bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo gene expression of Pseudomonas putida KT2440 in the rhizosphere of different plants
Authors: Fernández Matilde , Conde Susana , Duque Estrella , Ramos Juan‐Luis
Published: February 2013

Pseudomonas putida KT2440 has the ability to colonize the rhizosphere of a wide range of plants and can reach cell densities in the range of 105–106 cfu g soil−1. Using the IVET technology we investigated which KT2440 genes were expressed in the rhizosphere of four different plants: pine, cypress, evergreen oak and rosemary. We identified 39 different transcriptional fusions containing the promoters of annotated genes that were preferentially expressed in the rhizosphere. Six of them were expressed in the rhizosphere of all the plant types tested, 11 were expressed in more than one plant and the remaining 22 fusions were found to be expressed in only one type of plant. Another 40 fusions were found to correspond to likely promoters that encode antisense RNAs of unknown function, some of which were isolated as fusions from the bacteria recovered in the rhizosphere from all of the plants, while others were specific to one or several of the plants. The results obtained in this study suggest that plant‐specific signals are sensed by KT2440 in the rhizosphere and that the signals and consequent gene expression are related to the bacteria's successful establishment in this niche.
Advancing nematode barcoding: A primer cocktail for the cytochrome c oxidase subunit I gene from vertebrate parasitic nematodes
Authors: Prosser Sean W. J. , Velarde‐Aguilar Maria G. , León‐Règagnon Virginia , Hebert Paul D. N.
Published: February 2013

Although nematodes are one of the most diverse metazoan phyla, species identification through morphology is difficult. Several genetic markers have been used for their identification, but most do not provide species‐level resolution in all groups, and those that do lack primer sets effective across the phylum, precluding high‐throughput processing. This study describes a cocktail of three novel primer pairs that overcome this limitation by recovering cytochrome c oxidase I (COI) barcodes from diverse nematode lineages parasitic on vertebrates, including members of three orders and eight families. Its effectiveness across a broad range of nematodes enables high‐throughput processing.
Characterization of the role of distinct plasma cell‐free DNA species in age‐associated inflammation and frailty
Authors: Jylhävä Juulia , Nevalainen Tapio , Marttila Saara , Jylhä Marja , Hervonen Antti , Hurme Mikko
Published: February 2013

Plasma cell‐free DNA (cf‐DNA) has recently emerged as a potential biomarker of aging, reflecting systemic inflammation, and cell death. In addition, it has been suggested that cf‐DNA could promote autoinflammation. Because the total cf‐DNA pool comprises different cf‐DNA species, we quantified the plasma levels of gene‐coding cf‐DNA, Alu repeat cf‐DNA, mitochondrial DNA (mtDNA) copy number, and the amounts of unmethylated and total cf‐DNAs. We identified the relationships between these cf‐DNA species and age‐associated inflammation, immunosenescence, and frailty. Additionally, we determined the cf‐DNA species‐specific transcriptomic signatures in blood mononuclear cells to elucidate the age‐linked leukocyte responses to cf‐DNA. The study population consisted of n = 144 nonagenarian participants of the Vitality 90+ Study and n = 30 young controls. In the nonagenarians, higher levels of total and unmethylated cf‐DNAs were associated with systemic inflammation and increased frailty. The mtDNA copy number was also directly correlated with increased frailty but not with inflammation. None of the cf‐DNA species were associated with immunosenescence. The transcriptomic pathway analysis revealed that higher levels of total and unmethylated cf‐DNAs were associated with immunoinflammatory activation in the nonagenarians but not in the young controls. The plasma mtDNA appeared to be inert in terms of inflammatory activation in both the nonagenarians and young controls. These data demonstrate that the plasma levels of total and unmethylated cf‐DNA and the mtDNA copy number could serve as biomarkers of frailty. In addition, we suggest that circulating self‐DNA, assessed as total or unmethylated cf‐DNA, might aggravate immunoinflammatory reactivity in very old individuals.
Dietary restriction of rodents decreases aging rate without affecting initial mortality rate – a meta‐analysis
Authors: Simons Mirre J. P. , Koch Wouter , Verhulst Simon
Published: February 2013

Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz–Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age‐dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta‐analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life‐extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often‐reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously.
Characterizing the longitudinal patterns of substance use among individuals diagnosed with serious mental illness after psychiatric hospitalization
Authors: Bahorik Amber L. , Newhill Christina E. , Eack Shaun M.
Published: February 2013

Aim

To characterize longitudinal patterns of substance use across a large sample of psychiatric patients discharged from inpatient admission, followed for 1‐year post‐hospitalization.

