bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder
Authors: Zou Zhili , Huang Yulan , Wang Jinyu , Min Wenjiao , Zhou Bo
Published: July 2020

Background

A number of studies have shown that genetic factor plays an important role in etiology of panic disorder (PD). The aim of the present study was to examine the association of serotonin-related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug.

Methods

Two hundred thirty-three patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), 5-HTR1A rs6295, 5-HTR2A rs6313 and COMT rs4680 gene polymorphisms were genotyped and assessed for the potential association.

Results

The allelic model showed that the SLC6A4 rs140701 polymorphism variant was significantly associated with increased risk of PD (OR = 0.624, 95% CI 0.450–0.864, p < 0.05), and a significant result was found in the dominant model (OR = 0.546; 95% CI, 0.371–0.804, p < 0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128–0.328; OR = 0.249, 95% CI 0.155–0.401, both p < 0.001), indicating the PD patients with S-allele had a poorer response to sertraline than L-allele carriers.

Conclusions

The present study suggests that the SLC6A4 rs140701 polymorphism variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertraline in the treatment of PD.
Development and validation of the fracture risk scale home care (FRS-HC) that predicts one-year incident fracture: an electronic record-linked longitudinal cohort study
Authors: McArthur Caitlin , Ioannidis George , Jantzi Micaela , Adachi Jonathon D. , Giangregorio Lora , Hirdes John , Papaioannou Alexandra
Published: July 2020

Background

Fractures have dire consequences including pain, immobility, and death. People receiving home care are at higher risk for fractures than the general population. Yet, current fracture risk assessment tools require additional testing and assume a 10-year survival rate, when many die within one year. Our objectives were to develop and validate a scale that predicts one-year incident hip fracture using the home care resident assessment instrument (RAI-HC).

Methods

This is a retrospective cohort study of linked population data. People receiving home care in Ontario, Canada between April 1st, 2011 and March 31st, 2015 were included. Clinical data were obtained from the RAI-HC which was linked to the Discharge Abstract Database and National Ambulatory Care Reporting System to capture one-year incident hip fractures. Seventy-five percent (n = 238,011) of the sample were randomly assigned to a derivation and 25% (n = 79,610) to a validation sample. A decision tree was created with the derivation sample using known fracture risk factors. The final nodes of the decision tree were collapsed into 8 risk levels and logistic regression was performed to determine odds of having a fracture for each level. c-Statistics were calculated to compare the discriminative properties of the full, derivation, and validation samples.

Results

Approximately 60% of the sample were women and 53% were 80 years and older. A total of 11,526 (3.6%) fractures were captured over the 1-year time period. Of these, 5057 (43.9%) were hip fractures. The proportion who experienced a hip fracture in the next year ranged from 0.3% in the lowest risk level to 5.2% in the highest risk level. People in the highest risk level had 18.8 times higher odds (95% confidence interval, 14.6 to 24.3) of experiencing a hip fracture within one year than those in the lowest. c-Statistics were similar for the full (0.658), derivation (0.662), and validation (0.645) samples.

Conclusions

The FRS-HC predicts hip fracture over one year and should be used to guide clinical care planning for home care recipients at high risk for fracture. Our next steps are to develop a fracture risk clinical assessment protocol to link treatment recommendations with identified fracture risk.
Services for women’s sexual and reproductive health in India: an analysis of treatment-seeking for symptoms of reproductive tract infections in a nationally representative survey
Authors: Bhasin Shikha , Shukla Ankita , Desai Sapna
Published: July 2020

Background

Women’s health policy in India has had a longstanding focus on maternal health and family planning. Recent policy highlights the importance of expanding women’s access to a broader range of sexual and reproductive health services. However, there has been very limited analysis of national survey data to examine the current status of treatment utilisation, variation across states and progress over time.

Methods

This paper examines women’s treatment patterns for reproductive tract infections in India, based on data collected in the National Family Health Survey, a cross-sectional, nationally representative household survey conducted between 2015-16. The survey covered 699,686 women between the ages 15 and 49, of which 91,818 ever sexually active women responded to questions related to symptoms of reproductive tract infections. We estimate prevalence of reported symptoms and treatment-seeking, describe regional variation and utilise multivariable logistic regression to identify factors associated with women’s treatment-seeking patterns.

Results

Thirty-nine percent of women who reported symptoms of reproductive tract infections sought any advice or treatment. Women’s reported treatment-seeking in India has not changed since the last national survey a decade earlier. Reported symptoms and treatment-seeking varied widely across India, ranging from 64% in Punjab to 8% in Nagaland, with no clear regional pattern that emerged. Seventeen percent of symptomatic women sought services in the public sector, an improvement from 11% in 2005–06. Twenty-two percent utilised the private sector, with wide variation by states. National-level multivariable logistic regression indicated that treatment-seeking was associated with age, higher education, higher household wealth and having been employed in the past year. Women in the 25–35 age group had higher odds (aOR1.27; 95% CI: 1.10,1.50) of seeking treatment compared to both younger (15–19 years) and older (35 years and above) women, along with women with more than eight years of schooling (aOR: 1.23; 95% CI: 1.05,1.44) and from richer wealth quintiles (aOR: 1.53; 95% CI: 1.35,1.83).

