bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of night-time dyspnoea in COPD and its implications for prognosis
Authors: Lange Peter , Marott Jacob Louis , Vestbo Jørgen , Nordestgaard Børge Grønne
Published: February 2014

The information on night-time symptoms in chronic obstructive pulmonary disease (COPD) is sparse.

We investigated the prevalence of night-time dyspnoea in 6616 individuals with COPD recruited from the general population in the Copenhagen area, Denmark, and described characteristics and prognosis of subjects with this symptom.

The prevalence of night-time dyspnoea was 4.3%: 2.1% in Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A, 12.9% in GOLD B, 2.6% in GOLD C and 16.3% in GOLD D. Compared with individuals without night-time dyspnoea, those with night time dyspnoea had lower forced expiratory volume in 1 s, higher daytime dyspnoea scores (modified Medical Research Council scale) and more wheezing, more often had chronic mucus hypersecretion, ischaemic heart disease and atrial fibrillation, and more often reported stress, nervousness and tiredness. After adjustment for age and sex, the presence of night-time dyspnoea was associated with future COPD exacerbations (hazard ratio (HR) 2.3, 95% CI 1.7–3.0), hospital admissions due to COPD (HR 3.2, 95% CI 2.3–4.4) and mortality (HR 1.7, 95% CI 1.2–2.3).

Prevalence of night-time dyspnoea in COPD increases with disease severity according to both spirometric and clinical GOLD classification, and is associated with presence of daytime respiratory symptoms and cardiac comorbidities. Night-time dyspnoea is a significant predictor of poor prognosis in individuals with COPD.
Inferring clonal evolution of tumors from single nucleotide somatic mutations
Authors: Jiao Wei , Vembu Shankar , Deshwar Amit G , Stein Lincoln , Morris Quaid
Published: February 2014

Background

High-throughput sequencing allows the detection and quantification of frequencies of somatic single nucleotide variants (SNV) in heterogeneous tumor cell populations. In some cases, the evolutionary history and population frequency of the subclonal lineages of tumor cells present in the sample can be reconstructed from these SNV frequency measurements. But automated methods to do this reconstruction are not available and the conditions under which reconstruction is possible have not been described.

Results

We describe the conditions under which the evolutionary history can be uniquely reconstructed from SNV frequencies from single or multiple samples from the tumor population and we introduce a new statistical model, PhyloSub, that infers the phylogeny and genotype of the major subclonal lineages represented in the population of cancer cells. It uses a Bayesian nonparametric prior over trees that groups SNVs into major subclonal lineages and automatically estimates the number of lineages and their ancestry. We sample from the joint posterior distribution over trees to identify evolutionary histories and cell population frequencies that have the highest probability of generating the observed SNV frequency data. When multiple phylogenies are consistent with a given set of SNV frequencies, PhyloSub represents the uncertainty in the tumor phylogeny using a “partial order plot”. Experiments on a simulated dataset and two real datasets comprising tumor samples from acute myeloid leukemia and chronic lymphocytic leukemia patients demonstrate that PhyloSub can infer both linear (or chain) and branching lineages and its inferences are in good agreement with ground truth, where it is available.

Conclusions

PhyloSub can be applied to frequencies of any “binary” somatic mutation, including SNVs as well as small insertions and deletions. The PhyloSub and partial order plot software is available from https://github.com/morrislab/phylosub/.
uPEPperoni: An online tool for upstream open reading frame location and analysis of transcript conservation
Authors: Skarshewski Adam , Stanton-Cook Mitchell , Huber Thomas , Al Mansoori Sumaya , Smith Ross , Beatson Scott A , Rothnagel Joseph A
Published: February 2014

Background

Several small open reading frames located within the 5′ untranslated regions of mRNAs have recently been shown to be translated. In humans, about 50% of mRNAs contain at least one upstream open reading frame representing a large resource of coding potential. We propose that some upstream open reading frames encode peptides that are functional and contribute to proteome complexity in humans and other organisms. We use the term uPEPs to describe peptides encoded by upstream open reading frames.

Results

We have developed an online tool, termed uPEPperoni, to facilitate the identification of putative bioactive peptides. uPEPperoni detects conserved upstream open reading frames in eukaryotic transcripts by comparing query nucleotide sequences against mRNA sequences within the NCBI RefSeq database. The algorithm first locates the main coding sequence and then searches for open reading frames 5′ to the main start codon which are subsequently analysed for conservation. uPEPperoni also determines the substitution frequency for both the upstream open reading frames and the main coding sequence. In addition, the uPEPperoni tool produces sequence identity heatmaps which allow rapid visual inspection of conserved regions in paired mRNAs.