Design

Prospective cohort study.

Setting

Kansas City, MO, USA; Pittsburgh, PA, USA; Worcester, MA, USA.

Participants

Eight hundred and one schizophrenia‐spectrum (n = 204), bipolar (n = 137) and depressive disorder (n = 460) patients from the MacArthur Violence Risk Assessment Study.

Measurements

Symptoms, functioning, drug/alcohol use assessed by the Brief Psychiatric Rating Scale, the Global Assessment of Functioning, and substance use interviews.

Findings

Patients used alcohol (67.0%;n = 540) and cannabis (30.0%;n = 237) more frequently than other substances up to 30 days before admission, and those with depressive and schizophrenia‐spectrum used heroin more than individuals with bipolar (P = 0.023). Post‐hospitalization, patients using alcohol (B = −0.15,P < 0.001) and cannabis (B = −0.27,P < 0.001) decreased, but patterns varied across diagnosis and genders. Patients using cannabis decreased at greater rates in depressive and schizophrenia‐spectrum compared with bipolar (allP < 0.05), and more men used alcohol (B = 0.76,P < 0.001) and cannabis (B = 1.56,P < 0.001) than women. Cannabis (B = 1.65,P < 0.001) and alcohol (B = 1.04,P = 0.002) were associated with higher symptomatology; cannabis (B = −2.33,P < 0.001) and alcohol (B = −1.45,P = 0.012) were associated with lower functioning.

Conclusions

Substance use is frequent and associated with poor recovery in patients with serious mental illness recently discharged from psychiatric hospitalization. Addiction treatments personalized by diagnosis and gender may be effective for improving outcomes in people with serious mental illness.
Deep Interactions with MRP: Election Turnout and Voting Patterns Among Small Electoral Subgroups
Authors: Ghitza Yair , Gelman Andrew
Published: February 2013

Using multilevel regression and poststratification (MRP), we estimate voter turnout and vote choice within deeply interacted subgroups: subsets of the population that are defined by multiple demographic and geographic characteristics. This article lays out the models and statistical procedures we use, along with the steps required to fit the model for the 2004 and 2008 presidential elections. Though MRP is an increasingly popular method, we improve upon it in numerous ways: deeper levels of covariate interaction, allowing for nonlinearity and nonmonotonicity, accounting for unequal inclusion probabilities that are conveyed in survey weights, postestimation adjustments to turnout and voting levels, and informative multidimensional graphical displays as a form of model checking. We use a series of examples to demonstrate the flexibility of our method, including an illustration of turnout and vote choice as subgroups become increasingly detailed, and an analysis of both vote choice changes and turnout changes from 2004 to 2008.
Citizenship and Belonging in the Rural Fringe: A Case Study of a Hindu Temple in Sydney, Australia
Authors: Bugg Laura Beth
Published: February 2013

Despite Australian multicultural policy that asserts the right of all citizens to maintain and practice their religion, formal citizenship has not guaranteed the welcome or belonging of migrant religious groups at the neighbourhood scale. This is most starkly reflected in contests over the inclusion of minority religious spaces in the Australian landscape, which increasingly take place in the rural–urban fringe of metropolitan areas. This work examines the controversy over a proposed Hindu temple in metropolitan Sydney and reveals insights into the way that rural–urban fringe space is imagined, understood and experienced by land use planners, residents and temple members. Critical discourse analysis of policy documentation along with interviews reveals that land use planners circumscribe belonging in the landscape through the use of zoning ordinances and design controls, local residents mark the boundaries of white privilege through narratives of heritage and cultural difference and temple members claim rights to citizenship based on assertions of sameness.
DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice
Authors: Kawamura Yoshiya , Takahashi Taiki , Liu Xiaoxi , Nishida Nao , Tokunaga Katsushi , Ukawa Ko , Noda Yoshihiro , Yoshikawa Akane , Shimada Takafumi , Umekage Tadashi , Sasak Tsukasa
Published: February 2013

Introduction

Impulsivity in intertemporal choice has been operationalized as “delay discounting”, referring to the preference for a sooner, smaller reward. FK506 binding protein 5 (FKBP5) is a co‐chaperone of the glucocorticoid receptor (GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma cortisol levels. High cortisol levels are associated with low impulsivity in intertemporal choice. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in FKBP5 on delay discounting.

Methods

The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed Kirby's monetary choice questionnaire (MCQ) and donated a whole blood sample. Five SNPs in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time‐discount rate (k).

