bluuebunny/crossref_metadata_2025 huggingface dataset:
Family History–Wide Association Study to Identify Clinical and Environmental Risk Factors for Common Chronic Diseases
Authors: Rasooly Danielle , Ioannidis John P A , Khoury Muin J , Patel Chirag J
Published: May 2019

Family history is a strong risk factor for many common chronic diseases and summarizes shared environmental and genetic risk, but how this increased risk is mediated is unknown. We developed a “family history–wide association study” (FamWAS) to systematically and comprehensively test clinical and environmental quantitative traits (CEQTs) for their association with family history of disease. We implemented our method on 457 CEQTs for association with family history of diabetes, asthma, and coronary heart disease (CHD) in 42,940 adults spanning 8 waves of the 1999–2014 US National Health and Nutrition Examination Survey. We conducted pooled analyses of the 8 survey waves and analyzed trait associations using survey-weighted logistic regression. We identified 172 (37.6% of total), 32 (7.0%), and 78 (17.1%) CEQTs associated with family history of diabetes, asthma, and CHD, respectively, in subcohorts of individuals without the respective disease. Twenty associated CEQTs were shared across family history of diabetes, asthma, and CHD, far more than expected by chance. FamWAS can examine traits not previously studied in association with family history and uncover trait overlap, highlighting a putative shared mechanism by which family history influences disease risk.
Gene set enrichment for reproducible science: comparison of CERNO and eight other algorithms
Authors: Zyla Joanna , Marczyk Michal , Domaszewska Teresa , Kaufmann Stefan H E , Polanska Joanna , Weiner January
Published: May 2019

Motivation

Analysis of gene set (GS) enrichment is an essential part of functional omics studies. Here, we complement the established evaluation metrics of GS enrichment algorithms with a novel approach to assess the practical reproducibility of scientific results obtained from GS enrichment tests when applied to related data from different studies.

Results

We evaluated eight established and one novel algorithm for reproducibility, sensitivity, prioritization, false positive rate and computational time. In addition to eight established algorithms, we also included Coincident Extreme Ranks in Numerical Observations (CERNO), a flexible and fast algorithm based on modified Fisher P-value integration. Using real-world datasets, we demonstrate that CERNO is robust to ranking metrics, as well as sample and GS size. CERNO had the highest reproducibility while remaining sensitive, specific and fast. In the overall ranking Pathway Analysis with Down-weighting of Overlapping Genes, CERNO and over-representation analysis performed best, while CERNO and GeneSetTest scored high in terms of reproducibility.

Availability and implementation

tmod package implementing the CERNO algorithm is available from CRAN (cran.r-project.org/web/packages/tmod/index.html) and an online implementation can be found at http://tmod.online/. The datasets analyzed in this study are widely available in the KEGGdzPathwaysGEO, KEGGandMetacoreDzPathwaysGEO R package and GEO repository.

Supplementary information

Supplementary data are available at Bioinformatics online.
A dynamic programing approach to integrate gene expression data and network information for pathway model generation
Authors: Jiang Yuexu , Liang Yanchun , Wang Duolin , Xu Dong , Joshi Trupti
Published: May 2019

Motivation

As large amounts of biological data continue to be rapidly generated, a major focus of bioinformatics research has been aimed toward integrating these data to identify active pathways or modules under certain experimental conditions or phenotypes. Although biologically significant modules can often be detected globally by many existing methods, it is often hard to interpret or make use of the results toward pathway model generation and testing.

Results

To address this gap, we have developed the IMPRes algorithm, a new step-wise active pathway detection method using a dynamic programing approach. IMPRes takes advantage of the existing pathway interaction knowledge in Kyoto Encyclopedia of Genes and Genomes. Omics data are then used to assign penalties to genes, interactions and pathways. Finally, starting from one or multiple seed genes, a shortest path algorithm is applied to detect downstream pathways that best explain the gene expression data. Since dynamic programing enables the detection one step at a time, it is easy for researchers to trace the pathways, which may lead to more accurate drug design and more effective treatment strategies. The evaluation experiments conducted on three yeast datasets have shown that IMPRes can achieve competitive or better performance than other state-of-the-art methods. Furthermore, a case study on human lung cancer dataset was performed and we provided several insights on genes and mechanisms involved in lung cancer, which had not been discovered before.

Availability and implementation

IMPRes visualization tool is available via web server at http://digbio.missouri.edu/impres.

Supplementary information

Supplementary data are available at Bioinformatics online.
Enhanced Bottom-Up and Reduced Top-Down fMRI Activity Is Related to Long-Lasting Nonreinforced Behavioral Change
Authors: Botvinik-Nezer Rotem , Salomon Tom , Schonberg Tom
Published: May 2019

