bluuebunny/crossref_metadata_2025 huggingface dataset:
Florbetapir positron emission tomography and cerebrospinal fluid biomarkers
Authors: Hake Ann , Trzepacz Paula T. , Wang Shufang , Yu Peng , Case Michael , Hochstetler Helen , Witte Michael M. , Degenhardt Elisabeth K. , Dean Robert A. ,   Alzheimer's Disease Neuroimaging Initiative
Published: April 2015

Background

We evaluated the relationship between florbetapir‐F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers.

Methods

Alzheimer's Disease Neuroimaging Initiative‐Grand Opportunity and Alzheimer's Disease Neuroimaging Initiative 2 (GO/2) healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression.

Results

In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1–42) and tau/Aβ1–42 ratios. Using logistic regression, Aβ1–42, total tau (t‐tau), phosphorylated tau181P (p‐tau), and FBP PET composite each differentiated HC versus AD. Aβ1–42 and t‐tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p‐tau added discriminative power to FBP PET when classifying HC versus AD.

Conclusion

Based on cross‐sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed.
Initiative Aims to End Routine Flaring of Natural Gas
Authors: Showstack Randy
Published: April 2015

A new initiative to curtail the wasteful burning of natural gas associated with oil production could lead to significant environmental and public health benefits.
Anion-induced AgIself-assemblies with electron deficient aromatic ligands: anion–π-system interactions as a driving force for templated coordination networks
Authors: Safin Damir A. , Pialat Amélie , Leitch Alicea A. , Tumanov Nikolay A. , Korobkov Ilia , Filinchuk Yaroslav , Brusso Jaclyn L. , Murugesu Muralee
Published: April 2015

1D, 2D and 3D AgIcoordination polymers were isolated using nitrogen based 3,6-bis(2′-pyrimidyl)-1,2,4,5-tetrazine and 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine ligands.
A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters
Authors: Gui Yong-Yuan , Yang Jian , Qi Liang-Wen , Wang Xiao , Tian Fang , Li Xiao-Nian , Peng Lin , Wang Li-Xin
Published: April 2015

Enantioselective sulfa-Michael/aldol reaction of isoindigos has been successfully developed to afford bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters.
Data-Based Decision Making in Professional Learning for School Speech-Language Pathologists
Authors: Murza Kimberly A. , Ehren Barbara J.
Published: April 2015

Purpose

School-based speech-language pathologists (SLPs) are often asked to adopt new policies or practices at the school, district, or state level. Professional learning (PL) opportunities usually accompany these changes but are often delivered in a one-size-fits-all workshop format. The authors challenge school-based SLPs and district leadership to consider PL in a new light, guided by data-based decision making to ultimately improve student outcomes.

Method

This article discusses the research supporting the assessment and delivery of high-quality PL for school professionals, including SLPs, and a specific model for measuring change: the concerns-based adoption model (CBAM; Hall & Hord, 2015). An example of how CBAM was used to examine the adoption process with school-based SLPs in a large school district is provided.

Conclusion

Based on the review of the literature, the current approach to PL experienced by most SLPs is problematic. High-quality PL should target improvement in student outcomes and should be focused, ongoing, supported, and evaluated.
Addressing false discoveries in network inference
Authors: Petri Tobias , Altmann Stefan , Geistlinger Ludwig , Zimmer Ralf , Küffner Robert
Published: April 2015

Motivation: Experimentally determined gene regulatory networks can be enriched by computational inference from high-throughput expression profiles. However, the prediction of regulatory interactions is severely impaired by indirect and spurious effects, particularly for eukaryotes. Recently, published methods report improved predictions by exploiting the a priori known targets of a regulator (its local topology) in addition to expression profiles.

Results: We find that methods exploiting known targets show an unexpectedly high rate of false discoveries. This leads to inflated performance estimates and the prediction of an excessive number of new interactions for regulators with many known targets. These issues are hidden from common evaluation and cross-validation setups, which is due to Simpson’s paradox. We suggest a confidence score recalibration method (CoRe) that reduces the false discovery rate and enables a reliable performance estimation.

Conclusions: CoRe considerably improves the results of network inference methods that exploit known targets. Predictions then display the biological process specificity of regulators more correctly and enable the inference of accurate genome-wide regulatory networks in eukaryotes. For yeast, we propose a network with more than 22 000 confident interactions. We point out that machine learning approaches outside of the area of network inference may be affected as well.

Availability and implementation: Results, executable code and networks are available via our website http://www.bio.ifi.lmu.de/forschung/CoRe.

