bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic epistasis for different alleles of the same gene
Authors: Xu Lin , Barker Brandon , Gu Zhenglong
Published: June 2012

Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including pathway organization, evolution of sexual reproduction, mutational load, ploidy, genomic complexity, speciation, and the origin of life. Nevertheless, current understandings for the genome-wide distribution of epistasis are mostly inferred from interactions among one mutant type per gene, whereas how epistatic interaction partners change dynamically for different mutant alleles of the same gene is largely unknown. Here we address this issue by combining predictions from flux balance analysis and data from a recently published high-throughput experiment. Our results show that different alleles can epistatically interact with very different gene sets. Furthermore, between two random mutant alleles of the same gene, the chance for the allele with more severe mutational consequence to develop a higher percentage of negative epistasis than the other allele is 50∼70% in eukaryotic organisms, but only 20∼30% in bacteria and archaea. We developed a population genetics model that predicts that the observed distribution for the sign of epistasis can speed up the process of purging deleterious mutations in eukaryotic organisms. Our results indicate that epistasis among genes can be dynamically rewired at the genome level, and call on future efforts to revisit theories that can integrate epistatic dynamics among genes in biological systems.
Conscious updating is a rhythmic process
Authors: Chakravarthi Ramakrishna , VanRullen Rufin
Published: June 2012

As the visual world changes, its representation in our consciousness must be constantly updated. Given that the external changes are continuous, it appears plausible that conscious updating is continuous as well. Alternatively, this updating could be periodic, if, for example, its implementation at the neural level relies on oscillatory activity. The flash-lag illusion, where a briefly presented flash in the vicinity of a moving object is misperceived to lag behind the moving object, is a useful tool for studying the dynamics of conscious updating. Here, we show that the trial-by-trial variability in updating, measured by the flash-lag effect (FLE), is highly correlated with the phase of spontaneous EEG oscillations in occipital (5–10 Hz) and frontocentral (12–20 Hz) cortices just around the reference event (flash onset). Further, the periodicity in each region independently influences the updating process, suggesting a two-stage periodic mechanism. We conclude that conscious updating is not continuous; rather, it follows a rhythmic pattern.
Diverse genetic basis of field-evolved resistance to Bt cotton in cotton bollworm from China
Authors: Zhang Haonan , Tian Wen , Zhao Jing , Jin Lin , Yang Jun , Liu Chunhui , Yang Yihua , Wu Shuwen , Wu Kongming , Cui Jinjie , Tabashnik Bruce E. , Wu Yidong
Published: June 2012

Evolution of pest resistance reduces the efficacy of insecticidal proteins from
Bacillus thuringiensis
(Bt) used in sprays or in transgenic crops. Although several pests have evolved resistance to Bt crops in the field, information about the genetic basis of field-evolved resistance to Bt crops has been limited. In particular, laboratory-selected resistance to Bt toxin Cry1Ac based on recessive mutations in a gene encoding a toxin-binding cadherin protein has been identified in three major cotton pests, but previous work has not determined if such mutations are associated with field-selected resistance to Bt cotton. Here we show that the most common resistance alleles in field populations of cotton bollworm,
Helicoverpa armigera
, selected with Bt cotton in northern China, had recessive cadherin mutations, including the deletion mutation identified via laboratory selection. However, unlike all previously studied cadherin resistance alleles, one field-selected cadherin resistance allele conferred nonrecessive resistance. We also detected nonrecessive resistance that was not genetically linked with the cadherin locus. In field-selected populations, recessive cadherin alleles accounted for 75–84% of resistance alleles detected. However, most resistance alleles occurred in heterozygotes and 59–94% of resistant individuals carried at least one nonrecessive resistance allele. The results suggest that resistance management strategies must account for diverse resistance alleles in field-selected populations, including nonrecessive alleles.
Anions dramatically enhance proton transfer through aqueous interfaces
Authors: Mishra Himanshu , Enami Shinichi , Nielsen Robert J. , Hoffmann Michael R. , Goddard William A. , Colussi Agustín J.
Published: June 2012

Proton transfer (PT) through and across aqueous interfaces is a fundamental process in chemistry and biology. Notwithstanding its importance, it is not generally realized that interfacial PT is quite different from conventional PT in bulk water. Here we show that, in contrast with the behavior of strong nitric acid in aqueous solution, gas-phase HNO
3
does not dissociate upon collision with the surface of water unless a few ions (> 1 per 10
6
H
2
O) are present. By applying online electrospray ionization mass spectrometry to monitor in situ the surface of aqueous jets exposed to HNO
3(g)
beams we found that

production increases dramatically on > 30-μM inert electrolyte solutions. We also performed quantum mechanical calculations confirming that the sizable barrier hindering HNO
3
dissociation on the surface of small water clusters is drastically lowered in the presence of anions. Anions electrostatically assist in drawing the proton away from

lingering outside the cluster, whose incorporation is hampered by the energetic cost of opening a cavity therein. Present results provide both direct experimental evidence and mechanistic insights on the counterintuitive slowness of PT at water-hydrophobe boundaries and its remarkable sensitivity to electrostatic effects.
Cleavage of a putative metal permease in
Chlamydia trachomatis
yields an iron-dependent transcriptional repressor
Authors: Thompson Christopher C. , Nicod Sophie S. , Malcolm Denise S. , Grieshaber Scott S. , Carabeo Rey A.
Published: June 2012