Behavioral change studies and interventions focus on self-control and external reinforcements to influence preferences. Cue-approach training (CAT) has been shown to induce preference changes lasting months by merely associating items with neutral cues and speeded responses. We utilized this paradigm to study neural representation of preferences and their modification without external reinforcements. We scanned 36 participants with fMRI during a novel passive viewing task before, after and 30 days following CAT. We preregistered the predictions that activity in memory, top-down attention, and value-processing regions will underlie preference modification. While most theories associate preferences with prefrontal regions, we found that “bottom-up” perceptual mechanisms were associated with immediate change, whereas reduced “top-down” parietal activity was related to long-term change. Activity in value-related prefrontal regions was enhanced immediately after CAT for trained items and 1 month after for all items. Our findings suggest a novel neural mechanism of preference representation and modification. We suggest that nonreinforced change of preferences occurs initially in perceptual representation of items, putatively leading to long-term changes in “top-down” processes. These findings offer implementation of bottom-up instead of top-down targeted interventions for long-lasting behavioral change.
The Emperor’s New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE)
Authors: Lodise Thomas P , Rosenkranz Susan L , Finnemeyer Matthew , Evans Scott , Sims Matthew , Zervos Marcus J , Creech C Buddy , Patel Pratish C , Keefer Michael , Riska Paul , Silveira Fernanda P , Scheetz Marc , Wunderink Richard G , Rodriguez Martin , Schrank John , Bleasdale Susan C , Schultz Sara , Barron Michelle , Stapleton Ann , Wray Dannah , Chambers Henry , Fowler Vance G , Holland Thomas L
Published: May 2019

Background

Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.

Methods

This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320.

Results

Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI).

Conclusions

Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.
Community-acquired Invasive Bacterial Disease in Urban Gambia, 2005–2015: A Hospital-based Surveillance
Authors: Darboe Saffiatou , Okomo Uduak , Muhammad Abdul-Khalie , Ceesay Buntung , Jallow Mamadou , Usuf Effua , Tweed Sam , Akpalu Edem , Kwambana-Adams Brenda , Kariuki Samuel , Antonio Martin , Bradbury Richard S , Forrest Karen , de Silva Thushan I , Lawal Bolarinde Joseph , Nwakanma Davis , Secka Ousman , Roca Anna
Published: May 2019

Background. Invasive bacterial diseases cause significant disease and death in sub-Saharan Africa. Several are vaccine preventable, although the impact of new vaccines and vaccine policies on disease patterns in these communities is poorly understood owing to limited surveillance data.

Methods. We conducted a hospital-based surveillance of invasive bacterial diseases in The Gambia where blood and cerebrospinal fluid (CSF) samples of hospitalized participants were processed. Three surveillance periods were defined in relation to the introduction of pneumococcal conjugate vaccines (PCVs), before (2005- 2009), during (2010–2011) and after (2012–2015) PCV introduction. We determined the prevalences of commonly isolated bacteria and compared them between the different surveillance periods.

Results. A total of 14 715 blood and 1103 CSF samples were collected over 11 years; overall, 1045 clinically significant organisms were isolated from 957 patients (972 organisms [6.6%] from blood and 73 [6.6%] from CSF). The most common blood culture isolates were Streptococcus pneumoniae (24.9%), Staphylococcus aureus (22.0%), Escherichia coli (10.9%), and nontyphoidal Salmonella (10.0%). Between the pre-PCV and post-PCV eras, the prevalence of S. pneumoniae bacteremia dropped across all age groups (from 32.4% to 16.5%; odds ratio, 0.41; 95% confidence interval, .29–.58) while S. aureus increased in prevalence, becoming the most prevalent bacteria (from 16.9% to 27.2%; 1.75; 1.26–2.44). Overall, S. pneumoniae (53.4%), Neisseria meningitidis (13.7%), and Haemophilus influenzae (12.3%) were the predominant isolates from CSF. Antimicrobial resistance to common antibiotics was low.

Conclusions. Our findings demonstrate that surveillance data on the predominant pathogens associated with invasive disease is necessary to inform vaccine priorities and appropriate management of patients.
The Costs of Economic Nationalism: Evidence from the Brexit Experiment*
Authors: Born Benjamin , Müller Gernot J , Schularick Moritz , Sedláček Petr
Published: May 2019

Economic nationalism is on the rise, but at what cost? We study this question using the unexpected outcome of the Brexit referendum vote as a natural macroeconomic experiment. Employing synthetic control methods, we first show that the Brexit vote has caused a UK output loss of 1.7% to 2.5% by year-end 2018. An expectations-augmented VAR suggests that these costs are, to a large extent, driven by a downward revision of growth expectations in response to the vote. Linking quasi-experimental identification to structural time-series estimation allows us not only to quantify the aggregate costs but also to understand the channels through which expected economic disintegration impacts the macroeconomy.
Medication-taking after stroke: a qualitative meta-synthesis of the perspectives of stroke survivors, informal carers and health professionals
Authors: Gibson Josephine M E , Miller Colette , Coupe Jacqueline , Jones Stephanie P
Published: May 2019

Background

Lifelong secondary prevention medication is recommended after stroke or transient ischaemic attack. However, poor medication adherence and persistence, which lead to suboptimal health outcomes, are common, but the reasons for this are not well understood, mainly because there have been few studies reporting adherence barriers in stroke survivors.

Objective

The aim of this review was to undertake a meta-synthesis of qualitative studies of medication-taking after stroke. Outcomes of interest were: lived experiences, views and beliefs, and strategies and solutions used by community-dwelling stroke and transient ischaemic attack survivors, informal carers and health care professionals in relation to medication-taking.

Method

The review protocol was registered on PROSPERO (CRD42018086792). A search of online bibliographic databases was performed using key search terms of stroke, persistence, adherence and medication for years 1980–2018. Citation tracking was also carried out. Studies using qualitative or mixed methods were included. Systematic data extraction and synthesis were conducted using a meta-ethnographic approach.

