bluuebunny/crossref_metadata_2025 huggingface dataset:
HomSI: a homozygous stretch identifier from next-generation sequencing data
Authors: Görmez Zeliha , Bakir-Gungor Burcu , Sağıroğlu Mahmut Şamil
Published: December 2013

Summary: In consanguineous families, as a result of inheriting the same genomic segments through both parents, the individuals have stretches of their genomes that are homozygous. This situation leads to the prevalence of recessive diseases among the members of these families. Homozygosity mapping is based on this observation, and in consanguineous families, several recessive disease genes have been discovered with the help of this technique. The researchers typically use single nucleotide polymorphism arrays to determine the homozygous regions and then search for the disease gene by sequencing the genes within this candidate disease loci. Recently, the advent of next-generation sequencing enables the concurrent identification of homozygous regions and the detection of mutations relevant for diagnosis, using data from a single sequencing experiment. In this respect, we have developed a novel tool that identifies homozygous regions using deep sequence data. Using *.vcf (variant call format) files as an input file, our program identifies the majority of homozygous regions found by microarray single nucleotide polymorphism genotype data.

Availability and implementation: HomSI software is freely available at www.igbam.bilgem.tubitak.gov.tr/softwares/HomSI, with an online manual.

Contact:  bakirburcu@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
HEFT: eQTL analysis of many thousands of expressed genes while simultaneously controlling for hidden factors
Authors: Gao Chuan , Tignor Nicole L. , Salit Jacqueline , Strulovici-Barel Yael , Hackett Neil R. , Crystal Ronald G. , Mezey Jason G.
Published: December 2013

Motivation: Identification of expression Quantitative Trait Loci (eQTL), the genetic loci that contribute to heritable variation in gene expression, can be obstructed by factors that produce variation in expression profiles if these factors are unmeasured or hidden from direct analysis.

Methods: We have developed a method for Hidden Expression Factor analysis (HEFT) that identifies individual and pleiotropic effects of eQTL in the presence of hidden factors. The HEFT model is a combined multivariate regression and factor analysis, where the complete likelihood of the model is used to derive a ridge estimator for simultaneous factor learning and detection of eQTL. HEFT requires no pre-estimation of hidden factor effects; it provides P-values and is extremely fast, requiring just a few hours to complete an eQTL analysis of thousands of expression variables when analyzing hundreds of thousands of single nucleotide polymorphisms on a standard 8 core 2.6 G desktop.

Results: By analyzing simulated data, we demonstrate that HEFT can correct for an unknown number of hidden factors and significantly outperforms all related hidden factor methods for eQTL analysis when there are eQTL with univariate and multivariate (pleiotropic) effects. To demonstrate a real-world application, we applied HEFT to identify eQTL affecting gene expression in the human lung for a study that included presumptive hidden factors. HEFT identified all of the cis-eQTL found by other hidden factor methods and 91 additional cis-eQTL. HEFT also identified a number of eQTLs with direct relevance to lung disease that could not be found without a hidden factor analysis, including cis-eQTL for GTF2H1 and MTRR, genes that have been independently associated with lung cancer.

Availability: Software is available at http://mezeylab.cb.bscb.cornell.edu/Software.aspx.

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  jgm45@cornell.edu
Joint estimation of isoform expression and isoform-specific read distribution using multisample RNA-Seq data
Authors: Suo Chen , Calza Stefano , Salim Agus , Pawitan Yudi
Published: December 2013

Motivation: RNA-sequencing technologies provide a powerful tool for expression analysis at gene and isoform level, but accurate estimation of isoform abundance is still a challenge. Standard assumption of uniform read intensity would yield biased estimates when the read intensity is in fact non-uniform. The problem is that, without strong assumptions, the read intensity pattern is not identifiable from data observed in a single sample.

Results: We develop a joint statistical model that accounts for non-uniform isoform-specific read distribution and gene isoform expression estimation. The main challenge is in dealing with the large number of isoform-specific read distributions, which potentially are as many as the number of splice variants in the genome. A statistical regularization via a smoothing penalty is imposed to control the estimation. Also, for identifiability reasons, the method uses information across samples from the same region. We develop a fast and robust computational procedure based on the iterated-weighted least-squares algorithm, and apply it to simulated data and two real RNA-Seq datasets with reverse transcription–polymerase chain reaction validation. Empirical tests show that our model performs better than existing methods in terms of increasing precision in isoform-level estimation.

Availability and implementation: We have implemented our method in an R package called Sequgio as a pipeline for fast processing of RNA-Seq data.

