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Winfred Wang

and 8 more

Introduction: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including ischemic lesions and neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods: We examined prospectively the effects of one year of treatment with hydroxyurea on brain function in a cohort of children with SCA (HbSS/HbSβ0-thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI [silent cerebral infarcts (SCI), gray matter cerebral blood flow (GM-CBF), and blood oxygen level dependent (BOLD) signal from visual stimulation]. Results: Nineteen patients with SCA, mean age 12.4 years (range 7.2-17.8), were evaluated. At baseline, subjects had these mean values: full scale IQ (FSIQ) 81.9, TCD velocity 133 cm/sec, GM-CBF 64.4 ml/100g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After one year of hydroxyurea, there were significant increases in FSIQ (+2.8, p=0.036) and reading comprehension (+4.8, p=0.016), a significant decrease in TCD velocity (-11.4 cm/sec, p=0.007), and no significant changes in GM-CBF, BOLD, or SCI frequency. Furthermore, FSIQ was associated with higher hemoglobin F (HbF) and lower GM-CBF, but not with hemoglobin level. Discussion: Significant improvement of neurocognition and decreased TCD velocity following one year of treatment support the use of hydroxyurea for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.

Deborah Leigh

and 4 more

Identifying local adaptation in bottlenecked species is essential for conservation management. Selection detection methods have an important role in species management plans, assessments of adaptive capacity, and looking for responses to climate change. Yet, the allele frequency changes exploited in selection detection methods are similar to those caused by the strong neutral genetic drift expected during a bottleneck. Consequently, it is often unclear what accuracy selection detection methods have across bottlenecked populations. In this study, simulations were used to explore if signals of selection could be confidently distinguished from genetic drift across 23 bottlenecked and reintroduced populations of Alpine ibex (Capra ibex). The meticulously recorded demographic history of the Alpine ibex was used to generate comprehensive simulated SNP data. The simulated SNPs were then used to benchmark the confidence we could place in outliers identified in empirical Alpine ibex SNP data. Within the simulated dataset, the false positive rates were high for all selection detection methods but fell substantially when two or more methods were combined. True positive rates were consistently low and became negligible with increased stringency. Despite finding many outlier loci in the empirical Alpine ibex SNPs, none could be distinguished from genetic drift-driven false positives. Unfortunately, the low true positive rate also prevents the exclusion of recent local adaptation within the Alpine ibex. The baselines and stringent approach outlined here should be applied to other bottlenecked species to ensure the risk of false positive, or negative, signals of selection are accounted for in conservation management plans.

Aaminah Verity

and 2 more

Rationale, Aims & Objectives COVID-19 mandated a rapid and dramatic transformation of general practice. ‘Total Triage’ (TT), where all consultations should be triaged first, and ‘Remote-by-Default’ (RbD) consulting, where a clinician should consult remotely unless there is a “clinical exception”, were advised. It is unclear how these new ways of working were implemented in practice, and how they impacted vulnerable patients. We provide a first look at how these changes are impacting those with historic difficulties in accessing primary care under the traditional GP model. This service evaluation aimed to assess the impact of TT and RbD on vulnerable patients and identify mitigation strategies using a mixed methods service evaluation in Lewisham, London, an area of high deprivation. Method Three parallel datasets were collected and analysed: Semi-structured interviews with stakeholders working with vulnerable groups and qualitative data from forums with black and ethnic minority patients, a survey of General Practitioners exploring implementation of TT and RbD, and a mystery shopper exercise reviewing access and messaging of ten practices. Results Barriers to access for vulnerable patients included challenges navigating the new model, difficulty engaging with remote consultations and digital exclusion. There was wide variation in messaging regarding changes to services and the practical application of TT and RbD. Potential solutions included clearer practice guidance and patient messaging, more consistent implementation, and identification and recording of patient access needs, to enable better tailoring of care provision. Conclusion We identified perceived and actual barriers to accessing general practice for vulnerable patients following the rapid introduction of TT and RbD consulting in Lewisham. We recommend immediate steps that can be implemented at a local level to mitigate some of these impacts, and propose further work to gain better insights into the issues identified.