Results

Twelve studies were eligible for inclusion, with a total of 412 participants, two-thirds of whom were stroke survivors, ranging from 1 month to over 20 years post-stroke. Third-order themes identified were ‘Medicines Work’—Information Work; Health Care Work; Carer Work; Emotional Work; Practical Work and an underpinning theme of Trust. However, many studies had significant methodological weaknesses.

Conclusions

This synthesis suggests that the burden of ‘medicines work’ after stroke is substantial and multifaceted. Its successful undertaking depends on mutual trust between stroke survivors, carers and health care professionals and trust in the benefits of medicines themselves.
Introduction
Authors: Berger Stefan
Published: May 2019

This article introduces the Special Issue and contextualizes it within recent developments in the field of German labour history.
An Ecologist’s Guide to Mitochondrial DNA Mutations and Senescence
Authors: Hood Wendy R , Williams Ashley S , Hill Geoffrey E
Published: May 2019

Longevity plays a key role in the fitness of organisms, so understanding the processes that underlie variance in senescence has long been a focus of ecologists and evolutionary biologists. For decades, the performance and ultimate decline of mitochondria have been implicated in the demise of somatic tissue, but exactly why mitochondrial function declines as individual’s age has remained elusive. A possible source of decline that has been of intense debate is mutations to the mitochondrial DNA. There are two primary sources of such mutations: oxidative damage, which is widely discussed by ecologists interested in aging, and mitochondrial replication error, which is less familiar to most ecologists. The goal of this review is to introduce ecologists and evolutionary biologists to the concept of mitochondrial replication error and to review the current status of research on the relative importance of replication error in senescence. We conclude by detailing some of the gaps in our knowledge that currently make it difficult to deduce the relative importance of replication error in wild populations and encourage organismal biologists to consider this variable both when interpreting their results and as viable measure to include in their studies.
Genes coding for LysM domains in the dermatophyte Trichophyton rubrum: A transcription analysis
Authors: Lopes Lúcia , Bitencourt Tamires A , Lang Elza A S , Sanches Pablo R , Peres Nalu T A , Rossi Antonio , Martinez-Rossi Nilce M
Published: May 2019

The filamentous fungus Trichophyton rubrum is a pathogen that causes superficial mycoses in humans, predominantly in keratinized tissues. The occurrence of dermatophytoses has increased in the last decades, mainly in immunocompromised patients, warranting research on the mechanisms involved in dermatophyte virulence. The genomes of dermatophytes are known to be enriched in genes coding for proteins containing the LysM domain, a carbohydrate-binding module, indicating the possible involvement of these genes in virulence. Although the LysM domains have already been described in other fungi, their biological functions in dermatophytes are unknown. Here we assessed the transcription of genes encoding proteins containing the LysM domains in T. rubrum grown on different substrates using quantitative real-time polymerase chain reaction. Some of these genes showed changes in transcription levels when T. rubrum was grown on keratin. In silico analyses suggest that some of these proteins share features, namely, they are anchored in the plasma membrane and contain the catalytic domain chitinase II and signal peptide domains. Here we show a detailed study of genes encoding the proteins with LysM-containing domains in T. rubrum, aiming to contribute to the understanding of their functions in dermatophytes.
Weak lensing measurements of the APEX-SZ galaxy cluster sample
Authors: Klein Matthias , Israel Holger , Nagarajan Aarti , Bertoldi Frank , Pacaud Florian , Lee Adrian T , Sommer Martin , Basu Kaustuv
Published: May 2019

We present a weak lensing analysis for galaxy clusters from the APEX-SZ survey. For 39 massive galaxy clusters that were observed via the Sunyaev–Zel’dovich effect (SZE) with the APEX telescope, we analyse deep optical imaging data from WFI(@2.2mMPG/ESO) and Suprime-Cam(@SUBARU) in three bands. The masses obtained in this study, including an X-ray selected sub-sample of 27 clusters, are optimized for and used in studies constraining the mass to observable scaling relations at fixed cosmology. A novel focus of our weak lensing analysis is the multicolour background selection to suppress effects of cosmic variance on the redshift distribution of source galaxies. We investigate the effects of cluster member contamination through galaxy density, shear profile, and recovered concentrations. We quantify the impact of variance in source redshift distribution on the mass estimate by studying nine sub-fields of the COSMOS survey for different cluster redshift and magnitude limits. We measure a standard deviation of ∼6 per cent on the mean angular diameter distance ratio for a cluster at z = 0.45 and shallow imaging data of R ≈ 23 mag. It falls to ∼1 per cent for deep, R = 26 mag, observations. This corresponds to 8.4 per cent and 1.4 per cent scatter in M200. Our background selection reduces this scatter by 20−40 per cent, depending on cluster redshift and imaging depth. We derived cluster masses with and without using a mass concentration relation and find consistent results, and concentrations consistent with the used mass–concentration relation.
Inelastic processes in oxygen–hydrogen collisions
Authors: Belyaev A K , Voronov Ya V , Mitrushchenkov A , Guitou M , Feautrier N
Published: May 2019

