall sheared thermal convection.

J Fluid Mech 2020 Aug 17;897:A22. Epub 2020 Jun 17.

Physics of Fluids Group, Max Planck Center for Complex Fluid Dynamics,J. M. Burgers Center for Fluid Dynamics and MESA+ Research Institute, Department of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede,The Netherlands.

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http://dx.doi.org/10.1017/jfm.2020.378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405937PMC
August 2020

Reply to "Calibration slope versus discrimination slope: shoes on the wrong feet": validation stands on three feet, not two.

J Clin Epidemiol 2020 09 1;125:162-163. Epub 2020 Jul 1.

Nuffield Department of Primary Care Health Sciences, University of Oxford.

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http://dx.doi.org/10.1016/j.jclinepi.2020.06.001DOI Listing
September 2020

Relative contributions of ecological drift and selection on bat community structure in interior Atlantic Forest of Paraguay.

Oecologia 2020 Jul 24;193(3):645-654. Epub 2020 Jun 24.

Department of Natural Resources Management, Texas Tech University, Lubbock, TX, 79409, USA.

Despite extensive focus on numerous mechanisms that potentially structure Neotropical bat communities, understanding of the relative importance of any is still illusive. Recently, it has been demonstrated that all mechanisms used to explain community organization can be conceptualized as one or a combination of the few higher-level processes of dispersal, drift, selection and speciation. These four higher-level processes have not been addressed equally by Neotropical bat community ecologists. In particular, predictions formulated from a hypothesis of ecological drift have not been tested for any Neotropical bat community. Herein we contrast efficacy of predictions based on the higher-level processes of drift and selection in describing community structure of bats in the Atlantic Forest of eastern Paraguay. Predictions apply to species-environment interactions, patterns of trait variation and beta-diversity, predictability of dominant competitors and responses to seasonality. At best, there was inconsistent support for the operation of either drift or selection within this bat community. Selection, however, had more various forms of support including strong species-environment relationships, predictable patterns of dominant competitors and strong responses to seasonality. Despite stronger support for selection, a number of predictions of drift were supported as well. It is likely that a combination of both of these processes operates across the variable environments experienced in Atlantic Forest. Predictions of both processes are difficult to make operational. Support for drift often comes from failure to demonstrate a significant pattern and should not be considered strong support of a prediction. Similarly, many predictions of selection predict phenotypic patterns among species without specifying a particular trait. This is problematic because the phenotype is multifaceted and a lack of pattern in one measured trait might mask a strong pattern in some other unmeasured trait. Distilling mechanisms of community organization into four higher level processes is a substantial innovation in community ecology. Nonetheless, efforts need to be made to develop a suite of mutually exclusive and falsifiable predictions to facilitate future and more rapid understanding of community organization.
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http://dx.doi.org/10.1007/s00442-020-04683-zDOI Listing
July 2020

Accuracy of blood-pressure monitors owned by patients with hypertension (ACCU-RATE study): a cross-sectional, observational study in central England.

Br J Gen Pract 2020 08 30;70(697):e548-e554. Epub 2020 Jul 30.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Background: Home blood-pressure (BP) monitoring is recommended in guidelines and is increasingly popular with patients and health professionals, but the accuracy of patients' own monitors in real-world use is not known.

Aim: To assess the accuracy of home BP monitors used by people with hypertension, and to investigate factors affecting accuracy.

Design And Setting: Cross-sectional, observational study in urban and suburban settings in central England.

Method: Patients ( = 6891) on the hypertension register at seven practices in the West Midlands, England, were surveyed to ascertain whether they owned a BP monitor and wanted it tested. Monitor accuracy was compared with a calibrated reference device at 50 mmHg intervals between 0-280/300 mmHg (static pressure test); a difference from the reference monitor of +/-3 mmHg at any interval was considered a failure. Cuff performance was also assessed. Results were analysed by frequency of use, length of time in service, make and model, monitor validation status, purchase price, and any previous testing.