The regulation of iron homeostasis is essential for most organisms, because iron is required for a variety of conserved biochemical processes, yet can be toxic at high concentrations. Upon experiencing iron starvation in vitro, the obligate intracellular human pathogen
Chlamydia trachomatis
exhibits elevated expression of a putative iron-transport system encoded by the
ytg
operon. The third component of the
ytg
operon, CT069 (YtgCR), encodes a protein with two distinct domains: a membrane-anchored metal ion permease and a diphtheria toxin repressor (DtxR)-like transcriptional repressor. In this report, we demonstrate that the C-terminal domain of CT069 (YtgR) serves as an iron-dependent autorepressor of the
ytg
operon. Moreover, the nascent full-length metal permease-transcriptional repressor protein was processed during the course of infection, and heterologously when expressed in
Escherichia coli
. The products produced by heterologous cleavage in
E. coli
were functional in the repression of a reporter gene downstream of a putative YtgR operator. We report a bona fide mechanism of iron-dependent regulation of transcription in
Chlamydia
. Moreover, the unusual membrane permease-DNA-binding polypeptide fusion configuration was found in several bacteria. Therefore, the DNA-binding capability and liberation of the YtgR domain from a membrane-anchored permease in
C. trachomatis
could represent a previously uncharacterized mechanism for prokaryotic regulation of iron-homeostasis.
Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants
Authors: Eisenberg Dan T. A. , Hayes M. Geoffrey , Kuzawa Christopher W.
Published: June 2012

Telomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide. Telomere length (TL) shortens with age in most proliferating tissues, limiting cell division and thereby contributing to senescence. However, TL increases with age in sperm, and, correspondingly, offspring of older fathers inherit longer telomeres. Using data and samples from a longitudinal study from the Philippines, we first replicate the finding that paternal age at birth is associated with longer TL in offspring (
n
= 2,023,
P
= 1.84 × 10
−6
). We then show that this association of paternal age with offspring TL is cumulative across multiple generations: in this sample, grandchildren of older paternal grandfathers at the birth of fathers have longer telomeres (
n
= 234,
P
= 0.038), independent of, and additive to, the association of their father’s age at birth with TL. The lengthening of telomeres predicted by each year that the father’s or grandfather’s reproduction are delayed is equal to the yearly shortening of TL seen in middle-age to elderly women in this sample, pointing to potentially important impacts on health and the pace of senescent decline in tissues and systems that are cell-replication dependent. This finding suggests a mechanism by which humans could extend late-life function as average age at reproduction is delayed within a lineage.
Rapidly growing tropical trees mobilize remarkable amounts of nitrogen, in ways that differ surprisingly among species
Authors: Russell Ann E. , Raich James W.
Published: June 2012

Fast-growing forests such as tropical secondary forests can accumulate large amounts of carbon (C), and thereby play an important role in the atmospheric CO2balance. Because nitrogen (N) cycling is inextricably linked with C cycling, the question becomes: Where does the N come from to match high rates of C accumulation? In unique experimental 16-y-old plantations established in abandoned pasture in lowland Costa Rica, we used a mass-balance approach to quantify N accumulation in vegetation, identify sources of N, and evaluate differences among tree species in N cycling. The replicated design contained four broad-leaved evergreen tree species growing under similar environmental conditions. Nitrogen uptake was rapid, reaching 409 (±30) kg⋅ha−1⋅y−1, double the rate reported from a Puerto Rican forest and greater than four times that observed at Hubbard Brook Forest (New Hampshire, USA). Nitrogen amassed in vegetation was 874 (±176) kg⋅ha−1, whereas net losses of soil N (0–100 cm) varied from 217 (±146) to 3,354 (±915) kg⋅ha−1(P= 0.018) over 16 y. Soil C:N, δ13C values, and N budgets indicated that soil was the main source of biomass N. InVochysia guatemalensis, however, N fixation contributed >60 kg⋅ha−1⋅y−1. All species apparently promoted soil N turnover, such that the soil N mean residence time was 32–54 y, an order of magnitude lower than the global mean. High rates of N uptake were associated with substantial N losses in three of the species, in which an average of 1.6 g N was lost for every gram of N accumulated in biomass.
Conserved genetic determinant of motor organ identity in
Medicago truncatula
and related legumes
Authors: Chen Jianghua , Moreau Carol , Liu Yu , Kawaguchi Masayoshi , Hofer Julie , Ellis Noel , Chen Rujin
Published: June 2012