New accurate theoretical rate coefficients for (de)-excitation and charge transfer in low-energy O + H, O+ + H− and O− + H+ collisions are reported. The calculations of cross-sections and rate coefficients are performed by means of the quantum probability current method, using full configuration interaction ab initio electronic structure calculations that provide a global description of all 43 lowest molecular states from short to asymptotic internuclear distances. Thus, both long- and short-range non-adiabatic regions are taken into account for the first time. All the doublet, quartet and sextet OH molecular states, with excitation energy asymptotes up to 12.07 eV, as well as the two lowest ionic states with the asymptotes O−H+ and O+H− are treated. Calculations are performed for the collision energy range 0.01–100eV and the temperature range 1 000–10 000 K. The mechanisms underlying the processes are analysed: it is shown that the largest rate coefficients, with values exceeding 10−8 cm3 s−1, are due to ionic–covalent interactions present at large internuclear distances, while short-range interactions play an important role for rates with moderate values involved in (de)-excitation processes. As a consequence, a comparison of the present data with previously published results shows that differences of up to several orders of magnitude exist for rate coefficients with moderate values. It is worth pointing out the relatively large rate coefficients for triplet–quintuplet oxygen transitions, as well as for transitions between the O$(\rm 2p^{3}3s\, ^{5}$So) and O$(\rm 2p^{3}3p\, ^{5}$P) levels of the oxygen triplet and H(n = 2) levels. The calculated data are important for modelling stellar spectra, leading to accurate oxygen abundances.
Dark Energy Survey Year 1 results: measurement of the galaxy angular power spectrum
Authors: Camacho H , Kokron N , Andrade-Oliveira F , Rosenfeld R , Lima M , Lacasa F , Sobreira F , da Costa L N , Avila S , Chan K C , Crocce M , Ross A J , Troja A , García-Bellido J , Abbott T M C , Abdalla F B , Allam S , Annis J , Bernstein R A , Bertin E , Bridle S L , Brooks D , Buckley-Geer E , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Cawthon R , Cunha C E , D’Andrea C B , De Vicente J , Desai S , Diehl H T , Doel P , Estrada J , Evrard A E , Flaugher B , Fosalba P , Frieman J , Gerdes D W , Giannantonio T , Gruendl R A , Gschwend J , Gutierrez G , Hollowood D L , Honscheid K , Hoyle B , James D J , Johnson M W G , Johnson M D , Kent S , Kirk D , Krause E , Kuehn K , Kuropatkin N , Lin H , Marshall J L , Miquel R , Percival W J , Plazas A A , Romer A K , Roodman A , Sanchez E , Schubnell M , Sevilla-Noarbe I , Smith M , Smith R C , Soares-Santos M , Suchyta E , Swanson M E C , Tarle G , Thomas D , Tucker D L , Walker A R , Zuntz J ,   (DES Collaboration)
Published: May 2019

We use data from the first-year observations of the DES collaboration to measure the galaxy angular power spectrum (APS), and search for its BAO feature. We test our methodology in a sample of 1800 DES Y1-like mock catalogues. We use the pseudo-Cℓ method to estimate the APS and the mock catalogues to estimate its covariance matrix. We use templates to model the measured spectra and estimate template parameters firstly from the Cℓ’s of the mocks using two different methods, a maximum likelihood estimator and a Markov Chain Monte Carlo, finding consistent results with a good reduced χ2. Robustness tests are performed to estimate the impact of different choices of settings used in our analysis. Finally, we apply our method to a galaxy sample constructed from DES Y1 data specifically for LSS studies. This catalogue comprises galaxies within an effective area of 1318 deg2 and 0.6 < z < 1.0. We find that the DES Y1 data favour a model with BAO at the $2.6 \sigma$ C.L. However, the goodness of fit is somewhat poor, with χ2/(d.o.f.)  = 1.49. We identify a possible cause showing that using a theoretical covariance matrix obtained from Cℓ’s that are better adjusted to data results in an improved value of χ2/(dof)  = 1.36 which is similar to the value obtained with the real-space analysis. Our results correspond to a distance measurement of DA(zeff = 0.81)/rd = 10.65 ± 0.49, consistent with the main DES BAO findings. This is a companion paper to the main DES BAO article showing the details of the harmonic space analysis.
Proprotein convertase subtilisin/kexin type 9 in kidney disease
Authors: Schmit David , Fliser Danilo , Speer Thimoteus
Published: May 2019

Chronic kidney disease (CKD) is associated with a substantially increased risk for the development of atherosclerotic cardiovascular (CV) disease. Accordingly, CV mortality is increased even in the earliest stages of CKD. In the general population and in CKD patients, high plasma levels of low-density lipoprotein cholesterol (LDL-C) are crucially involved in the initiation and progression of atherosclerotic vascular lesions. Lowering LDL-C by use of statins and/or ezetimibe represents the gold standard of lipid-lowering therapy, with a great body of evidence from several large clinical trials. Statin therapy reduces CV events in patients with normal and impaired kidney function alike, while the evidence for patients on maintenance haemodialysis is weaker. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease represents a novel lipid-lowering tool. Currently the monoclonal antibodies evolocumab and alirocumab are the approved PCSK9 inhibitors. Despite maximum-tolerated statin therapy, they efficiently further reduce LDL-C plasma levels without any major adverse effects. Moreover, in large clinical outcome trials, both antibodies have been proven to lower CV events. Notably, the LDL-lowering capacity was independent of baseline kidney function and also efficient in patients with moderate CKD. However, patients with severely impaired kidney function, that is, the population at the highest CV risk, have been excluded from those trials. The relevance of the LDL-independent effects of PCSK9 inhibitors, such as lowering lipoprotein(a) or ameliorating dyslipidaemia in patients with nephrotic syndrome, has to be determined. Therefore further specific studies assessing the effects and outcomes of PCSK9-inhibiting treatment in CKD patients are warranted.
Pneumococcal Carriage, Serotype Distribution, and Risk Factors in Children With Community-Acquired Pneumonia, 5 Years After Introduction of the 10-Valent Pneumococcal Conjugate Vaccine in Ethiopia
Authors: Negash Abel Abera , Asrat Daniel , Abebe Workeabeba , Hailemariam Tewodros , Gebre Meseret , Verhaegen Jan , Aseffa Abraham , Vaneechoutte Mario
Published: May 2019

