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Andre Son

and 8 more

Background: Limb ischemia is a major complication of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Use of ankle-brachial index (ABI) to monitor limb perfusion in VA-ECMO has not been described. We report our experience monitoring femoral VA-ECMO patients with serial ABI and the relationships between ABI and near infrared spectroscopy (NIRS). Methods: This is a retrospective single-center review of consecutive adult patients placed on femoral VA-ECMO between January 2019 and October 2019. Data were collected on patients with paired ABI and NIRS values. Relationships between NIRS and ABI of the cannulated (E-NIRS and E-ABI) and non-cannulated legs (N-NIRS and N-ABI) along with the difference between legs (D-NIRS and D-ABI) were determined using Pearson correlation. Results: Overall, 22 patients (mean age 56.5±14.0 years, 72.7% male) were assessed with 295 E-ABI and E-NIRS measurements, and 273 N-ABI and N-NIRS measurements. Mean duration of ECMO support was 129.8±78.3 hours. ECMO-mortality was 13.6% and in-hospital mortality was 45.5%. N-ABI and N-NIRS were significantly higher than their ECMO counterparts (ABI mean difference 0.16, 95%CI 0.13-0.19, p<0.0001; NIRS mean difference 2.51, 95%CI 1.48-3.54, p<0.0001). There was no correlation between E-ABI vs. E-NIRS (r=0.032, p=0.59), N-ABI vs. N-NIRS (r=0.097, p=0.11), or D-NIRS vs. D-ABI (r=0.11, p=0.069). Conclusions: ABI is a quantitative metric that may be used to monitor limb perfusion and supplement clinical exams to identify limb ischemia in femorally cannulated VA-ECMO patients. More studies are needed to characterize the significance of ABI in femoral VA-ECMO and its value in identifying limb ischemia in this patient population.

Hong-Wu Chen

and 2 more

Objective:To integrate the effects of duration of using intraaortic balloon pump (IABP) on renal function, major adverse cardiac events (MACEs) and all-cause mortality in patients with acute myocardial infarction (AMI) complicating pump failure. Methods:Between March 2017 and June 2018, a retrospective study enrolled 306 patients with AMI complicating pump failure who underwent coronary artery angiography (CAG) or percutaneous coronary intervention (PCI) was conducted. Patients were divided into the duration ≤4 days and the duration>4 days in basis of median the IABP duration. We compared the renal function parameters at the three time section of IABP implantation between two groups. Analysis of factors of contrast-induced nephropathy (CIN), 12-month MACEs and all-cause mortality were also performed. Results:There were 146 patients in IABP duration ≤4 days and 92 patients in IABP duration > 4 days. Renal function was only correlated with IABP duration instead of timing of IABP implantation. On multivariate analysis, CIN risk increased by 81.2% (RR= 1.812, 95%CI, 1.167–3.763) for every 100mL increment of contrast agent. Hematocrit, blood platelet, IABP use >4 days were significantly inversely associated with CIN. Cox-regression analysis suggested that IABP duration was not significantly correlated with the incidence of 12-month MACEs and all-cause mortality. Conclusion:Longer duration of IABP implantation was beneficial to renal function, but was not significantly correlated with the incidence of 12-month MACEs and all-cause mortality in patients with AMI complicating pump failure. Patients undergoing PCI or CABG should notice that the potential damage of high dose of contrast agents on the renal function.

Muharrem Kocyigit

and 5 more

Background: Red blood cell (RBC) transfusion increases morbidity and mortality after cardiac surgery. Despite the use of patient blood management methods, blood transfusions may still be needed in cardiac surgery. This study aims to determine the risk factors for blood transfusions in isolated coronary bypass graft surgery with the use of a restrictive transfusion strategy along with individualized patient blood management. Methods: A total of 198 consecutive patients (28 females, 170 males; age range 38–87) who underwent isolated CABG surgery in single private hospital using a restrictive transfusion strategy between April 2015 and October 2020 were included in the study. Patients were divided into two groups: with RBC transfusion and without RBC transfusion. Preoperative, intraoperative, and postoperative values were compared between groups. The risk factors for transfusion and transfusion probability were analyzed. Results: Preoperative hematocrit level and female gender (OR: 0.752; 95% CI 0.639–0.884; p = 0.001; OR: 7.874; 95% CI 1.678–36.950; p = 0.009, respectively) were the statistically significant independent risk factors for red blood cell transfusion. In female patients, the RBC transfusion probability was 61.08% when the preoperative hematocrit was 30%. The intensive care unit and hospital stay were longer in the blood transfusion group. Conclusions: The risk factors for RBC transfusion were preoperative anemia and female gender in isolated CABG surgery with restrictive blood transfusion strategies. Keywords: anemia, blood transfusion, coronary artery bypass, patient blood management, restrictive blood transfusion