Plants exhibit various kinds of movements that have fascinated scientists and the public for centuries. Physiological studies in plants with the so-called motor organ or pulvinus suggest that cells at opposite sides of the pulvinus mediate leaf or leaflet movements by swelling and shrinking. How motor organ identity is determined is unknown. Using a genetic approach, we isolated a mutant designated
elongated petiolule1
(
elp1
) from
Medicago truncatula
that fails to fold its leaflets in the dark due to loss of motor organs. Map-based cloning indicated that
ELP1
encodes a putative plant-specific LOB domain transcription factor. RNA in situ analysis revealed that
ELP1
is expressed in primordial cells that give rise to the motor organ. Ectopic expression of
ELP1
resulted in dwarf plants with petioles and rachises reduced in length, and the epidermal cells gained characteristics of motor organ epidermal cells. By identifying
ELP1
orthologs from other legume species, namely pea (
Pisum sativum
) and
Lotus japonicus
, we show that this motor organ identity is regulated by a conserved molecular mechanism.
Dynamics of TGF-β signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4
Authors: Warmflash Aryeh , Zhang Qixiang , Sorre Benoit , Vonica Alin , Siggia Eric D. , Brivanlou Ali H.
Published: June 2012

The TGF-β pathway plays a vital role in development and disease and regulates transcription through a complex composed of receptor-regulated Smads (R-Smads) and Smad4. Extensive biochemical and genetic studies argue that the pathway is activated through R-Smad phosphorylation; however, the dynamics of signaling remain largely unexplored. We monitored signaling and transcriptional dynamics and found that although R-Smads stably translocate to the nucleus under continuous pathway stimulation, transcription of direct targets is transient. Surprisingly, Smad4 nuclear localization is confined to short pulses that coincide with transcriptional activity. Upon perturbation, the dynamics of transcription correlate with Smad4 nuclear localization rather than with R-Smad activity. In
Xenopus
embryos, Smad4 shows stereotyped, uncorrelated bursts of nuclear localization, but activated R-Smads are uniform. Thus, R-Smads relay graded information about ligand levels that is integrated with intrinsic temporal control reflected in Smad4 into the active signaling complex.
Wave equation with damping affecting only a subset of static Wentzell boundary is uniformly stable
Authors: Cavalcanti Marcelo , Lasiecka Irena , Toundykov Daniel
Published: June 2012

A stabilization/observability estimate and asymptotic energy decay rates are derived for a wave equation with nonlinear damping in a portion of the interior and Wentzell condition on the boundary:∂νu+u=ΔTu\partial _{\nu } u + u = \Delta _{T}u. The dissipation does not affect a full collar of the boundary, thus leaving out a portion subjected to the high-order Wentzell condition.

Observability of wave equations with damping supported away from theNeumannboundary is known to be intrinsically more difficult than the corresponding Dirichlet problem because the uniform Lopatinskii condition is not satisfied by such a system. In the case of a Wentzell boundary, the situation is more difficult since the “natural” energy now includes theH1H^{1}Sobolev norm of the solution on the boundary. To establish uniform stability it is necessary not only to overcome the presence of the Neumann boundary operator, but also to establish an inverse-type coercivity estimate on theH1H^{1}trace norm of the solution. This goal is attained by constructing multipliers based on a refinement ofnonradialvector fields employed for “unobserved” Neumann conditions. These multipliers, along with a suitable geometry (local convexity), allow reconstruction of the high-order part of the potential energy from the damping that is supported only in a far-off region of the domain.
synbreed: a framework for the analysis of genomic prediction data using R
Authors: Wimmer Valentin , Albrecht Theresa , Auinger Hans-Jürgen , Schön Chris-Carolin
Published: June 2012

Summary: We present a novel R package named synbreed to derive genome-based predictions from high-throughput genotyping and large-scale phenotyping data. The package contains a comprehensive collection of functions required to fit and cross-validate genomic prediction models. All functions are embedded within the framework of a single, unified data object. Thereby a versatile genomic prediction analysis pipeline covering data processing, visualization and analysis is established within one software package. The implementation is flexible with respect to a wide range of data formats and models. The package fills an existing gap in the availability of user-friendly software for next-generation genetics research and education.

Availability:  synbreed is open-source and available through CRAN http://cran.r-project.org/web/packages/synbreed. The latest development version is available from R-Forge. The package synbreed is released with a vignette, a manual and three large-scale example datasets (from package synbreedData).

Contact:  chris.schoen@wzw.tum.de

Supplementary Information:  Supplementary data are available at Bioinformatics online.
SAAP-RRBS: streamlined analysis and annotation pipeline for reduced representation bisulfite sequencing
Authors: Sun Zhifu , Baheti Saurabh , Middha Sumit , Kanwar Rahul , Zhang Yuji , Li Xing , Beutler Andreas S. , Klee Eric , Asmann Yan W. , Thompson E. Aubrey , Kocher Jean-Pierre A.
Published: June 2012

Summary: Reduced representation bisulfite sequencing (RRBS) is a cost-effective approach for genome-wide methylation pattern profiling. Analyzing RRBS sequencing data is challenging and specialized alignment/mapping programs are needed. Although such programs have been developed, a comprehensive solution that provides researchers with good quality and analyzable data is still lacking. To address this need, we have developed a Streamlined Analysis and Annotation Pipeline for RRBS data (SAAP-RRBS) that integrates read quality assessment/clean-up, alignment, methylation data extraction, annotation, reporting and visualization. This package facilitates a rapid transition from sequencing reads to a fully annotated CpG methylation report to biological interpretation.

Availability and implementation: SAAP-RRBS is freely available to non-commercial users at the web site http://ndc.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm.