Background

There is a scarcity of data on pneumococcal serotypes carried by children in Ethiopia. We studied pneumococcal nasopharyngeal carriage rate, serotypes, and risk factors among children with community acquired pneumonia (CAP).

Methods

A prospective observational cohort study was performed in children with CAP, aged 0–15 years, in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Nasopharyngeal swabs were cultured, and serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. Risk factors were analyzed by using binary logistic regression.

Results

Nasopharyngeal swabs were collected from 362 children with CAP. Pneumococcal carriage rate was 21.5% (78 of 362). The most common serotypes were 19A (27%), 16F (8.5%), and 6A (4.9%). In addition, 8.5% of the pneumococcal isolates were nontypeable. In bivariate analysis, children with a parent that smokes were more likely to carry pneumococci (crude odds ratio, 3.9; 95% confidence interval [CI], 1.2–12.3; P = .023) than those with parents that do not smoke. In multivariable analysis, living in a house with ≥2 rooms (adjusted odds ratio [AOR], 0.48; 95% CI, 0.28–0.82; P = .007) and vaccination with ≥2 doses of 10-valent pneumococcal conjugate vaccine (PCV10) (AOR, 0.37; 95% CI, 0.15–0.92; P = .033) were protective of pneumococcal carriage.

Conclusions

Five years after introduction of PCV10 in Ethiopia, the vaccine-related serotype 19A was predominant in the nasopharynx of children with CAP. Continued evaluation of the direct and indirect impact of PCV10 on pneumococcal serotype distribution in Ethiopia is warranted.
Optimal Duration of Follow-up for Assessing Antimalarial Efficacy in Pregnancy: A Retrospective Analysis of a Cohort Followed Up Until Delivery on the Thailand–Myanmar Border
Authors: Saito Makoto , Mansoor Rashid , Wiladphaingern Jacher , Paw Moo Kho , Pimanpanarak Mupawjay , Proux Stephane , Guérin Philippe J , White Nicholas J , Nosten François , McGready Rose
Published: May 2019

Background

Follow-up for 28–42 days is recommended by the World Health Organization to assess antimalarial drug efficacy for nonpregnant populations. This study aimed to determine the optimal duration for pregnant women, as no specific guidance currently exists.

Methods

The distributions of time to recrudescence (treatment failure), confirmed by polymerase chain reaction genotyping for different antimalarial drugs in pregnancy, were analyzed by accelerated failure time models using secondary data on microscopically confirmed recurrent falciparum malaria collected in prospective studies on the Thailand–Myanmar border between 1994 and 2010.

Results

Of 946 paired isolates from 703 women, the median duration of follow-up for each genotyped recurrence (interquartile range) was 129 (83–174) days, with 429 polymerase chain reaction–confirmed recrudescent. Five different treatments were evaluated, and 382 Plasmodium falciparum recrudescences were identified as eligible. With log-logistic models adjusted for baseline parasitemia, the predicted cumulative proportions of all the recrudescences that were detected by 28 days were 70% (95% confidence interval [CI], 65%–74%) for quinine monotherapy (n = 295), 66% (95% CI, 53%–76%) for artesunate monotherapy (n = 43), 62% (95% CI, 42%–79%) for artemether–lumefantrine (AL; n = 19), 46% (95% CI, 26%–67%) for artesunate with clindamycin (n = 19), and 34% (95% CI, 11%–67%) for dihydroartemisinin–piperaquine (DP; n = 6). Corresponding figures by day 42 were 89% (95% CI, 77%–95%) for AL and 71% (95% CI, 38%–91%) for DP. Follow-up for 63 days was predicted to detect ≥95% of all recrudescence, except for DP.

Conclusions

In low-transmission settings, antimalarial drug efficacy assessments in pregnancy require longer follow-up than for nonpregnant populations.
Durability of Satisfactory Functional Outcomes Following Surgical Adult Spinal Deformity Correction: A 3-Year Survivorship Analysis
Authors: Passias Peter G , Bortz Cole A , Lafage Virginie , Lafage Renaud , Smith Justin S , Line Breton , Eastlack Robert , Gupta Munish C , Hostin Richard A , Horn Samantha R , Segreto Frank A , Egers Max , Sciubba Daniel M , Gum Jeffrey L , Kebaish Khaled M , Klineberg Eric O , Burton Douglas C , Schwab Frank J , Shaffrey Christopher I , Ames Christopher P , Bess Shay ,   on behalf of the International Spine Study Group (ISSG)
Published: May 2019

BACKGROUND

Despite reports showing positive long-term functional outcomes following adult spinal deformity (ASD)-corrective surgery, it is unclear which factors affect the durability of these outcomes.