Results

Two SNPs were excluded from analysis because of their low minor allelic frequencies. The SNP rs1360780 showed a significant association; participants with more minor alleles (T) were less impulsive in intertemporal choice for delayed gain (multiplicity‐corrected P = 0.047).

Discussion

The significant SNP rs1360780 is located in the region adjacent to the hormone response element (HRE)‐binding sequence where transcription factors bind and alter the transcription of FKBP5. A minor allele (T) of rs1360780, which causes FKBP5 overexpression, may reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR resistance and the subsequent high cortisol levels. This is the first study to demonstrate an association between FKBP5 and impulsivity in intertemporal choice.
Aripiprazole for the treatment of pediatric bipolar I disorder: a 30‐week, randomized, placebo‐controlled study
Authors: Findling Robert L , Correll Christoph U , Nyilas Margaretta , Forbes Robert A , McQuade Robert D , Jin Na , Ivanova Svetlana , Mankoski Raymond , Carson William H , Carlson Gabrielle A
Published: February 2013

Objective:  To evaluate the long‐term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder.

Methods:  A randomized, double‐blind, 30‐week, placebo‐controlled study of aripiprazole (10 or 30 mg/day) in youths (10–17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double‐blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change.

Results:  Of the 210 subjects who entered the 26‐week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol‐specified last observation carried forward analyses, but not in observed case or mixed‐model repeated measures at week 30. Overall time to all‐cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children’s Global Assessment of Functioning and Clinical Global Impressions‐Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder.

Conclusions:  Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.
A phase 2 multicentre study of siltuximab, an anti‐interleukin‐6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma
Authors: Voorhees Peter M. , Manges Robert F. , Sonneveld Pieter , Jagannath Sundar , Somlo George , Krishnan Amrita , Lentzsch Suzanne , Frank Richard C. , Zweegman Sonja , Wijermans Pierre W. , Orlowski Robert Z. , Kranenburg Britte , Hall Brett , Casneuf Tineke , Qin Xiang , van de Velde Helgi , Xie Hong , Thomas Sheeba K.
Published: February 2013

Interleukin‐6 (IL6) plays a central role in multiple myeloma pathogenesis and confers resistance to corticosteroid‐induced apoptosis. We therefore evaluated the efficacy and safety of siltuximab, an anti‐IL6 monoclonal antibody, alone and in combination with dexamethasone, for patients with relapsed or refractory multiple myeloma who had ≥2 prior lines of therapy, one of which had to be bortezomib‐based. Fourteen initial patients received siltuximab alone, 10 of whom had dexamethasone added for suboptimal response; 39 subsequent patients were treated with concurrent siltuximab and dexamethasone. Patients received a median of four prior lines of therapy, 83% were relapsed and refractory, and 70% refractory to their last dexamethasone‐containing regimen. Suppression of serum C‐reactive protein levels, a surrogate marker of IL6 inhibition, was demonstrated. There were no responses to siltuximab but combination therapy yielded a partial (17%) + minimal (6%) response rate of 23%, with responses seen in dexamethasone‐refractory disease. The median time to progression, progression‐free survival and overall survival for combination therapy was 4·4, 3·7 and 20·4 months respectively. Haematological toxicity was common but manageable. Infections occurred in 57% of combination‐treated patients, including ≥grade 3 infections in 18%. Further study of siltuximab in modern corticosteroid‐containing myeloma regimens is warranted, with special attention to infection‐related toxicity.
Using mixture models with known class membership to address incomplete covariance structures in multiple‐group growth models
Authors: Kim Su‐Young , Mun Eun‐Young , Smith Stevens
Published: February 2013

Multi‐group latent growth modelling in the structural equation modelling framework has been widely utilized for examining differences in growth trajectories across multiple manifest groups. Despite its usefulness, the traditional maximum likelihood estimation for multi‐group latent growth modelling is not feasible when one of the groups has no response at any given data collection point, or when all participants within a group have the same response at one of the time points. In other words, multi‐group latent growth modelling requires a complete covariance structure for each observed group. The primary purpose of the present study is to show how to circumvent these data problems by developing a simple but creative approach using an existing estimation procedure for growth mixture modelling. A Monte Carlo simulation study was carried out to see whether the modified estimation approach provided tangible results and to see how these results were comparable to the standard multi‐group results. The proposed approach produced results that were valid and reliable under the mentioned problematic data conditions. We also present a real data example and demonstrate that the proposed estimation approach can be used for the chi‐square difference test to check various types of measurement invariance as conducted in a standard multi‐group analysis.
The Role of Chromatin Remodeling in Medulloblastoma
Authors: Jones David T. W. , Northcott Paul A. , Kool Marcel , Pfister Stefan M.
Published: February 2013