Contact:  yudi.pawitan@ki.se

Supplementary information:  Supplementary data are available at Bioinformatics online.
Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament
Authors: Fornander Louise H. , Renodon-Cornière Axelle , Kuwabara Naoyuki , Ito Kentaro , Tsutsui Yasuhiro , Shimizu Toshiyuki , Iwasaki Hiroshi , Nordén Bengt , Takahashi Masayuki
Published: December 2013

The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.
DICE, an efficient system for iterative genomic editing in human pluripotent stem cells
Authors: Zhu Fangfang , Gamboa Matthew , Farruggio Alfonso P. , Hippenmeyer Simon , Tasic Bosiljka , Schüle Birgitt , Chen-Tsai Yanru , Calos Michele P.
Published: December 2013

To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.
Identification of Zeoliarus oppositus (Hemiptera: Cixiidae) as a Vector of ‘Candidatus Phytoplasma australiense’
Authors: Winks C. J. , Andersen M. T. , Charles J. G. , Beever R. E.
Published: December 2013

‘Candidatus Phytoplasma australiense’ is associated with a number of plant diseases in New Zealand. The only known vector of this pathogen was Zeoliarus atkinsoni, a planthopper considered to be monophagous on New Zealand flax (Phormium spp.). The work carried out shows that Z. oppositus, which is polyphagous, is able to vector ‘Ca. P. australiense’ to both Coprosma robusta (karamu) and Cordyline australis (New Zealand cabbage tree). Although transmission was achieved to both these species, the disease symptomatology was more evident in C. australis. Two approaches were taken to achieve transmission. First, insects were collected from areas around symptomatic Coprosma plants and caged directly on test plants. Second, insects were collected from grasses and sedges in areas where disease was less evident and were fed on known infected Coprosma plants prior to being caged on test plants. Transmission was achieved using both approaches, although transmission was far greater (30% compared with 4%) from insects that were directly applied. Phytoplasma DNA was detected in 12% of Z. oppositus individuals tested during all the trials. This work identifies a new vector for ‘Ca. P. australiense’ and contributes to our understanding of the ecology of Cordyline sudden decline and Coprosma lethal decline.
Commitment to cyst formation in Giardia
Authors: Sulemana Alimatu , Paget Timothy A. , Jarroll Edward L.
Published: December 2013

Giardia trophozoites differentiate into infectious cysts (encystment) in response to physiological stimuli; encystment is crucial for Giardia’s transmission, survival and pathogenesis. In vitro, Giardia encysts when bile sequesters lipids necessary for this lipid auxotroph, and in vivo they encyst to infect new hosts. In this study, we investigated, for the first time, commitment to encystment in Giardia using both molecular and cellular techniques. We show that after 3–6 h in inducing conditions, encysting trophozoites continue to encyst regardless of whether the inducing stimulus remains. We propose that a trophozoite’s inability to revert to a growing or dividing trophozoite represents a commitment to encystment. The onset of commitment correlated with the appearance of encystment specific vesicles (ESVs) and encystment specific protein synthesis. These observations suggest the involvement of regulatory pathways with the ability to ‘remember’ a transient signal long after its removal; a property that enables encysting trophozoites to complete the encystment process should the unfavourable triggering condition(s) change. The ability to form cysts in response to transient signals or, as we have highlighted in this paper, the ability of a small percentage of the population to form cysts without an inducer is vital for the maintenance of infection within populations.
A Bayesian Method to Incorporate Hundreds of Functional Characteristics with Association Evidence to Improve Variant Prioritization
Authors: Gagliano Sarah A. , Barnes Michael R. , Weale Michael E. , Knight Jo
Published: December 2013

The increasing quantity and quality of functional genomic information motivate the assessment and integration of these data with association data, including data originating from genome-wide association studies (GWAS). We used previously described GWAS signals (“hits”) to train a regularized logistic model in order to predict SNP causality on the basis of a large multivariate functional dataset. We show how this model can be used to derive Bayes factors for integrating functional and association data into a combined Bayesian analysis. Functional characteristics were obtained from the Encyclopedia of DNA Elements (ENCODE), from published expression quantitative trait loci (eQTL), and from other sources of genome-wide characteristics. We trained the model using all GWAS signals combined, and also using phenotype specific signals for autoimmune, brain-related, cancer, and cardiovascular disorders. The non-phenotype specific and the autoimmune GWAS signals gave the most reliable results. We found SNPs with higher probabilities of causality from functional characteristics showed an enrichment of more significant p-values compared to all GWAS SNPs in three large GWAS studies of complex traits. We investigated the ability of our Bayesian method to improve the identification of true causal signals in a psoriasis GWAS dataset and found that combining functional data with association data improves the ability to prioritise novel hits. We used the predictions from the penalized logistic regression model to calculate Bayes factors relating to functional characteristics and supply these online alongside resources to integrate these data with association data.

