bluuebunny/crossref_metadata_2025 huggingface dataset:
Annotation of tandem mass spectrometry data using stochastic neural networks in shotgun proteomics
Authors: Sulimov Pavel , Voronkova Anastasia , Kertész-Farkas Attila
Published: March 2020

Motivation

The discrimination ability of score functions to separate correct from incorrect peptide-spectrum-matches in database-searching-based spectrum identification is hindered by many superfluous peaks belonging to unexpected fragmentation ions or by the lacking peaks of anticipated fragmentation ions.

Results

Here, we present a new method, called BoltzMatch, to learn score functions using a particular stochastic neural networks, called restricted Boltzmann machines, in order to enhance their discrimination ability. BoltzMatch learns chemically explainable patterns among peak pairs in the spectrum data, and it can augment peaks depending on their semantic context or even reconstruct lacking peaks of expected ions during its internal scoring mechanism. As a result, BoltzMatch achieved 50% and 33% more annotations on high- and low-resolution MS2 data than XCorr at a 0.1% false discovery rate in our benchmark; conversely, XCorr yielded the same number of spectrum annotations as BoltzMatch, albeit with 4–6 times more errors. In addition, BoltzMatch alone does yield 14% more annotations than Prosit (which runs with Percolator), and BoltzMatch with Percolator yields 32% more annotations than Prosit at 0.1% FDR level in our benchmark.

Availability and implementation

BoltzMatch is freely available at: https://github.com/kfattila/BoltzMatch.

Contact

akerteszfarkas@hse.ru

Supporting information

Supplementary data are available at Bioinformatics online.
Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome
Authors: Reynaud-Dulaurier Robin , Benegiamo Giorgia , Marrocco Elena , Al-Tannir Racha , Surace Enrico Maria , Auwerx Johan , Decressac Michael
Published: March 2020

Mutations in nuclear-encoded mitochondrial genes are responsible for a broad spectrum of disorders among which Leigh syndrome is the most common in infancy. No effective therapies are available for this severe disease mainly because of the limited capabilities of the standard adeno-associated viral (AAV) vectors to transduce both peripheral organs and the CNS when injected systemically in adults. Here, we used the brain-penetrating AAV-PHP.B vector to reinstate gene expression in the Ndufs4 knockout mouse model of Leigh syndrome. Intravenous delivery of an AAV.PHP.B-Ndufs4 vector in 1-month-old knockout mice restored mitochondrial complex I activity in several organs including the CNS. This gene replacement strategy extended lifespan, rescued metabolic parameters, provided behavioural improvement, and corrected the pathological phenotype in the brain, retina, and heart of Ndufs4 knockout mice. These results provide a robust proof that gene therapy strategies targeting multiple organs can rescue fatal neurometabolic disorders with CNS involvement.
Hepatitis B e Antigen (HBeAg) Rapid Test and Alanine Aminotransferase Level–Based Algorithm to Identify Pregnant Women at Risk of HBV Mother-to-Child Transmission: The ANRS 12345 TA PROHM Study
Authors: Segeral Olivier , Dim Bunnet , Durier Christine , Prak Sophearot , Chhim Kearena , Vong Chanlina , Pech Sothy , Tiv Say , Nem Bunthoeun , Hout Kay , Nouhin Janin , Chhun Samsorphea , Borand Laurence
Published: March 2020

Background

The paucity of hepatitis B virus (HBV) DNA measurement in low-/middle-income countries hinders the identification of HBV-infected pregnant women at risk of perinatal transmission. This study evaluates the validity of an algorithm selecting HBeAg-positive women and HBeAg-negative women with alanine aminotransferase (ALT) ≥40 IU/L as a predictor of high HBV DNA level.

Methods

All women with reactive samples for hepatitis B surface antigen (HBsAg) were assessed with an SD BIOLINE HBeAg rapid test and HBV DNA quantification was performed. Validities of HBeAg and of the algorithm to identify HBV DNA >2 thresholds (5.3 and 7.3 log10 IU/mL) were evaluated.

Results

For the 515 HBsAg-positive women, median age was 29 years, 92 (17.9%) were HBeAg positive, 47 (9.1%) were HBeAg negative with ALT ≥40 IU/L, and 144 (28.0%) had an HBV DNA >5.3 log10 IU/mL. Sensitivity and specificity of HBeAg were 61.8% and 99.2% for HBV DNA >5.3 log10 IU/mL and 81.3% and 96.7% for HBV DNA >7.3 log10 IU/mL. For the algorithm, sensitivity and specificity were 79.2% and 93.3% for HBV DNA level >5.3 log10 IU/mL and 92.7% and 88.1% for HBV DNA >7.3 log10 IU/mL. The AUCs for the algorithm (0.92 and 0.94 for HBV DNA >5.3 and 7.3, respectively) were significantly greater (P < .001) than the AUCs for HBeAg (0.81 and 0.89 for HBV DNA >5.3 and 7.3, respectively).