The unexpectedly high frequency and universality of alterations to the chromatin machinery is one of the most striking themes emerging from the current deluge of cancer genomics data. Medulloblastoma (MB), a malignant pediatric brain tumor, is no exception to this trend, with a wealth of recent studies indicating multiple alterations at all levels of chromatin processing. MB is typically now regarded as being composed of four major molecular entities (WNT, SHH, Group 3 and Group 4), which vary in their clinical and biological characteristics. Similarities and differences across these subgroups are also reflected in the specific chromatin modifiers that are found to be altered in each group, and each new cancer genome sequence or microarray profile is adding to this important knowledge base. These data are fundamentally changing our understanding of tumor developmental pathways, not just for MB but also for cancer as a whole. They also provide a new class of targets for the development of rational, personalized therapeutic approaches. The mechanisms by which these chromatin remodelers are dysregulated in MB, and the consequences both for future basic research and for translation to the clinic, will be examined here.
Emerging Insights into the Ependymoma Epigenome
Authors: Mack Stephen C. , Witt Hendrik , Wang Xin , Milde Till , Yao Yuan , Bertrand Kelsey C. , Korshunov Andrey , Pfister Stefan M. , Taylor Michael D.
Published: February 2013

Ependymoma is the third most common pediatric brain tumor, yet because of the paucity of effective therapeutic interventions, 45% of patients remain incurable. Recent transcriptional and copy number profiling of the disease has identified few driver genes and in fact points to a balanced genomic profile. Candidate gene approaches looking at hypermethylated promoters and genome‐wide epigenetic arrays suggest that DNA methylation may be critical to ependymoma pathogenesis. This review attempts to highlight existing and emerging evidence implicating the ependymoma epigenome as a key player and that epigenetic modifiers may offer new targeted therapeutic avenues for patients.
Chromatin Remodeling Defects in Pediatric and Young Adult Glioblastoma: A Tale of a Variant Histone 3 Tail
Authors: Fontebasso Adam M. , Liu Xiao‐Yang , Sturm Dominik , Jabado Nada
Published: February 2013

Primary brain tumors occur in 8 out of 100 000 people and are the leading cause of cancer‐related death in children. Among brain tumors, high‐grade astrocytomas (HGAs) including glioblastoma multiforme (GBM) are aggressive and are lethal human cancers. Despite decades of concerted therapeutic efforts, HGAs remain essentially incurable in adults and children. Recent discoveries have revolutionized our understanding of these tumors in children and young adults. Recurrent somatic driver mutations in the tail of histone 3 variant 3 (H3.3), leading to amino acid substitutions at key residues, namely lysine (K) 27 (K27M) and glycine 34 (G34R/G34V), were identified as a new molecular mechanism in pediatric GBM. These mutations represent the pediatric counterpart of the recurrent mutations in isocitrate dehydrogenases (IDH) identified in young adult gliomas and provide a much‐needed new pathway that can be targeted for therapeutic development. This review will provide an overview of the potential role of these mutations in altering chromatin structure and affecting specific molecular pathways ultimately leading to gliomagenesis. The distinct changes in chromatin structure and the specific downstream events induced by each mutation need characterizing independently if progress is to be made in tackling this devastating cancer.
PDGFRA Amplification is Common in Pediatric and Adult High‐Grade Astrocytomas and Identifies a Poor Prognostic Group in IDH1 Mutant Glioblastoma
Authors: Phillips Joanna J. , Aranda Derick , Ellison David W. , Judkins Alexander R. , Croul Sidney E. , Brat Daniel J. , Ligon Keith L. , Horbinski Craig , Venneti Sriram , Zadeh Gelareh , Santi Mariarita , Zhou Shengmei , Appin Christina L. , Sioletic Stefano , Sullivan Lisa M. , Martinez‐Lage Maria , Robinson Aaron E. , Yong William H. , Cloughesy Timothy , Lai Albert , Phillips Heidi S. , Marshall Roxanne , Mueller Sabine , Haas‐Kogan Daphne A. , Molinaro Annette M. , Perry Arie
Published: February 2013

High‐grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non‐amplified (normal and polysomy) or amplified (low‐level and high‐level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)R132H mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA amplification is common and can manifest as high‐level and focal or low‐level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.
Online Lexical Competition During Spoken Word Recognition and Word Learning in Children and Adults
Authors: Henderson Lisa , Weighall Anna , Brown Helen , Gaskell Gareth
Published: February 2013