Contact:  robert.kueffner@helmholtz-muenchen.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inferring data-specific micro-RNA function through the joint ranking of micro-RNA and pathways from matched micro-RNA and gene expression data
Authors: Patrick Ellis , Buckley Michael , Müller Samuel , Lin David M. , Yang Jean Y. H.
Published: April 2015

Motivation: In practice, identifying and interpreting the functional impacts of the regulatory relationships between micro-RNA and messenger-RNA is non-trivial. The sheer scale of possible micro-RNA and messenger-RNA interactions can make the interpretation of results difficult.

Results: We propose a supervised framework, pMim, built upon concepts of significance combination, for jointly ranking regulatory micro-RNA and their potential functional impacts with respect to a condition of interest. Here, pMim directly tests if a micro-RNA is differentially expressed and if its predicted targets, which lie in a common biological pathway, have changed in the opposite direction. We leverage the information within existing micro-RNA target and pathway databases to stabilize the estimation and annotation of micro-RNA regulation making our approach suitable for datasets with small sample sizes. In addition to outputting meaningful and interpretable results, we demonstrate in a variety of datasets that the micro-RNA identified by pMim, in comparison to simpler existing approaches, are also more concordant with what is described in the literature.

Availability and implementation: This framework is implemented as an R function, pMim, in the package sydSeq available from http://www.ellispatrick.com/r-packages.

Contact:  jean.yang@sydney.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
iFoldRNA v2: folding RNA with constraints
Authors: Krokhotin Andrey , Houlihan Kevin , Dokholyan Nikolay V.
Published: April 2015

Summary: A key to understanding RNA function is to uncover its complex 3D structure. Experimental methods used for determining RNA 3D structures are technologically challenging and laborious, which makes the development of computational prediction methods of substantial interest. Previously, we developed the iFoldRNA server that allows accurate prediction of short (<50 nt) tertiary RNA structures starting from primary sequences. Here, we present a new version of the iFoldRNA server that permits the prediction of tertiary structure of RNAs as long as a few hundred nucleotides. This substantial increase in the server capacity is achieved by utilization of experimental information such as base-pairing and hydroxyl-radical probing. We demonstrate a significant benefit provided by integration of experimental data and computational methods.

Availability and implementation:  http://ifoldrna.dokhlab.org

Contact:  dokh@unc.eu
PDBest: a user–friendly platform for manipulating and enhancing protein structures
Authors: Gonçalves Wellisson R. S. , Gonçalves-Almeida Valdete M. , Arruda Aleksander L. , Meira Wagner , da Silveira Carlos H. , Pires Douglas E. V. , de Melo-Minardi Raquel C.
Published: April 2015

Summary: PDBest (PDB Enhanced Structures Toolkit) is a user-friendly, freely available platform for acquiring, manipulating and normalizing protein structures in a high-throughput and seamless fashion. With an intuitive graphical interface it allows users with no programming background to download and manipulate their files. The platform also exports protocols, enabling users to easily share PDB searching and filtering criteria, enhancing analysis reproducibility.

Availability and implementation: PDBest installation packages are freely available for several platforms at http://www.pdbest.dcc.ufmg.br

Contact:  wellisson@dcc.ufmg.br, dpires@dcc.ufmg.br, raquelcm@dcc.ufmg.br

Supplementary information:  Supplementary data are available at Bioinformatics online.
Data-dependent bucketing improves reference-free compression of sequencing reads
Authors: Patro Rob , Kingsford Carl
Published: April 2015

Motivation: The storage and transmission of high-throughput sequencing data consumes significant resources. As our capacity to produce such data continues to increase, this burden will only grow. One approach to reduce storage and transmission requirements is to compress this sequencing data.

Results: We present a novel technique to boost the compression of sequencing that is based on the concept of bucketing similar reads so that they appear nearby in the file. We demonstrate that, by adopting a data-dependent bucketing scheme and employing a number of encoding ideas, we can achieve substantially better compression ratios than existing de novo sequence compression tools, including other bucketing and reordering schemes. Our method, Mince, achieves up to a 45% reduction in file sizes (28% on average) compared with existing state-of-the-art de novo compression schemes.

Availability and implementation: Mince is written in C++11, is open source and has been made available under the GPLv3 license. It is available at http://www.cs.cmu.edu/∼ckingsf/software/mince.