Conclusions

An algorithm using HBeAg and ALT level could be an effective strategy to identify HBV-infected pregnant women at risk of perinatal transmission in countries where HBV DNA quantification is not routinely available.
Pharmacokinetics, Safety, and Antiviral Effects of Multiple Doses of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678, in Infants Hospitalized With RSV Infection: A Randomized Phase 1b Study
Authors: Martinón-Torres Federico , Rusch Sarah , Huntjens Dymphy , Remmerie Bart , Vingerhoets Johan , McFadyen Katie , Ferrero Fernando , Baraldi Eugenio , Rojo Pablo , Epalza Cristina , Stevens Marita
Published: March 2020

Background

This phase 1b study evaluated the pharmacokinetics, safety, and antiviral effects of the respiratory syncytial virus (RSV)–specific fusion inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 to ≤24 months.

Methods

Patients categorized by age (cohort 1: ≥6 to ≤24 months; cohort 2: ≥3 to < 6 months; cohort 3: > 1 to < 3 months) were randomized to oral JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using reverse-transcription quantitative polymerase chain reaction.

Results

Patients received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were similar at the highest doses for cohorts 1–3 (area under the plasma concentration–time curve from time of administration up to 24 hours postdosing at day 7: 35 840, 34 980, and 39 627 ng × hour/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by day 3 was −1.98 vs −0.32 log10 copies/mL.

Conclusions

In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed.

Clinical Trials Registration

NCT02593851.
Riskscapes, politics of scaling and climate change: towards the post-carbon society?
Authors: Everts Jonathan , Müller Katja
Published: March 2020

The concept of riskscapes has so far not embraced the concept of scale in any deeper sense. A conceptual integration of scale is needed, however, when dealing with the diversity of risks involved in opposing economic and environmental rationalities. Drawing on research conducted in a German coal-mining area, the article shows how the risk of regional economic decline and the risk of global climate change are pitted against each other. The article explores this ‘politics of scaling’ that lead to a reconfiguration of the coal riskscape, including a tentative step towards decarbonising German energy production.
Worsening proteinuria and renal function after intravitreal vascular endothelial growth factor blockade for diabetic proliferative retinopathy
Authors: Shye Michael , Hanna Ramy M , Patel Sapna S , Tram-Tran Ngoc , Hou Jean , Mccannel Collin , Khalid Maham , Hanna Mina , Abdelnour Lama , Kurtz Ira
Published: March 2020

Systemic vascular endothelial growth factor (VEGF) inhibitions can induce worsening hypertension, proteinuria and glomerular diseases of various types. These agents can also be used to treat ophthalmic diseases like proliferative diabetic retinopathy, diabetic macular edema, central retinal vein occlusion and age-related macular degeneration. Recently, pharmacokinetic studies confirmed that these agents are absorbed at levels that result in biologically significant suppression of intravascular VEGF levels. There have now been 23 other cases published that describe renal sequela of intravitreal VEGF blockade, and they unsurprisingly mirror known systemic toxicities of VEGF inhibitors. We present three cases where stable levels of proteinuria and chronic kidney disease worsened after initiation of these agents. Two of our three patients were biopsied. The first patient’s biopsy showed diabetic nephropathy and focal and segmental glomerulosclerosis (FSGS) with collapsing features and acute interstitial nephritis (AIN). The second patient’s biopsy showed AIN in a background of diabetic glomerulosclerosis. This is the second patient seen by our group, whose biopsy revealed segmental glomerulosclerosis with collapsing features in the setting of intravitreal VEGF blockade. Though FSGS with collapsing features and AIN are not the typical lesions seen with systemic VEGF blockade, they have been reported as rare case reports previously. In addition to reviewing known elements of intravitreal VEGF toxicity, the cases presented encompass renal pathology data supporting that intravitreal VEGF blockade can result in deleterious systemic and renal pathological disorders.
Empiricism in Microsampling: Utilizing a Novel Lateral Flow Device and Intrinsic Normalization to Provide Accurate and Precise Clinical Analysis from a Finger Stick
Authors: Crawford Matthew L , Collier Bradley B , Bradley Meghan N , Holland Patricia L , Shuford Christopher M , Grant Russell P
Published: March 2020

Background

Phlebotomy plays a key role in clinical laboratory medicine but poses certain challenges for the patient and the laboratory. Dried blood spots simplify collection and stabilize specimens effectively, but clinical reference intervals are based primarily on serum or plasma. We evaluated use of dried separated blood plasma specimens to simplify plasma sample collection via finger stick; however, this sampling technique posed substantial analytical challenges. We discuss herein our efforts to overcome these challenges and provide accurate and precise clinical measurements.

Methods

Microsamples of whole blood were collected via finger stick using a collection device employing laminar-flow separation of cellular blood and plasma fractions with subsequent desiccation. Samples were analyzed on modern autoanalyzers with FDA-approved reagent and calibration systems, as well as commercially available reagents with laboratory-developed assay parameters. Measured analyte concentrations from extracted dried plasma samples were normalized to a coextracted endogenous analyte, chloride.

Results

Chloride normalization reduced variability incurred through extraction and undefined plasma volume. Excellent correlation of normalized measurements from dried finger-stick samples (whole blood and plasma) versus matched venous samples facilitated developing mathematical transformations to provide concordance between specimen types. Independent end-to-end performance verification yielded mean biases <3% for the 5 analytes evaluated relative to venous drawn samples analyzed on FDA-approved measurement systems.