Lexical competition that occurs as speech unfolds is a hallmark of adult oral language comprehension crucial to rapid incremental speech processing. This study used pause detection to examine whether lexical competition operates similarly at 7–8 years and tested variables that influence “online” lexical activity in adults. Children (n = 20) and adults (n = 17) were slower to detect pauses in familiar words with later uniqueness points. Faster latencies were obtained for words with late uniqueness points in constraining compared with neutral sentences; no such effect was observed for early unique words. Following exposure to novel competitors (“biscal”), children (n = 18) and adults (n = 18) showed competition for existing words with early uniqueness points (“biscuit”) after 24 hr. Thus, online lexical competition effects are remarkably similar across development.
Preschoolers Use Emotion in Speech to Learn New Words
Authors: Berman Jared M. J. , Graham Susan A. , Callaway Dallas , Chambers Craig G.
Published: February 2013

Two experiments examined 4‐ and 5‐year‐olds' use of vocal affect to learn new words. In Experiment 1 (n = 48), children were presented with two unfamiliar objects, first in their original state and then in an altered state (broken or enhanced). An instruction produced with negative, neutral, or positive affect, directed children to find the referent of a novel word. During the novel noun, eye gaze measures indicated that both 4‐ and 5‐year‐olds were more likely to consider an object congruent with vocal affect cues. In Experiment 2, 5‐year‐olds (n = 15) were asked to extend and generalize their initial mapping to new exemplars. Here, 5‐year‐olds generalized these newly mapped labels but only when presented with negative vocal affect.
A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study
Authors: Theofylaktopoulou D , Midttun Ø , Ulvik A , Ueland P M , Tell G S , Vollset S E , Nygård O , Eussen S J P M
Published: February 2013

Circulating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine pathway. We measured neopterin, tryptophan, kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid in plasma in two age groups, 45–46 years (n = 3723) and 70–72 years (n = 3329). Differences across categories of the potential determinants, including age, gender, renal function, body mass index (BMI), smoking and physical activity, were tested by Mann–Whitney U-test and multiple linear regression including age group, gender, renal function and lifestyle factors. In this multivariate model, neopterin, KTR and most kynurenines were 20–30% higher in the older group, whereas tryptophan was 7% lower. Men had 6–19% higher concentrations of tryptophan and most kynurenines than women of the same age. Compared to the fourth age-specific estimated glomerular filtration rate (eGFR) quartile, the first quartile was associated with higher concentrations of neopterin (25%) and KTR (24%) and 18–36% higher concentrations of kynurenines, except 3-hydroxyanthranilic acid. Additionally, KTR, tryptophan and all kynurenines, except anthranilic acid, were 2–8% higher in overweight and 3–17% higher in obese, than in normal-weight individuals. Heavy smokers had 4–14% lower levels of tryptophan and most kynurenines than non-smokers. Age and renal function were the strongest determinants of plasma neopterin, KTR and most kynurenines. These findings are relevant for the design and interpretation of studies investigating the role of plasma neopterin, KTR and kynurenines in chronic diseases.
Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases
Authors: Frauenknecht V , Thiel S , Storm L , Meier N , Arnold M , Schmid J-P , Saner H , Schroeder V
Published: February 2013

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.
Doing the right thing for one's children: deciding whether to take the genetic test for Huntington's disease as a moral dilemma
Authors: Smith JA , Stephenson M , Jacobs C , Quarrell O
Published: February 2013

This is a qualitative examination of candidates' decision‐making in relation to the genetic test for Huntington's disease. Semi‐structured interviews were conducted with nine participants who were asked about factors influencing their decision whether to take up predictive genetic testing. Transcripts of interviews were subjected to interpretative phenomenological analysis to elicit emergent themes. A key factor for participants was to do the right thing for their children. Interestingly, this factor presents a moral dilemma to participants and can direct them either towards or away from testing. This article offers a detailed examination of how participants think through this dilemma.
Modes of delivery of genetic testing services and the uptake of cancer risk management strategies in BRCA1 and BRCA2 carriers
Authors: Pal T , Lee J‐H , Besharat A , Thompson Z , Monteiro ANA , Phelan C , Lancaster JM , Metcalfe K , Sellers TA , Vadaparampil S , Narod SA
Published: February 2013