Conclusion

Women’s use of services for reproductive tract infections remains a challenge in most parts of India. Our findings highlight the need to address barriers to seeking care and to improve measurement of gynaecological ailments in national surveys.
Establishment of a functional system for recombinant production of secreted proteins at 50 °C in the thermophilic Bacillus methanolicus
Authors: Irla Marta , Drejer Eivind B. , Brautaset Trygve , Hakvåg Sigrid
Published: July 2020

Background

The suitability of bacteria as microbial cell factories is dependent on several factors such as price of feedstock, product range, production yield and ease of downstream processing. The facultative methylotroph Bacillus methanolicus is gaining interest as a thermophilic cell factory for production of value-added products from methanol. The aim of this study was to expand the capabilities of B. methanolicus as a microbial cell factory by establishing a system for secretion of recombinant proteins.

Results

Native and heterologous signal peptides were tested for secretion of α-amylases and proteases, and we have established the use of the thermostable superfolder green fluorescent protein (sfGFP) as a valuable reporter protein in B. methanolicus. We demonstrated functional production and secretion of recombinant proteases, α-amylases and sfGFP in B. methanolicus MGA3 at 50 °C and showed that the choice of signal peptide for optimal secretion efficiency varies between proteins. In addition, we showed that heterologous production and secretion of α-amylase from Geobacillus stearothermophilus enables B. methanolicus to grow in minimal medium with starch as the sole carbon source. An in silico signal peptide library consisting of 169 predicted peptides from B. methanolicus was generated and will be useful for future studies, but was not experimentally investigated any further here.

Conclusion

A functional system for recombinant production of secreted proteins at 50 °C has been established in the thermophilic B. methanolicus. In addition, an in silico signal peptide library has been generated, that together with the tools and knowledge presented in this work will be useful for further development of B. methanolicus as a host for recombinant protein production and secretion at 50 °C.
The biological function of m6A demethylase ALKBH5 and its role in human disease
Authors: Wang Jinyan , Wang Jinqiu , Gu Quan , Ma Yajun , Yang Yan , Zhu Jing , Zhang Quan’an
Published: July 2020

Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.
Intra-subject approach for gait-event prediction by neural network interpretation of EMG signals
Authors: Di Nardo Francesco , Morbidoni Christian , Mascia Guido , Verdini Federica , Fioretti Sandro
Published: July 2020

Background

Machine learning models were satisfactorily implemented for estimating gait events from surface electromyographic (sEMG) signals during walking. Most of them are based on inter-subject approaches for data preparation. Aim of the study is to propose an intra-subject approach for binary classifying gait phases and predicting gait events based on neural network interpretation of sEMG signals and to test the hypothesis that the intra-subject approach is able to achieve better performances compared to an inter-subject one. To this aim, sEMG signals were acquired from 10 leg muscles in about 10.000 strides from 23 healthy adults, during ground walking, and a multi-layer perceptron (MLP) architecture was implemented.

Results

Classification/prediction accuracy was tested vs. the ground truth, represented by the foot–floor-contact signal provided by three foot-switches, through samples not used during training phase. Average classification accuracy of 96.1 ± 1.9% and mean absolute value (MAE) of 14.4 ± 4.7 ms and 23.7 ± 11.3 ms in predicting heel-strike (HS) and toe-off (TO) timing were provided. Performances of the proposed approach were tested by a direct comparison with performances provided by the inter-subject approach in the same population. Comparison results showed 1.4% improvement of mean classification accuracy and a significant (p < 0.05) decrease ofMAEin predicting HS and TO timing (23% and 33% reduction, respectively).

Conclusions

The study developed an accurate methodology for classification and prediction of gait events, based on neural network interpretation of intra-subject sEMG data, able to outperform more typical inter-subject approaches. The clinically useful contribution consists in predicting gait events from only EMG signals from a single subject, contributing to remove the need of further sensors for the direct measurement of temporal data.
Modeling the risk factors for dyslipidemia and blood lipid indices: Ravansar cohort study
Authors: Rezaei Mansour , Fakhri Negin , Pasdar Yahya , Moradinazar Mehdi , Najafi Farid
Published: July 2020

Background

Lipid disorder is one of the most important risk factors for chronic diseases. Identifying the factors affecting the development of lipid disorders helps reduce chronic diseases, especially Chronic Heart Disease (CHD). The aim of this study was to model the risk factors for dyslipidemia and blood lipid indices.