Contact:  baheti.saurabh@mayo.edu or sun.zhifu@mayo.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Cyclic imides and an open-chain amide carboxylic acid from the facile reaction ofcis-cyclohexane-1,2-carboxylic anhydride with the isomeric monofluoroanilines
Authors: Smith Graham , Wermuth Urs D.
Published: June 2012

The structures of the cyclic imidescis-2-(2-fluorophenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione, C14H14FNO2, (I), andcis-2-(4-fluorophenyl)-3a,4,5,6,7,7a-hexahydroisoindoline-1,3-dione, C14H14FNO2, (III), and the open-chain amide acidrac-cis-2-[(3-fluorophenyl)carbamoyl]cyclohexane-1-carboxylic acid, C14H16FNO3, (II), are reported. Cyclic imides (I) and (III) are conformationally similar, with comparable ring rotations about the imide N—Carbond [the dihedral angles between the benzene ring and the five-membered isoindole ring are 55.40 (8)° for (I) and 51.83 (7)° for (III)]. There are no formal intermolecular hydrogen bonds involved in the crystal packing of either (I) or (III). With the acid (II), in which themeta-related F-atom substituent is rotationally disordered (0.784:0.216), the amide group lies slightly out of the benzene plane [the interplanar dihedral angle is 39.7 (1)°]. Intermolecular amide–carboxyl N—H...O hydrogen-bonding interactions between centrosymmetrically related molecules form stacks extending downb, and these are linked acrosscby carboxyl–amide O—H...O hydrogen bonds, giving two-dimensional layered structures which lie in the (011) plane. The structures reported here represent examples of compounds analogous to the phthalimides or phthalanilic acids and have little precedence in the crystallographic literature.
Association of alcohol dehydrogenase polymorphisms and life‐style factors with excessive alcohol intake within the Spanish population (EPIC‐Spain)
Authors: Muñoz Xavier , Amiano Pilar , Celorrio David , Dorronsoro Miren , Sánchez María‐José , Huerta José M. , Barricarte Aurelio , Arriola Larraitz , Navarro Carmen , Molina‐Montes Esther , Chirlaque M. Dolores , Ardanaz Eva , Rodriguez Laudina , Duell Eric J. , Hijona Elizabeth , Herreros‐Villanueva Marta , Sala Núria , Bujanda Luis
Published: June 2012

Aims

To analyse associations between alcohol dehydrogenase (ADH) polymorphisms and alcohol intake in Spanish men and women.

Design and settings

We analysed the relationship between 21 genetic variants in ADH genes and excessive alcohol intake in both men and women. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array and a sex‐stratified analysis was performed.

Measurements

Ethanol intake was calculated using a validated dietary history questionnaire.

Participants

Heavy consumers of alcohol (≥70 g/day in men, ≥42 g/day in women) (653 cases) and very low or non‐consumers (<2 g/day) (880 controls) from the Spanish cohort of the European Prospective Investigation into Cancer (EPIC).

Findings

We found statistically significant associations between alcohol intake and known life‐style factors; namely, smoking and food energy intake (meat and fruit/seeds) in both men and women, as well as with physical activity in women and educational level in men. Additionally, we found that a non‐synonymous coding SNP in ADH1B (rs1229984) is associated inversely with excessive alcohol intake in men [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.11–0.33; P = 4.77E−10) and women (OR = 0.48, 95% CI = 0.27–0.83; P = 0.0067). Furthermore, ADH6 rs3857224 was found associated with heavy alcohol intake in women (OR = 1.61, 95% CI = 1.21–2.14; P = 1.01E−3), but not in men.

Conclusions

In the Spanish population, the single nucleotide polymorphism of alcohol dehydrogenase ADH1B, rs1229984, is associated inversely with alcohol intake in both men and women. Another polymorphism of ADH6, rs3857224, is associated with heavy alcohol intake in women.
Review article: vitamin D and inflammatory bowel disease – established concepts and future directions
Authors: Garg M. , Lubel J. S. , Sparrow M. P. , Holt S. G. , Gibson P. R.
Published: June 2012

Background

Understanding of the role of vitamin D in health and disease has increased markedly in the past decade, with its involvement extending well beyond traditional roles in calcium and phosphate homeostasis and musculoskeletal health. This conceptual expansion has been underpinned by identification and exploration of components of this axis including vitamin D‐binding protein, key enzymes and receptors in multiple cell types, and a greater recognition of nonclassical autocrine and paracrine effects. Its influence in IBD remains uncertain.

Aim

To review the role of vitamin D in bone health, immune regulation and cancer prevention in IBD, and to outline practical issues and limitations of its use.

Methods

An extensive online literature review including PubMed and Medline.

Results

In patients with IBD, the vitamin D axis provides an important and often underutilised pathway to preserving bone health. Furthermore, an exciting body of clinical and basic science research demonstrates that these pathways may have an integral part to play in regulation of the immune response in IBD, through effects on the intestinal barrier, antigen presenting cells and adaptive T cells. The possibility of chemoprevention requires further study. The optimal target level of 25‐hydroxy vitamin D in patients with IBD is currently uncertain, as is the best therapeutic modality.