Author Summary

Large-scale genetic studies have had success identifying genes that play a role in complex traits. Advanced statistical procedures suggest that there are still genetic variants to be discovered, but these variants are difficult to detect. Incorporating biological information that affect the amount of protein or other product produced can be used to prioritise the genetic variants in order to identify which are likely to be causal. The method proposed here uses such biological characteristics to predict which genetic variants are most likely to be causal for complex traits.
FROGG high‐risk prostate cancer workshop: Patterns of practice and literature review
Authors: Lehman Margot , Hayden Amy J , Martin Jarad M , Christie David , Kneebone Andrew B , Sidhom Mark , Skala Marketa , Tai Keen‐Hun
Published: December 2013

Australian and New Zealand radiation oncologists with an interest in uro‐oncology were invited to participate in a pattern‐of‐practice survey dealing with the management of intact high‐risk prostate cancer. Responses from 46 practitioners (representing 73% of all potential respondents) revealed that high‐dose radiation therapy is the standard of care. However, there is variability in practice with regard to the methods used to achieve dose escalation, the use of whole‐pelvic radiation therapy and the optimal duration of androgen deprivation therapy employed. A review of the literature outlining the current body of knowledge and the planned and ongoing studies in intact high‐risk prostate cancer is presented.
Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple sheep flocks
Authors: White S. N. , Mousel M. R. , Reynolds J. O. , Herrmann‐Hoesing L. M. , Knowles D. P.
Published: December 2013

Ovine lentivirus (OvLV) is a macrophage‐tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker‐assisted selective breeding might improve odds of infection and control of OvLV post‐infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post‐infection in multiple animal sets. Proviral concentration is a live‐animal diagnostic measure of OvLV control post‐infection related to severity of OvLV‐induced lesions. A recent genome‐wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P < 0.05). These animal sets contained Rambouillet, Polypay and crossbred sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/μg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV‐positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P < 0.0001). Future work will test additional breeds, management conditions and viral subtypes, and identify functional properties of the haplotype this deletion variant tracks. To our knowledge, this is the first genetic variant consistently associated with host control of OvLV post‐infection in multiple sheep flocks.
Polymorphisms in calpastatin and mu‐calpain genes are associated with beef iron content
Authors: Casas E. , Duan Q. , Schneider M. J. , Shackelford S. D. , Wheeler T. L. , Cundiff L. V. , Reecy J. M.
Published: December 2013

The objective of this study was to assess the association of markers in the calpastatin and mu‐calpain loci with iron in beef cattle muscle. The population consisted of 259 cross‐bred steers from Beefmaster, Brangus, Bonsmara, Romosinuano, Hereford and Angus sires. Total iron and heme iron concentrations were measured. Markers in the calpastatin (referred to as CAST) and mu‐calpain (referred to as CAPN4751) genes were used to assess their association with iron levels. The mean and standard error for iron and heme iron content in the population was 35.6 ± 1.3 μg and 27.1 ± 1.4 μg respectively. Significant associations (P < 0.01) of markers were observed for both iron and heme iron content. For CAST, animals with the CC genotype had higher levels of iron and heme iron in longissimus dorsi muscle. For CAPN4751, individuals with the TT genotype had higher concentrations of iron and heme iron than did animals with the CC and CT genotypes. Genotypes known to be associated with tougher meat were associated with higher levels of iron concentration.
Should general anaesthesia be avoided in the elderly?
Authors: Strøm C. , Rasmussen L. S. , Sieber F. E.
Published: December 2013

Surgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, manifest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cognitive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderly surgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with a particular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitive decline, and describe the treatment strategies by which such decline may be prevented.
The assessment and management of peri‐operative pain in older adults
Authors: Schofield P. A.
Published: December 2013

A number of recent reports have highlighted the inadequate provision of pain relief for older inpatients. Despite the availability of numerous validated pain measures, pain remains poorly assessed in some cases and, particularly, in the cognitively impaired. Without proper assessment, patients may receive inadequate or inappropriate analgesia, both of which can worsen outcome. Most drugs and techniques that are used for analgesia in younger patients are also suitable for older patients, although dosages may have to be adjusted to avoid the side‐effects that are consequent upon age‐related changes in drug pharmacokinetics and pharmacodynamics, co‐morbidity, frailty, cognitive impairment and polypharmacy. This paper reviews current guidelines and methods of assessing pain in the older adult, and describes the use of, and problems with, mild, moderate, strong, adjuvant and local anaesthetic drugs in the older population for analgesia, advocating multimodal intervention to reduce dose‐related side‐effects, particularly of opioids.
P‐wave Morphology Is Associated with Echocardiographic Response to Cardiac Resynchronization Therapy in MADIT‐CRT Patients
Authors: Holmqvist Fredrik , Platonov Pyotr G. , Solomon Scott D. , Petersson Richard , McNitt Scott , Carlson Jonas , Zareba Wojciech , Moss Arthur J. ,   MADIT‐CRT Investigators
Published: December 2013

Background

In this study we hypothesized that signs of atypical atrial activation would be associated with cardiac resynchronization therapy (CRT) response in patients with mildly symptomatic heart failure (CHF), left ventricular dysfunction, and wide QRS complex.