Contact:  carlk@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
CiVi: circular genome visualization with unique features to analyze sequence elements
Authors: Overmars Lex , van Hijum Sacha A. F. T. , Siezen Roland J. , Francke Christof
Published: April 2015

Summary: We have developed CiVi, a user-friendly web-based tool to create custom circular maps to aid the analysis of microbial genomes and sequence elements. Sequence related data such as gene-name, COG class, PFAM domain, GC%, and subcellular location can be comprehensively viewed. Quantitative gene-related data (e.g. expression ratios or read counts) as well as predicted sequence elements (e.g. regulatory sequences) can be uploaded and visualized. CiVi accommodates the analysis of genomic elements by allowing a visual interpretation in the context of: (i) their genome-wide distribution, (ii) provided experimental data and (iii) the local orientation and location with respect to neighboring genes. CiVi thus enables both experts and non-experts to conveniently integrate public genome data with the results of genome analyses in circular genome maps suitable for publication.

Contact:  L.Overmars@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.

Availability and implementation: CiVi is freely available at http://civi.cmbi.ru.nl
Tailoring of alerts substantially reduces the alert burden in computerized clinical decision support for drugs that should be avoided in patients with renal disease
Authors: Czock David , Konias Michael , Seidling Hanna M , Kaltschmidt Jens , Schwenger Vedat , Zeier Martin , Haefeli Walter E
Published: April 2015

Objective Electronic alerts are often ignored by physicians, which is partly due to the large number of unspecific alerts generated by decision support systems. The aim of the present study was to analyze critical drug prescriptions in a university-based nephrology clinic and to evaluate the effect of different alerting strategies on the alert burden.

Methods In a prospective observational study, two advanced strategies to automatically generate alerts were applied when medication regimens were entered for discharge letters, outpatient clinic letters, and written prescriptions and compared to two basic reference strategies. Strategy A generated alerts whenever drug-specific information was available, whereas strategy B generated alerts only when the estimated glomerular filtration rate of a patient was below a drug-specific value. Strategies C and D included further patient characteristics and drug-specific information to generate even more specific alerts.

Results Overall, 1012 medication regimens were entered during the observation period. The average number of alerts per drug preparation in medication regimens entered for letters was 0.28, 0.080, 0.019, and 0.011, when using strategy A, B, C, or D (P<0.001, for comparison between the strategies), leading to at least one alert in 87.5%, 39.3%, 13.5%, or 7.81 % of the regimens. Similar average numbers of alerts were observed for medication regimens entered for written prescriptions.

Conclusions The prescription of potentially hazardous drugs is common in patients with renal impairment. Alerting strategies including patient and drug-specific information to generate more specific alerts have the potential to reduce the alert burden by more than 90 %.
Peanuts, brezels and bananas: food for thought on the orbital structure of the Galactic bulge
Authors: Portail Matthieu , Wegg Christopher , Gerhard Ortwin
Published: April 2015

Recent observations have discovered the presence of a box/peanut or X-shape structure in the Galactic bulge. Such box/peanut structures are common in external disc galaxies, and are well known in N-body simulations where they form following the buckling instability of a bar. From studies of analytical potentials and N-body models, it has been claimed in the past that box/peanut bulges are supported by ‘bananas’, or x1v1 orbits. We present here a set of N-body models where instead the peanut bulge is mainly supported by brezel-like orbits, allowing strong peanuts to form with short extent relative to the bar length. This shows that stars in the X-shape do not necessarily stream along banana orbits which follow the arms of the X-shape. The brezel orbits are also found to be the main orbital component supporting the peanut shape in our recent made-to-measure dynamical models of the Galactic bulge. We also show that in these models the fraction of stellar orbits that contribute to the X-structure account for 40–45 per cent of the stellar mass.
Dark matter-induced collapse of neutron stars: a possible link between fast radio bursts and the missing pulsar problem
Authors: Fuller Jim , Ott Christian D.
Published: April 2015

Fast radio bursts (FRBs) are an emerging class of short and bright radio transients whose sources remain enigmatic. Within the Galactic Centre, the non-detection of pulsars within the inner ∼10 pc has created a missing pulsar problem that has intensified with time. With all reserve, we advance the notion that the two problems could be linked by a common solution: the collapse of neutron stars (NS) due to capture and sedimentation of dark matter (DM) within their cores. Bramante & Linden showed that certain DM properties allow for rapid NS collapse within the high DM density environments near galactic centres while permitting NS survival elsewhere. Each DM-induced collapse could generate an FRB as the NS magnetosphere is suddenly expelled. This scenario could explain several features of FRBs: their short time scales, large energies, locally produced scattering tails, and high event rates. We predict that FRBs are localized to galactic centres, and that our own galactic centre harbours a large population of NS-mass (M ∼ 1.4 M⊙) black holes. The DM-induced collapse scenario is intrinsically unlikely because it can only occur in a small region of allowable DM parameter space. However, if observed to occur, it would place tight constraints on DM properties.
Applied catalysis for sustainable development of chemical industry in China
Authors: Xie Zaiku , Liu Zhicheng , Wang Yangdong , Jin Zhonghao
Published: April 2015