Conclusions

uPEPperoni features user-nominated settings including, nucleotide match/mismatch, gap penalties, Ka/Ks ratios and output mode. The heatmap output shows levels of identity between any two sequences and provides easy recognition of conserved regions. Furthermore, this web tool allows comparison of evolutionary pressures acting on the upstream open reading frame against other regions of the mRNA. Additionally, the heatmap web applet can also be used to visualise the degree of conservation in any pair of sequences. uPEPperoni is freely available on an interactive web server at http://upep-scmb.biosci.uq.edu.au.
Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies
Authors: Kalko Susana Graciela , Paco Sonia , Jou Cristina , Rodríguez Maria Angels , Meznaric Marija , Rogac Mihael , Jekovec-Vrhovsek Maja , Sciacco Monica , Moggio Maurizio , Fagiolari Gigliola , De Paepe Boel , De Meirleir Linda , Ferrer Isidre , Roig-Quilis Manel , Munell Francina , Montoya Julio , López-Gallardo Ester , Ruiz-Pesini Eduardo , Artuch Rafael , Montero Raquel , Torner Ferran , Nascimento Andres , Ortez Carlos , Colomer Jaume , Jimenez-Mallebrera Cecilia
Published: February 2014

Background

Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays.

Results

We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression.

Conclusion

Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required.
Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines
Authors: Li Liang , Fridley Brooke L , Kalari Krishna , Niu Nifang , Jenkins Gregory , Batzler Anthony , Abo Ryan P , Schaid Daniel , Wang Liewei
Published: February 2014

Background

Two cytidine analogues, gemcitabine and cytosine arabinoside (AraC), are widely used in the treatment of a variety of cancers with a large individual variation in response. To identify potential genetic biomarkers associated with response to these two drugs, we used a human lymphoblastoid cell line (LCL) model system with extensive genomic data, including 1.3 million SNPs and 54,000 basal expression probesets to perform genome-wide association studies (GWAS) with gemcitabine and AraC IC50 values.

Results

We identified 11 and 27 SNP loci significantly associated with gemcitabine and AraC IC50 values, respectively. Eleven candidate genes were functionally validated using siRNA knockdown approach in multiple cancer cell lines. We also characterized the potential mechanisms of genes by determining their influence on the activity of 10 cancer-related signaling pathways using reporter gene assays. Most SNPs regulated gene expression in a trans manner, except 7 SNPs in the PIGB gene that were significantly associated with both the expression of PIGB and gemcitabine cytotoxicity.

Conclusion

These results suggest that genetic variation might contribute to drug response via either cis- or trans- regulation of gene expression. GWAS analysis followed by functional pharmacogenomics studies might help identify novel biomarkers contributing to variation in response to these two drugs and enhance our understanding of underlying mechanisms of drug action.
Aberrant phenotype and transcriptome expression during fiber cell wall thickening caused by the mutation of the Im gene in immature fiber (im) mutant in Gossypium hirsutum L
Authors: Wang Cheng , Lv Yuanda , Xu Wentin , Zhang Tianzhen , Guo Wangzhen
Published: February 2014

Background

The immature fiber (im) mutant ofGossypium hirsutumL. is a special cotton fiber mutant with non-fluffy fibers. It has low dry weight and fineness of fibers due to developmental defects in fiber secondary cell wall (SCW).

Results

We compared the cellulose content in fibers, thickness of fiber cell wall and fiber transcriptional profiling during SCW development inimmutant and its near-isogenic wild-type line (NIL) TM-1. Theimmutant had lower cellulose content and thinner cell walls than TM-1 at same fiber developmental stage. During 25 ~ 35 day post-anthesis (DPA), sucrose content, an important carbon source for cellulose synthesis, was also significantly lower inimmutant than in TM-1. Comparative analysis of fiber transcriptional profiling from 13 ~ 25 DPA indicated that the largest transcriptional variations between the two lines occurred at the onset of SCW development. TM-1 began SCW biosynthesis approximately at 16 DPA, whereas the same fiber developmental program inimmutant was delayed until 19 DPA, suggesting an asynchronous fiber developmental program between TM-1 andimmutant. Functional classification and enrichment analysis of differentially expressed genes (DEGs) between the two NILs indicated that genes associated with biological processes related to cellulose synthesis, secondary cell wall biogenesis, cell wall thickening and sucrose metabolism, respectively, were significantly up-regulated in TM-1. Twelve genes related to carbohydrate metabolism were validated by quantitative reverse transcription PCR (qRT-PCR) and confirmed a temporal difference at the earlier transition and SCW biosynthesis stages of fiber development between TM-1 andimmutant.