Methods

Patients included in the CRT‐D arm in MADIT‐CRT were studied (n = 892). Unfiltered signal‐averaged P waves were analyzed to determine orthogonal P‐wave morphology (typical morphologies were predefined as having positive signals in Leads X and Y and a negative or negative–positive signal in Lead Z. All other patterns were classified as atypical). The association between P‐wave morphology and data on echocardiographic response at 1 year was analyzed.

Results

Atypical P‐wave morphology was found in 21% (n = 186) of the patients at baseline. Patients with atypical P‐wave morphology were more often female (31% vs. 24%, P = 0.025), had lower BMI (28 ± 5 kg/m2 vs. 29 ± 5 kg/m2, P = 0.008), had more ischemic CHF (60% vs. 52%, P = 0.026) and had smaller left atrial volumes (90 ± 20 mL vs. 94 ± 22 mL, P = 0.034).

Atypical P‐wave morphology at baseline was associated with superior response to CRT at 1 year with a larger reduction in left ventricular end‐diastolic volume (−23 ± 12% vs. −20 ± 11%, P = 0.009), left ventricular end‐systolic volume (−36 ± 16% vs. −31 ± 16%, P = 0.006), and left atrial volume (−31 ± 12% vs. −27 ± 12%, P = 0.005), with a slightly larger absolute increase in left ventricular ejection fraction (LVEF) (12 ± 5% vs. 11 ± 5%, P = 0.009). These associations were found to be independent of traditional predictors.

Conclusion

The presence of atypical P‐wave morphology recorded is independently associated with a favorable echocardiographic cardiac remodeling response to CRT.
PACAP receptor pharmacology and agonist bias: analysis in primary neurons and glia from the trigeminal ganglia and transfected cells
Authors: Walker C S , Sundrum T , Hay D L
Published: December 2013

Background and Purpose

A major challenge in the development of new medicines targeting GPCRs is the ability to quantify drug action in physiologically relevant models. Primary cell models that closely resemble the clinically relevant in vivo site of drug action are important translational tools in drug development. However, pharmacological studies in these models are generally very limited due to the methodology used.

Experimental Approach

We used a neuropeptide system to demonstrate the applicability of using highly sensitive signalling assays in primary cells. We quantified the action of pituitary adenylate cyclase‐activating peptide (PACAP)‐38, PACAP‐27 and vasoactive intestinal polypeptide in primary cultures of neurons and glia derived from rat trigeminal ganglia (TG), comparing our observations to transfected cells.

Key Results

PACAP‐responsive receptors in rat trigeminal neurons, glia and transfected PAC1n receptors were pharmacologically distinct. PACAP‐38, but not PACAP‐27, activated ERK in glia, while both forms stimulated cellular cAMP production. PACAP(6–38) also displayed cell‐type‐dependent, agonist‐specific, antagonism.

Conclusions and Implications

The complexity of PACAP pharmacology in the TG may help to direct, more effectively, the development of disease treatments targeting the PACAP receptor. We suggest that these methodologies are broadly applicable to other primary cell types of human or animal origin, and that our approach may allow more thorough characterization of ligand properties in physiologically relevant cell types.
Long‐term outcome of robotic‐assisted laparoscopic rectopexy for full‐thickness rectal prolapse in elderly patients
Authors: Germain A. , Perrenot C. , Scherrer M.‐L. , Ayav C. , Brunaud L. , Ayav A. , Bresler L.
Published: December 2013

Aim

Full‐thickness rectal prolapse is common in the elderly, but there are no particular practice guidelines for its surgical management. We evaluated retrospectively the perioperative and long‐term clinical results and function in elderly and younger patients with complete rectal prolapse after robotic‐assisted laparoscopic rectopexy (RALR).

Method

Seventy‐seven patients who underwent RALR between 2002 and 2010 were divided into Group A (age < 75 years, n = 59) and Group B (age > 75 years, n = 18). Operative time, intra‐ and postoperative complications, length of hospital stay, short‐term and long‐term outcomes, recurrence rate and degree of satisfaction were evaluated.