Conclusion

Challenges inherent with this microsampling technique and alternate sample matrix were obviated through capabilities of modern autoanalyzers and implementation of chloride normalization. These results demonstrate that self-collected microsamples from a finger stick can give results concordant with those of venous samples.
Aldosterone-induced hypertension is sex-dependent, mediated by T cells and sensitive to GPER activation
Authors: Dinh Quynh Nhu , Vinh Antony , Kim Hyun Ah , Saini Narbada , Broughton Brad R S , Chrissobolis Sophocles , Diep Henry , Judkins Courtney P , Drummond Grant R , Sobey Christopher G
Published: March 2020

Aims

The G protein-coupled estrogen receptor 1 (GPER) may modulate some effects of aldosterone. In addition, G-1 (a GPER agonist) can lower blood pressure (BP) and promote T cell-mediated anti-inflammatory responses. This study aimed to test the effects of G-1 and G-15 (a GPER antagonist) on aldosterone-induced hypertension in mice and to examine the cellular mechanisms involved.

Methods and results

C57Bl/6 (wild-type, WT), RAG1-deficient and GPER-deficient mice were infused with vehicle, aldosterone (0.72 mg/kg/day S.C. plus 0.9% NaCl for drinking) ± G-1 (0.03 mg/kg/day S.C.) ± G-15 (0.3 mg/kg/day S.C.) for 14 days. G-1 attenuated aldosterone-induced hypertension in male WT but not male GPER-deficient mice. G-15 alone did not alter hypertension but it prevented the anti-hypertensive effect of G-1. In intact female WT mice, aldosterone-induced hypertension was markedly delayed and suppressed compared with responses in males, with BP remaining unchanged until after Day 7. In contrast, co-administration of aldosterone and G-15 fully increased BP within 7 days in WT females. Similarly, aldosterone robustly increased BP by Day 7 in ovariectomized WT females, and in both sexes of GPER-deficient mice. Whereas aldosterone had virtually no effect on BP in RAG1-deficient mice, adoptive transfer of T cells from male WT or male GPER-deficient mice into male RAG1-deficient mice restored the pressor response to aldosterone. This pressor effect could be attenuated by G-1 in RAG1-deficient mice that were reconstituted with either WT or GPER-deficient T cells, suggesting that G-1 does not act via T cells to lower BP.

Conclusion

Our findings indicate that although aldosterone-induced hypertension is largely mediated by T cells, it can be attenuated by activation of GPER on non-T cells, which accounts for the sex difference in sensitivity to the pressor effect.
Assessment of Endoscopic Healing by Using Advanced Technologies Reflects Histological Healing in Ulcerative Colitis
Authors: Iacucci Marietta , Cannatelli Rosanna , Gui Xianyong , Zardo Davide , Bazarova Alina , Gkoutos Georgios V , Lethebe Brendan Cord , Kaplan Gilaad G , Panaccione Remo , Kiesslich Ralf , Ghosh Subrata
Published: March 2020

Background

Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC.

Methods

A prospective study enrolling 82 UC patients [male 66%] was conducted. High-definition colonoscopy was performed to evaluate the activity of the disease with MES assessed with High-Definition MES [HD-MES] and modified PICaSSO and targeted biopsies were taken; pCLE was then performed. Receiver operating characteristic [ROC] curves were plotted to determine the best thresholds for modified PICaSSO and pCLE scores that predicted histological healing according to the Robarts Histopathology Index [RHI] and ECAP ‘Extension, Chronicity, Activity, Plus’ histology score.

Results

A modified PICaSSO of ≤ 4 predicted histological healing at RHI ≤ 3, with sensitivity, specificity, accuracy and area under the ROC curve [AUROC] of 89.8%, 95.7%, 91.5% and 95.9% respectively. The sensitivity, specificity, accuracy and AUROC of HD-MES to predict histological healing by RHI were 81.4%, 95.7%, 85.4% and 92.1%, respectively. A pCLE ≤ 10 predicted histological healing with sensitivity of 94.9%, specificity of 91.3%, accuracy of 93.9% and AUROC of 96.5%. An ECAP of ≤ 10 was predicted by modified PICaSSO ≤ 4 with accuracy of 91.5% and AUROC of 95.9%.

Conclusion

Histological healing by RHI and ECAP is accurately predicted by HD-MES and modified virtual electronic chromoendoscopy PICaSSO, endoscopic score; and the use of pCLE did not improve the accuracy any further.
Balloon pulmonary angioplasty improves right atrial reservoir and conduit functions in chronic thromboembolic pulmonary hypertension
Authors: Yamasaki Yuzo , Abe Kohtaro , Kamitani Takeshi , Hosokawa Kazuya , Kawakubo Masateru , Sagiyama Koji , Hida Tomoyuki , Matsuura Yuko , Murayama Yuriko , Funatsu Ryohei , Tsutsui Hiroyuki , Yabuuchi Hidetake
Published: March 2020

Aims

Right atrial (RA) function largely contributes to the maintenance of right ventricular (RV) function. This study investigated the effect of balloon pulmonary angioplasty (BPA) on RA functions in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) using cardiac magnetic resonance imaging (CMRI).