Conclusions

We propose thatImis an important regulatory gene influencing temporal differences in expression of genes related to fiber SCW biosynthesis. This study lays a foundation for cloning theImgene, elucidating molecular mechanism of fiber SCW development and further genetic manipulation for the improvement of fiber fineness and maturity.
Smoking cessation advice recorded during pregnancy in United Kingdom primary care
Authors: Hardy Bethany , Szatkowski Lisa , Tata Laila J , Coleman Tim , Dhalwani Nafeesa N
Published: February 2014

Background

United Kingdom (UK) national guidelines recommend that all pregnant women who smoke should be advised to quit at every available opportunity, and brief cessation advice is an efficient and cost-effective means to increase quit rates. The Quality and Outcomes Framework (QOF) implemented in 2004 requires general practitioners to document their delivery of smoking cessation advice in patient records. However, no specific targets have been set in QOF for the recording of this advice in pregnant women. We used a large electronic primary care database from the UK to quantify the pregnancies in which women who smoked were recorded to have been given smoking cessation advice, and the associated maternal characteristics.

Methods

Using The Health Improvement Network database we calculated annual proportions of pregnant smokers between 2000 and 2009 with cessation advice documented in their medical records during pregnancy. Logistic regression was used to assess variation in the recording of cessation advice with maternal characteristics.

Results

Among 45,296 pregnancies in women who smoked, recorded cessation advice increased from 7% in 2000 to 37% in 2004 when the QOF was introduced and reduced slightly to 30% in 2009. Pregnant smokers from the youngest age group (15–19) were 21% more likely to have a record of cessation advice compared to pregnant smokers aged 25–29 (OR 1.21, 95% CI 1.10-1.35) and pregnant smokers from the most deprived group were 38% more likely to have a record for cessation advice compared to pregnant smokers from the least deprived group (OR 1.38, 95% CI 1.14-1.68). Pregnant smokers with asthma were twice as likely to have documentation of cessation advice in their primary care records compared to pregnant smokers without asthma (OR 1.97, 95% CI 1.80-2.16). Presence of comorbidities such as diabetes, hypertension and mental illness also increased the likelihood of having smoking cessation advice recorded. No marked variations were observed in the recording of cessation advice with body mass index.

Conclusion

Recorded delivery of smoking cessation advice for pregnant smokers in primary care has increased with some fluctuation over the years, especially after the implementation of the QOF, and varies with maternal characteristics.
Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis
Authors: Barry Emma , Galvin Rose , Keogh Claire , Horgan Frances , Fahey Tom
Published: February 2014

Background

The Timed Up and Go test (TUG) is a commonly used screening tool to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall predictive value of the TUG in community-dwelling older adults.

Methods

A literature search was performed to identify all studies that validated the TUG test. The methodological quality of the selected studies was assessed using the QUADAS-2 tool, a validated tool for the quality assessment of diagnostic accuracy studies. A TUG score of ≥13.5 seconds was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled estimates of sensitivity and specificity at ≥13.5 seconds. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity.

Results

Twenty-five studies were included in the systematic review and 10 studies were included in meta-analysis. The TUG test was found to be more useful at ruling in rather than ruling out falls in individuals classified as high risk (>13.5 sec), with a higher pooled specificity (0.74, 95% CI 0.52-0.88) than sensitivity (0.31, 95% CI 0.13-0.57). Logistic regression analysis indicated that the TUG score is not a significant predictor of falls (OR = 1.01, 95% CI 1.00-1.02, p = 0.05).

Conclusion

The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at high risk of falls in this setting.
A metabolic biosignature of early response to anti-tuberculosis treatment
Authors: Mahapatra Sebabrata , Hess Ann M , Johnson John L , Eisenach Kathleen D , DeGroote Mary A , Gitta Phineas , Joloba Moses L , Kaplan Gilla , Walzl Gerhard , Boom W Henry , Belisle John T
Published: February 2014

Background

The successful treatment of tuberculosis (TB) requires long-term multidrug chemotherapy. Clinical trials to evaluate new drugs and regimens for TB treatment are protracted due to the slow clearance of Mycobacterium tuberculosis (Mtb) infection and the lack of early biomarkers to predict treatment outcome. Advancements in the field of metabolomics make it possible to identify metabolic profiles that correlate with disease states or successful chemotherapy. However, proof-of-concept of this approach has not been provided for a TB-early treatment response biosignature (TB-ETRB).