Results: In total, 251 (76%, 95% confidence interval [95% CI] = 71 to 80%) of 331 tested devices passed all tests (monitors and cuffs), and 86% (CI] = 82 to 90%) passed the static pressure test; deficiencies were, primarily, because of monitors overestimating BP. A total of 40% of testable monitors were not validated. The pass rate on the static pressure test was greater in validated monitors (96%, 95% CI = 94 to 98%) versus unvalidated monitors (64%, 95% CI = 58 to 69%), those retailing for >£10 (90%, 95% CI = 86 to 94%), those retailing for ≤£10 (66%, 95% CI = 51 to 80%), those in use for ≤4 years (95%, 95% CI = 91 to 98%), and those in use for >4 years (74%, 95% CI = 67 to 82%). All in all, 12% of cuffs failed.

Conclusion: Patients' own BP monitor failure rate was similar to that demonstrated in studies performed in professional settings, although cuff failure was more frequent. Clinicians can be confident of the accuracy of patients' own BP monitors if the devices are validated and ≤4 years old.
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http://dx.doi.org/10.3399/bjgp20X710381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274541PMC
August 2020

Zhu et al. Reply.

Phys Rev Lett 2019 12;123(25):259402

Physics of Fluids Group and Max Planck Center for Complex Fluid Dynamics, MESA+ Institute and J. M. Burgers Centre for Fluid Dynamics, University of Twente, P.O. Box 217, 7500AE Enschede, Netherlands.

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http://dx.doi.org/10.1103/PhysRevLett.123.259402DOI Listing
December 2019

Comparison of Complication and Reoperation Rates for Minimally Invasive Versus Open Cheilectomy of the First Metatarsophalangeal Joint.

Foot Ankle Int 2020 01 6;41(1):31-36. Epub 2019 Sep 6.

Northern General Hospital, Sheffield, UK.

Background: Dorsal cheilectomy of the first metatarsophalangeal joint is an accepted treatment to alleviate dorsal impingement, pain, and reduced dorsiflexion in hallux rigidus. Traditionally performed via an open incision, this procedure has more recently been performed using minimally invasive techniques despite limited supportive published evidence.

Methods: From December 2012 through December 2017, a retrospective analysis of all cheilectomies performed in our institution was done. The surgical technique was recorded along with any subsequent procedures performed for either persistent or recurrent pain, and complications were also noted. A comparison between open and minimally invasive outcomes was performed. In total, 171 cheilectomies were performed during this period. There were 38 open and 133 minimally invasive procedures.

Results: At a mean 3-year follow-up, the reoperation rates of the 2 groups were different with only 1 (2.6%) of the open group requiring a fusion, while 17 (12.8%) of the minimally invasive surgical (MIS) group required further surgery (relative risk, 4.86; = .059). In the open group, there was 1 (2.6%) complication, compared with 15 (11.3%) in the minimally invasive group (relative risk, 4.29; = .076).

Conclusion: While patients may opt for MIS cheilectomy with a proposed faster recovery time and better cosmesis, they should be counseled about the risks and benefits of both methods, and that the technique of MIS cheilectomy utilized in this study appears to have an increased relative risk of requiring a further procedure.

Level Of Evidence: Level III, retrospective comparative series.
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http://dx.doi.org/10.1177/1071100719873846DOI Listing
January 2020

Impact of Changes to National Hypertension Guidelines on Hypertension Management and Outcomes in the United Kingdom.

Hypertension 2020 02 23;75(2):356-364. Epub 2019 Dec 23.

From the Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK (S.L.L.-F., J.P.S., R.J.S., C.H., F.D.R.H., R.J.M.).

In recent years, national and international guidelines have recommended the use of out-of-office blood pressure monitoring for diagnosing hypertension. Despite evidence of cost-effectiveness, critics expressed concerns this would increase cardiovascular morbidity. We assessed the impact of these changes on the incidence of hypertension, out-of-office monitoring and cardiovascular morbidity using routine clinical data from English general practices, linked to inpatient hospital, mortality, and socio-economic status data. We studied 3 937 191 adults with median follow-up of 4.2 years (49% men, mean age=39.7 years) between April 1, 2006 and March 31, 2017. Interrupted time series analysis was used to examine the impact of changes to English hypertension guidelines in 2011 on incidence of hypertension (primary outcome). Secondary outcomes included rate of out-of-office monitoring and cardiovascular events. Across the study period, incidence of hypertension fell from 2.1 to 1.4 per 100 person-years. The change in guidance in 2011 was not associated with an immediate change in incidence (change in rate=0.01 [95% CI, -0.18-0.20]) but did result in a leveling out of the downward trend (change in yearly trend =0.09 [95% CI, 0.04-0.15]). Ambulatory monitoring increased significantly in 2011/2012 (change in rate =0.52 [95% CI, 0.43-0.60]). The rate of cardiovascular events remained unchanged (change in rate =-0.02 [95% CI, -0.05-0.02]). In summary, changes to hypertension guidelines in 2011 were associated with a stabilisation in incidence and no increase in cardiovascular events. Guidelines should continue to recommend out-of-office monitoring for diagnosis of hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055938PMC
February 2020