Progressing green chemical technologies is significant to the sustainable development of chemical industry in China, as the energy and environment problems increasingly became great challenges to the whole society. The scientific connotation of sustainable energy chemical engineering can be generalized as green carbon/hydrogen science which means optimization of carbon/hydrogen atom economics based on high efficient catalysis and low-carbon emission. This review illustrated recent advances in developing sustainable technologies for applied catalysis in chemical industry of China, including the fields of high efficient conversion of heavy oil, green petrochemical catalytic technologies, clean utilization of coal and natural gas, promoting sustainable resources and clean energy, etc. Moreover, from the view of industrial point, some important common scientific problems were discussed and summarized, such as the relation between molecular diffusion and catalyzing efficiency, homogeneous catalysis in heterogeneous catalysts, in situ or operando characterization of industrial catalysis, etc., aiming to supplying a forward roadmap to academia and/or industry.
Effects of an Innovative Psychotherapy Program for Surgical Patients
Authors: Kerper Léonie F. , Spies Claudia D. , Salz Anna-Lena , Weiß-Gerlach Edith , Balzer Felix , Neumann Tim , Tafelski Sascha , Lau Alexandra , Neuner Bruno , Romanczuk-Seiferth Nina , Glaesmer Heide , Wernecke Klaus-Dieter , Brähler Elmar , Krampe Henning
Published: April 2015

AbstractAbstract

In 220 surgical patients with comorbid mental disorders (primarily mood, anxiety and adjustment disorders, or alcohol or tobacco abuse), those randomized to psychotherapy sessions perioperatively and up to 3 months postoperatively were more likely to participate in psychosocial mental health care 6 months after surgery than those randomized to brief written advice only.

Background:

The stepped care program Bridging Intervention in Anesthesiology (BRIA) aims at motivating and supporting surgical patients with comorbid mental disorders to engage in psychosocial mental healthcare options. This study examined the efficacy of BRIA.

Methods:

This randomized, parallel-group, open-label, controlled trial was conducted in the preoperative anesthesiological assessment clinics and surgical wards of a large university hospital in Germany. A total of 220 surgical patients with comorbid mental disorders were randomized by using the computer-generated lists to one of two intervention groups: BRIA psychotherapy sessions up to 3 months postoperatively (BRIA) versus no psychotherapy/computerized brief written advice (BWA) only. Primary outcome was participation in psychosocial mental healthcare options at month 6. Secondary outcome was change of self-reported general psychological distress (Global Severity Index of the Brief Symptom Inventory) between baseline and month 6.

Results:

At 6-month follow-up, the rate of patients who engaged in psychosocial mental healthcare options was 30% (33 of 110) in BRIA compared with 11.8% (13 of 110) in BWA (P = 0.001). Number needed to treat and relative risk reduction were 6 (95% CI, 4 to 13) and 0.21 (0.09 to 0.31), respectively. In BRIA, Global Severity Index decreased between baseline and month 6 (P < 0.001), whereas it did not change significantly in BWA (P = 0.197).

Conclusions:

Among surgical patients with comorbid mental disorders, BRIA results in an increased engagement in subsequent therapy options and a decrease of general psychological distress. These data suggest that it is reasonable to integrate innovative psychotherapy programs into the context of interdisciplinary surgical care.
A novel subgroup 16SrVII-D phytoplasma identified in association with erigeron witches' broom
Authors: Flôres Daniela , Amaral Mello Ana Paula de Oliveira , Pereira Thays Benites Camargo , Rezende Jorge Alberto Marques , Bedendo Ivan Paulo
Published: April 2015

Erigeron sp. plants showing symptoms of witches' broom and stunting were found near orchards of passion fruit in São Paulo state, Brazil. These symptoms were indicative of infection by phytoplasmas. Thus, the aim of this study was to detect and identify possible phytoplasmas associated with diseased plants. Total DNA was extracted from symptomatic and asymptomatic plants and used in nested PCR conducted with the primer pairs P1/Tint and R16F2n/16R2. Amplification of genomic fragments of 1.2 kb from the 16S rRNA gene confirmed the presence of phytoplasma in all symptomatic samples. The sequence identity scores between the 16S rRNA gene of the phytoplasma strain identified in the current study and those of previously reported ‘Candidatus Phytoplasma fraxini’-related strains ranged from 98 % to 99 % indicating the phytoplasma to be a strain affiliated with ‘Candidatus Phytoplasma fraxini’. The results from a phylogenetic analysis and virtual RFLP analysis of the 16S rRNA gene sequence with 17 restriction enzymes revealed that the phytoplasma strain belongs to the ash yellows phytoplasma group (16SrVII); the similarity coefficient of RFLP patterns further suggested that the phytoplasma represents a novel subgroup, designated 16SrVII-D. The representative of this new subgroup was named EboWB phytoplasma (Erigeron bonariensis Witches' Broom).
Isaria takamizusanensis is the anamorph of Cordyceps ryogamimontana, warranting a new combination, Purpureocillium takamizusanense comb. nov.
Authors: Ban Sayaka , Azuma Yuta , Sato Hiroki , Suzuki Ken-ichiro , Nakagiri Akira
Published: April 2015