Methods

Urine samples collected at baseline and during treatment from 48 Ugandan and 39 South African HIV-seronegative adults with pulmonary TB were divided into discovery and qualification sets, normalized to creatinine concentration, and analyzed by liquid chromatography-mass spectrometry to identify small molecule molecular features (MFs) in individual patient samples. A biosignature that distinguished baseline and 1 month treatment samples was selected by pairwise t-test using data from two discovery sample sets. Hierarchical clustering and repeated measures analysis were applied to additional sample data to down select molecular features that behaved consistently between the two clinical sites and these were evaluated by logistic regression analysis.

Results

Analysis of discovery samples identified 45 MFs that significantly changed in abundance at one month of treatment. Down selection using an extended set of discovery samples and qualification samples confirmed 23 MFs that consistently changed in abundance between baseline and 1, 2 and 6 months of therapy, with 12 MFs achieving statistical significance (p < 0.05). Six MFs classified the baseline and 1 month samples with an error rate of 11.8%.

Conclusions

These results define a urine based TB-early treatment response biosignature (TB-ETRB) applicable to different parts of Africa, and provide proof-of-concept for further evaluation of this technology in monitoring clinical responses to TB therapy.
Efficient extraction of proteins from formalin-fixed paraffin-embedded tissues requires higher concentration of tris(hydroxymethyl)aminomethane
Authors: Kawashima Yusuke , Kodera Yoshio , Singh Anil , Matsumoto Masaomi , Matsumoto Hiroyuki
Published: February 2014

Background

Numerous formaldehyde-fixed and paraffin-embedded clinical tissues have been created in the past decades and stored in pathological depositories at hospitals as well as in clinical laboratories worldwide. In addition to the archived tissues, formaldehyde-fixation is also mandatory for preparing proteomics samples from diseased patients or animal models in order to inactivate contagious agents. Protein extraction from formaldehyde-fixed tissues is hampered by the Schiff base formation between the amino groups of proteins and formaldehyde. Although achievement of the highest extraction efficiency of proteins from the formaldehyde-fixed tissues is essential for obtaining maximum proteomics information, no attention has been paid to the concentration dependence of tris(hydroxymethyl)aminomethane on the extraction efficacy. We suspected that the concentration of tris(hydroxymethyl)aminomethane affects the protein extraction efficiency because of its property as a primary amine that reverses the Schiff base formation between the primary amines of proteins and formaldehyde. Thus we pursued optimization of the component and protocol of protein extraction buffer to achieve better extraction efficiency of proteins from formaldehyde-fixed and paraffin-embedded tissues.

Results

In order to simulate protein extraction from diseased tissues we made formaldehyde-fixed and paraffin-embedded samples from mouse liver slices and investigated the protein extraction efficiency and speed by changing the concentration of the protein extraction buffer component tris(hydroxymethyl)aminomethane under various extraction conditions. We find, as expected, that tris(hydroxymethyl)aminomethane significantly affects the performance of protein extraction from the formaldehyde-fixed and paraffin-embedded samples both in the extraction yield and in the extraction speed.

Conclusions

We recommend the concentration of tris(hydroxymethyl)aminomethane in protein extraction buffer to be higher than 300 mM when extraction is conducted for 90 min at 90°C to achieve the most efficient protein extraction in a shorter time. The information will be essential for performing the most efficient protein extraction from formaldehyde-fixed and paraffin-embedded tissue samples for proteomics analysis.
Achieving low-complexity maximum-likelihood detection for the 3D MIMO code
Authors: Liu Ming , Crussière Matthieu , Hélard Maryline , Hélard Jean-François
Published: February 2014

The 3D Multiple-input multiple-output (MIMO) code is a robust and efficient space-time block code (STBC) for the distributed MIMO broadcasting but suffers from high maximum-likelihood (ML) decoding complexity. In this paper, we first analyze some properties of the 3D MIMO code to show that the 3D MIMO code is fast decodable. It is proven that the ML decoding performance can be achieved with a complexity of O(M
4.5) instead of O(M
8) in quasi-static channel with M-ary square QAM modulations. Consequently, we propose a simplified ML decoder exploiting the unique properties of the 3D MIMO code. Simulation results show that the proposed simplified ML decoder can achieve much lower processing time latency compared to the classical sphere decoder with Schnorr-Euchner enumeration.
Fetal demise and associated factors following umbilical cord prolapse in Mulago hospital, Uganda: a retrospective study
Authors: Wasswa Esau Wangi , Nakubulwa Sarah , Mutyaba Twaha
Published: February 2014

Background

Umbilical cord prolapse is an obstetric complication associated with high perinatal morbidity and mortality. A few interventions may improve fetal outcome. In developed countries these have advanced to giving intrauterine fetal resuscitation. Conditions in low resource settings do not allow for some of these advanced techniques. Putting the mother in knee chest position and immediate delivery may be the only options possible.