Methods

This study was conducted based on the data collected in the initial phase of Ravansar cohort study (2014–16). At the beginning, all the 453 available variables were examined in 33 stages of sensitivity analysis by perceptron Artificial Neural Network (ANN) data mining model. In each stage, the variables that were more important in the diagnosis of dyslipidemia were identified. The relationship among the variables was investigated using stepwise regression. The data obtained were analyzed in SPSS software version 25, at 0.05 level of significance.

Results

Forty percent of the subjects were diagnosed with lipid disorder. ANN identified 12 predictor variables for dyslipidemia related to nutrition and physical status. Alkaline phosphatase, Fat Free Mass (FFM) index, and Hemoglobin (HGB) had a significant relationship with all the seven blood lipid markers. The Waist Hip Ratio was the most effective variable that showed a stronger correlation with cholesterol and Low-Density Lipid (LDL). The FFM index had the greatest effect on triglyceride, High-Density Lipid (HDL), cholesterol/HDL, triglyceride/HDL, and LDL/HDL. The greatest coefficients of determination pertained to the triglyceride/HDL (0.203) and cholesterol/HDL (0.188) model with nine variables and the LDL/HDL (0.180) model with eight variables.

Conclusion

According to the results, alkaline phosphatase, FFM index, and HGB were three common predictor variables for all the blood lipid markers. Specialists should focus on controlling these factors in order to gain greater control over blood lipid markers.
Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
Authors: Heymans Marjolein , Figueiredo Ricardo , Dehouck Lucie , Francisco David , Sano Yasuteru , Shimizu Fumitaka , Kanda Takashi , Bruggmann Rémy , Engelhardt Britta , Winter Peter , Gosselet Fabien , Culot Maxime
Published: July 2020

Formation, maintenance, and repair of the blood–brain barrier (BBB) are critical for central nervous system homeostasis. The interaction of endothelial cells (ECs) with brain pericytes is known to induce BBB characteristics in brain ECs during embryogenesis and can be used to differentiate human ECs from stem cell source in in vitro BBB models. However, the molecular events involved in BBB maturation are not fully understood. To this end, human ECs derived from hematopoietic stem cells were cultivated with either primary bovine or cell line-derived human brain pericytes to induce BBB formation. Subsequently, the transcriptomic profiles of solocultured vs. cocultured ECs were analysed over time by Massive Analysis of cDNA Ends (MACE) technology. This RNA sequencing method is a 3′-end targeted, tag-based, reduced representation transcriptome profiling technique, that can reliably quantify all polyadenylated transcripts including those with low expression. By analysing the generated transcriptomic profiles, we can explore the molecular processes responsible for the functional changes observed in ECs in coculture with brain pericytes (e.g. barrier tightening, changes in the expression of transporters and receptors). Our results identified several up- and downregulated genes and signaling pathways that provide a valuable data source to further delineate complex molecular processes that are involved in BBB formation and BBB maintenance. In addition, this data provides a source to identify novel targets for central nervous system drug delivery strategies.
Screening of postpartum depression among new mothers in Istanbul: a psychometric evaluation of the Turkish Edinburgh Postnatal Depression Scale
Authors: Boran Perran , Waqas Ahmed , Aşkan Öykü Özbörü , Topçu İrem , Dogan Tugay , Rahman Atif
Published: July 2020

Objective

This study is the first concerted effort to ascertain factor structure of EPDS using evidence based analytical techniques. It is the most widely used scale for assessing postpartum depression in Turkey, and yet no investigations have been conducted to assess it factor structure. This study was conducted from April 2012 to April 2018 at the Marmara University Hospital operating under the name of Marmara University Pendik Training and Research Hospital in Istanbul Turkey.

Results

A total of 1700 women were included in this study, who responded to the EPDS, in addition to demographic characteristics and well-being of their offspring. A total of 1615 mothers provided adequate data for inclusion in analysis. Standardized Chronbach’s alpha for EPDS was 0.81 with corrected item-total correlations ranging from 0.35 to 0.62. Parallel analysis, MAP Velicer Test and Hull’s method dictated retaining of one factor structure. All the items revealed adequate communalities (> 0.20) except item 2 (enjoyment) and item 10 (self-harm). Their communalities were 0.16 and 0.19, however, these items were not dropped. All of the items yielded moderate to strong factor loadings. Minimum factor loading was for item 2 (0.40) and highest for item 8 (0.71).
Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer
Authors: Baart V. M. , Houvast R. D. , de Geus-Oei L. F. , Quax P. H. A. , Kuppen P. J. K. , Vahrmeijer A. L. , Sier C. F. M.
Published: July 2020