OBJECTIVE

To assess durability of functional gains following ASD-corrective surgery; determine predictors for postoperative loss of functionality.

METHODS

Surgical ASD patients > 18 yr with 3-yr Oswestry Disability Index (ODI) follow-up, and 1-yr postoperative (1Y) ODI scores reaching substantial clinical benefit (SCB) threshold (SCB < 31.3 points). Patients were grouped: those sustaining ODI at SCB threshold beyond 1Y (sustained functionality) and those not (functional decline). Kaplan-Meier survival analysis determined postoperative durability of functionality. Multivariate Cox regression assessed the relationship between patient/surgical factors and functional decline, accounting for age, sex, and levels fused.

RESULTS

All 166 included patients showed baseline to 1Y functional improvement (mean ODI: 35.3 ± 16.5-13.6 ± 9.2, P < .001). Durability of satisfactory functional outcomes following the 1Y postoperative interval was 88.6% at 2-yr postoperative, and 71.1% at 3-yr postoperative (3Y). Those sustaining functionality after 1Y had lower baseline C2-S1 sagittal vertical axis (SVA) and T1 slope (both P < .05), and lower 1Y thoracic kyphosis (P = .035). From 1Y to 3Y, patients who sustained functionality showed smaller changes in alignment: pelvic incidence minus lumbar lordosis, SVA, T1 slope minus cervical lordosis, and C2-C7 SVA (all P < .05). Those sustaining functionality beyond 1Y were also younger, less frail at 1Y, and had lower rates of baseline osteoporosis, hypertension, and lung disease (all P < .05). Lung disease (Hazard Ratio:4.8 [1.4-16.4]), 1Y frailty (HR:1.4 [1.1-1.9]), and posterior approach (HR:2.6 [1.2-5.8]) were associated with more rapid decline.

CONCLUSION

Seventy-one percent of ASD patients maintained satisfactory functional outcomes by 3Y. Of those who failed to sustain functionality, the largest functional decline occurred 3-yr postoperatively. Frailty, preoperative comorbidities, and surgical approach affected durability of functional gains following surgery.
118 Predictors of intravenous rehydration in children with acute gastroenteritis in the United States and Canada
Authors: Poonai Naveen , Powell Elizabeth C , Schnadower David , Casper Charlie , Roskind Cindy , Olsen Cody , Tarr Philip , Mahajan Prashant , Rogers Alexander J , Schuh Suzanne , Hurley Katrina , Gouin Serge , Vance Cheryl , Farion Ken , Sapien Robert E , O’Connell Karen J , Levine Adam C , Bhatt Seema , Freedman Stephen B
Published: May 2019

Background

Although oral rehydration therapy is recommended for children with acute gastroenteritis (AGE) with none to some dehydration, intravenous (IV) rehydration is still commonly administered to these children in high-income countries. IV rehydration is associated with pain, anxiety, and emergency department (ED) revisits in children with AGE.

Objectives

We sought to better understand the factors associated with IV rehydration in children with AGE in order to inform knowledge translation strategies.

Design/Methods

This was a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) randomized, controlled trials of oral probiotics in children with AGE-associated diarrhea. Eligible children were aged 3–48 months and reported >3 watery stools in a 24-hour period. The primary outcome was administration of IV rehydration at the index ED visit. We used mixed-effects logistic regression model to explore univariable and multivariable relationships between IV rehydration and a prioririsk factors.

Results

From the parent study sample of 1848 participants, 1846 had data available for analysis: mean (SD) age of 19.1 ± 11.4 months, 45.4% females. 70.2% (1292/1840) vomited within 24 hours of the index ED visit and 34.1% (629/1846) received ondansetron in the ED. 13.0% (240/1846) were administered IV rehydration at the index ED visit, and 3.6% (67/1842) were hospitalized. Multivariable predictors of IV rehydration were Clinical Dehydration Scale (CDS) score [compared to none: mild to moderate (OR: 8.1, CI: 5.5–11.8); severe (OR: 45.9, 95% CI: 20.1–104.7), P<0.001], ondansetron in the ED (OR: 1.8, CI: 1.2–2.6, P=0.003), previous healthcare visit for the same illness [compared to no prior visit: prior visit with no IV (OR: 1.9, 95% CI: 1.3–2.9); prior visit with IV (OR: 10.5, 95% CI: 3.2–34.8), P<0.001], and country [compared to Canada: US (OR: 4.1, CI: 2.3–7.4, P<0.001]. Significantly more participants returned to the ED with symptoms of AGE within 3 days if IV fluids were administered at the index visit [30/224 (13.4%) versus 88/1453 (6.1%), P<0.001].