BRCA testing services are now offered by various healthcare providers, thus it is important to evaluate whether the implementation of cancer risk management (CRM) strategies varies by service provider. Using a registry‐based sample of 795 female BRCA mutation carriers, we explored the association between uptake of CRM strategies with duration of genetic counseling (GC) sessions, provider type, and other demographic and clinical variables. All participants completed a baseline questionnaire. Information about uptake of CRM strategies was collected for a subset of 438 participants who completed additional questions. Summary statistics and Pearson chi‐squared analysis were used to examine the associations between demographic and clinical variables with service delivery factors and with the uptake of various CRM strategies. Overall uptake of CRM strategies was high across all provider types. However, GC sessions were longer when provided by a genetics professional than by another provider (p < 0.001). Furthermore, higher frequencies of uptake of most CRM strategies were associated with longer GC sessions and when testing was performed by a genetics professional. Identification of factors to optimize delivery of these specialized GC services is important to maximize implementation of CRM strategies in BRCA carriers.
A randomized controlled clinical multicenter trial comparing the clinical and histological performance of a new, modified polylactide‐co‐glycolide acid membrane to an expanded polytetrafluorethylene membrane in guided bone regeneration procedures
Authors: Schneider David , Weber Franz E. , Grunder Ueli , Andreoni Claude , Burkhardt Rino , Jung Ronald E.
Published: February 2013

Objectives

To compare the clinical and histological outcomes of a resorbable modified polylactide/polyglycolide acid (PLGA) test membrane and a titanium‐reinforced expanded polytetrafluorethylene (ePTFE) control membrane used for guided bone regeneration (GBR) around dental implants.

Materials and methods

A total of 40 patients with peri‐implant dehiscence‐type defects were randomly allocated to a GBR procedure using either a modified PLGA test or an ePTFE control membrane. Soft tissue condition, implant integration, adverse events and quality of life were recorded during the 6‐month healing period. At re‐entry peri‐implant bone defect dimensions were measured and compared with values recorded at implant/GBR surgery. A biopsy was retrieved for qualitative and quantitative histological analyses. A comparison between the groups was conducted using non‐parametric statistical tests.

Results

Soft tissue complications were observed in five test patients and two control patients. Except for soft tissue complications and incomplete regeneration, no procedure‐ or device‐related adverse events were observed. The vertical bone defect component was, in mean, reduced by−5.1 mm (95% CI −6.8, −3.3) in the test group and −6.9 mm (95% CI −8.2, −5.5 mm) in the control group. The mean residual vertical defect height measured 1.2 ± 2.4 mm in the test group and 0.3 ± 1.1 mm in the control group meaning a mean defect resolution of 81% in the test group and 96% in the control group (P = 0.161). The horizontal bone thickness at implant shoulder level decreased from a mean of 3.2 mm to 1.4 mm (−56%, mean −1.7 mm, 95% CI −2.3, −1.1) in the test group and from 3.3 mm to 2.5 mm (−24%, mean −0.8 mm, 95% CI −1.3, −0.3) in the control group (P = 0.022). Qualitative and quantitative histological analyses did not show significant differences in the tissue composition between groups.

Conclusion

Peri‐implant GBR was successfully performed using either of the membranes. The control membrane was able to better maintain the horizontal thickness of regenerated bone and revealed less soft tissue complications. No statistically valid evidence about the superiority of one membrane was found in any other parameters. Soft tissue dehiscences occur with both types of membranes and can impair the amount of regenerated bone.
Reosseointegration of mechanically disintegrated implants in dogs: mechanical and histometric analyses
Authors: Kim Sungtae , Lee Jung‐Seok , Hwang Ji‐Wan , Kim Min‐Soo , Choi Seong‐Ho , Jung Ui‐Won
Published: February 2013

Objectives

This study evaluated the reosseointegration of implants that had been reinserted following the mechanical disintegration of immature osseointegration in dogs.

Materials and methods

Rotationally mobile implants were installed into an oversized drill space in five canine mandibles. After a healing period of 4 weeks, the immature osseointegration of the implant was intentionally disintegrated by the application of a mechanical countertorque and then reinserted at the same site (experimental group); in the control group, the mobile implant remained submerged without any surgical intervention. The animals were euthanized 4 weeks after the disruption of osseointegration. Changes in the implant stability quotient (ISQ) and Periotest value (PTV) were analyzed, and the bone‐implant contact (%) was measured histometrically.

Results

All experimental and control sites showed successful mechanical stability at 8‐week healing period. The mean ISQ was significantly higher in the experimental group than in the control group at 8 weeks (P < 0.01). In histology, immature woven‐bone that bridged between the parent bone and the pre‐existing residual bone on implant surface could be observed in experimental sites. The mean bone‐implant contact was significantly higher in the experimental group than in the control group (P < 0.05).