The entomogenous anamorphic fungusIsaria takamizusanensishas not been resolved clearly in its teleomorphic state. We succeeded in inducing ascostroma formation by incubating conidiomata ofI. takamizusanensison cicada adults in a moist chamber. We observed the ascostroma and conducted a phylogenetic analysis based on ITS rDNA andEF-1αgenes. The morphology of the ascostroma was identical to that ofCordyceps ryogamimontana. In the phylogenetic tree inferred fromEF-1α, the isolate from the partspores grouped with nine strains derived from conidia ofI. takamizusanensis, which was distinct from a clade includingPurpureocillium lilacinum. Moreover, a conidial structure identical to that ofI. takamizusanensiswas rediscovered on the holotype specimen ofC. ryogamimontana. As a result, we propose a new name,Purpureocillium takamizusanense, which is a combination of the teleomorph–anamorph connection ofC. ryogamimontana–I. takamizusanensis, in accordance with the ‘one fungus, one name’ concept of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN).
A quasi-digital approach to peptide sequencing using tandem nanopores with endo- and exo-peptidases
Authors: Sampath G.
Published: April 2015

A method of sequencing peptides using tandem cells (RSC Adv., 2015,5, 167-171;RSC Adv., 2015,5, 30694-30700) and peptidases is considered. A double tandem cell (two tandem cells in tandem) has three nanopores in series, an amino-acid-specific endopeptidase attached downstream of the first pore, and an exopeptidase attached downstream of the second pore. The endopeptidase cleaves a peptide threaded through the first pore into fragments that are well separated in time. Fragments pass through the second pore and are each cleaved by the exopeptidase into a series of single residues; the latter pass through the third pore and cause separate current blockades that can be counted. This leads to an ordered list of integers corresponding to the number of residues in each fragment. With 20 cells, one per amino acid type, and 20 peptide copies, the resulting 20 lists of integers are used by a simple algorithm to assemble the sequence. This is a quasi-digital process that uses the lengths of subsequences to sequence the peptide, it differs from conventional analog methods which seek to identify monomers in a polymer via differences in blockade levels, residence times, or transverse currents. Several implementation issues are discussed. In particular the problem of fast analyte translocation, widely considered intransigent, may be resolved through the use of a sufficiently long (40-60 nm) third pore. This translates to a required bandwidth of 1-2 MHz, which is within the range of currently available CMOS circuits.
SCT promoter methylation is a highly discriminative biomarker for lung and many other cancers
Authors: Sathe Adwait , Zhang Yu-An , Ma Xiaotu , Ray Pradipta , Cadinu Daniela , Wang Yi-Wei , Yao Xiao , Liu Xiaoyun , Tang Hao , Wang Yunfei , Huang Ying , Liu Changning , Gu Jin , Akerman Martin , Mo Yifan , Cheng Chao , Xuan Zhenyu , Chen Lei , Xiao Guanghua , Xie Yang , Girard Luc , Wang Hongyang , Lam Stephen , Wistuba Ignacio I , Zhang Li , Gazdar Adi F , Zhang Michael Q
Published: April 2015

Aberrant DNA methylation has long been implicated in cancers. In this work we present a highly discriminative DNA methylation biomarker for non-small cell lung cancers and fourteen other cancers. Based on 69 NSCLC cell lines and 257 cancer-free lung tissues we identified a CpG island in SCT gene promoter which was verified by qMSP experiment in 15 NSCLC cell lines and 3 immortalized human respiratory epithelium cells. In addition, we found that SCT promoter was methylated in 23 cancer cell lines involving >10 cancer types profiled by ENCODE. We found that SCT promoter is hyper-methylated in primary tumors from TCGA lung cancer cohort. Additionally, we found that SCT promoter is methylated at high frequencies in fifteen malignancies and is not methylated in ∼1000 non-cancerous tissues across >30 organ types. Our study indicates that SCT promoter methylation is a highly discriminative biomarker for lung and many other cancers.
A pooling-based approach to mapping genetic variants associated with DNA methylation
Authors: Kaplow Irene M. , MacIsaac Julia L. , Mah Sarah M. , McEwen Lisa M. , Kobor Michael S. , Fraser Hunter B.
Published: April 2015

DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover <2% of the genome and cannot account for allele-specific methylation (ASM). Other studies have performed whole-genome bisulfite sequencing on a few individuals, but these lack statistical power to identify variants associated with DNA methylation. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified more than 2000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.
Medical constructions of long‐term exhaustion, past and present
Authors: Lian Olaug S. , Bondevik Hilde
Published: April 2015

Culture and history affect the ways in which medical knowledge is shaped, sustained and changed. The less knowledge we have, the larger the space for the cultural imprint becomes. Based on these assumptions, we ask: how have medical constructions of long‐term exhaustion changed over time, and how are changing constructions related to societal change? To discuss these questions we conducted a comparative study of medical texts from two historical periods: 1860–1930 and 1970–2013. Our data are limited to two diagnoses: neurasthenia and encephalomyelitis. After comparing the two periods by identifying diverging and converging aspects, we interpreted observed continuities and interruptions in relation to historical developments. We found that in the medical literature, long‐term exhaustion became transformed from a somatic ailment bred by modern civilisation to a self‐inflicted psychiatric ailment. At the same time, it changed from being a male‐connoted high‐status condition to a female‐connoted low‐status condition. We interpret these changes as contingent upon culturally available modes of interpretations. Medical knowledge thereby becomes infused with cultural norms and values which give them a distinct cultural bias. The historical controversies surrounding this medically contested condition neatly display the socially contingent factors that govern the social construction of medical knowledge.
The risk experience: the social effects of health screening and the emergence of a proto‐illness
Authors: Gillespie Chris
Published: April 2015

Those who undergo health screening often experience physical and emotional effects as a result of the screening process. However, the effects of health screening go beyond these physical and mental complications, often having profound social effects for those who are screened. This study explores the social implications of health screening for people who undergo it and are designated as being at risk for potential disease. Through a qualitative analysis of the experiences of individuals with elevated cholesterol levels and men with elevated prostate‐specific antigen (PSA) levels, this research offers a description of the experience of being at risk, identifying three primary components: increased medical contact, a restructuring of everyday routines and altered social relationships. Whereas the at‐risk health status engendered by current clinical approaches to screening and surveillance has been characterised as proto‐disease, this study develops a companion definition of proto‐illness to characterise the social experience of life with an identified health risk. Those who are at risk act in ways that are similar to those who are ill. The concept of proto‐illness implies that the experience of risk is parallel to the experience of illness and contributes to the sociology of medical screening by establishing a much needed bridge between the two experiences.
INTIMATE PARTNER VIOLENCE IN YOUNG ADULTHOOD: NARRATIVES OF PERSISTENCE AND DESISTANCE
Authors: GIORDANO PEGGY C. , JOHNSON WENDI L. , MANNING WENDY D. , LONGMORE MONICA A. , MINTER MALLORY D.
Published: April 2015

Prior research on patterns of intimate partner violence (IPV) has documented changes over time, but few studies have focused directly on IPV desistance processes. This analysis identifies unique features of IPV, providing a rationale for the focus on this form of behavior cessation. We develop a life‐course perspective on social learning as a conceptual framework and draw on qualitative interviews (n = 89) elicited from a sample of young adults who participated in a larger longitudinal study (Toledo Adolescent Relationships Study). The respondents’ backgrounds reflected a range of persistence and desistance from IPV perpetration. Our analyses revealed that relationship‐based motivations and changes were central features of the narratives of successful desisters, whether articulated as a stand‐alone theme or in tandem with other potential “hooks” for change. The analysis provides a counterpoint to individualistic views of desistance processes, highlighting ways in which social experiences foster attitude shifts and associated behavioral changes that respondents tied to this type of behavior change. The analyses of persisters and those for whom change seemed to be a work in progress provide points of contrast and highlight barriers that limit a respondent's desistance potential. We describe implications for theories of desistance as well as for IPV prevention and intervention efforts.
Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock
Authors: Dahl R. M. , Grønlykke L. , Haase N. , Holst L. B. , Perner A. , Wetterslev J. , Rasmussen B. S. , Meyhoff C. S. ,   the 6S‐Trial and TRISS Trial investigators
Published: April 2015

Background

Supplemental oxygen therapy is used for intensive care (ICU) patients with severe sepsis, but with no general guidelines and few safety data. The aim of this observational study was to describe the variability in oxygen administration as well as the association between partial pressure of arterial oxygen (PaO2) and mortality.

Methods

We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2) from trial inclusion and the following 5 days, and assessed the association between PaO2 and 90‐day mortality.