Results

There was no significant difference between the groups regarding operation time, conversion, morbidity or length of hospital stay. At a median follow‐up of 51.8 (5–115) months, there was no difference in the improvement of faecal incontinence, recurrence and the degree of satisfaction.

Conclusion

Robotic‐assisted laparoscopic rectopexy is safe in patients aged over 75 years and gives similar results to those in patients aged < 75 years.
Sequential Evaluation of Coronary Flow Patterns after Primary Angioplasty in Acute Anterior ST‐Elevation Myocardial Infarction Predicts Recovery of Left Ventricular Systolic Function
Authors: Sharif Dawod , Sharif‐Rasslan Amal , Makhoul Nabeel , Shefer Arie , Hassan Amin , Rosenschein Uri
Published: December 2013

Background

Function of the microcirculation after primary percutaneous coronary intervention (PCI) is dynamic and contributes to unpredictability of recovery of left ventricular (LV) systolic function.

Aim

This study was conducted to evaluate sequential Doppler velocity parameters of the left anterior descending coronary artery (LAD) in predicting recovery of global and regional LV systolic function.

Methods

Thirty‐five consecutive patients, 24 males, age 59 ± 12 years, with acute anterior ST‐elevation myocardial infarction (STEMI) who had primary PCI were studied. Thrombolysis in myocardial infarction (TIMI) and myocardial blush grades were evaluated. Transthoracic echocardiographic (TTE) studies, evaluation of left ventricular ejection fraction (LVEF), LAD territory wall‐motion score index (WMSI), and sampling of LAD Doppler velocities up to 6 hours post‐PCI, 48 hours postprocedure, and predischarge were performed.

Results

Thrombolysis in myocardial infarction grade before PCI averaged 0.86 ± 1.19 and post‐PCI 2.89 ± 0.32, P < 0.05. Myocardial blush grade before PCI was 0.41 ± 0.98 and after PCI 2.22 ± 0.93, P < 0.05. Diastolic velocity deceleration time (DDT) in the LAD early after PCI was less than 600 ms in 16 subjects. Immediately after PCI, in subjects with DDT > 600 ms, LVEF was 38.5 ± 6% and predischarge 49.2 ± 8.7%, P = 9.77 × 10−5 and LAD‐WMSI decreased from 2 ± 0.38 to 1.4 ± 0.48, P = 0.000163. In subjects with DDT < 600 ms LAD‐WMSI did not change significantly. Early and minimal LAD‐DDT correlated with improvement in LV systolic function, r = 0.6, whereas post‐PCI blush grade had lower correlation with LVEF, r = 0.39.

Conclusions

Global and regional LV systolic function after PCI in acute anterior MI can be predicted by LAD‐DDT better than by post‐PCI myocardial blush.
Incremental Value of Left Ventricular Systolic and Diastolic Function to Determine Outcome in Patients with Acute ST‐Segment Elevation Myocardial Infarction: The Echocardiographic Substudy of the OASIS‐6 Trial
Authors: Dokainish Hisham , Rajaram Mahadevan , Prabhakaran Dorairaj , Afzal Rizwan , Orlandini Andres , Staszewsky Lidia , Franzosi Maria Grazia , Llanos Javier , Martinoli Elena , Roy Ambuj , Yusuf Salim , Mehta Shamir , Lonn Eva
Published: December 2013

Background

The echocardiographic substudy of the OASIS‐6 trial evaluated the prognostic implications of left ventricle (LV) systolic and diastolic dysfunction early postacute ST‐segment elevation myocardial infarction (STEMI) in patients treated with fondaparinux versus usual care.

Methods

Comprehensive echocardiograms were performed a median of 6 days after the index STEMI in 528 patients, 258 randomized to fondaparinux and 270 to usual care (unfractionated heparin or placebo), to assess LV systolic and diastolic function, LV mass, and LV end‐systolic and end‐diastolic volumes. A total of 245 (46.4%) patients were followed up for 3 months and 283 (53.6%) for 6 months. Major cardiac events (MACE) were defined as the composite of death, reinfarction, heart failure, or cardiogenic shock and resuscitated cardiac arrest.

Results

Patients with LV ejection fraction (LVEF) ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of MACE (hazard ratio [HR] = 8.85, 95% CI, 4.21–18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR = 4.38, 95% CI, 1.52–12.60) and in multivariate models adjusted for LVEF, LV end‐systolic volume, and clinical variables.