Marta Cocciolo

and 12 more

Background: The worldwide escalation of Coronavirus Disease 2019 (COVID-19) has urgently required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of disease. The BNT162b2 (Pfizer–BioNTech) RNA-based vaccine confers 95% protection against COVID-19 by encoding a mutated isoform of SARS-CoV-2 full-length spike (S) protein. Objective: Here, we report the antigen-specific immune profile against SARS-CoV-2 S protein after vaccination with a single dose of BNT162b2 in order to define the immunological landscape required for an efficient response to the SARS-CoV-2 vaccine. Methods: We determined the levels of antibodies and antigen-specific B, T and NK-T cells against a recombinant GFP tagged SARS-CoV-2 S protein in subjects up to 20 days after injection of a single dose of BNT162b2 vaccine using a combined approach involving serological assays and flow cytometry analyses. Former COVID-19 patients have been also included in this study to evaluate the effect of vaccine after exposition to SARS-CoV-2. Results: The level of antigen-specific helper T-cells against SARS-CoV-2 S protein was reduced in subjects, low responsive or unresponsive to vaccination with respect to the highly responsive individuals, while the numbers of antigen-specific regulatory and cytotoxic T-cells were comparable. Of interest, in former COVID-19 patients, a single dose of BNT162b2 vaccine induced a significant increase of antibody production simultaneous with an antigen-specific B and NK-T cell response. Conclusion: Taken together, these results suggest that favorable immune profiles support the progression and an effective reaction to BNT162b2 vaccination.

Emily Koot

and 13 more

Leptospermum scoparium J. R. Forst et G. Forst, known as mānuka by Māori, the indigenous people of Aotearoa (New Zealand), is a culturally and economically significant shrub species, native to New Zealand and Australia. Chemical, morphological and phylogenetic studies have indicated geographical variation of mānuka across its range in New Zealand, and genetic differentiation between New Zealand and Australia. We used pooled whole genome re-sequencing of 76 L. scoparium and outgroup populations from New Zealand and Australia to compile a dataset totalling ~2.5 million SNPs. We explored the genetic structure and relatedness of L. scoparium across New Zealand, and between populations in New Zealand and Australia, as well as the complex demographic history of this species. Our population genomic investigation suggests there are five geographically distinct mānuka gene pools within New Zealand, with evidence of gene flow occurring between these pools. Demographic modelling suggests three of these gene pools have undergone expansion events, whilst the evolutionary histories of the remaining two have been subjected to contractions. Furthermore, mānuka populations in New Zealand are genetically distinct from populations in Australia, with coalescent modelling suggesting these two clades diverged ~9 –12 million years ago. We discuss the evolutionary history of this species and the benefits of using pool-seq for such studies. Our research will support the management and conservation of mānuka by landowners, particularly Māori, and the development of a provenance story for the branding of mānuka based products.

Jennifer Walsh

and 9 more

Improved global access to novel age-appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age-appropriate paediatric medicines. This position paper proposes the use of a paediatric Quality Target Product Profile (pQTPP) as an efficient tool to facilitate early planning and decision making during the children-centric formulation design for new chemical entities, or to repurpose/reformulate off-patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age-appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure post-marketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however the proposed pQTPP could be a valuable collaborative tool for planning and decision making to expedite paediatric product development.