Results

The median PaO2 was 9.8 kPa [5–95% range 6.4–19.9] and FiO2 was 0.51 [5–95% range 0.27–1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19–1.65] in patients with average PaO2 < 8 kPa and 1.29 [95% CI: 0.84–1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10–12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17–1.58] in patients with an average FiO2 0.60–0.80 and 2.10 [95% CI: 1.88–2.23] in patients with an average FiO2 ≥ 0.80 as compared to patients with an average FiO2 ≤ 0.40.

Conclusion

Administration of oxygen in patients with severe sepsis resulted in a wide range of PaO2. Significantly higher mortality was observed in patients with an average PaO2 < 8 kPa and FiO2 ≥ 0.60. The results do not imply causation and the associations between average PaO2 and adverse outcomes have to be assessed further.
Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta‐analysis
Authors: Nielsen B. N. , Henneberg S. W. , Schmiegelow K. , Friis S. M. , Rømsing J.
Published: April 2015

Background

Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain.

Methods

We searched PubMed (1966 to June 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra‐articularly or as peripheral nerve blocks were excluded.

Results

Data from 26 studies, including 1531 patients and 13 different surgical interventions were included. Clinical heterogeneity of the studies was substantial. Meta‐analysis indicated statistically significant, but not clinically relevant, reductions in VAS score at 6–8 h (mean difference −4 mm, 95% CI: −6 to −2) and 12 h postoperatively (mean difference −5 mm, 95% CI: −7 to −3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41–265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved postoperative analgesia.

Conclusion

Evidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation.
DNA methylation and healthy human aging
Authors: Jones Meaghan J. , Goodman Sarah J. , Kobor Michael S.
Published: April 2015

The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.
Oral candidal carriage in asymptomatic patients
Authors: Mun MSS , Yap T , Alnuaimi AD , Adams GG , McCullough MJ
Published: April 2015

Background

Interest in the association between oral cancer risk and Candida‐associated promotion of mucosal dysplasia continues. However, little is known of the presence and amount of oral yeast in the mouths of healthy patients without mucosal lesions. The purpose of this prospective cross‐sectional clinical study was to ascertain the prevalence and degree of carriage of Candida in the oral cavities of a non‐cancer population, with reference to a range of parameters affecting the oral environment.

Methods

Oral rinse samples were collected from a sample of 203 patients attending the Royal Dental Hospital of Melbourne and analysed for the presence and degree of colonization of yeast species that were phenotypically identified as albicans and non‐albicans species.

Results

Oral yeast carriage was found in 98/203 patients (48.3%), and of these, 83 (84.7%) patients carried C. albicans. There was no statistical difference in carriage when comparing gender, age, or presence of a removable prosthesis.

Conclusions

Both smoking and the presence of active carious lesions were found to be positively correlated with the carriage of oral Candida. Individuals who are current smokers are nearly seven times more likely to have oral Candida, and participants with high candidal colonization are more likely to be current smokers. Participants with active carious lesions were also more likely to carry oral Candida.
Pregnancies in women with childhood vesicoureteral reflux
Authors: Roihuvuo‐Leskinen Hanna‐Mari , Vainio Merja I. , Niskanen Kaija M. , Lahdes‐Vasama Tuija T.
Published: April 2015

Objective

The frequency of pregnancy complications together with renal scarring and voiding dysfunction‐related risk factors were investigated in a cohort of women with a history of childhood vesicoureteral reflux (VUR).

Design

A retrospective cross‐sectional cohort study.

Population

Eighty‐seven primi‐ or multiparous middle‐aged women diagnosed with primary non‐obstructive VUR in childhood.

Methods

Pregnancy outcome was assessed from case records and from patient interviews. Urine flow tests for voiding patterns, renal ultrasound for detecting scars, and blood samples for renal function were investigated. The median follow‐up time was 38 years.

Main outcome measures

Prevalence of pregnancy complications in women with childhood VUR in relation to renal scars and voiding abnormalities.

Results

Maternal complications were seen in 64% of the women and fetal complications in 13%. The women with renal scars (48/87) more often had hypertension (33%), proteinuria (40%) and urinary tract infections (42%) during pregnancy than women without scarring. The frequency of fetal complications was not increased by renal scarring or proteinuria during pregnancy. Urinary tract infections during pregnancy (33% of the women) and voiding abnormalities (18%) did not increase the frequency of fetal or maternal complications. The women with fetal complications were more predisposed to frequent urinary tract infections during adult life (55%) than were those without fetal complications (24%) (p = 0.04).