Conclusion

In this large international trial, LV systolic and diastolic function, as determined by echocardiography early following STEMI, are incremental predictors of MACE. In addition, RDF is a strong independent predictor of MACE after STEMI across a broad range of LVEF.
Left dorsal displacement of the large colon in the horse
Authors: Albanese V. , Caldwell F. J.
Published: December 2013

Left dorsal displacement of the large colon is a condition unique to the horse that results in an obstruction of the colon and signs of colic. This condition may be successfully treated medically with analgesia, i.v. or oral fluids and feed restriction, exercise with or without administration of phenylephrine, or rolling under general anaesthesia with or without administration of phenylephrine, or a combination of these conservative options. Surgical correction via standing left flank laparotomy or, more commonly, ventral midline laparotomy under general anaesthesia, is required in cases where conservative therapy is unsuccessful. Recurrence rates range from 3.2% to 21%. Surgical attempts to prevent recurrence of this condition include large colon resection, colopexy, and ablation of the nephrosplenic space.
Efficacy of intramuscular meperidine hydrochloride versus placebo in experimental foot lameness in horses
Authors: Foreman J. H. , Ruemmler R.
Published: December 2013

Reasons for performing study

There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses.

Objectives

Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo.

Study design

Crossover pharmacodynamic experiment.

Methods

Eight healthy adultThoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1 ml/45 kg bwt) or meperidine hydrochloride (1 mg/kg bwt i.m.). Heart rate (HR) and lameness score (LS) responses were assessed by a blinded observer every 20 min for 5 h after lameness induction and then hourly through 12 h after treatment. Jugular venous blood samples were obtained at ‐1, 0, 0:05, 1, 2, 4, 6, 8, 10 and 12 h and were subsequently analysed for drug concentrations (lower limit of detection, 1 ng/ml). Repeated measuresANOVAandpost hoc Tukey's test were used to identify analgesic effects at a significance level of P<0.05.

Results

Mean (± s.e.)HRwere lower in meperidine trials at 2.3, 3.3 and 3.7 h post administration (P<0.05). MeanLSwere lower in meperidine trials at 2.0, 2.3 and 3.3 h post administration (P<0.05). Mean plasma (meperidine) peaked at 227 ± 52 ng/ml at 1 h post administration and decreased to 2.7 ± 0.3 ng/ml at 12 h post administration. In 3 of 8 subjects, plasma (meperidine) was below the lower limit of detection at 12 h after administration.

Conclusions

Intramuscular meperidine was more effective than the saline placebo but only for 2.0–3.7 h post administration compared with the 8–12 h durations of efficacy reported previously using this same model when horses were treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). Meperidine may be a suitable nonNSAIDalternative analgesic for acute foot pain with efficacy lasting from 2–3 h after a single i.m. dose.
Organizational Capital and Investment‐Cash Flow Sensitivity: The Effect of Management Quality Practices
Authors: Attig Najah , Cleary Sean
Published: December 2013

This paper examines the influence of organizational capital, as evident in management quality practices, on the response of firm investment to internal cash flows. We provide novel and strong evidence that investment sensitivity to internal cash flows decreases in the presence of superior management practices. We also find that superior management practices reduce the firm's financing frictions, evident in lower capital constraints. Our results are robust to numerous tests. Overall, our findings suggest that intangible organizational capital is important for investment decisions and that superior management practices contribute to value‐maximizing behavior.
Litter decomposition in a temperate and a tropical stream: the effects of species mixing, litter quality and shredders
Authors: Bruder Andreas , Schindler Markus H. , Moretti Marcelo S. , Gessner Mark O.
Published: December 2013

The current rapid decline in biodiversity has led to concerns about the consequences for stream ecosystem processes, one of which is the decomposition of leaf litter derived from riparian vegetation.

We conducted field experiments in a tropical and a temperate stream to test for the effects of mixing leaf species differing in resource quality on the decomposition of leaf litter and on the colonisation of the litter by leaf‐shredding invertebrates.

The effects of litter mixing were minor compared with the effects of litter quality and the presence or absence of shredders. Low shredder abundance in the tropical stream and poor quality of the tropical leaf species, particularly in terms of phosphorus content and toughness, were associated with low decomposition rates in the tropical compared with the temperate stream. This is especially true when considering the 20 °C temperature differences between the two streams.

In the presence of shredders, the decomposition rate of a standard litter type, leaves of Alnus glutinosa, was 2.6‐fold faster in the temperate stream, whereas rates were similar when shredders were absent. This indicates that differences in environmental conditions other than temperature had a strong effect. Differences in water chemistry, such as higher concentrations of dissolved nutrients in the temperate stream, might account for this effect.