The urokinase plasminogen activator receptor (uPAR) plays a multifaceted role in almost any process where migration of cells and tissue-remodeling is involved such as inflammation, but also in diseases as arthritis and cancer. Normally, uPAR is absent in healthy tissues. By its carefully orchestrated interaction with the protease urokinase plasminogen activator and its inhibitor (plasminogen activator inhibitor-1), uPAR localizes a cascade of proteolytic activities, enabling (patho)physiologic cell migration. Moreover, via the interaction with a broad range of cell membrane proteins, like vitronectin and various integrins, uPAR plays a significant, but not yet completely understood, role in differentiation and proliferation of cells, affecting also disease progression. The implications of these processes, either for diagnostics or therapeutics, have received much attention in oncology, but only limited beyond. Nonetheless, the role of uPAR in different diseases provides ample opportunity to exploit new applications for targeting. Especially in the fields of oncology, cardiology, rheumatology, neurology, and infectious diseases, uPAR-targeted molecular imaging could offer insights for new directions in diagnosis, surveillance, or treatment options.
Study protocol for a group-based motivational interviewing brief intervention to reduce substance use and sexual risk behavior among young adults experiencing homelessness
Authors: Tucker Joan S. , D’Amico Elizabeth J. , Pedersen Eric R. , Rodriguez Anthony , Garvey Rick
Published: July 2020

Background

Young people experiencing homelessness have alarmingly high rates of alcohol and other drug (AOD) use, which is associated with sexual risk behaviors such as unprotected sex, trading sex, and sex with multiple casual partners. Few risk reduction programs for this population have been developed and rigorously evaluated, particularly those that address both of these interrelated behaviors, use a collaborative and non-judgmental approach, and are feasible to deliver in settings where homeless young people seek services. This paper describes the protocol of a study evaluating a four-session Motivational Interviewing (MI)-based group risk reduction intervention for this population. The protocol has been shown to be efficacious in pilot work over 3 months with 200 homeless young adults [1]. The current study seeks to refine the intervention protocol and evaluate the program on a larger scale.

Methods/design

In a cluster-cross-over randomized controlled trial, 18–25 year olds will receive the AWARE risk reduction program (n = 200) or standard care (n = 200) at one of three drop-in centers serving homeless youth in the Los Angeles area. We will evaluate intervention effects on primary outcomes of AOD use and sexual risk behavior, as well as secondary outcomes of health-related quality of life and social stability, over a 12-month period.

Discussion

This project has the potential to fill a significant gap in prevention services by demonstrating that a brief intervention, feasible to deliver within settings where young people experiencing homelessness typically seeks services, can significantly reduce the interrelated problems of AOD use and sexual risk behavior.

Trial registration ClinicalTrials.gov Identifier: NCT03735784. Registered November 18, 2018, https://clinicaltrials.gov/ct2/show/record/NCT03735784 (retrospectively registered)
Prevalence and abundance of selected genes conferring macrolide resistance genes in COPD patients during maintenance treatment with azithromycin
Authors: Djamin Remco S. , Talman Sander , Schrauwen Eefje J. A. , von Wintersdorff Christian J. H. , Wolffs Petra F. , Savelkoul Paul H. M. , Uzun Sevim , Kerstens René , van der Eerden Menno M. , Kluytmans Jan A. J. W.
Published: July 2020

Objectives

Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients.

Methods

This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period.

Results

There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients. However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012). The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin.

Conclusions

The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo.

This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244).
Contribution of common chronic conditions to midlife physical function decline: The Study of Women’s Health Across the Nation
Authors: Lange-Maia Brittney S. , Karavolos Kelly , Avery Elizabeth F. , Strotmeyer Elsa S. , Karvonen-Gutierrez Carrie A. , Appelhans Bradley M. , Janssen Imke , Dugan Sheila A. , Kravitz Howard M.
Published: July 2020

Background

Chronic conditions are associated with worse physical function and commonly develop during midlife. We tested whether the presence of 8 chronic conditions, or the development of these conditions, is associated with declines in physical function among midlife women as they transition into early late life.

Methods

Participants (N = 2283) were from the Study of Women’s Health Across the Nation. Physical function was assessed at 8 visits starting at the study’s fourth clinic visit in 2000/2001 through follow-up visit 15 (2015/2017) using the Short Form-36 Physical Function subscale. Chronic conditions included diabetes, hypertension, osteoarthritis, osteoporosis, stroke, heart disease, cancer, and depressive symptoms. Repeated-measures Poisson regression modeled associations between 1) prevalent chronic conditions at analytic baseline (visit 4) and longitudinal physical function, and 2) change in physical function associated with developing a new condition. Models were adjusted with the total number of other chronic conditions at visit 4.