Methods and results

CMRI and RV catheterization were performed before BPA sessions and at the follow-up periods in 29 CTEPH patients. Reservoir [RA longitudinal strain (RA-LS)], passive conduit [RA early LS rate (LSR)], and active (RA late LSR) phases were assessed by using cine CMRI and a feature-tracking algorithm. The relationships between the changes in RA functions and in brain natriuretic peptide (BNP) were evaluated in both the dilated and non-dilated RA groups. RA-LS (32.4% vs. 42.7%), RA LSR (6.3% vs. 8.3%), and RA early LSR (−2.3% vs. −4.3%) were improved after BPA, whereas no significant change was seen in RA late LSR. The changes in RA peak LS and in RA early LSR were significantly correlated with the changes in BNP (ΔRA-LS: r = −0.63, ΔRA-early LSR: r = 0.65) and pulmonary vascular resistance (PVR) (ΔRA-LS: r = −0.69, ΔRA-early LSR: r = 0.66) in the nondilated RA group.

Conclusion

The RA reservoir and passive conduit functions were impaired in inoperable CTEPH, whereas RA active function was preserved. BPA markedly reversed these impaired functions. The improvements in RA reservoir and conduit functions were significantly correlated with the changes in BNP levels and PVR in CTEPH patients with normal RA sizes.
PASS versus MBT™ for evaluation of anchorage control in three-dimensional measurements: a randomized controlled trial
Authors: Chen Huizhong , Han Bing , Jiang Ruoping , Su Hong , Feng Tingting , Teng Fei , Xu Tianmin
Published: March 2020

Background

Growth and development might lead to anchorage loss during orthodontic treatment, such as the mesial drift of molars, the compensation characteristics of upper molars following mandibular growth, or the angulation of molars before treatment. Different anchorage reinforcement devices have been developed to prevent mechanical anchorage loss, but the anchorage loss resulting from physiological factors should also be taken into account.

Objective

To explore the efficacy of a new strategy to control physiologic anchorage compared with that of the conventional straight-wire appliance.

Trial design

Randomized controlled trial (RCT).

Methods

Participants of Han ethnicity were randomized into the physiologic anchorage spee-wire system (PASS) group or McLaughlin–Bennett–Trevisi (MBT™) straight-wire group by minimization random allocation. The eligibility criteria were patients with a Class I or II molar relationship, permanent dentition (11–35 years old), fixed appliances involving the extraction of at least two upper first premolars, and medium or maximum anchorage requirements. Pre-treatment and post-treatment dental casts were scanned into digital casts and measured using a blinded method. Mesial displacements of the upper first molars were considered as the primary outcome for evaluating anchorage control. Measurements were taken for subgroups based on age.

Results

Data from 60 participants were analysed. The baseline characteristics were not significantly different between groups. Mesial displacement of the upper first molar (in mm) was 2.96 ± 1.52 in the PASS group and 2.70 ± 1.66 in the MBT group (P = 0.521). The variation in incisor torque was −6.94 ± 6.35 degree in the PASS group and −11.76 ± 7.65 degree in the MBT group (P = 0. 010). The incisor retraction (in mm) was 4.24 ± 1.99 and 5.67 ± 2.27 in the PASS and MBT groups, respectively (P = 0.012). Adverse effects were not documented in any patient.

Limitation

The study was a single-centre study.

Conclusions

Compared with the MBT group, the PASS group without additional anchorage devices could attain well anchorage control by considering the dentoalveolar compensation of anchor teeth.

Registration

This RCT was registered at the Chinese Clinical Trial Registry (Chictr.org.cn) ChiCTR-TRC-13003260.
Reasons for encounter in primary health care in Brazil
Authors: Chueiri Patricia S , Gonçalves Marcelo Rodrigues , Hauser Lisiane , Wollmann Lucas , Mengue Sotero Serrate , Roman Rudi , Rodrigues Agostinho Rech Milena , Soares Marcelo de Araújo Vianna , Pertile Jamily , Harzheim Erno
Published: March 2020

Background

Primary health care (PHC) delivery in Brazil has improved in the last decades. However, it remains unknown whether the Family Health Strategy teams are meeting the health needs of the population.

Objectives

To describe the reasons for encounter (RFEs) in PHC in Brazil and to examine variations in RFEs according to sex, age and geographic region.

Methods

This descriptive study is part of a national cross-sectional study conducted in 2016. The sample was stratified by the number of PHC physicians per geographic region. Physicians who had been working for at least 1 year in the same PHC unit were included. For every participating physician, 12 patients aged ≥18 years who had attended at least two encounters were included. Patients were asked about their RFEs, which were classified according to the International Classification of Primary Care.

Results

In 6160 encounters, a total of 8046 RFEs were coded. Seven reasons accounted for 50% of all RFEs. There was a high frequency of codes related to test results, medication renewal and preventive medicine. RFEs did not vary significantly by sex or geographic region, but they did by age group (P < 0.001). The rates of prescriptions, requests for investigations and referrals to specialized care were 71.1%, 42.8%, and 21.3%, respectively.