We set out to determine the incidence of fetal demise and associated factors following umbilical cord prolapsed (UCP) in Mulago Hospital, Uganda.

Methods

In a retrospective study conducted in Mulago hospital, Uganda, file records of mothers who delivered between 1st January 2000 to 31st December 2009 and had pregnancies complicated by umbilical cord prolapse with live fetus were selected. We collected information on referral status, cord position, cervical dilatation, fetal heart state at the time of diagnosis of UCP, diagnosis to delivery interval, use of knee chest position, mode of delivery, birth weight and fetal outcome.

We computed incidence of fetal demise following UCP and determined factors associated with fetal demise in pregnancies complicated by UCP.

Results

Of 438 cases with prolapsed cord, 101(23%) lost their babies within 24 hours after birth or were delivered dead. This gave annual cumulative incidence of fetal death following UCP of 23/1000 live UCP cases delivered /year.

The major factors associated with fetal outcome in pregnancies complicated by UCP included; diagnosis to delivery interval <30 min, RR 0.79 (CI 0.74-0.85), mode of delivery, RR 1.14 (CI 1.02-1.28), knee chest position, RR 0.81 (CI 0.70-0.95).

Conclusions

The annual cumulative incidence of fetal death in our study was 23/1000 live UCP cases delivery per year for the period of 10 years studied. Cesarean section reduced perinatal mortality by a factor of 2. Diagnosis to delivery interval <30 minutes and putting mother in knee chest position were protective against fetal death.
Uptake and sorption of aluminium and fluoride by four green algal species
Authors: Pitre Danaé , Boullemant Amiel , Fortin Claude
Published: February 2014

Background

We examined the uptake and sorption of aluminium (Al) and fluoride (F) by green algae under conditions similar to those found in the effluents of the aluminium industry. We took into account the speciation of Al in the medium since Al can form stable complexes with F and these complexes may play a role in the uptake and sorption of Al. We compared the capacity of four species of green algae (i.e. Chlamydomonas reinhardtii, Pseudokirchneriella subcapitata, Chlorella vulgaris, and Scenedesmus obliquus) to accumulate and adsorb Al and F. The selected algae were exposed during 4 days, covering all growth phases of algae, to a synthetic medium containing Al and F at pH 7.0. During this period, dissolved Al as well as cellular growth were followed closely. At the end of the exposure period, the solutions were filtered in order to harvest the algal cells. The cells were then rinsed with enough ethylene diaminetetraacetic acid to remove loosely bound ions from the algal surface, determined from the filtrates. Finally, the filters were digested in order to quantify cellular uptake.

Results

Little difference in Al removal was observed between species. Aluminium sorption (15%) and uptake (26%) were highest in P. subcapitata, followed by C. reinhardtii (7% and 17% respectively), S. obliquus (13% and 5%), and C. vulgaris (7% and 2%). However, none of these species showed significant uptake or sorption of F. We also studied the influence of pH on the uptake and sorption of Al and F by P. subcapitata. We measured a combined uptake and sorption of Al of 50% at pH 7.5, of 41% at pH 7.0, and of 4% at pH 5.5. Thus, accumulation was reduced with acidification of the medium as expected by the increased competition with protons and possibly by a reduced bioavailability of the Al-F complexes which dominated the solution at low pH.

Conclusion

Out of the four tested species, P. subcapitata showed the highest sorption of aluminium and fluoride under our test conditions. These results provide key information on the development of an environmental biotechnology which can be applied to industrial effluents.
Half-life measurements of chemical inducers for recombinant gene expression
Authors: Politi Nicolo’ , Pasotti Lorenzo , Zucca Susanna , Casanova Michela , Micoli Giuseppina , Cusella De Angelis Maria Gabriella , Magni Paolo
Published: February 2014

Background

Inducible promoters are widely spread genetic tools for triggering, tuning and optimizing the expression of recombinant genes in engineered biological systems. Most of them are controlled by the addition of a specific exogenous chemical inducer that indirectly regulates the promoter transcription rate in a concentration-dependent fashion. In order to have a robust and predictable degree of control on promoter activity, the degradation rate of such chemicals should be considered in many applications like recombinant protein production.