Results

In separate fully-adjusted longitudinal models, prevalent heart disease and osteoporosis were associated with 18% (IRR = 0.815, 95% confidence interval [CI]: 0.755–0.876) and 12% (IRR = 0.876, 95% CI: 0.825–0.927) worse initial physical function, respectively. Prevalent osteoarthritis was associated with approximately 6% (IRR = 0.936, 95% CI: 0.913–0.958) worse initial physical function, and a slight additional worsening over time (IRR = 0.995, 95% CI: 0.994–0.996). A 12% (IRR = 0.878, 95% CI: 0.813–0.950) decrease in physical function concurrent with stroke development was evident, as was accelerated decline in physical function concurrent with heart disease development (IRR = 0.991, 95% CI: 0.988–0.995).

Conclusions

Initial prevalent conditions related to the musculoskeletal system were associated with worse initial physical function, with some evidence of accelerated decline in physical function with osteoarthritis. Stroke and heart disease are less common than osteoarthritis in this age group, but the severe effects of these conditions on physical function shows the need for a greater focus on cardiovascular health during midlife. Women who develop chronic conditions during midlife may be at particular risk for poor physical function as they age, warranting disability prevention efforts focused on this population.
Performance evaluation of high-volume electret filter air samplers in aerosol microbiome research
Authors: Bøifot Kari Oline , Gohli Jostein , Skogan Gunnar , Dybwad Marius
Published: July 2020

Background

Reliable identification and quantification of bioaerosols is fundamental in aerosol microbiome research, highlighting the importance of using sampling equipment with well-defined performance characteristics. Following advances in sequencing technology, shotgun metagenomic sequencing (SMS) of environmental samples is now possible. However, SMS of air samples is challenging due to low biomass, but with the use of high-volume air samplers sufficient DNA yields can be obtained. Here we investigate the sampling performance and comparability of two hand-portable, battery-operated, high-volume electret filter air samplers, SASS 3100 and ACD-200 Bobcat, previously used in SMS-based aerosol microbiome research.

Results

SASS and Bobcat consistently delivered end-to-end sampling efficiencies > 80% during the aerosol chamber evaluation, demonstrating both as effective high-volume air samplers capable of retaining quantitative associations. Filter recovery efficiencies were investigated with manual and sampler-specific semi-automated extraction procedures. Bobcat semi-automated extraction showed reduced efficiency compared to manual extraction. Bobcat tended towards higher sampling efficiencies compared to SASS when combined with manual extraction. To evaluate real-world sampling performance, side-by-side SASS and Bobcat sampling was done in a semi-suburban outdoor environment and subway stations. SMS-based microbiome profiles revealed that highly abundant bacterial species had similar representation across samplers. While alpha diversity did not vary for the two samplers, beta diversity analyses showed significant within-pair variation in subway samples. Certain species were found to be captured only by one of the two samplers, particularly in subway samples.

Conclusions

SASS and Bobcat were both found capable of collecting sufficient aerosol biomass amounts for SMS, even at sampling times down to 30 min. Bobcat semi-automated filter extraction was shown to be less effective than manual filter extraction. For the most abundant species the samplers were comparable, but systematic sampler-specific differences were observed at species level. This suggests that studies conducted with these highly similar air samplers can be compared in a meaningful way, but it would not be recommended to combine samples from the two samplers in joint analyses. The outcome of this work contributes to improved selection of sampling equipment for use in SMS-based aerosol microbiome research and highlights the importance of acknowledging bias introduced by sampling equipment and sample recovery procedures.
The pharmacological and clinical aspects behind dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs): rationale and systematic narrative review of clinical evidence
Authors: Geurts-Voerman Gerlienke E. , Verhoef Lise M. , van den Bemt Bart J. F. , den Broeder Alfons A.
Published: July 2020

Background

Dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs) is performed to achieve steady state drug concentrations earlier after treatment start compared to dosing regimens without loading. Although loading inherently results in increased costs, treatment targets in terms of reduced disease activity may be achieved at an earlier state. It is an interesting topic that, surprisingly, has not received much attention in literature.

Methods

In this review, we aimed at providing a theoretical description of the pharmacodynamic / -kinetic rationale for dose loading of bDMARDs in AIRDs and to systematically review the clinical evidence on the effectiveness of dose loading on disease activity in AIRDs.

Results

Only a small number of studies (n = 5) has been published comparing the effectiveness of dose loading versus a regimen without dose loading of bDMARDs in AIRDs, addressing abatacept (n = 2), certolizumab pegol (n = 1), and secukinumab (n = 2). These studies provide insufficient evidence on superiority of dose loading in terms of disease activity compared to a dosing regimen without loading, while safety issues might be comparable.