Conclusion

This novel study opened the ‘black box’ of RFEs in PHC in Brazil. These findings can contribute to redefining the scope of PHC services and reorienting work practices in order to improve the quality of PHC in Brazil.
Detecting regime shifts in communities using estimated rates of change
Authors: Pedersen Eric J , Koen-Alonso Mariano , Tunney Tyler D
Published: March 2020

Regime shifts (periods of rapid change punctuating longer periods of lower variability) are observed in a wide range of ecosystems, and effective fisheries management requires the ability to detect these shifts. Detecting shifts is straightforward in single-species time series when transitions are detectable as periods of rapid change. However, shifts in complex and spatially structured communities may be harder to detect. We propose an approach to characterize community regime shifts, using nonparametric spatiotemporal regression models to estimate three indicators of community change (the among-species mean rate of change, mean per-capita rate of change, and standard deviation of per-capita rate of change). These indicators can detect shifts that result in either changes in abundance or composition. We applied our approach to a 37-year community biomass time series that spans the Newfoundland Shelf groundfish collapse. Our method detected a community shift earlier than alternative single-indicator breakpoint approaches and gave additional insight into the spatiotemporal pattern of the change, including detecting three separate periods of change and characterizing the first locations to show signs of recovery. The indicators applied in this study provide novel insights into Newfoundland groundfish dynamics and should be useful in the characterization of other abrupt ecological changes.
Natural mortality estimation using tree-based ensemble learning models
Authors: Liu Chanjuan , Zhou Shijie , Wang You-Gan , Hu Zhihua
Published: March 2020

Empirical studies are popular in estimating fish natural mortality rate (M). However, these empirical methods derive M from other life-history parameters and are often perceived as being less reliable than direct methods. To improve the predictive performance and reliability of empirical methods, we develop ensemble learning models, including bagging trees, random forests, and boosting trees, to predict M based on a dataset of 256 records of both Chondrichthyes and Osteichthyes. Three common life-history parameters are used as predictors: the maximum age and two growth parameters (growth coefficient and asymptotic length). In addition, taxonomic variable class is included to distinguish Chondrichthyes and Osteichthyes. Results indicate that tree-based ensemble learning models significantly improve the accuracy of M estimate, compared to the traditional statistical regression models and the basic regression tree model. Among ensemble learning models, boosting trees and random forests perform best on the training dataset, but the former performs a slightly better on the test dataset. We develop four boosting trees models for estimating M based on varying life-history parameters, and an R package is provided for interested readers to estimate M of their new species.
Understanding the Intersection of Behavioral Risk and Social Determinants of Health and the Impact on an Outbreak of Human Immunodeficiency Virus Among Persons Who Inject Drugs in Philadelphia
Authors: Kim Melissa M , Conyngham S Caitlin , Smith Champagnae , Higgins Dana , Nassau Tanner , Terrell Coleman , Brady Kathleen A
Published: March 2020

Background

In 2018, Philadelphia identified an outbreak of new human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID). Although conventional HIV surveillance systems capture individual-level behavioral risk, they are not able to capture the social and environmental factors contributing to rapid transmission.

Methods

HIV surveillance data were used to assess demographic, clinical, and behavioral factors for PWID with HIV diagnosed during 2017 and 2018. Social factors such as homelessness, disruption of encampments, and trends in sexual behaviors, drug use and syringe availability among PWID were captured through National HIV Behavioral Surveillance, routine hepatitis and sexually transmitted infection surveillance, and shelter and homeless outreach data.

Results

In 2018, there were 71 new infections among PWID, an increase of 115% since 2016. During this time, opioid overdose deaths peaked at 59 deaths per 100 000 persons, 85% of which involved the use of fentanyl. While overall reported homelessness increased, rates of those living unsheltered rose by 13%. The Philadelphia Department of Public Health identified increased injection frequency, encampment closures, and lack of syringe access as promoters of continued HIV transmission.

Conclusion

The use of conventional surveillance methods only is inadequate for determining HIV risk during outbreaks. Incorporation of individual and aggregate level data on social and environmental determinants is necessary to develop effective outbreak response interventions.
Development and validation of a generic patient experience instrument for measuring specialist outpatient service in Hong Kong
Authors: Wong Eliza Lai-Yi , Cheung Annie Wai-Ling , Xu Richard Huan , Yam Carrie Ho-Kwan , Lui Sui-Fai , Yeoh Eng-Kiong
Published: March 2020

Objective

The measurement of patients’ experience is an important performance indicator of health care service quality. A reliable and validated instrument to elicit patients’ experience is an important step. This study aimed to develop a generic instrument to elicit patients’ experience in specialist outpatient clinic provision with a rigorous and systematic methodology.

Design

The instrument framework was developed according to findings of a literature review, patient focus group discussions, individual patient in-depth interviews and expert discussion. The framework was tested for psychometric performance with a cross-sectional telephone survey in terms of practicality, validity, reliability and responsiveness.

Setting

26 Public specialist outpatient clinics in Hong Kong were selected.

Participants

Cantonese speaking patients aged 18 or above. Intervention(s): None. Main outcome measure(s): A validated generic patient experience questionnaire measuring Specialist Outpatient Service (SOPEQ).

Results

A proportional sample total of 513 patients from 26 specialist outpatient clinics were recruited, response rate of 56%. The findings indicated that the instrument is practicable and concise. A structure of nine dimensions with 47 items structure was confirmed based on exploratory factor analysis and content validity. These items showed satisfactory internal reliability consistency (α = 0.793) and test–retest reliability ranged from 0.618 to 0.829.