Conclusions

Study of vitamin D pathways may result in the development of relatively inexpensive therapeutic options to optimise patient outcomes. Further prospective clinical research is required to address efficacy and long‐term safety.
The validity and reliability of the Turkish version of short‐form McGill Pain Questionnaire in patients with leukemia
Authors: Biçici Berna , Yapucu Güneş Ülkü
Published: June 2012

Aims and objectives.  To assess reliability and validity of the Turkish version of the Short‐form McGill Pain Questionnaire.

Background.  Pain is one of the most frequent and significant problems encountered by nurses practice across the world. The Short‐form McGill Pain Questionnaire was widely translated and used to assess the pain experience of several types of patients because it combines the properties of the standard McGill Pain Questionnaire but takes substantially less time to administer.

Design.  The study used psychometric testing to establish reliability and validity of the Turkish version of Short‐form McGill Pain Questionnaire.

Methods.  A convenience sample of 160 patients with leukaemia in Turkey was used to collect data regarding pain evaluation. The original version of the Short‐form McGill Pain Questionnaire, adapted into Turkish, was tested for internal consistency, content validity, construct validity and concurrent validity.

Results.  Internal consistency was found adequate at both assessments with Cronbach’s α 0·88 for test and 0·91 for retest. For reliability of the total, sensory, affective and evaluative total pain intensity, high intraclass correlations were demonstrated (0·85, 0·84, 0·82 and 0·70, respectively). Correlation of total, sensory and affective score with the numerical rating scale was tested for construct validity demonstrating r = 0·61 (p < 0·01) for test and r = 0·68 (p < 0·01) for retest. Correlation with blood pressure values for concurrent validity was found to be r = 0·78 (p < 0·001) for test and r = 0·73 (p < 0·001) for retest.

Conclusion.  Turkish version of the Short‐form McGill Pain Questionnaire has shown statistically acceptable levels of reliability and validity for pain evaluation in patients with leukaemia.

Relevance to clinical practice.  This study provided evidence that the Turkish version of the Short‐form McGill Pain Questionnaire is a reliable and valid instrument for assessing pain. This scale can be used to assess nursing interventions aimed at decreasing pain and efficacy of the treatment.
The minimal relationship between simulation fidelity and transfer of learning
Authors: Norman Geoff , Dore Kelly , Grierson Lawrence
Published: June 2012

Medical Education 2012

Context  High‐fidelity simulators have enjoyed increasing popularity despite costs that may approach six figures. This is justified on the basis that simulators have been shown to result in large learning gains that may transfer to actual patient care situations. However, most commonly, learning from a simulator is compared with learning in a ‘no‐intervention’ control group. This fails to clarify the relationship between simulator fidelity and learning, and whether comparable gains might be achieved at substantially lower cost.

Objectives  This analysis was conducted to review studies that compare learning from high‐fidelity simulation (HFS) with learning from low‐fidelity simulation (LFS) based on measures of clinical performance.

Methods  Using a variety of search strategies, a total of 24 studies contrasting HFS and LFS and including some measure of performance were located. These studies referred to learning in three areas: auscultation skills; surgical techniques, and complex management skills such as cardiac resuscitation.

Results  Both HFS and LFS learning resulted in consistent improvements in performance in comparisons with no‐intervention control groups. However, nearly all the studies showed no significant advantage of HFS over LFS, with average differences ranging from 1% to 2%.

Discussion  The factors influencing learning, and the reasons for this surprising finding, are discussed.
Motivation, learning strategies, participation and medical school performance
Authors: Stegers‐Jager Karen M , Cohen‐Schotanus Janke , Themmen Axel P N
Published: June 2012

Medical Education 2012: 46:678–688

Context  Medical schools wish to better understand why some students excel academically and others have difficulty in passing medical courses. Components of self‐regulated learning (SRL), such as motivational beliefs and learning strategies, as well as participation in scheduled learning activities, have been found to relate to student performance. Although participation may be a form of SRL, little is known about the relationships among motivational beliefs, learning strategies, participation and medical school performance.

Objectives  This study aimed to test and cross‐validate a hypothesised model of relationships among motivational beliefs (value and self‐efficacy), learning strategies (deep learning and resource management), participation (lecture attendance, skills training attendance and completion of optional study assignments) and Year 1 performance at medical school.

Methods  Year 1 medical students in the cohorts of 2008 (n = 303) and 2009 (n = 369) completed a questionnaire on motivational beliefs and learning strategies (sourced from the Motivated Strategies for Learning Questionnaire) and participation. Year 1 performance was operationalised as students’ average Year 1 course examination grades. Structural equation modelling was used to analyse the data.

Results  Participation and self‐efficacy beliefs were positively associated with Year 1 performance (β = 0.78 and β = 0.19, respectively). Deep learning strategies were negatively associated with Year 1 performance (β = − 0.31), but positively related to resource management strategies (β = 0.77), which, in turn, were positively related to participation (β = 0.79). Value beliefs were positively related to deep learning strategies only (β = 0.71). The overall structural model for the 2008 cohort accounted for 47% of the variance in Year 1 grade point average and was cross‐validated in the 2009 cohort.