Conclusions

Although dose loading is commonly adopted for several bDMARDs in AIRDs, scientific evidence on its effectiveness and safety is surprisingly scarce and does not suggest superiority compared to a regimen without dose loading. More research in this field, also with regard to the pharmaco-economic consequences of dose loading, is urgently needed.
A new validated stability-indicating RP-HPLC method for simultaneous quantification of dolutegravir and lamivudine in bulk and pharmaceutical dosage form
Authors: Noorbasha Khaleel , Nurbhasha Sharmila
Published: July 2020

Background

A fresh selective, rapid, accurate, precise and RP-HPLC stability-indicating method was developed and validated for the quantitative simultaneous determination of dolutegravir and lamivudine in the bulk as well as pharmaceutical dosage form. A chromatographic separation was done by using Inertsil ODS 3V (250 × 4.6 mm, 5 μm) column and mobile phase composed of phosphate buffer, pH 3.0:acetonitrile:methanol (50:20:30% v/v/v) with flow rate of 1.0 mL/min, and the detection of eluents was carried out at a wavelength of 257 nm utilizing a PDA detector. The drugs, dolutegravir and lamivudine, were subjected to varied conditions like base hydrolysis, acid hydrolysis, oxidation, thermal, photochemical and UV. The suggested method was analysed statistically and validated to fulfil requirements of International Conference on Harmonisation (ICH) and the validation covered accuracy, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), robustness, ruggedness and specificity.

Results

The retention time of dolutegravir and lamivudine were observed to be 6.36 and 2.16 min, respectively. The method was found to be linear within the range of 14.98 to 91.25 μg/mL for lamivudine and 2.54 to 15.35 μg/mL for dolutegravir. The percentage recoveries (accuracy) for dolutegravir and lamivudine were in the range of 98.35 to 102.14% and 98.01 to 101.5%. The computed relative variance (%RSD) was within the suitable criterion of less than 2.0.

Conclusion

The suggested method was set to be precise as well as stability-indicating since no interfering degradant peaks and excipients were evident. All the peaks of degradation were successfully resolved by the use of the developed analytical method with altered retention times. Results obtained were analysed statistically and found to be acceptable in line with the ICH guidelines. Hence, such method is often employed successfully for routine analysis of active analytes in the bulk as well as pharmaceutical dosage form. It is going to be extended to review for its estimation in plasma and other biological fluids and may even be employed for quality control stability sample estimation and in cleaning method analysis during cleaning validation.
Self-Efficacy and Performance of Research Skills among First-Semester Bioscience Doctoral Students
Authors: Lachance Katherine , Heustis Ronald J. , Loparo Joseph J. , Venkatesh Madhvi J.
Published: July 2020

Incoming doctoral students have gaps in research skills that are not correlated with duration of prior research experience. During their first semester of training, most students improve in both research skills self-efficacy and experimental design performance. They attribute changes to many factors, including research, course work, and mentoring.
From Theory to Practice: Gathering Evidence for the Validity of Data Collected with the Interdisciplinary Science Rubric (IDSR)
Authors: Tripp Brie , Shortlidge Erin E.
Published: July 2020

This study developed a new instrument, the Interdisciplinary Science Rubric, or IDSR, to measure undergraduate students’ interdisciplinary science thinking. Evidence of reliability and validity was established on the constructs and criteria of the rubric, resulting in an instrument that accurately assesses this competency.
A frequency-decomposed nonstationary convolutional model for amplitude-versus-angle-and-frequency forward waveform modeling in attenuative media
Authors: Yang Jingkang , Geng Jianhua , Zhao Luanxiao
Published: July 2020

The conventional convolutional model (CCM) is widely applied to generate synthetic seismic data for numerous applications including amplitude variation with offset forward modeling, seismic well tie, and inversion. This approach assumes frequency-independent reflection coefficients and time-invariant seismic wavelets in laterally homogeneous elastic media. We have extended CCM to heterogeneous poroelastic media in which reflection coefficients are frequency dependent and the seismic wave is attenuated as it propagates. First, we decompose the seismic wavelet into monofrequency components through the Fourier transform. Then, to account for the attenuation effects at the reflection interfaces, we multiply the frequency-dependent reflection coefficients series with an attenuation function of frequency-variant quality factor [Formula: see text]. Finally, we convolve this product results with a monofrequency wavelet and sum all of the frequencies together to obtain the synthetic seismograms. The advantage of the proposed frequency-decomposed nonstationary convolutional model is that it takes into account the effects of attenuation on the wave reflections and propagation in attenuative media. In addition, it uses the frequency-dependent [Formula: see text] instead of the constant [Formula: see text] that is used by the traditional nonstationary convolutional model. The technique has been applied to amplitude-versus-angle-and-frequency forward waveform modeling in attenuative media, and it shows good agreement between synthetic and real data on seismic well ties.
Novel transient multicomponent induction logging method for the determination of dip angle and anisotropy of formation
Authors: Yuan Xiyong , Deng Shaogui , Fan Yiren , Hu Xufei , Wu Zhenguan , Zhang Pan , Cai Lianyun
Published: July 2020