Conclusion

Higher CDS scores, antiemetic use, previous healthcare visits and country were independent predictors of IV rehydration which was also associated with increased ED revisits. Knowledge translation focused on optimizing the use of antiemetics (i.e. for those with dehydration) and reducing the geographic variation in IV rehydration use may improve the ED experience and reduce ED-revisits.
No Theory-Free Lunches in Well-Being Policy
Authors: Hersch Gil
Published: May 2019

Generating an account that can sidestep the disagreement among substantive theories of well-being, while at the same time still providing useful guidance for well-being public policy, would be a significant achievement. Unfortunately, the various attempts to remain agnostic regarding what constitutes well-being fail to either (a) be an account of well-being, (b) provide useful guidance for well-being policy, or (c) avoid relying on a substantive well-being theory. There are no theory-free lunches in well-being policy. Instead, I propose an intermediate account, according to which well-being is constituted by endorsed veridical experiences. This account refers back to theories of well-being but does so as agnostically as possible. An intermediate account of well-being is meant as a policy guiding compromise between the different theories of well-being that make claims regarding what constitutes well-being. An intermediate account does as well as can be hoped for in providing a basis for well-being policy.
Mean and Variance of Phylogenetic Trees
Authors: Brown Daniel G , Owen Megan
Published: May 2019

We describe the use of the Fréchet mean and variance in the Billera–Holmes–Vogtmann (BHV) treespace to summarize and explore the diversity of a set of phylogenetic trees. We show that the Fréchet mean is comparable to other summary methods, and, despite its stickiness property, is more likely to be binary than the majority-rule consensus tree. We show that the Fréchet variance is faster and more precise than commonly used variance measures. The Fréchet mean and variance are more theoretically justified, and more robust, than previous estimates of this type and can be estimated reasonably efficiently, providing a foundation for building more advanced statistical methods and leading to applications such as mean hypothesis testing and outlier detection.
Zebras in Foreskin Dermatopathology: A Review
Authors: Alhatem Albert , Patel Nitin , Lambert W. Clark , Heller Debra S.
Published: May 2019

Objectives

The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically.

Methods

A database search of PubMed and Google Scholar were extracted between March 1, 2009, and March 1, 2019, using the search terms “foreskin,” “prepuce,” “penis,” “pathology,” “dermatology,” and “rare.” The search was limited to “humans” and “dermatopathology.” Full article texts were reviewed. Reference lists were screened for additional articles. Patient details (diagnosis, dermatopathology, treatment, and follow-up if available) were extracted. We excluded articles written in the non-English language, unusual variants of common conditions, and cases of common dermatologic conditions.

Results

A list of 369 articles was identified and another screening identified 30 articles for rare foreskin pathologies. Those are divided into categories based on the following etiologies: (a) benign, including congenital (e.g., aposthia), infectious (graft versus host disease and histoplasma), autoimmune (Crohn's disease and pyoderma gangrenosum), and benign neoplasms (neurofibroma, apocrine hidrocystoma, verruciform xanthoma, porokeratosis, penile cutaneous horn, localized amyloidosis) and (b) malignancies, including primary (myeloid sarcoma, basal cell carcinoma, Kaposi's sarcoma, mucosal-associated lymphoid tissue lymphoma), and metastasis.

Conclusions

We reviewed and discussed unusual benign and malignant dermatopathology conditions that can affect the foreskin.
A randomized-controlled trial of early endotherapy versus wait-and-see policy for mild symptomatic pancreatic stones in chronic pancreatitis
Authors: Saito Tomotaka , Nakai Yousuke , Mizuno Suguru , Isayama Hiroyuki , Sasahira Naoki , Watanabe Takeo , Matsubara Saburo , Arizumi Toshihiko , Togawa Osamu , Hirano Kenji , Tsujino Takeshi , Ishigaki Kazunaga , Hakuta Ryunosuke , Saito Kei , Takahara Naminatsu , Hamada Tsuyoshi , Kogure Hirofumi , Tada Minoru , Koike Kazuhiko
Published: May 2019

Background

Although surgical or endoscopic treatment is effective for pain control in symptomatic calcified chronic pancreatitis, it is still unknown whether early intervention in mild symptomatic pancreatic stones would reduce the frequency of acute exacerbation and improve long-term outcomes. The aim of this randomized-controlled trial was to explore the efficacy of early endotherapy for mild symptomatic pancreatic stones in comparison with the wait-and-see policy.

Materials and methods

Patients with mild symptoms because of pancreatic stones were assigned randomly to the endotherapy or the wait-and-see group. The wait-and-see group received endotherapy only when they developed refractory exacerbation or intractable pain. The primary outcome was the cumulative incidence of intolerable pain attacks and acute exacerbation. The secondary outcomes were the development of pancreatic insufficiency and the progression of pancreatic atrophy.

Results

A total of 20 patients were enrolled between March 2008 and March 2011. The study was terminated prematurely because of the poor patient enrollment. Early endotherapy tended to reduce the cumulative incidence of pain attacks and exacerbation, (P=0.17) with the composite incidence of pain attacks and exacerbation of 30% in the endotherapy group and 60% in the wait-and-see group. There were no significant differences in terms of diabetic status and the presence of steatorrhea. The thickness of the pancreas decreased significantly in the wait-and-see group (9.2–6.8 mm, P=0.041), but not in the endotherapy group (8.7–9.0 mm, P=0.60).