Results

In this work, we use whole-cell biosensors to assess the half-life of three commonly used chemical inducers for recombinant Escherichia coli: Isopropyl β-D-1-thiogalactopyranoside (IPTG), anhydrotetracycline (ATc) and N-(3-oxohexanoyl)-L-homoserine lactone (HSL). A factorial study was conducted to investigate the conditions that significantly contribute to the decay rate of these inducers. Temperature has been found to be the major factor affecting ATc, while medium and pH have been found to highly affect HSL. Finally, no significant degradation was observed for IPTG among the tested conditions.

Conclusions

We have quantified the decay rate of IPTG, ATc and HSL in many conditions, some of which were not previously tested in the literature, and the main effects affecting their degradation were identified via a statistics-based framework. Whole-cell biosensors were successfully used to conduct this study, yielding reproducible measurements via simple multiwell-compatible assays. The knowledge of inducer degradation rate in several contexts has to be considered in the rational design of synthetic biological systems for improving the predictability of induction effects, especially for prolonged experiments.
The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
Authors: Franco Pedro , Porta Nuria , Holliday John D , Willett Peter
Published: February 2014

Background

In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought.

Results

143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset.

Conclusions

Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities.
Development of STS and CAPS markers for variety identification and genetic diversity analysis of tea germplasm in Taiwan
Authors: Hu Chih-Yi , Tsai You-Zen , Lin Shun-Fu
Published: February 2014

Background

Tea (Camellia sinensis) is an important economic crop in Taiwan. Particularly, two major commercial types of tea (Paochong tea and Oolong tea) which are produced in Taiwan are famous around the world, and they must be manufactured with specific cultivars. Nevertheless, many elite cultivars have been illegally introduced to foreign countries. Because of the lower cost, large amount of “Taiwan-type tea” are produced and imported to Taiwan, causing a dramatic damage in the tea industry. It is very urgent to develop the stable, fast and reliable DNA markers for fingerprinting tea cultivars in Taiwan and protecting intellectual property rights for breeders. Furthermore, genetic diversity and phylogenetic relationship evaluations of tea germplasm in Taiwan are imperative for parental selection in the cross-breeding program and avoidance of genetic vulnerability.

Results

Two STS and 37 CAPS markers derived from cytoplasmic genome and ESTs of tea have been developed in this study providing a useful tool for distinguishing all investigated germplasm. For identifying 12 prevailing tea cultivars in Taiwan, five core markers, including each one of mitochondria and chloroplast, and three nuclear markers, were developed. Based on principal coordinate analysis and cluster analysis, 55 tea germplasm in Taiwan were divided into three groups: sinensis type (C. sinensis var. sinensis), assamica type (C. sinensis var. assamica) and Taiwan wild species (C. formosensis). The result of genetic diversity analysis revealed that both sinensis (0.44) and assamica (0.41) types had higher genetic diversity than wild species (0.25). The close genetic distance between the first (Chin-Shin-Oolong) and the third (Shy-Jih-Chuen) prevailing cultivars was found, and many recently released varieties are the descents of Chin-Shin-Oolong. This implies the potential risk of genetic vulnerability for tea cultivation in Taiwan.

Conclusions

We have successfully developed a tool for tea germplasm discrimination and genetic diversity analysis, as well as a set of core markers for effective identification of prevailing cultivars in Taiwan. According to the results of phylogenetic analysis on prevailing tea cultivars, it is necessary to broaden genetic diversity from wild species or plant introduction in future breeding programs.
‘Water dripping on stone’? Industry lobbying and UK alcohol policy
Authors: Hawkins Ben , Holden Chris
Published: February 2014

Despite a growing literature on corporations as political actors, relatively little is known about how alcohol industry actors attempt to influence public policy. In the context of contemporary debates about the minimum pricing of alcoholic beverages, and drawing on semi-structured interviews with a range of key informants, this article investigates the means by which alcohol industry actors gain access to policy makers and the strategies used to influence policy. It finds that the strategies of alcohol industry actors are focused on long-term relationship building with policy makers, involving the provision and interpretation of information and the promotion of various forms of self-regulation.
‘Multiculturalism is never talked about’: community cohesion and local policy contradictions in England
Authors: Lewis Hannah , Craig Gary
Published: February 2014

The concept and policy of ‘multiculturalism’ are under continuing attack. A broad policy language has replaced ‘race’ and ethnicity agendas. We demonstrate how ‘community cohesion’ and ‘equalities’ became dominant concepts in managing cultural relations in England. Local authority and community perspectives in one northern city reveal good local practice being undermined by national discourses stigmatising British Muslims, creating barriers to integration, resulting in a dual, conflicting process. While community cohesion de-emphasises ‘race’, ethnic and religious differences are highlighted in security and immigration discourses.
Ethnic residential segregation stability in England, 1991–2001
Authors: Farley Katherine , Blackman Tim
Published: February 2014