The relative dip angle and anisotropy of the anisotropic formation are generally determined through an inversion process. We have studied the responses of the novel transient multicomponent induction logging method and find that all of the components measured in the instrument coordinate system have the same decay with time. However, the cross component decays much faster than the coaxial or coplanar components in the formation coordinate system. We adopt an algebraic time-domain method to calculate the dip angle and anisotropy coefficient and thereby avoid the inversion process. The accuracy and applicability of this pseudoinversion method are studied theoretically. Numerical results demonstrate that coaxial, coplanar, and cross components are used to calculate the apparent relative dip angle that yields the exactly true value at very early times and then goes through a transition deviating from the true dip and gradually approaches the true value again at late times. The apparent anisotropy is calculated by the coaxial and coplanar components and is equal to zero at early times and nonzero to the true anisotropy during the transition times. Moreover, by using realistic source dipole moments as well as adding random measurement errors, the practicality of this algebraic method is also investigated. Determination of the relative dip is still stable and valid. Determination of the anisotropy is more easily affected by measurement error and has some application limitations.
Seismic imaging of S-wave structures of shallow sediments in the East China Sea using OBN multicomponent Scholte-wave data
Authors: Wang Yuan , Li Zhiwei , Geng Jianhua , You Qingyu , Hao Tianyao , Hu Yaoxing , Zhao Chunlei , Zhang Yan , Liu Yuzhu
Published: July 2020

The shear-wave (S-wave) structures of shallow marine sediments are important for offshore geotechnical studies, deep crustal S-wave imaging, multicomponent seismic exploration, and underwater acoustics studies. We have applied the multicomponent Scholte-wave analysis technique to an active-source shallow marine seismic profile in the East China Sea. Scholte waves have been excited by shots from a 5450 inch3air-gun array and their recordings have been conducted at the seafloor using ocean bottom nodes (OBNs). First, we extract the common-receiver gathers (CRGs) and correct for the time drift simultaneously using a forward and inverse fast Fourier transform resampling algorithm. Three CRGs of seismic sensors are used for Scholte-wave analysis. Raw sensor CRGs are rotated to the inline, crossline, and vertical coordinate system. The rotated tilt and roll angle are directed using the inner electric compass log value, and the shot inline azimuth is estimated using the particle motion method. Then, the velocity spectra are calculated from the inline and vertical components using the phase-shift method. Higher Scholte-wave modes dominate on the horizontal components, whereas the stronger fundamental mode dominates on the vertical components. The multicomponent velocity spectrum stacking method is adopted to produce the final dispersion energy image. Up to four modes of dispersion curves are retrieved within the 1.1–4.3 Hz frequency band. The multimode dispersion curve inversion is constructed for imaging the shallow sediments. The results suggest a low [Formula: see text] of 180–650 m/s and few lateral variations within the top 0.5 km of shallow marine sediments in the East China Sea. This model can provide an important reference for offshore geotechnical investigations, especially for OBN multicomponent seismic exploration data processing. The use of OBNs has high feasibility in [Formula: see text] imaging for shallow marine sediments when combined with the Scholte-wave dispersion-curve inversion.
Cost-effectiveness of WHO Problem Management Plus for adults with mood and anxiety disorders in a post-conflict area of Pakistan: randomised controlled trial
Authors: Hamdani Syed Usman , Huma Zill-e- , Rahman Atif , Wang Duolao , Chen Tao , van Ommeren Mark , Chisholm Dan , Farooq Saeed
Published: July 2020

Background

With the development of evidence-based interventions for treatment of priority mental health conditions in humanitarian settings, it is important to establish the cost-effectiveness of such interventions to enable their scale-up.

Aims

To evaluate the cost-effectiveness of the Problem Management Plus (PM+) intervention compared with enhanced usual care (EUC) for common mental disorders in primary healthcare in Peshawar, Pakistan. Trial registration ACTRN12614001235695 (anzctr.org.au).

Method

We randomly allocated 346 participants to either PM+ (n = 172) or EUC (n = 174). Effectiveness was measured using the Hospital Anxiety and Depression Scale (HADS) at 3 months post-intervention. Cost-effectiveness analysis was performed as incremental costs (measured in Pakistani rupees, PKR) per unit change in anxiety, depression and functioning scores.

Results

The total cost of delivering PM+ per participant was estimated at PKR 16 967 (US$163.14) using an international trainer and supervisor, and PKR 3645 (US$35.04) employing a local trainer. The mean cost per unit score improvement in anxiety and depression symptoms on the HADS was PKR 2957 (95% CI 2262–4029) (US$28) with an international trainer/supervisor and PKR 588 (95% CI 434–820) (US$6) with a local trainer/supervisor. The mean incremental cost-effectiveness ratio (ICER) to successfully treat a case of depression (PHQ-9 ≥ 10) using an international supervisor was PKR 53 770 (95% CI 39 394–77 399) (US$517), compared with PKR 10 705 (95% CI 7731–15 627) (US$102.93) using a local supervisor.