A High-Quality Reference Genome Assembly of the Saltwater Crocodile, Crocodylus porosus, Reveals Patterns of Selection in Crocodylidae.

Genome Biol Evol 2020 01;12(1):3635-3646

Department of Biological Sciences, Texas Tech University.

Crocodilians are an economically, culturally, and biologically important group. To improve researchers' ability to study genome structure, evolution, and gene regulation in the clade, we generated a high-quality de novo genome assembly of the saltwater crocodile, Crocodylus porosus, from Illumina short read data from genomic libraries and in vitro proximity-ligation libraries. The assembled genome is 2,123.5 Mb, with N50 scaffold size of 17.7 Mb and N90 scaffold size of 3.8 Mb. We then annotated this new assembly, increasing the number of annotated genes by 74%. In total, 96% of 23,242 annotated genes were associated with a functional protein domain. Furthermore, multiple noncoding functional regions and mappable genetic markers were identified. Upon analysis and overlapping the results of branch length estimation and site selection tests for detecting potential selection, we found 16 putative genes under positive selection in crocodilians, 10 in C. porosus and 6 in Alligator mississippiensis. The annotated C. porosus genome will serve as an important platform for osmoregulatory, physiological, and sex determination studies, as well as an important reference in investigating the phylogenetic relationships of crocodilians, birds, and other tetrapods.
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http://dx.doi.org/10.1093/gbe/evz269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946029PMC
January 2020

Insights into the assembly rules of a continent-wide multilayer network.

Nat Ecol Evol 2019 11 14;3(11):1525-1532. Epub 2019 Oct 14.

Department of Natural Resources Management and Museum of Texas Tech University, Lubbock, TX, USA.

How are ecological systems assembled? Identifying common structural patterns within complex networks of interacting species has been a major challenge in ecology, but researchers have focused primarily on single interaction types aggregating in space or time. Here, we shed light on the assembly rules of a multilayer network formed by frugivory and nectarivory interactions between bats and plants in the Neotropics. By harnessing a conceptual framework known as the integrative hypothesis of specialization, our results suggest that phylogenetic constraints separate species into different layers and shape the network's modules. Then, the network shifts to a nested structure within its modules where interactions are mainly structured by geographic co-occurrence. Finally, organismal traits related to consuming fruits or nectar determine which bat species are central or peripheral to the network. Our results provide insights into how different processes contribute to the assemblage of ecological systems at different levels of organization, resulting in a compound network topology.
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http://dx.doi.org/10.1038/s41559-019-1002-3DOI Listing
November 2019

Validation of clinical prediction models: what does the "calibration slope" really measure?

J Clin Epidemiol 2020 02 9;118:93-99. Epub 2019 Oct 9.

Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Background And Objectives: Definitions of calibration, an aspect of model validation, have evolved over time. We examine use and interpretation of the statistic currently referred to as the calibration slope.

Methods: The history of the term "calibration slope", and usage in papers published in 2016 and 2017, were reviewed. The behaviour of the slope in illustrative hypothetical examples and in two examples in the clinical literature was demonstrated.

Results: The paper in which the statistic was proposed described it as a measure of "spread" and did not use the term "calibration". In illustrative examples, slope of 1 can be associated with good or bad calibration, and this holds true across different definitions of calibration. In data extracted from a previous study, the slope was correlated with discrimination, not overall calibration. Many authors of recent papers interpret the slope as a measure of calibration; a minority interpret it as a measure of discrimination or do not explicitly categorise it as either. Seventeen of thirty-three papers used the slope as the sole measure of calibration.