Kazuma Handa

and 4 more

Background and aim: Mitral valve (MV) repair is a well-accepted surgical approach for infective endocarditis (IE). In our hospital, extensive MV reconstruction with fresh autologous pericardium (AP) and artificial chordae (AC) has been performed for patients with profoundly extensive and destructive IE in which valve reconstruction would be extremely challenging, especially in young patients to avoid mechanical valve replacement. Long-term outcome including the future performance of the newly created leaflet has not been established. Methods: Five patients (50 ± 30 years of age; 3 men, 2 women) underwent this procedure from January 2011 to December 2020. In all patients, preoperative cardiac function was good (left ventricular ejection fraction, 70% ± 5%). After complete debridement of the infective valve tissue, the MV was reconstructed with large, fresh, trimmed AP and AC. Results: The reconstructed leaflets were anterior in three patients and posterior in four, and AC were placed in four patients. All patients showed an uneventful postoperative course and were discharged to home 35 ± 5 days postoperatively after completion of intravenous antibiotic therapy. Pre-discharge echocardiography revealed no or trivial mitral regurgitation (MR) in all patients. The mean follow-up period was 7.2 (range, 1.3–9.5) years, and no patients developed recurrence of the IE. The latest echocardiography in four patients showed trivial/mild MR with good leaflet function. One patient developed recurrence of MR, 5 months postoperatively. Conclusions: The short- and long-term outcomes of this procedure were satisfactory. This procedure might be considered as an effective and valuable option, especially in young patients.
Background: Despite major advances in basic and advanced life supports, patients who survived from out of hospital cardiac arrest (OHCA) has still poor prognosis. Several inflammatory parameters have been used to determine early and long-term prognosis in patients with OHCA. C-reactive protein-to-albumin ratio (CAR) is also a novel marker of systemic inflammation. To our knowledge, there is no study evaluating the clinical importance of CAR in OHCA patients. Aims: To evaluate the effect of CAR on mortality in patients with OHCA. Methods: A total of 102 patients with OHCA were included in this study. The study population were divided into two groups as survivor (n = 43) and non-survivor (n = 59) during follow-up. Complete blood cell counts, biochemical and blood gas analysis were recorded for all patients. Neutrophil to lymphocyte ratio (NLR) was calculated as the ratio of neutrophil to lymphocyte. CAR was calculated as the ratio of CRP to the albumin. Results: NLR (P=0.012), CAR (P<0.001) and serum lactate level (P =0.002) were significantly higher whereas lymphocyte (P=0.008) and serum albumin (P<0.001) were significantly lower in non-survivor group compared to survivor group. Multivariate logistic regression analysis showed that NLR (odds ratio [OR]: 1.044, 95% confidence interval [CI]: 1.044-1.437, P=0.013), CAR (OR: 1.971, 95% CI: 1.327-2.930, P=0.001), and lactate level (OR: 1.268, 95% CI: 1.095-1.469, P=0.002) were independent predictors of mortality. Conclusions: We have demonstrated for the first time that CAR was an independent predictor of in-hospital mortality in OHCA patients.

Ayhan Karaköse

and 1 more

Introduction:To evaluate the efficacy, safety and postoperative outcomes of the BiVap saline vaporization and Twister™ Diode Laser systems with benign prostatic obstruction (BPO) in prostate volüm between 90-150 ml. Methods:In total, we included 131 patients treated with BiVap system (n=68) and Twister system (n=63). Postoperative complications including urinary tract infection, transient hematuria, severe dysuria and fever >38° C, urinary incontinence and urethral stricture were also noted. All patients were evaluated at the postoperative 1st, 3rd, 6th and 12th month and preoperative and postoperative values of IPSS score, QoL score, total PSA, IIEF 15, PVR, Qmax and Qave were compared. Statistical analyses were performed with SPSS version 18. A P-value<0.05 was considered significant. Results:Preoperative demographic characteristics were similar in the 2 groups. There was observed significant improvement for IPSS, Qmax, Qave, PVR, and QoL score by the postoperative first month compared to the preoperative values in both groups. Maximum improvement in the IPSS, Qmax, Qave, QoL score and PVR were achieved at postoperative 6, 3, 12, 3 and 12th months respectively in group 1. In group 2 maximum improvement in the IPSS, Qmax, Qave, QoL score and PVR were achieved at postoperative 6, 3, 6, 6 and 12th months, respectively. There was no significant difference between the two groups in terms of IPSS, Qmax, Qave, QoL score, PSA, PVR, IIEF-EF and IIEF-OS during the 1 year follow-up period postoperatively. Conclusions:BiVap and Twister systems are safe, effective, and useful technique, which can be used in the surgical treatment of BPO between 90-150ml.