Zhaomeng Zhuang

and 3 more

Objective To analyze the effect of nasopharyngeal ventilation on the detection rate of colorectal polyps in 200 middle-aged and elderly overweight patients during painless colonoscopy. Methods A total of 100 patients aged 50-75 years, body mass index (BMI) ≥24 or abdominal circumference ≥85 cm in males and ≥82 cm in females, without underlying diseases, who underwent nasopharyngeal ventilation during painless colonoscopy at physical examinations in our hospital from 2019 to 2020, were selected as the observation subjects (n = 100). The control sample area was determined by propensity matching according to the basic information characteristics presented by the observation group. 100 patients received mask oxygen at physical examinations were randomly selected in the control group (n = 100). Results The verification analysis after matching indicated that there were no intraoperative and postoperative adverse reactions, the number of intraoperative limb movements was less than 1, and the intestinal peristalsis intervals were more than 5s in both groups, without atropine intervention. Colonoscopy was performed by senior endoscopists with a withdrawal time of 6-8 min. When the intraoperative SpO2 was lower than 90% but higher than 85%, the patients in the observation group underwent nasopharyngeal ventilation while those in the control group received mask oxygen assisted chin-lift. As a result, the SpO2 was maintained higher than 90%. The detection rate of colorectal polyps was compared between the two groups. Conclusion The detection rate of colorectal polyps in the observation group was higher than that in the control group, with a statistically significant difference. It may result from the reduction of ineffective respiratory movement and intraoperative intestinal peristalsis in middle-aged and elderly overweight patients.
Reply to Betts et al. “When are hypotheses useful in ecology and conservation?”Meredith Root-Bernstein1, 2, 3UMR CESCO, CNRS, Muséum National d’Histoire Naturelle, Paris, FranceCenter of Applied Ecology and Sustainability, Santiago, ChileInstitute of Ecology and Biodiversity, Santiago, ChileWords: 2045It is difficult to disagree with Betts et al. (2021) when they claim that hypotheses are often useful but sometimes not necessary. The difficulty with Betts et al. does not lie with any of their individual points, but rather with the lack of a clear argument giving them structure. This is not just a critique of style. It is relevant because it is an example of what I think is the real problem in ecological research. In my view, the lack of hypotheses in ecology and conservation is not just about the rise of big data approaches, or the documentation of applied work. More generally, I argue that the low use of hypotheses reflects the failure of ecology and conservation to value and develop discipline-specific forms of argument, logic and reasoning. I first address the particular nature of the hypothesis as an argument form, and then the question of whether there are specifically ecological argument forms. Finally I argue that we need a broad set of arguments and logics suitable to the broad set of phenomona in ecology, and that hypotheses are usually derived from non-hypothetico-deductive reasoning and logic. If we want more or better hypotheses, we need more and better forms of non-hypothetico-deductive ecological reasoning.A hypothesis is a form of argument structured so that it can be answered in only one of two ways: rejection or non-rejection. Hypotheses are also characterized by particular ways of framing questions that are considered legitimate, interesting, or elegant, which varies by the discipline or subject matter. I will illustrate my points about the need for forms of argument that fit a subject matter with the Betts et al. paper itself. Betts et al. present their argument about why ecologists should use hypotheses in the form of a couple of hypotheses, the predictions of which they test in a hypothetico-deductive manner on quantitative data using statistical reasoning. They structure their hypothesis as though it were an evolutionary argument: they identify potential discrete individual benefits of adopting a behaviour within a specific environment.

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Mohammed Al-Sadawi

and 7 more

Abstract: Background: This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: We searched the databases including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26th, 2020. The search was not restricted to time, publication status or language. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography (PSG) or home sleep apnea testing (HSAT), and patients without OSA in relation to established markers of diastolic dysfunction. Results: Primary search identified 2512 studies. A total of 18 studies including 2509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater LAVI (3.94 CI [0.8, 7.07]; p=0.000) and left ventricular mass index (11.10 CI [2.56,19.65]; p=0.000) as compared to control group. The presence of OSA was also associated with more prolonged DT (10.44 ms CI [0.71,20.16]; p=0.04), IVRT (7.85 ms CI[4.48, 11.22]; p=0.000), and lower E/A ratio (-0.62 CI [-1,-0.24]; p=0.001) suggestive of early DD. The E/e’ ratio (0.94 CI[0.44, 1.45]; p=0.000) was increased. Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of CPAP therapy in reversing or ameliorating diastolic dysfunction is recommended.