Conclusion: Misunderstanding about this statistic has led to many papers in which it is the sole measure of calibration, which should be discouraged.
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http://dx.doi.org/10.1016/j.jclinepi.2019.09.016DOI Listing
February 2020

Identification and characterization of an IgG sequence variant with an 11 kDa heavy chain C-terminal extension using a combination of mass spectrometry and high-throughput sequencing analysis.

MAbs 2019 Nov-Dec;11(8):1452-1463. Epub 2019 Oct 1.

Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca , Gaithersburg , MD , USA.

Protein primary structure is a potential critical quality attribute for biotherapeutics. Identifying and characterizing any sequence variants present is essential for product development. A sequence variant ~11 kDa larger than the expected IgG mass was observed by size-exclusion chromatography and two-dimensional liquid chromatography coupled with online mass spectrometry. Further characterization indicated that the 11 kDa was added to the heavy chain (HC) Fc domain. Despite the relatively large mass addition, only one unknown peptide was detected by peptide mapping. To decipher the sequence, the transcriptome of the manufacturing cell line was characterized by Illumina RNA-seq. Transcriptome reconstruction detected an aberrant fusion transcript, where the light chain (LC) constant domain sequence was fused to the 3' end of the HC transcript. Translation of this fusion transcript generated an extended peptide sequence at the HC C-terminus corresponding to the observed 11 kDa mass addition. Nanopore-based genome sequencing showed multiple copies of the plasmid had integrated in tandem with one copy missing the 5' end of the plasmid, deleting the LC variable domain. The fusion transcript was due to read-through of the HC terminator sequence into the adjacent partial LC gene and an unexpected splicing event between a cryptic splice-donor site at the 3' end of the HC and the splice acceptor site at the 5' end of the LC constant domain. Our study demonstrates that combining protein physicochemical characterization with genomic and transcriptomic analysis of the manufacturing cell line greatly improves the identification of sequence variants and understanding of the underlying molecular mechanisms.
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http://dx.doi.org/10.1080/19420862.2019.1667740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816433PMC
June 2020

and Gene Expression: Diurnal Variability and Influence of Shift Work

Cancers (Basel) 2019 08 9;11(8). Epub 2019 Aug 9.

Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy.

and genes are involved in DNA double-strand break repair and related to breast cancer. Shift work is associated with biological clock alterations and with a higher risk of breast cancer. The aim of this study was to investigate the variability of expression of genes through the day in healthy subjects and to measure expression levels in shift workers. The study was approached in two ways. First, we examined diurnal variation of and genes in lymphocytes of 15 volunteers over a 24-hour period. Second, we measured the expression of these genes in lymphocytes from a group of shift and daytime workers. The change in 24-hour expression levels of and genes was statistically significant, decreasing from the peak at midday to the lowest level at midnight. Lower levels for both genes were found in shift workers compared to daytime workers. Diurnal variability of and expression suggests a relation of DNA double-strand break repair system with biological clock. Lower levels of and found in shift workers may be one of the potential factors related to the higher risk of breast cancer.
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http://dx.doi.org/10.3390/cancers11081146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721503PMC
August 2019

Simultaneous TE Analysis of 19 Heliconiine Butterflies Yields Novel Insights into Rapid TE-Based Genome Diversification and Multiple SINE Births and Deaths.

Genome Biol Evol 2019 08;11(8):2162-2177

Department of Organismic and Evolutionary Biology, Harvard University.

Transposable elements (TEs) play major roles in the evolution of genome structure and function. However, because of their repetitive nature, they are difficult to annotate and discovering the specific roles they may play in a lineage can be a daunting task. Heliconiine butterflies are models for the study of multiple evolutionary processes including phenotype evolution and hybridization. We attempted to determine how TEs may play a role in the diversification of genomes within this clade by performing a detailed examination of TE content and accumulation in 19 species whose genomes were recently sequenced. We found that TE content has diverged substantially and rapidly in the time since several subclades shared a common ancestor with each lineage harboring a unique TE repertoire. Several novel SINE lineages have been established that are restricted to a subset of species. Furthermore, the previously described SINE, Metulj, appears to have gone extinct in two subclades while expanding to significant numbers in others. This diversity in TE content and activity has the potential to impact how heliconiine butterflies continue to evolve and diverge.
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http://dx.doi.org/10.1093/gbe/evz125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685494PMC
August 2019
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