Conclusions  This study suggests that participation mediates the relationships between motivation and learning strategies, and medical school performance. However, participation and self‐efficacy beliefs also made unique contributions towards performance. Encouraging participation and strengthening self‐efficacy may help to enhance medical student performance.
Maturational differences in undergraduate medical students’ perceptions about feedback
Authors: Murdoch‐Eaton Deborah , Sargeant Joan
Published: June 2012

Medical Education 2012: 46:711–721

Context  Although medical students receive varied feedback throughout their training programmes, research demonstrates that they frequently perceive it as insufficient. However, supervisors tend to perceive that it is adequate. Students’ responses to, and use of, feedback are not clearly understood. The purposes of this study were to investigate how medical students recognise, respond to and utilise feedback, and to determine whether there are maturational differences in understandings of the role of feedback across academic years in medical school.

Methods  This was a mixed‐methods study collecting qualitative (focus group and open‐ended questionnaire items) and quantitative (questionnaire) data across the 5 years of an undergraduate programme.

Results  A total of 68 students participated in 10 focus groups. The questionnaire response rate was 46% (564/1233). Data analysis investigated the students’ perceptions of feedback and explored patterns of responses across the continuum of undergraduate medical school stages. Maturational differences among the year cohorts within the programme emerged in three general areas: (i) student perceptions of the purpose of feedback; (ii) student recognition of feedback, and (iii) student perceptions regarding the credibility of feedback providers.

Conclusions  Junior students generally perceived the receiving of feedback as a passive activity and preferred positive feedback that confirmed their progress and provided reassurance. More senior students viewed feedback as informing their specific learning needs and personal development. They valued immediate informal verbal feedback and feedback from peers and others, as well as that from senior teachers. Exploring students’ progressive degrees of engagement with feedback and its relationship with self‐esteem are subjects for further study.
Prevalence and trend of HIV infection among voluntary blood donors in China since implementation of the Blood Donation Law: a systematic review and meta‐analysis
Authors: Hong Yan , Huang Xia , Ling Hua , Liao Hongwen
Published: June 2012

Objective  In 1998, the Blood Donation Law was enacted in China in response to the outbreak of HIV endemic in central rural China as a result of unhygienic and commercial blood collection. This study aims to provide a first comprehensive review of available data on the prevalence, trend and other epidemiological characteristics of HIV infection among voluntary blood donors since 1998.

Methods  Major English and Chinese databases were searched and a systematic review was constructed. Pooled infection rates by province and year were calculated using random‐effect or fixed‐effect models.

Results  A total of 87 studies met our inclusion criteria. A total of 2573 HIV‐positive cases were identified among voluntary blood donors in the past 10 years; the pooled prevalence was 13.22/100 000, with a range of 0.74–125.97 per 100 000. Among the 24 provinces that reported yearly data, the prevalence of HIV increased from 5.62/100 000 to 28.90/100 000. The male‐to‐female ratio was 2.8; about 60% were below the age of 30 years.

Conclusions  The prevalence of HIV in voluntary blood donors has risen steadily and fast. Efficient measures need to be taken urgently to prevent HIV test‐seeking through blood donor programmes, to promote voluntary blood donation in low‐risk groups and to enforce the Blood Donation Law strictly.
Scaling up Xpert MTB/RIF technology: the costs of laboratory‐ vs. clinic‐based roll‐out in South Africa
Authors: Schnippel Kathryn , Meyer‐Rath Gesine , Long Lawrence , MacLeod William , Sanne Ian , Stevens Wendy S. , Rosen Sydney
Published: June 2012

Objective  The World Health Organization recommends using Xpert MTB/RIF for diagnosis of pulmonary tuberculosis (PTB), but there is little evidence on the optimal placement of Xpert instruments in public health systems. We used recent South African data to compare the cost of placing Xpert at points of TB treatment (all primary clinics and hospitals) with the cost of placement at sub‐district laboratories.

Methods  We estimated Xpert’s cost/test in a primary clinic pilot and in the pilot phase of the national Xpert roll‐out to smear microscopy laboratories; the expected future volumes for each of 223 laboratories or 3799 points of treatment; the number and cost of Xpert instruments required and the national cost of using Xpert for PTB diagnosis for each placement scenario in 2014.

Results  In 2014, South Africa will test 2.6 million TB suspects. Laboratory placement requires 274 Xpert instruments, while point‐of‐treatment placement requires 4020 instruments. With an Xpert cartridge price of $14.00, the cost/test is $26.54 for laboratory placement and $38.91 for point‐of‐treatment placement. Low test volumes and a high number of sites are the major contributors to higher point‐of‐treatment costs. National placement of Xpert at laboratories would cost $71 million/year; point‐of‐treatment placement would cost $107 million/year, 51% more.