In conclusion, despite a lack of clear effects of litter mixing on decomposition, our results highlight the importance of litter identity and environmental conditions for both microbial and shredder‐mediated litter decomposition, suggesting that changes in riparian vegetation and other stream characteristics will affect stream ecosystems in the face of widespread environmental change.
Incorporating continuous trait variation into biomonitoring assessments by measuring and assigning trait values to individuals or taxa
Authors: Orlofske Jessica M. , Baird Donald J.
Published: December 2013

Traits‐based analyses of insect assemblages support biomonitoring programme objectives. To date, however, few traits‐based metrics have demonstrated the degree of sensitivity or discriminatory power required by biomonitoring programmes. Trait information used for analyses is typically based on static descriptions of dynamic communities and is attributed only to taxonomic units. Given that traits can vary even among specimens from the same species, quantifying trait variation and its consequences could be essential for successful traits‐based biomonitoring.

Here, we study the consequences of measuring trait expression among individual specimens versus assigning trait states from published databases at the taxon level (genus or family) for the interpretation of trait patterns within aquatic insect assemblages. Specifically, do database body size trait states accurately reflect measured body size values of aquatic insects collected in biomonitoring samples and should body size data be aggregated at the taxon level or assessed at the specimen level to detect differences among sites?

We assessed body size, a continuous trait linked to fundamental organism properties and ecological function, for four orders of aquatic insects: Ephemeroptera, Plecoptera, Trichoptera and Odonata. Invertebrate samples were collected from the Miramichi River basin (New Brunswick, Canada) according to the Canadian Aquatic Biomonitoring Network method.

Concordance between measured specimen sizes and published trait states was poor; 55% of taxa expressed body sizes considerably smaller or larger than assigned database states. Recalibration of size classes based on specimen measurements yielded three size classes that facilitated detection of assemblage‐aggregated size differences among reference sites. Measured body size trait values were able to distinguish these differences in community structure, while values derived from databases yielded erroneous patterns in the size structure among sites.

Gaining accurate ecological insights from traits‐based biomonitoring may require assessing trait properties at the scale of individual specimens. The benefits of this approach, however, should be balanced against additional effort required in the context of specific study or programme objectives.
Invertebrate assemblages of pools in arid‐land streams have high functional redundancy and are resistant to severe drying
Authors: Boersma Kate S. , Bogan Michael T. , Henrichs Brian A. , Lytle David A.
Published: December 2013

Seasonal droughts are predictable components of arid‐land stream hydrology, and many arid‐land aquatic taxa have adapted to their extreme environment. However, climate change is altering this predictable hydrology, producing longer and more severe droughts and creating novel disturbance regimes for resident organisms.

The hydrologic transitions from flowing stream to fragmented pools to dry stream bed are frequently associated with steep decreases in taxonomic and functional diversity, referred to as thresholds of biodiversity loss. Less is known about how taxa respond between these thresholds, as fragmented pools gradually dry and abiotic conditions intensify. While an increasingly extreme environment may be expected to reduce taxonomic and trait richness, species adapted to predictable seasonal fragmentation may be resistant to declining water levels until all surface water is lost. We used aquatic mesocosms to test two competing hypotheses of the relationship between richness and pool drying for arid‐land stream invertebrates: (i) the drought vulnerability hypothesis (richness gradually decreases with drying) and (ii) the drought resistance hypothesis (richness remains constant until complete drying occurs).

We inoculated replicate mesocosms with aquatic invertebrates from arid‐land streams in Arizona, U.S.A., and applied three drying treatments representing a continuum of drying stress commonly observed in local streams during the summer dry season (water depths: 10, 7 and 1 cm). Mesocosms were covered to restrict dispersal and colonisation processes and to isolate resistance (in situ survival of species) from resilience (community recovery following disturbance). After 45 days, we destructively sampled all invertebrates in the mesocosms and calculated various taxonomic and functional trait metrics.

Taxonomic richness and composition did not differ between drying treatments, providing strong support for the drought resistance hypothesis. Severe drying was associated with lower invertebrate abundances and higher densities than the moderate and control treatments. This finding suggests that density‐dependent processes generated by decreased available habitat may be more important determinants of community composition during droughts than abiotic stress in this system.

We observed a near‐complete overlap of trophic traits (body size and functional feeding group) and resistance traits (respiration mode and diapause) among the three treatments. This high functional redundancy may provide a buffer against changes to ecosystem functioning, even in cases of severe‐drying‐induced habitat contraction and fragmentation.
The development and management of social workers in Ethiopia: A situational analysis
Authors: Hailu Daniel
Published: December 2013