Conclusions

The SOPEQ was established with satisfactory psychometric properties. A valid and reliable measure to evaluate patients’ experience is an important step in providing valuable input from patients’ perspective for policy makers to improve patient-centred services. It also serves as a platform to engage patients and thereby, in improving health care quality and enhancing health outcomes.
Feasibility of de-linking reimbursement of antimicrobials from sales: the Australian perspective as a qualitative case study
Authors: Hillock Nadine T , Merlin Tracy L , Karnon Jonathan , Turnidge John , Eliott Jaklin
Published: March 2020

Background

There is a disparity in the economic return achievable for antimicrobials compared with other drugs because of the need for stewardship. This has led to a decline in pharmaceutical companies’ willingness to invest in the development of these drugs and a consequent global interest in funding models where reimbursement is de-linked from sales.

Objectives

To explore the perspective of stakeholders regarding the feasibility of de-linked reimbursement of antimicrobials in Australia.

Methods

Semi-structured interviews were conducted with 18 participants sourced from the pharmaceutical industry and individuals representing public-sector payers or regulators. Interviews were transcribed verbatim, coded and thematically analysed using the framework method.

Results

Five key themes were identified in the interviews: funding silos are a barrier to de-linking reimbursement; varying levels of supporting evidence are (currently) required for funding depending upon setting; funding status or cost is used as a stewardship tool; a de-linked model may cost more; and concerns regarding governance and access to antimicrobials exist in the private sector.

Conclusions

Australia’s current multi-tiered funding of medicines across different levels of government was perceived as a barrier to de-linked reimbursement. Participants felt that the responsibility for antimicrobial funding and stewardship should be integrated and centralized. Implementing a nationally funded de-linked reimbursement model for new antimicrobials would require a review of funding decision-making criteria, given that most MDR infections are off-label indications and could not then be funded through the Australian Pharmaceutical Benefits Scheme. Findings from this study could be applicable to other countries with reimbursement frameworks similar to Australia.
Nazi Crimes Before West German Courts
Authors: Richter Ida
Published: March 2020

Fritz Bauer was one of the main figures of post-war West Germany who fought to bring Nazi perpetrators to trial before German courts at a time when the prevailing general climate and mentality was one of impunity and a need to make a ‘clean break’. This article investigates whether Bauer’s ideas can be set in relation to today’s notions of international criminal justice. Looking for this connection seems an obvious and necessary endeavour, since Bauer’s work focused on prosecuting Nazi crimes, which were dealt with initially by the International Military Tribunal of Nuremberg, the first international criminal tribunal in history. However, this connection has rarely been studied. By taking the example of Bauer’s views on criminal responsibility of the staff at Auschwitz, expressed in relation to the first Frankfurt Auschwitz trial (1963-1965), this article demonstrates that his ideas stood out from common legal opinions in West Germany at the time. It also shows elements in his thinking corresponding to the concept of joint criminal enterprise in today’s international criminal law. The article will also argue that although Bauer’s far-reaching understanding of criminal liability made its way into legal practice only to a limited extent, this must be seen within the historical context of West German jurisprudence concerning Nazi crimes in the 1960s, the period in which Bauer worked.
Synovial Sarcoma: A Series of Small Tumors in Active Duty Service Members
Authors: Bates Taylor , Kao Erica , Alderete Joseph , Lybeck Dustin
Published: March 2020

Synovial Sarcoma is a soft tissue sarcoma with a propensity to imitate a benign neoplasm. It is most common in males 15–40 years old, typically presents as a slow growing painful mass, and often arises insidiously without alarm to the patient. Three patients with synovial sarcomas who had each undergone an index procedure to treat a small presumedly benign mass that was later identified as synovial sarcoma were reviewed. All three patients required re-excision of the tumor and tumor bed and are currently undergoing routine surveillance. All patients exhibited the classic translocation t(X;18) (p11.2; q11.2) and all were of the monophasic type. All lesions were less than 35 mm in greatest longitudinal dimension on MRI. None have experienced recurrences of synovial sarcoma to date. Healthcare providers should be aware of the synovial sarcoma’s propensity to masquerade as a benign disease and the characteristic clinical and radiological findings. We advocate for a low threshold to obtain advanced imaging and consideration of a tissue diagnosis prior to excision. A referral to an orthopedic oncologist should be considered and biopsy should only be performed where the definitive treatment will take place if malignancy is identified.
Anisotropic infall in the outskirts of OmegaWINGS galaxy clusters
Authors: Salerno Juan Manuel , Martínez Héctor J , Muriel Hernán , Coenda Valeria , Vulcani Benedetta , Poggianti Bianca , Moretti Alessia , Gullieuszik Marco , Fritz Jacopo , Bettoni Daniela
Published: March 2020