Jessica Lundquist

and 5 more

When formulating a hydrologic model, scientists rely on parameterizations of multiple processes based on field data, but literature review suggests that more frequently people select parameterizations that were included in pre-existing models rather than re-evaluating the underlying field experiments. Problems arise when limited field data exist, when “trusted” approaches do not get reevaluated, and when processes fundamentally change in different environments. The physics and dynamics of snow interception by conifers, including both loading and unloading of snow, is just such a case. The most commonly used interception parameterization is based on data from four trees from one site, but field study results are not directly transferable between environments. The process varies dramatically between locations with relatively warmer versus colder winters. Here, we combine a comprehensive literature review with a model to demonstrate essential improvements to model representations of snow interception. We recommend that, as a first and essential step, all models include increased loading due to increased adhesion and cohesion when temperatures rise from -3 and 0°C. The commonly used parameters of a fixed maximum value for loading and an e-folding time for unloading are not supported by observations or physical understanding and are not necessary to reproduce observations. In addition to unloading based on physical processes, such as wind or canopy warming, all models must represent melting of in-canopy snow so that it can be unloaded in liquid form. As a second step, we propose field experiments across climates and forest types to investigate: a) a representation of the force balance between adhesion and cohesion versus gravity for both interception efficiency and rates of unloading, b) wind effects during and between storms, and c) lubrication when snow melts. For greatest impact, this framework requires dedicated field measurements. These processes are essential for models to accurately represent the impacts of dynamically changing forest cover and snow cover on both global albedo and water supplies.

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Gunter Sturm

and 38 more

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; number, NCT04269629)

Nazanin Kermani

and 12 more

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Xinyi Guan

and 4 more

Fabio Ramponi

and 6 more

Coronary artery and cerebrovascular disease represent a major cause of cardiovascular morbidity and mortality worldwide. Despite technological advancements in percutaneous interventions, surgical revascularization remains the preferred strategy in patients with left main or multivessel disease and in those with complex lesions with high SYNTAX score. As a result, an increasing number of older patients with diffuse atherosclerotic extracoronary disease are referred for coronary artery bypass grafting (CABG). Cerebrovascular complications after isolated coronary surgery occurs in 1-5% of patients; the magnitude of injury ranges from overt neurologic lesions with varying degree of permanent disability to “asymptomatic” cerebral events detected by dedicated neuro-imaging, nevertheless associated with significant long term cognitive and functional decline. Thromboembolic events due to manipulation of an atherosclerotic aorta are universally recognized as the leading etiology of early postoperative stroke following CABG. Coronary bypass surgery performed on an arrested heart relies on considerable aortic instrumentation associated with significant atheroembolic risk especially in older patients presenting with diffuse aortic calcifications. Surgical techniques to deal with a calcified ascending aorta during isolated coronary surgery have evolved over the last forty years. Moving away from aggressive aortic debridement or replacement, surgeons have developed strategies aimed to minimize aortic manipulation: from pump-assisted beating heart surgery with the use of composite grafts to complete avoidance of aortic manipulation with “anaortic” off-pump coronary artery bypass grafting, a safe and effective approach in significantly reducing the risk of intraoperative stroke.

Oktay Ucer

and 3 more

Nada A. Saad

and 3 more

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