Conclusion  Placing Xpert technology at points of treatment is substantially more expensive than placing the instruments in smear microscopy laboratories. The incremental benefits of point‐of‐treatment placement, in terms of better patient outcomes, will have to be equally substantial to justify the additional cost to the national health budget.
Skin thymic stromal lymphopoietin promotes airway sensitization to inhalant house dust mites leading to allergic asthma in mice
Authors: Jiang H. , Hener P. , Li J. , Li M.
Published: June 2012

Asthma is often preceded by atopic dermatitis (AD), a phenomenon known as ‘atopic march’. It has been suggested that sensitization to common inhalant allergens, which is developed in a majority of patients with AD and often during the course of AD, may play a critical role in triggering the atopic march. Yet, what signal(s) delivered by AD skin could promote sensitization to inhalant allergens remains elusive. Here, by employing an experimental mouse asthma protocol, which is induced by airway sensitization and challenge to inhalant house dust mite (HDM), we demonstrate that the overproduction of cytokine thymic stromal lymphopoietin (TSLP) by AD skin promotes airway sensitization to HDM, thereby triggering subsequently an allergic asthma. Together, this study provides, for the first time, the experimental proof that TSLP represents an AD skin‐delivered signal to promote sensitization to inhalant aeroallergen, which may account for one mechanism underlying the ‘atopic march’.
Impact of donor obesity and donation after cardiac death on outcomes after kidney transplantation
Authors: Ortiz Jorge , Gregg Austin , Wen Xuerong , Karipineni Farah , Kayler Liise K.
Published: June 2012

The effect of donor body mass index (BMI) and donor type on kidney transplant outcomes has not been well studied. Scientific Registry of Transplant Recipients data on recipients of deceased‐donor kidneys between 1997 and 2010 were reviewed. Donors were categorized by DCD status (DCD, 6932; non‐DCD, 90,158) and BMI groups at 5 kg/m2 increments: 18.5–24.9, 25–29.9, 30–34.9, 35–39.9, 40–44.9, and ≥ 45 kg/m2. The primary outcome, death‐censored graft survival (DCGS), was adjusted for donor, recipient, and transplant characteristics. Among recipients of non‐DCD kidneys, donor BMI was not associated with DCGS. Among DCD recipients, donor BMI was not associated with DCGS for donor BMI categories <45 kg/m2; however, donor BMI ≥45 kg/m2 was independently associated with DCGS compared to BMI of 20–24.9 kg/m2 (adjusted hazard ratio, 1.84; 95% CI, 1.23, 2.74). The adjusted odds of delayed graft function (DGF) was greater for each level of BMI above reference for both DCD and non‐DCD groups. There was no association of donor BMI with one‐yr acute rejection for either type of donor. Although BMI is associated with DGF, long‐term graft survival is not affected except in the combination of DCD with extreme donor BMI ≥45.
Adherence with immunosuppressive treatment after transplantation: results from the French trial PREDICT
Authors: Dharancy Sebastien , Giral Magali , Tetaz Rachel , Fatras Michel , Dubel Laurence , Pageaux Georges‐Philippe
Published: June 2012

Although immunosuppressive therapy after organ transplantation is paramount for long‐term outcomes, patients do not comply with their immunosuppressive treatment as much as might be expected. In this observational study, patients having undergone a kidney or liver transplantation were enrolled. Adherence was evaluated by patients using the compliance evaluation test and by physicians using a visual analogic scale. A linear regression was performed to identify determinants of adherence. Less patients having undergone kidney transplantation (27%) described themselves as good compliers than liver transplanted patients (40%). Discrepancy was noted between the physician and patient assessments. Rates of good adherence were significantly different depending on gender, age at transplantation, retransplantation, and time elapsed since transplantation, in at least one of the groups evaluated (whole cohort, kidney liver transplantation groups). In all three groups, adherence decreased with the number of immunosuppressants prescribed. In the whole cohort, the rate of good adherence was significantly higher in patients taking lower number of immunosuppressive drugs (45% for 1 vs. 24% for 3 immunosuppressants; p = 0.02). In this study, which is the first study of this scale in France, we confirmed that adherence with immunosuppressant treatment was low and that simpler treatment regimens may favor adherence.
The transcriptional regulator, CosR, controls compatible solute biosynthesis and transport, motility and biofilm formation in Vibrio cholerae
Authors: Shikuma Nicholas J. , Davis Kimberly R. , Fong Jiunn N. C. , Yildiz Fitnat H.
Published: June 2012

Vibrio cholerae inhabits aquatic environments and colonizes the human digestive tract to cause the disease cholera. In these environments, V. cholerae copes with fluctuations in salinity and osmolarity by producing and transporting small, organic, highly soluble molecules called compatible solutes, which counteract extracellular osmotic pressure. Currently, it is unclear how V. cholerae regulates the expression of genes important for the biosynthesis or transport of compatible solutes in response to changing salinity or osmolarity conditions. Through a genome‐wide transcriptional analysis of the salinity response of V. cholerae, we identified a transcriptional regulator we name CosR for compatible solute regulator. The expression of cosR is regulated by ionic strength and not osmolarity. A transcriptome analysis of a ΔcosR mutant revealed that CosR represses genes involved in ectoine biosynthesis and compatible solute transport in a salinity‐dependent manner. When grown in salinities similar to estuarine environments, CosR activates biofilm formation and represses motility independently of its function as an ectoine regulator. This is the first study to characterize a compatible solute regulator in V. cholerae and couples the regulation of osmotic tolerance with biofilm formation and motility.
Breakfast consumption in UK schoolchildren and provision of school breakfast clubs
Authors: Hoyland A. , McWilliams K. A. , Duff R. J. , Walton J. L.
Published: June 2012