We study the effects of the environment on galaxy quenching in the outskirts of clusters at 0.04 < z < 0.08. We use a subsample of 14 WINGS and OmegaWINGS clusters that are linked to other groups/clusters by filaments and study separately galaxies located in two regions in the outskirts of these clusters according to whether they are located towards the filaments’ directions or not. We also use samples of galaxies in clusters and field as a comparison. Filamentary structures linking galaxy groups/clusters were identified over the Six Degree Field Galaxy Redshift Survey Data Release 3. We find a fraction of passive galaxies in the outskirts of clusters intermediate between that of the clusters and the field’s. We find evidence of a more effective quenching in the direction of the filaments. We also analyse the abundance of post-starburst (PS) galaxies in the outskirts of clusters focusing our study on two extreme sets of galaxies according to their phase-space position: backsplash and true infallers. We find that up to $\sim 70{{\ \rm per\ cent}}$ of PS galaxies in the direction of filaments are likely backsplash, while this number drops to $\sim 40{{\ \rm per\ cent}}$ in the isotropic infall region. The presence of this small fraction of galaxies in filaments that are falling into clusters for the first time and have been recently quenched, supports a scenario in which a significant number of filament galaxies have been quenched long time ago.
Proactively Offered Text Messages and Mailed Nicotine Replacement Therapy for Smokers in Primary Care Practices: A Pilot Randomized Trial
Authors: Kruse Gina R , Park Elyse R , Chang Yuchiao , Haberer Jessica E , Abroms Lorien C , Shahid Naysha N , Howard Sydney , Haas Jennifer S , Rigotti Nancy A
Published: March 2020

Introduction

Proactive, population health cessation programs can guide efforts to reach smokers outside of the clinic to encourage quit attempts and treatment use.

Aims and Methods

This study aimed to measure trial feasibility and preliminary effects of a proactive intervention offering text messages (TM) and/or mailed nicotine replacement therapy (NRT) to smokers in primary care clinics. From 2017 to 2019 we performed a pilot randomized trial comparing brief telephone advice (control: BA), TM, 2 weeks of mailed NRT, or both interventions (TM + NRT). Patients were identified using electronic health records and contacted proactively by telephone to assess interest in the study. We compared quit attempts, treatment use, and cessation in the intervention arms with BA.

Results

Of 986 patients contacted, 153 (16%) enrolled (mean age 53 years, 57% female, 76% white, 11% black, 8% Hispanic, 52% insured by Medicaid) and 144 (94%) completed the 12-week assessment. On average, patients in the TM arms received 159 messages (99.4% sent, 0.6% failed), sent 19 messages, and stayed in the program for 61 days. In all groups, a majority of patients reported quit attempts (BA 67% vs. TM 86% [p = .07], NRT 81% [p = .18], TM + NRT 79% [p = .21]) and NRT use (BA 51% vs. NRT 83% [p = .007], TM 65% [p = .25], TM + NRT 76% [p = .03]). Effect estimates for reported 7-day abstinence were BA 10% versus TM 26% (p = .09), NRT 28% (p = .06), and TM + NRT 23% (p = .14).

Conclusions

Proactively offering TM or mailed nicotine medications was feasible among primary care smokers and a promising approach to promote quit attempts and short-term abstinence.

Implications

Proactive intervention programs to promote quit attempts outside of office visits among smokers enrolled in primary care practices are needed. TM have potential to engage smokers not planning to quit or to support smokers to make a planned quit attempt. This pilot study demonstrates the feasibility of testing a proactive treatment model including TM and/or mailed NRT to promote quit attempts, treatment use, and cessation among nontreatment-seeking smokers in primary care.

ClinicalTrials.gov Identifier

NCT03174158.
Predictors of Smoking Cessation Attempts and Success Following Motivation-Phase Interventions Among People Initially Unwilling to Quit Smoking
Authors: Klemperer Elias M , Mermelstein Robin , Baker Timothy B , Hughes John R , Fiore Michael C , Piper Megan E , Schlam Tanya R , Jorenby Douglas E , Collins Linda M , Cook Jessica W
Published: March 2020

Introduction

Most people who smoke cigarettes are not willing (ie, not ready) to make a quit attempt (QA) at any given time. Unfortunately, interventions intended to increase QAs and the success of QAs are only modestly effective. Identifying processes leading to QAs and quitting success could guide intervention development.

Aims and Methods

This is a secondary analysis of a randomized factorial trial of 6 weeks of motivation-phase interventions among primary care patients (N = 517) who were initially unwilling to quit but were willing to reduce their smoking. Using logistic regression, we controlled for treatment condition and tested whether baseline or change in smoking-related constructs after 6 weeks of treatment predicted (1) making an at least 24 h QA between weeks 6 and 26 and (2) quitting success at week 26 (7-day point-prevalence abstinence among those who made a QA). Predictors included cigarettes/day, time to first cigarette, motivation to quit, quitting self-efficacy, anticipated urges to smoke if quit, positive affect, negative affect, and time spent around others who smoke.

Results

In multivariable models that included all smoking-related constructs, changes in the following variables predicted initiating a QA above and beyond other variables: greater baseline time to first cigarette (odds ratio [OR] = 1.60), increases in time to first cigarette (OR = 1.27), and increases in quitting self-efficacy (OR = 1.14). Increased motivation to quit predicted conversion of a QA into quitting success at 26 weeks (OR = 1.36).

Conclusion

Predictors of making a QA differed from predictors of quitting success. Predictors of QAs and success could each serve as important treatment targets of motivation-phase interventions.