Conclusion

In a small group of patients, early endotherapy in mild symptomatic chronic pancreatitis was associated with a trend toward a minor number of acute attacks and atrophy progression of the pancreas.
Discrete Community Assemblages Within Hypersaline Paleolake Sediments of Pilot Valley, Utah
Authors: Lynch Kennda L. , Rey Kevin A. , Bond Robin J. , Biddle Jennifer F. , Spear John R. , Rosenzweig Frank , Munakata-Marr Junko
Published: May 2019

Hypersaline paleolake sediments are understudied ecosystems whose microbial ecology is largely unknown. Here we present mineralogical, geochemical, and small-subunit 16S rRNA gene sequence data on one such environment, the Pilot Valley Basin (PVB), a sub-basin of ancient Lake Bonneville located in northwest Utah. PVB exhibits a variety of aqueous minerals including phyllosilicates, carbonates, and sulfates, as well as microbially-induced sedimentary structures. As perchlorate occurs naturally (up to 6.5 ppb) in Pilot Valley sediments, and because recent evidence suggests that it is subject to biotic reduction, PVB has been proposed as a Mars analog site for astrobiological studies. 16S rRNA gene sequencing was used to investigate microbial diversity and community structure along horizontal and vertical transects within the upper basin sediments and beta diversity analyses indicate that the microbial communities in Pilot Valley are structured into three discrete groups.Operational taxonomicunits (OTUs) belonging to the main archaeal phylum, Euryarchaeota, make up ~23% of the sequences, while OTUs belonging to three bacterial phyla, Proteobacteria, Bacteroides and Gemmatimonadetes, constitute ~60-70% of the sequences recovered at all sites. Diversity analyses indicate that the specific composition of each community correlates with sediment grain size, and with biogeochemical parameters such as nitrate and sulfate concentrations. Interestingly, OTUs belonging to the phylum Gemmatimonadetes are co-located with extreme halophilic archaeal and bacterial taxa, which suggests a potential new attribute, halophilicity, of this newly-recognized phylum. Altogether, results of this first comprehensive geomicrobial study of Pilot Valley reveal that basin sediments harbor a complex and diverse ecosystem.
Environmental (e)DNA detection of the invasive pink salmon Oncorhynchus gorbuscha during the 2017 Norwegian invasion
Authors: Gargan Laura M. , Fossøy Frode , Mo Tor A. , Carlsson Jeanette E. L. , Ball Bernard , Carlsson Jens
Published: May 2019

The pink salmon Oncorhynchus gorbuscha was introduced from its native range in the Pacific to Northwest Russia several times since the 1950’s. While this species has been regularly observed in rivers in Northern Norway since that time, there has been an upsurge in the numbers of odd-year O. gorbuscha individuals observed in rivers in southern Norway in recent years, and particularly in 2017. Although the wide-scale effects of this species presence are currently uncertain, there are concerns regarding potential competition between O. gorbuscha and native species – most notably the Atlantic salmon Salmo salar. Environmental (e)DNA is becoming a widely used tool to monitor rare and invasive species in aquatic environments. In the present pilot study, primers and a probe were developed to detect O. gorbuscha from eDNA samples taken from a Norwegian river system where the species was observed. Water samples were taken at both upstream and downstream locations of the Lysakerelva river during Autumn 2017 (to coincide with spawning) and during late Spring 2018. Autumn samples were positive for O. gorbuscha at both sampling locations, whereas Spring samples showed positive detection of this species in the upstream region of the river, when smolt should have left, or be in the process of leaving the river. These findings reveal that eDNA-based methods can be used detect the presence of O. gorbuscha during their spawning season. This suggests that odd-year populations have the potential to become established in the studied river system. We recommend that eDNA sampling is repeated to determine whether individuals of this odd-year population have survived at sea and return to spawn. Our assay specificity tests indicate that the tools developed in the present study can be used for detection of O. gorbuscha in both Norwegian and other European river systems where presence/absence data is required. We also suggest some modifications to our methodology that may improve upon the detection capabilities of O. gorbuscha using eDNA.
Integrated meditation and exercise therapy: A randomized controlled trial of a combined non-pharmacological intervention reduces disability and pain in patients with chronic low back pain
Authors: Polaski Anna M. , Phelps Amy L. , Smith Thomas J. , Helm Eric R. , Morone Natalia E. , Szucs Kimberly A. , Kostek Matthew C. , Kolber Benedict J.
Published: May 2019

Integrative and complementary non-pharmacological treatments have proven efficacious in treating both the physiological and psychological symptoms of chronic pain conditions but the potential of many combined therapies is unknown. This study examined the effects of a combined intervention of mindfulness meditation followed by aerobic walking exercise in chronic low back pain (cLBP) patients. We hypothesized that meditation before exercise would reduce disability and pain by increasing mindfulness prior to physical activity. Thirty-eight adults completed either meditation and exercise treatment (MedExT) (n=18) or an audiobook control condition (n=20). Over a 4-week period, participants in the MedExT group performed 12-17 minutes of guided meditation followed by 30 minutes of moderate intensity walking exercise 5 days per week. Measures of disability, pain, mindfulness and anxiety were taken at baseline and post-intervention. Ratings of pain were also assessed by participant self-report, before and after each intervention session. Following MedExT, participants showed significant improvement in our primary outcome of disability compared to the control group (p<0.05). From pre to post-intervention, MedExT also increased mindfulness (p<0.05), but had no significant effect on quantitative sensory testing on the low back. Mean ratings of low back pain intensity and unpleasantness significantly improved with MedExT from before the study to during participation, respectively (intensity p<0.05; unpleasantness p<0.05). Overall, four weeks of MedExT produced substantive changes in disability, mindfulness and measures of pain intensity and unpleasantness.