Conclusion

Within the limitation of the small sample used in this study, it is concluded that following the mechanical disruption of osseointegration, an implant can be successfully reosseointegrated with unloaded and submerged healing for a certain period.
GENDER INEQUALITY IN EDUCATION IN CHINA: A META‐REGRESSION ANALYSIS
Authors: ZENG JUNXIA , PANG XIAOPENG , ZHANG LINXIU , MEDINA ALEXIS , ROZELLE SCOTT
Published: February 2013

Although there is evidence that there was gender inequality in China's education system in the 1980s, the literature in China has mixed evidence on improvements in gender inequality in educational attainment over the past three decades. Some suggest gender inequality is still severe; others report progress. We seek to understand the progress China has made (if any) in reducing gender inequality in education since the 1980s. To meet this goal, we use a meta‐analysis approach which provides a new quantitative review of a relatively large volume of empirical literature on gender educational differentials. This article analyzes differences across both time and space, and also across different grade levels and ethnicities. Our results indicate that gender inequality in educational attainment still exists, but it has been narrowing over time. Moreover, it varies by area (rural versus urban) and grade level. There is nearly no significant gender inequality in the case of girls in urban areas or in the case of the 9 years of compulsory education (primary school and junior high school). Girls, however, still face inequality in rural areas (although inequality is falling over time) and when they reach high school or beyond. (JEL I24)
Temporal mood changes associated with different levels of adolescent drinking: Using mobile phones and experience sampling methods to explore motivations for adolescent alcohol use
Authors: Crooke Alexander H. D. , Reid Sophie C. , Kauer Sylvia D. , McKenzie Dean P. , Hearps Stephen J. C. , Khor Angela S. , Forbes Andrew B.
Published: February 2013

Introduction and Aims

Alcohol use during adolescence is associated with the onset of alcohol use disorders, mental health disorders, substance abuse as well as socially and physically damaging behaviours, the effects of which last well into adulthood. Nevertheless, alcohol use remains prevalent in this population. Understanding motivations behind adolescent alcohol consumption may help in developing more appropriate and effective interventions. This study aims to increase this understanding by exploring the temporal relationship between mood and different levels of alcohol intake in a sample of young people.

Design and Methods

Forty‐one secondary school students used a purpose‐designed mobile phone application to monitor their daily mood and alcohol use for 20 random days within a 31 day period. Generalised estimating equations were used to examine the relationship between differing levels of alcohol consumption (light, intermediate and heavy) and positive and negative mood three days before and after drinking episodes.

Results

While there was no relationship between light and heavy drinking and positive mood, there was an increase in positive mood before and after the drinking event for those that drank intermediate amounts. No statistically significant relationships were found between negative mood and any of the three drinking categories.

Discussion and Conclusion

Adolescents who drank in intermediate amounts on a single drinking occasion experienced an increase in positive mood over the three days leading up to and three days following a drinking event. These findings contribute to an understanding of the motivations that underpin adolescent alcohol use, which may help inform future interventions.
Behavioural recovery on simple and complex tasks by means of cell replacement therapy in unilateral 6‐hydroxydopamine‐lesioned mice
Authors: Heuer Andreas , Vinh Ngoc‐Nga , Dunnett Stephen B.
Published: February 2013

Before cell replacement therapies can enter the clinic, it is imperative to test the therapeutic benefits in well‐described animal models. In the present study, we aimed to investigate the effects of 6‐hydroxydopamine lesions to the medial forebrain bundle and subsequent grafting of embryonic day (E)12.5 ventral mesencephalon into the denervated striatum in C57/Bl6 mice on a battery of simple motor tests (drug‐induced rotation, rotarod, and corridor) and the lateralised choice reaction time task conducted in the mouse nine‐hole box. Histological analysis confirmed effective lesions and good graft survival. The lesion induced marked deficits in the choice reaction time task, the rotarod test, and corridor test, and these deficits were partially but significantly alleviated in the grafted mice. Although the lesions induced significant rotation following injections of amphetamine and apomorphine, respectively, the grafts did not, suprisingly, alleviate the rotation deficit. This study shows the ability of ventral mesencephalic tissue to ameliorate some of the lesion‐induced deficits, and the power of operant testing in detecting small but significant improvements. The behavioural tests presented are useful drug‐free approaches for evaluating cell‐based therapies.
Genetic and life‐history changes associated with fisheries‐induced population collapse
Authors: Pukk Lilian , Kuparinen Anna , Järv Leili , Gross Riho , Vasemägi Anti
Published: February 2013