Implications

Motivation-phase interventions for people initially unwilling to quit smoking cigarettes may be improved by striving to increase their (1) time to first cigarette and quitting self-efficacy to promote QAs and (2) motivation to quit to promote quit success. Future experimental tests of such interventions are needed to identify causal determinants of QAs and quitting success.
Intersectionality and Smoking Cessation: Exploring Various Approaches for Understanding Health Inequities
Authors: Potter Lindsey N , Lam Cho Y , Cinciripini Paul M , Wetter David W
Published: March 2020

Objective

Many marginalized groups smoke at higher rates and have greater difficulty quitting than less marginalized groups. Most research on smoking cessation inequities has focused on a single sociodemographic attribute (eg, race or socioeconomic status), yet individuals possess multiple attributes that may increase risk. The current study used an intersectionality framework to examine how the interplay between multiple marginalized attributes may impact smoking cessation outcomes.

Methods

A diverse sample of 344 adults enrolled in a smoking cessation program and reported on sociodemographic attributes (eg, race/ethnicity, gender, income) and continuous smoking abstinence on their quit date and at 1, 2, and 4 weeks postquit date. A Cox proportional hazard regression model was used to estimate whether intersectional links among race/ethnicity, gender, and income were related to smoking cessation outcomes.

Results

Lower household income may be related to higher risk of smoking cessation failure. There were no significant interactions among race/ethnicity, gender, and income in predicting relapse. Pairwise intersectional group differences suggested some groups may be at higher risk of relapse. Number of marginalized sociodemographic attributes did not predict relapse.

Conclusions

Intersectionality may be a promising framework for addressing health inequities, and may help elucidate how to best design and target intervention efforts for individuals characterized by sociodemographic intersections that concur particularly high risk for poor tobacco cessation outcomes.

Implications

Despite an overall decline in smoking rates, socioeconomic inequities in smoking prevalence and cancer mortality are widening. Efforts targeting tobacco cessation should incorporate new theory to capture the complex set of factors that may account for tobacco cessation inequities (eg, multiple aspects of identity that may influence access to tobacco cessation treatment and exposure to certain stressors that impede cessation efforts). Intersectionality may be a promising framework for addressing health inequities in tobacco use and cessation and may help elucidate how to best design and target intervention efforts for individuals that concur particularly high risk for poor tobacco cessation outcomes.
Secondhand Smoking and Obesity Among Nonsmoking Adolescents Aged 12–15 Years From 38 Low- and Middle-Income Countries
Authors: Koyanagi Ai , Smith Lee , Oh Hans , Yang Lin , Jackson Sarah E , Haro Josep Maria , Shin Jae I I , Carvalho Andre F , Jacob Louis
Published: March 2020

Introduction

Secondhand smoking (SHS) may be a risk factor for obesity in adolescence, but data on the association between SHS and obesity are scarce, especially from low- and middle-income countries (LMICs). Therefore, the aim of this study was to assess the association between SHS and obesity among adolescents aged 12–15 years from 38 LMICs.

Methods

Cross-sectional data from 38 LMICs that participated in the Global School-based Student Health Survey (GSHS) were analyzed. Body mass index was calculated based on measured weight and height. The 2007 WHO Child Growth reference was used to define obesity. SHS was categorized as no exposure, non-daily exposure (ie, 1–6 days), and daily exposure (ie, 7 days) based on the number of days exposed to secondhand smoke in the past 7 days. Multivariable logistic regression and meta-analyses were conducted to assess the associations.

Results

The analyzed sample consisted of 88 209 adolescents aged 12–15 years who never smoked. The overall prevalence of non-daily and daily SHS was 34.2% and 15.7%, respectively. After adjustment for potential confounders, compared with no SHS, there was no significant association between non-daily SHS and obesity (odds ratio [OR] = 0.94; 95% confidence interval [CI] = 0.86–1.02), but adolescents who reported daily SHS were significantly more likely to have obesity (OR = 1.19; 95% CI = 1.06–1.34).

Conclusions

The prevalence of SHS was high among adolescents in LMICs, and daily SHS was associated with a significant increase in odds of obesity. Future studies with longitudinal designs are warranted to assess causality and whether prevention of SHS can reduce the risk of obesity in adolescence.

Implications

In the present large multi-country study on adolescents aged 12–15 years from LMICs, nearly half of the students were exposed to non-daily or daily secondhand smoke. Overall, while non-daily SHS was not significantly associated with obesity, adolescents who reported daily SHS had a significant 1.19 (95% CI = 1.06–1.34) times higher odds of obesity than those who reported no exposure to secondhand smoke. To the best of our knowledge, this is the first multi-country study on SHS and obesity from LMICs, and also the largest study on this topic to date.
Socially Constructed Determinants of Health: The Case for Synergies to Arrive at Gendered Global Health Law
Authors: Hawkes Sarah , Buse Kent
Published: March 2020

Both gender and the law are significant determinants of health and well-being. Here, we put forward evidence to unpack the relationship between gender and outcomes in health and well-being, and explore how legal determinants interact and intersect with gender norms to amplify or reduce health inequities across populations. The paper explores the similarities between legal and health systems in their response to gender—both systems portray gender neutrality but would be better described as gender-blind. We conclude with a set of recommendations to address both law and gender in implementing the work of the Lancet Commission on the legal determinants of health to improve health outcomes for all, irrespective of gender.
Effective Versions of Two Theorems of RADO
Authors: Bell Jason , Funk Daryl , Du Kim Byoung , Mayhew Dillon
Published: March 2020

Let $M$ be a representable matroid on $n$ elements. We give bounds, in terms of $n$, on the least positive characteristic and smallest field over which $M$ is representable.