Social protection has become a policy of choice to address rising vulnerabilities and inequalities in Africa. Successful implementation of social protection polices requires proliferation of competent social workers. This article first abstracts elements of an emerging international norm in a comprehensive system for the development and management of social workers and then reviews the extent to which Ethiopia has introduced these elements. It reveals that Ethiopia is in a very early stage in putting in place almost all identified elements of such a system. Recent measures that the Ethiopian government is taking to address this gap are highlighted by way of conclusion.
Analysis of human B‐cell responses following ChAd63‐MVA MSP1 and AMA1 immunization and controlled malaria infection
Authors: Elias Sean C. , Choudhary Prateek , de Cassan Simone C. , Biswas Sumi , Collins Katharine A. , Halstead Fenella D. , Bliss Carly M. , Ewer Katie J. , Hodgson Susanne H. , Duncan Christopher J. A. , Hill Adrian V. S. , Draper Simon J.
Published: December 2013

Acquisition of non‐sterilizing natural immunity to Plasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective B‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific B cells has not been reported following controlled human malaria infection (CHMI). Here we analysed human B‐cell responses in a series of Phase I/IIa clinical trials, which include CHMI, using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory B‐cell (mBC) responses following CHMI. In contrast, unvaccinated malaria‐naive control volunteers developed an mBC response against MSP1 but not AMA1. Serum IgG correlated with the mBC response after booster vaccination but this relationship was less well maintained following CHMI. A significant reduction in peripheral MSP1‐specific mBC was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood B‐cell subsets expressing CXCR3 and elevated serum levels of interferon‐γ and CXCL9, suggesting migration away from the periphery. These CHMI data confirm that mBC and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure.
The locomotive assignment problem: a survey on optimization models
Authors: Piu F. , Speranza M. G.
Published: December 2013

The objective of the locomotive assignment problem (LAP) is to assign a fleet of locomotives to a set of trains while satisfying a rich set of operational and budget constraints and optimizing one or more crucial objectives. This paper presents a survey on optimization models for this class of scheduling problems. Depending on the context of application, the kind of model used to solve the LAP varies; accordingly, this influences the solution methodology and algorithms used. In this paper, we review and also suggest a classification of the various models.
Cohort Replacement and Homeostasis in World Population, 1950–2100
Authors: Billari Francesco C. , Dalla‐Zuanna Gianpiero
Published: December 2013

Using a simple empirical approach, we analyze world and regional‐level cohort replacement as determined by the key components of population dynamics, i.e. fertility, survival, and migration, for 1950–2010, using UN data. We define two kinds of homeostatic relationships among these components: fertility responses to mortality change (type I) and migration responses to changes in net reproduction (type II), and show that both can be observed to some degree in this period. We examine the extent of cohort replacement embodied in the medium‐variant UN population projections over 2010–2100 and consider how the international migration assumptions made in such projections would be affected by a homeostatic perspective.
Family Policies and the Western European Fertility Divide: Insights from a Natural Experiment in Belgium
Authors: Klüsener Sebastian , Neels Karel , Kreyenfeld Michaela
Published: December 2013

Countries in Northwestern Europe, including Belgium, report cohort fertility levels of close to two children per woman; whereas Central European countries, such as Germany, have levels of around 1.6 children. In seeking to explain these differences, some scholars have stressed the role of the social policy context, while others have pointed to variation in fertility‐related social norms. But because these influences are interdependent, it is difficult to isolate their effects on fertility trends. This study attempts to disentangle these two factors by drawing on a quasi‐natural experiment. After World War I Germany was compelled to cede the Eupen–Malmedy territory to Belgium. The population of this region has retained its German linguistic identity, but has been subject to Belgian social policies. We examine whether the fertility trends in this German‐speaking region of Belgium follow the Belgian or the German pattern. Our findings indicate that they generally resemble the Belgian pattern. This suggests that institutional factors are important for understanding the current fertility differences in Western Europe.
Effect of Ion Substitution for Nd3+ Based on Structural Characteristic on the Microwave Dielectric Properties of NdNbO4 Ceramic System
Authors: Zhang Ping , Song Zhenkun , Wang Yue , Li Lingxia
Published: December 2013

NdNbO4 ceramics with substituted Nd3+ were prepared by conventional mixed oxide route. The solid solubility limits of Sr, Ca, Mn, and Co in NdNbO4 were discussed. The generated second phases had a direct affect on the quality factors of NdNbO4 ceramic. The effects of ionic substitution on the microstructures and microwave dielectric properties based on structural characteristics of NdNbO4 ceramics were investigated systematically. The specimens presented single NdNbO4 phase that were used to explain the microwave dielectric properties of NdNbO4 based on the structural characteristics. From microscopy and phase analysis, it was determined the microwave dielectric properties were strongly dependent on structural characteristics. The dielectric constants were related to the relative density and ion polarizabilities, the temperature coefficients of the resonant frequency τƒ were effected by the octahedral structures, and the quality factors Q × ƒ was dependent on, and increased monotonically with, packing fraction.