The residential arrangements of ethnic groups became the subject of political interest when they were identified as a feature of urban areas that experienced unrest in 2001. Residential segregation was framed as both problematic for community relations and a cause of economic inequalities (Cantle, 2001; Denham, 2001). This article presents evidence that ethnic residential segregation in England was not increasing between 1991 and 2001 and that there was a trend for local authority areas to become more similar at a relatively low level of segregation. At neighbourhood level there is little evidence to regard ethnic residential segregation as a problem despite the policy priority it came to have.
The politics of behaviour change: nudge, neoliberalism and the state
Authors: Leggett Will
Published: February 2014

Behaviour change is increasingly central to policy and politics. The exemplar of nudge, and its relationship to behavioural economics and psychology, is outlined. Nudge’s claim to libertarian paternalism is evaluated in the context of the neoliberal state. A sociological critique of behavioural economic assumptions enables a still wider account of shifting state–citizen relations. Foucauldian analyses of such relations, as well as deliberative ‘think’ perspectives, are assessed. A more explicitly political, social-democratic model of the behaviour change state is advocated. This would be more attuned to the socioeconomic context of behaviour, and also be prepared to defend citizens against ubiquitous attempts to shape their subjectivity.
Transforming Vietnam: a quest for improved efficiency and transparency in central government procurement
Authors: Khorana Sangeeta , Mishra Nishikant , Kerr William A
Published: February 2014

This case study on Vietnam investigates how a country's institutional framework can determine its participation in the World Trade Organization's Government Procurement Agreement (GPA). Using a cost-benefit approach, this article explores the relationship between institutional framework and procurement liberalisation, and examines how effective institutional reforms can trigger liberalisation. Findings show that the critical success factors for institutional reform are political commitment, the ability to craft an appropriate agenda, and eventual compliance with rules. There is an inverse relationship between costs and benefits of institutional reform, suggesting that Vietnam might prefer employing GPA observer status as a means for procurement liberalisation.
Development of an Immunoassay for the Kidney-Specific Protein myo-Inositol Oxygenase, a Potential Biomarker of Acute Kidney Injury
Authors: Gaut Joseph P , Crimmins Dan L , Ohlendorf Matt F , Lockwood Christina M , Griest Terry A , Brada Nancy A , Hoshi Masato , Sato Bryan , Hotchkiss Richard S , Jain Sanjay , Ladenson Jack H
Published: February 2014

BACKGROUND

Acute kidney injury (AKI) affects 45% of critically ill patients, resulting in increased morbidity and mortality. The diagnostic standard, plasma creatinine, is nonspecific and may not increase until days after injury. There is significant need for a renal-specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal-specific biomarker of AKI.

METHODS

We analyzed gene expression data from normal mouse tissues to identify kidney-specific genes, one of which was Miox. We generated monoclonal antibodies to recombinant myo-inositol oxygenase (MIOX) and developed an immunoassay to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI.

RESULTS

Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Serum MIOX, undetectable at baseline, increased 24 h following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI [mean (SD) 12.4 (4.3) ng/mL, n = 42] compared with patients without AKI [0.5 (0.3) ng/mL, n = 17] and was highest in patients with oliguric AKI [20.2 (7.5) ng/mL, n = 23]. Plasma MIOX increased 54.3 (3.8) h before the increase in creatinine.

CONCLUSIONS

MIOX is a renal-specific, proximal tubule protein that is increased in serum of animals and plasma of critically ill patients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in human patients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker.
Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis
Authors: Haqq Liza , McFarlane James , Dieberg Gudrun , Smart Neil
Published: February 2014

Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.
Effect of supplemental vitamin D and calcium on serum sclerostin levels
Authors: Dawson-Hughes Bess , Harris Susan S , Ceglia Lisa , Palermo Nancy J
Published: February 2014

Objective

Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults.

Design

We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years.

Method

Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay.

Results

In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels.