Conclusions

The maternal complication rates in women with childhood VUR were increased only by renal scarring. Frequent urinary tract infections during adulthood seemed to predict an elevated risk of fetal complications.
Acceptance and Commitment Therapy and nicotine patch for smokers with bipolar disorder: preliminary evaluation of in‐person and telephone‐delivered treatment
Authors: Heffner Jaimee L , McClure Jennifer B , Mull Kristin E , Anthenelli Robert M , Bricker Jonathan B
Published: April 2015

Objectives

People with bipolar disorder are two to three times more likely to smoke and 50% less likely to quit than the general population. New treatments are needed to improve smoking cessation outcomes in this group. The study aim was to develop and pilot test a novel cessation intervention for smokers with bipolar disorder using Acceptance and Commitment Therapy (ACT) combined with nicotine patches.

Methods

The ten‐session ACT intervention was initially evaluated as in‐person, individual counseling (n = 10), then as telephone‐delivered counseling (n = 6). Participants were adult smokers with no more than mild current symptoms of bipolar disorder.

Results

For the in‐person protocol, end‐of‐treatment outcomes were: 80% retention, 40% of participants with carbon monoxide (CO)‐verified seven‐day point prevalence abstinence (PPA), 90% satisfied with treatment, 8.3 of ten sessions attended, and 54% increase in acceptance of cravings to smoke (i.e., ACT's theory‐based change process) from baseline. The seven‐day PPA at one‐month follow‐up was 30%. For the telephone protocol, end‐of‐treatment outcomes were: 67% retention, 33% reporting seven‐day PPA, 100% satisfied with treatment, 6.7 of ten treatment calls completed, and 55% increase in acceptance from baseline. At one‐month follow‐up, seven‐day PPA was 17%. The proportion of treatment completers who used at least 80% of the nicotine patches was 62.5% for the in‐person protocol and 0% for the telephone protocol.

Conclusions

Both in‐person and telephone‐delivered ACT were feasible. Despite low adherence to nicotine patches, the intervention showed preliminary evidence of facilitating quitting and impacting ACT's change mechanism. A randomized, controlled trial of this targeted ACT intervention is now needed.
CONSUMER DEBT STRESS, CHANGES IN HOUSEHOLD DEBT, AND THE GREAT RECESSION
Authors: Dunn Lucia F. , Mirzaie Ida A.
Published: April 2015

This research examines psychological debt stress and changes in household debt holdings for consumers during the Great Recession using data from a monthly national U.S. household survey covering the period 2006 through 2012. Debt stress measures in the population rose by over 50% at the bottom of the recession. Determining relative stress for eight different types of household debt, we find that noncollateralized debts are more stressful than collateralized debt and that during the recession the composition of debt shifted away from collateralized debt and toward noncollateralized. Our empirical results show that women and Hispanics experienced higher measured levels of stress. (JEL D12, D18)
A centroid model of species distribution with applications to the Carolina wrenThryothorus ludovicianusand house finchHaemorhous mexicanusin the United States
Authors: Huang Qiongyu , Sauer John R. , Swatantran Anu , Dubayah Ralph
Published: April 2015

Drastic shifts in species distributions are a cause of concern for ecologists. Such shifts pose great threat to biodiversity especially under unprecedented anthropogenic and natural disturbances. Many studies have documented recent shifts in species distributions. However, most of these studies are limited to regional scales, and do not consider the abundance structure within species ranges. Developing methods to detect systematic changes in species distributions over their full ranges is critical for understanding the impact of changing environments and for successful conservation planning. Here, we demonstrate a centroid model for range‐wide analysis of distribution shifts using the North American Breeding Bird Survey. The centroid model is based on a hierarchical Bayesian framework which models population change within physiographic strata while accounting for several factors affecting species detectability. Yearly abundance‐weighted range centroids are estimated. As case studies, we derive annual centroids for the Carolina wren and house finch in their ranges in the U.S. We further evaluate the first‐difference correlation between species’ centroid movement and changes in winter severity, total population abundance. We also examined associations of change in centroids from sub‐ranges. Change in full‐range centroid movements of Carolina wren significantly correlate with snow cover days (r = −0.58). For both species, the full‐range centroid shifts also have strong correlation with total abundance (r = 0.65, and 0.51 respectively). The movements of the full‐range centroids of the two species are correlated strongly (up to r = 0.76) with that of the sub‐ranges with more drastic population changes. Our study demonstrates the usefulness of centroids for analyzing distribution changes in a two‐dimensional spatial context. Particularly it highlights applications that associate the centroid with factors such as environmental stressors, population characteristics, and progression of invasive species. Routine monitoring of changes in centroid will provide useful insights into long‐term avian responses to environmental changes.