Huseyin Kazan

and 6 more

Objective: To investigate the factors, especially preoperative urinalysis, predicting postoperative early infection after retrograde intrarenal surgery (RIRS) in 1-2 cm renal stones. Methods: Of the 642 patients who underwent RIRS between September 2013 and July 2019, 289 patients with a total stone size of 1-2 cm were included in the study. Patients were divided into two groups as with and without postoperative urinary tract infection. The demographic data and perioperative findings of all patients were retrospectively reviewed. Sterile urine cultures were obtained in all patients during the preoperative 30-day period and urine analysis values were included in the data. Results: Urinary system infection (UTI) was seen in 20 (6.9%) of 289 patients. Patient demographics were similar between groups. There was no statistically significant difference between the two groups in terms of stone diameter and stone localization (median diameter 13.5 vs 15, p=0.285). Patients with postoperative UTI had a higher rate of UTI history (55% vs 20.5%, p=0.000) and longer operative times (62.5 vs 60 min., p=0.008). Rate of pyuria, leukocyte esterase and nitrite positivity were observed more frequently in patients with postoperative UTI. In multivariate analysis, UTI history, prolonged operative time, and nitrite positivity were found to be independent risk factors for postoperative UTI. Conclusion: Nitrite positivity in preoperative urinanalysis, history of UTI and prolonged operation time are the factors that predict the postoperative infection in RIRS for stones between 1-2 cm.

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; Clinicaltrials.gov 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.

Mehmet Pehlivaoğlu

and 5 more

Aim: This study evaluated the effect of intracavitary levobupivacaine infusion diluted with locally applied isotonic solution for pain control in cystoscopy. Methods: Included in this study are 100 patients who had previously undergone transurethral tumor resection for bladder tumor and were followed up by cystoscopy. The patients were randomized into five groups (n = 20). In the first, second, third, and fourth groups, 4, 6, 8, and 10 mL of levobupivacaine HCl (5.0 mg/mL) were mixed with 26, 24, 22, and 20 mL of isotonic solution, respectively. Hence, the total mixture was 30 mL for each group. The fifth group was the control group. In this group, the standard method commonly used in most clinics was utilized. That is, a gel containing Cathejell-2% lidocaine (25 mg lidocaine) was applied. Cystoscopic interventions were performed with a 17.5 Fr rigid cystoscope and 0°, 30°, and 70° lens. During cystoscopy and 30 min later, the pain status of patients was assessed using the Visual Analogue Scale (VAS), and patient satisfaction was questioned. Results: The mean VAS score during and after the cystoscopy procedure was significantly lower in the levobupivacaine groups compared to the lidocaine group. In addition, patient satisfaction in the levobupivacaine groups was significantly higher than in the lidocaine group. No drug-related side-effects were observed in all groups. Conclusion: Thus, levobupivacaine is a more effective drug than lidocaine alone to control pain during cystoscopy. The use of levobupivacaine is recommended to prevent possible complications of general anesthesia by eliminating the need for the aforementioned as well as its cost-saving advantage.

Yanhui Dong

and 4 more

Groundwater age is often used to estimate groundwater recharge through a simplified analytical approach. This estimated recharge is thought to be representative of the mean recharge between the point of entry and the sampling point. However, given the complexity in actual recharge, whether the mean recharge is reasonable is still unclear. This study examined the validity of the method to estimate long-term average groundwater recharge and the possibility of obtaining reasonable spatial recharge pattern. We first validated our model in producing reasonable age distributions using a constant flux boundary condition. We then generated different flow fields and age patterns by using various spatially-varying flux boundary conditions with different magnitudes and wavelengths. Groundwater recharge was estimated and analyzed afterwards using the method at the spatial scale. We illustrated the main findings with a field example in the end. Our results suggest that we can estimate long-term average groundwater recharge with 10% error in many parts of an aquifer. The size of these areas decreases with the increase in both the amplitude and the wavelength. The chance of obtaining a reasonable groundwater recharge is higher if an age sample is collected from the middle of an aquifer and at downstream areas. Our study also indicates that the method can also be used to estimate local groundwater recharge if age samples are collected close to the water table. However, care must be taken to determine groundwater age regardless of conditions.

Xinyi Guan

and 4 more

Adriana Bustamante

and 3 more

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