Conclusions

The PM+ intervention was more effective but also more costly than EUC in reducing symptoms of anxiety, depression and improving functioning in adults impaired by psychological distress in a post-conflict setting of Pakistan.
The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients
Authors: Mihalopoulos Meredith , Levine Alice C , Marayati Naoum Fares , Chubak Barbara M , Archer Maddison , Badani Ketan K , Tewari Ashutosh K , Mohamed Nihal , Ferrer Fernando , Kyprianou Natasha
Published: July 2020

Coronavirus disease–2019 (COVID-19), a disease caused by Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages in the United States, and the highest incidence and mortality in adult men. As the pandemic evolves there is limited understanding of a potential association between symptomatic viral infection and age. To date, there is no knowledge of the role children (prepubescent, ages 9-13 years) play as “silent” vectors of the virus, with themselves being asymptomatic. Throughout different time frames and geographic locations, the current evidence on COVID-19 suggests that children are becoming infected at a significantly lower rate than other age groups—as low as 1%. Androgens upregulate the protease TMPRSS2 (type II transmembrane serine protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. Owing to low levels of steroid hormones, prepubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells. As the world anticipates a vaccine against SARS-CoV-2, the role of prepubescent children as vectors transmitting the virus must be interrogated to prepare for a potential resurgence of COVID-19. This review discusses the current evidence on the low incidence of COVID-19 in children and the effect of sex-steroid hormones on SARS-CoV-2 viral infection and clinical outcomes of pediatric patients. On reopening society at large, schools will need to implement heightened health protocols with the knowledge that children as the “silent” viral transmitters can significantly affect the adult populations.
Revolution on Trial
Authors: Karla Anna , Pestel Friedemann
Published: July 2020

The Mémoires de Wéber, concernant Marie-Antoinette were of central importance to the wave of memoirs of the French Revolution published during the Restoration period. Commonly attributed to Joseph Weber, Marie-Antoinette's foster brother, the Mémoires' authorship has always remained doubtful. This article discusses the text's complex origins in the London émigré community around 1800 and analyzes the process by which it became a canonic eyewitness account with its republication in 1822. In light of newly discovered sources and recent scholarly interest in the emigration and postrevolutionary period, this article reexamines the Mémoires as a case of ghostwriting revolving around royalist loyalties, public emotions, and publication strategies. Highlighting personal networks reaching from the Revolution to the emigration and into Restoration France, this article makes a case for reconsidering generational factors, long-term relations, and interpretative struggles among the eyewitnesses of the Revolution in a period when memoirs became a key element of turning the Revolution into contemporary history.

Les Mémoires de Wéber, concernant Marie-Antoinette ont contribué de manière décisive à la vague des mémoires sur la Révolution française publiés pendant la Restauration. Généralement attribué à Joseph Weber, le frère de lait de Marie-Antoinette, la paternité littéraire de ce texte a pourtant toujours été douteuse. Cet article retrace les origines complexes du manuscrit au sein de la communauté d'émigrés à Londres autour de 1800. A travers l'édition de 1822, il démontre comment les Mémoires de Wéber se transformaient ensuite en témoignage oculaire canonique. Utilisant des sources jusque-là inconnues et des travaux récents sur l'émigration et la période postrévolutionnaire, nous proposons de réexaminer ces Mémoires comme un exemple de « ghostwriting » influencé par des loyautés royalistes, des émotions publiques et des stratégies de publication. En mettant l'accent sur les réseaux personnels reliant Révolution, émigration et Restauration, cet article souligne les facteurs générationnels, les relations à long terme et les combats d'interprétation parmi les témoins oculaires de la Révolution à une époque où les mémoires formaient un élément-clé de l'histoire contemporaine émergente de la Révolution française.
A Behavioral New Keynesian Model
Authors: Gabaix Xavier
Published: July 2020

This paper analyzes how bounded rationality affects monetary and fiscal policy via an empirically relevant enrichment of the New Keynesian model. It models agents’ partial myopia toward distant atypical events using a new microfounded “cognitive discounting” parameter. Compared to the rational model, (i) there is no forward guidance puzzle; (ii) the Taylor principle changes: with passive monetary policy but enough myopia equilibria are determinate and economies stable; (iii) the zero lower bound is much less costly; (iv) price-level targeting is not optimal; (v) fiscal stimulus is effective; (vi) the model is “ neo-Fisherian” in the long run, Keynesian in the short run. (JEL E12, E31, E43, E52, E62, E70)