Conclusion

Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.
Atuação do enfermeiro na prescrição de contraceptivos hormonais na rede de atenção primária em saúde
Authors: Dombrowski Jamille Gregório , Pontes Jéssika Abrantes , Assis Walédya Araújo Lopes de Melo e
Published: February 2014

O estudo teve como objetivo conhecer e analisar a atuação do enfermeiro na prescrição dos contraceptivos hormonais reversíveis na Rede de Atenção Primária a Saúde. Trata-se de um estudo transversal e descritivo, tendo como sujeitos 64 enfermeiros lotados nas unidades assistenciais no período de setembro a novembro de 2010 no município de Rio Branco-Acre. Os dados foram coletados mediante entrevistas estruturadas utilizando um questionário. Os resultados evidenciaram que 96,9% dos enfermeiros prescrevem os métodos anticoncepcionais e que 90,6% tem conhecimento da legislação que rege a prescrição de enfermagem. Foi observado que a escolha do método contraceptivo pelos enfermeiros baseia-se na escolha da cliente e anamnese (36% e 34% respectivamente), e que 90% sempre orientavam quanto às vantagens e desvantagens de cada método. Assim, para escolher um método contraceptivo de forma livre e informada, os métodos devem estar disponíveis e devem ser dispensados por profissionais capacitados, após orientação correta e completa.
Práticas da equipe de enfermagem no processo de alta do bebê pré-termo
Authors: Schmidt Kayna Trombini , Terassi Mariélli , Marcon Sonia Silva , Higarashi Ieda Harumi
Published: February 2014

O objetivo deste estudo foi identificar as estratégias utilizadas pela equipe de enfermagem atuante na unidade neonatal de um hospital-escola, durante o preparo da família para a alta do prematuro. Trata-se de estudo descritivo, com abordagem qualitativa. Os dados foram coletados entre março e junho de 2011, por meio de observação e entrevistas semiestruturadas. Da análise dos discursos emergiram duas categorias temáticas: Orientações e estratégias profissionais no preparo da família para a alta do prematuro e Dificuldades e potencialidades no espaço da atenção neonatal. A principal estratégia referida pelos profissionais foi a inserção precoce da família no processo de cuidar; a dificuldade destacada foi a ausência dos pais durante a internação do filho. As potencialidades e limitações apontadas por este estudo revelaram que o processo da assistência é dinâmico, necessitando de constantes reajustes e adequações para atender efetiva e integralmente o bebê prematuro e sua família.
Gestão do cuidado à tuberculose: da formação à prática do enfermeiro
Authors: Barrêto Anne Jaquelyne Roque , Evangelista Anna Luisa Figueiredo , Sá Lenilde Duarte de , Almeida Sandra Aparecida de , Nogueira Jordana de Almeida , Lopes Ana Maria Cavalcante
Published: February 2014

O estudo objetivou analisar a relação entre a formação do enfermeiro e as ações direcionadas à gestão do cuidado à tuberculose. De natureza qualitativa, foi realizada em um dos municípios da região metropolitana de João Pessoa-PB. Participaram do estudo dez enfermeiros da Estratégia Saúde da Família. A coleta de dados foi realizada em fevereiro de 2010 através de um roteiro de entrevista semiestruturado. Para análise do material empírico, utilizou-se a técnica de análise de conteúdo. Nos depoimentos dos enfermeiros há predominância da temática TB no espaço hospitalar, abordando tanto a superficialidade quanto o distanciamento do cuidado à TB no que concerne à relação entre a teoria e a prática, e a ausência de cuidados direto ao doente de TB durante a formação; a organização dos serviços aponta para uma prática mecanicista e tarefeira. Há necessidade das instituições formadoras se aproximarem dos serviços de saúde, numa relação dialógica, para melhor organizar os espaços de aprendizagem.
Multicausalidade nos acidentes de trabalho da Enfermagem com material biológico
Authors: Soares Leticia Gramazio , Sarquis Leila Maria Mansano , Kirchhof Ana Lúcia Cardoso , Felli Vanda Elisa Andres
Published: February 2014

Com o objetivo de analisar a multicausalidade dos acidentes de trabalho com exposição biológica em trabalhadores de enfermagem, foi realizada uma pesquisa descritiva e exploratória em um hospital de médio porte do Estado do Paraná, no período entre janeiro de 2008 a janeiro de 2009. A população foi de 26 trabalhadores de enfermagem da clínica médica. A coleta de dados foi realizada por entrevistas semiestruturadas com cinco dos oito acidentados no período; os conteúdos foram analisados pelo Diagrama de Causas e Efeitos. As categorias causas materiais, organizacionais, institucionais e comportamentais do trabalhador evidenciaram o descarte inadequado de perfurocortantes, a sobrecarga de trabalho, a não utilização das normas de biossegurança e a deficiente supervisão e capacitação do trabalhador como fatores determinantes para a ocorrência destes acidentes. A adoção da ferramenta do Diagrama de Causas e Efeitos proporcionou a análise dos acidentes na sua multicausalidade, mostrando a interação entre as mesmas.