Breakfast is known to confer benefits for children, including improvement in nutrient and weight status as well as cognitive performance. Reliable UK‐specific data regarding breakfast consumption patterns in schoolchildren and the provision of breakfast clubs in schools are limited, but are required to inform academics and policy makers alike. The aim of this study was to establish patterns in breakfast consumption in UK schoolchildren and to assess the current provision of breakfast clubs in England. Data were gathered by Childwise in June–July 2011. The large population representative sample included a total of 65 schools (38 primary and 27 secondary), from which 3311 children aged 5–15 years were surveyed at school regarding their breakfast consumption. Data regarding school breakfast club provision were collected from 2087 teachers via the National Foundation for Educational Research omnibus. The results indicated that 86% of children ate something before school (whether at home, on the way to school or at a school breakfast club). Of the remaining 14% of breakfast skippers, a third reported not eating anything until lunch time. The extent of breakfast skipping was higher in girls than boys, and higher in secondary than primary school pupils. Breakfast skipping also varied by UK region, such that the highest levels were evident in Scotland and the North West of England, and the lowest in the East of England. Within secondary schools, breakfast skipping was higher in schools from urban areas and areas of high deprivation. Of the 86% of children who did eat breakfast, 4% reported consuming it at a school breakfast club and a further 4% on the way to school. In contrast, 56% of schools in England were found to be operating a breakfast club at the time of survey, with greater availability at primary compared with secondary school. Overall, the findings suggest that breakfast skipping remains a considerable problem in UK schoolchildren, particularly in adolescents.
Election Cycles in MPs' outside Interests? The UK House of Commons, 2005–2010
Authors: Geys Benny
Published: June 2012

Politicians often implement popular changes in public policies prior to elections, with the aim of improving their Election Day outcome. This research note evaluates whether such ‘electioneering’ carries over also into politicians' extra-parliamentary activities. Evidence from the UK House of Commons over the period 2005–10 suggests that adjustments do occur in MPs' outside activities over the election cycle. The safety of the politician's seat and his or her decision to stand for re-election play an important mediating role.
Lockean Toleration: Dialogical not Theological?
Authors: Vernon Richard
Published: June 2012

It is often claimed that the idea of toleration emerged from and depends upon a Protestant context that limits its usefulness today. These claims implicate the political thought of John Locke, clearly a key figure for the history of toleration, and also an emphatically Protestant one. The fullest support for the claim in question is offered by Jeremy Waldron's God, Locke and Equality, which argues that the idea of equality on which Locke based his case cannot be separated from its religious foundations. Taking issue with Waldron's view, this article argues that in the course of defending toleration Locke came to advance an idea of equality that may be termed ‘dialogical’, in that it rested on the equality that is necessarily presupposed by argumentative exchange. While that idea of equality is fully consistent with Locke's Protestantism, it does not, the article argues, depend upon it. Rather, it depends on the minimum requirements of shared citizenship. Civil equality is modelled, in Locke's defence of toleration, on what is presupposed by shared membership in political society, and no religious view is indispensable to it. Moreover, while the ‘Protestant’ reading of Locke may seem unique in introducing an element of compulsion, the ‘dialogical’ reading may introduce as much compulsion as is needed for the purposes of contractualist political theory.
Predictors for long‐term seizure outcome in juvenile myoclonic epilepsy: 25–63 years of follow‐up
Authors: Geithner Julia , Schneider Felix , Wang Zhong , Berneiser Julia , Herzer Rosemarie , Kessler Christof , Runge Uwe
Published: June 2012

Purpose:  The long‐term seizure outcome of juvenile myoclonic epilepsy (JME) is still controversial; the value of factors that are potentially predictive for seizure outcome remains unclear. The aim of this study was both to investigate the long‐term seizure outcome in patients with JME after a follow‐up of at least 25 years and to identify factors that are predictive for the seizure outcome.

Methods:  Data from 31 patients (19 women) with JME were studied. All of them had a follow‐up of at least 25 years (mean 39.1 years) and were reevaluated with a review of their medical records and direct telephone or face‐to‐face interview.

Key Findings:  Of 31 patients 21 (67.7%) became seizure‐free; in six of them (28.6%) antiepileptic drug (AED) treatment was discontinued due to seizure freedom. The occurrence of generalized tonic–clonic seizures (GTCS) preceded by bilateral myoclonic seizures (BMS) (p = 0.03), a long duration of epilepsy with unsuccessful treatment (p = 0.022), and AED polytherapy (p = 0.023) were identified as significant predictors for a poor long‐term seizure outcome, whereas complete remission of GTCS under AED significantly increased the chance for complete seizure freedom (p = 0.012). The occurrence of photoparoxysmal responses significantly increases the risk of seizure recurrence after AED discontinuation (p = 0.05).

Significance:  This study shows conclusively that JME is a heterogeneous epilepsy syndrome. Life‐long AED treatment is not necessarily required to maintain seizure freedom. Several long‐term outcome predictors that can potentially increase the ability of clinicians and their confidence to recommend different treatment options to patients with JME were identified.