Over the recent years, growing number of studies suggests that intensive size‐selective fishing can cause evolutionary changes in life‐history traits in the harvested population, which can have drastic negative effects on populations, ecosystems and fisheries. However, most studies to date have overlooked the potential role of immigration of fish with different phenotypes as an alternative plausible mechanism behind observed phenotypic trends. Here, we investigated the evolutionary consequences of intensive fishing simultaneously at phenotypic and molecular level in Eurasian perch (Perca fluviatilis L.) population in the Baltic Sea over a 24‐year period. We detected marked changes in size‐ and age‐distributions and increase in juvenile growth rate. We also observed reduction of age at sexual maturity in males that has frequently been considered to support the hypothesis of fisheries‐induced evolution. However, combined individual‐based life‐history and genetic analyses indicated increased immigration of foreign individuals with different life‐history patterns as an alternative mechanism behind the observed phenotypic change. This study demonstrates the value of combining genetic and phenotypic analyses and suggests that replacement or breakdown of locally adapted gene complexes may play important role in impeding the recovery of fish populations.
Factors affecting live foal rates ofThoroughbred mares that undergo manual twin elimination
Authors: Schnobrich M. R. , Riddle W. T. , Stromberg A. J. , LeBlanc M. M.
Published: February 2013

Reasons for performing study

Mares diagnosed with twin vesicles at 13–17 days after ovulation commonly have one of 2 vesicles manually reduced. It is not known whether vesicle location (adjacent vs. nonadjacent), mare age, mare reproductive status, parity, month of breeding or mare plasma progesterone concentration affects live foal rates.

Objectives

To determine factors associated with a positive outcome (live foal) in mares undergoing manual twin reduction between 13 and 17 days post ovulation when performed by a single operator.

Study design

Retrospective case–control study.

Methods

Breeding records and theJockeyClub records of registeredThoroughbreds were used to evaluate factors affecting the outcome of pregnancies in mares undergoing twin elimination and mares with singleton pregnancies.Thoroughbred mares with twin pregnancies (n = 129) were matched by age, parity, farm location and month bred with mares diagnosed with a singleton pregnancy (n = 127). The effects of location of embryonic vesicles, mare age, reproductive status, parity, month of breeding, vesicle size and plasma progesterone concentration at pregnancy diagnosis on live foal rate were examined.

Results

Position of embryonic vesicles at time of manual elimination, parity and month bred had no effect on live foal rate. Live foal rates in mares >9 years of age were lower (71.8%) than in all mares ≤9 years (87.1%; P<0.05). Mares >9 years of age that had a twin reduced lost more pregnancies (34.8%) than age‐matched control mares (20.0%; P<0.005). Mean plasma progesterone concentration of twin‐reduced mares was greater than in control mares when compared on the same day post ovulation. Plasma progesterone concentrations did not differ between mares that lost their pregnancy and those that delivered a live foal.

Conclusions

Mare age of >9 years is associated with decreased pregnancy rate after twin reduction.

Potential relevance

Furthering the understanding of factors that affect live foal outcome following manual twin elimination in mares.

TheSummary is available inChinese – seeSupporting information.
Fish gut content analysis: robust measures of diet composition
Authors: Baker Ronald , Buckland Amanda , Sheaves Marcus
Published: February 2013

Trophic studies are fundamental components of our understanding of biology and ecology, from observing individual organisms to modelling ecosystem function. When measuring fish gut contents, we rely on collecting samples that represent snapshots in time. Many limitations in extrapolating from these snapshots are well understood. However, there seems to be a widespread belief that when quantifying the composition of gut contents, more detail always provides more information. We highlight some fundamental problems with the apparently more quantitative approaches (i.e. ‘bulk’ methods measuring biomass or volume of each prey type) and suggest that frequency of occurrence (%F) provides the most robust and interpretable measure of diet composition. The additional information provided by bulk methods contains unquantifiable and potentially significant error from a variety of sources. In our experience, the contents of most guts cannot be unambiguously separated into prey categories for quantification because of the presence of unidentifiable and inseparable partially digested material. Even where separation is possible, the composition of a gut at one point in time is affected by many unquantifiable factors unrelated to the actual composition of the diet. Consequently, bulk methods provide ambiguous interpretations from superficially quantitative models. Where research questions require more detail, these problems mean there is little alternative to time‐consuming approaches like prey reconstruction. However, for the descriptions of dietary composition presented in many studies, %F provides robust data that overcome many of the limitations of the more detailed approaches and provides considerable logistical and economic benefits.