bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Working Memory in Levels of Situation Awareness
Authors: Gutzwiller Robert S. , Clegg Benjamin A.
Published: June 2012

Situation awareness (SA) brings together theories in cognition to examine what an operator perceives, understands and predicts about their environment. Previous characterization of working memory (WM) influence in levels of awareness however is sparse and has several shortcomings, including how both WM and SA have been measured. In the current experiment, a factor analytic approach to WM was adopted based on performance on three different WM tasks. These factor scores were then related to SA which was measured over two forms of scenarios in a complex dynamic decision-making task. In one scenario, Level 1 SA was assessed, and the other assessed Level 3 processes implicitly. Findings from 99 participants indicate WM was unrelated to Level 1, but was related to Level 3 SA with the relationship strengthening with increasing task experience. These results refine and contribute to ongoing theory in the context of SA and dynamic task performance, and provide future directives to individual differences research in human factors.
Narratives in Local Television News Editing
Authors: Henderson Keren
Published: June 2012

This study offers a method for analyzing the narrative content of television news videos. Very few scholars approach the study of visual narratives in television news editing because the technique is highly specialized and not commonly articulated by practitioners. However, cognitive experiments are supporting the importance of understanding the way the brain processes video messages; in particular, those coming from television news. Based in norms and routines theory, this study combines an unprecedented method of content analysis with in-depth interviews of award-winning local news editors in order to reveal a contemporary state of narrative production in television news.
Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance
Authors: Palumbo Antonio , Palladino Carmela
Published: June 2012

Oral immunomodulatory drugs (IMiDs), namely thalidomide, lenalidomide and pomalidomide, interfere with several pathways important for disease progression. Today they play a crucial role in the treatment of multiple myeloma patients, and have considerably improved myeloma outcomes. These agents, and thalidomide in particular, are associated with higher rates of thromboembolic events, both venous and arterial. Individual risk factors for thromboembolic events include advanced age, previous history of thromboembolism, an indwelling central venous catheter, comorbid conditions (e.g. infections, diabetes, cardiac disease, obesity), current or recent immobilization, recent surgery and inherited thrombophilic abnormalities. Cancer therapy and cancer itself also increase the risk of thromboembolic events. The aim of this review is to help clinicians to define the risk of thrombotic events in patients treated with thalidomide and thus to provide practical recommendations to manage thromboprophylaxis in these patients.
Death of frontline allo-SCT in myeloma
Authors: Moreau Philippe
Published: June 2012

In this issue of Blood, Lokhorst et al report the results of a donor versus no-donor comparison trial, which unambiguously establishes that reduced intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT) should not be offered as part of frontline therapy in multiple myeloma (MM).1
Factors associated with elevated exhaled nitric oxide fraction in infants with recurrent respiratory symptoms
Authors: Kotaniemi-Syrjänen Anne , Malmberg L. Pekka , Malmström Kristiina , Pelkonen Anna S. , Mäkelä Mika J.
Published: June 2012

Exhaled nitric oxide fraction (FeNO) has been proposed as a noninvasive marker of eosinophilic bronchial inflammation in active asthma, and supposed to reflect responsiveness to corticosteroid therapy. There are several factors influencingFeNO, and its role in early childhood respiratory disorders needs to be established.

Between 2004 and 2008, 444 children aged <3 yrs with recurrent lower respiratory tract symptoms were referred to a tertiary centre for further investigation. 136 full-term, steroid-free, infection-free infants, median age of 16.4 months (range 4.0–26.7 months), successfully underwent measurement ofFeNO, lung function tests, and a dosimetric methacholine challenge test.

The median level ofFeNOwas 19.3 ppb (interquartile range 12.3–26.9 ppb). ElevatedFeNO(≥27 ppb, the highest quartile) was associated with maternal history of asthma (adjusted OR 3.2, 95% CI 1.3–8.1; p=0.012), and increased airway responsiveness (the provocative dose of methacholine causing a 40% fall in maximal expiratory flow at functional residual capacity ≤0.30 mg) (adjusted OR 4.1, 95% CI 1.4–12.7; p=0.012). Atopy, blood eosinophilia and lung function were not associated with elevatedFeNO.

In conclusion, maternal history of asthma, and increased airway responsiveness are associated with elevatedFeNOin infants with recurrent lower respiratory tract symptoms.
Novel approaches to the treatment ofPseudomonas aeruginosainfections in cystic fibrosis
Authors: Hurley Matthew N. , Cámara Miguel , Smyth Alan R.
Published: June 2012

Pseudomonas aeruginosachronically infects patients with cystic fibrosis and is associated with greater morbidity. There has been limited progress on the clinical development of new antibiotics with novel modes of action. This review addresses some of the latest research developments on the exploitation of candidate adjuvant therapeutic agents that may act alongside conventional antibiotics as an alternative therapeutic strategy. After considering key mechanisms this opportunistic pathogen employs to control virulence, the progress of various strategies including the inhibition of quorum sensing, efflux pumps and lectins, and the use of iron chelators, bacteriophages, immunisation and immunotherapy is reviewed. Both therapeutic approaches in early development and clinical phase are discussed.
Case-finding options for COPD: results from the Burden of Obstructive Lung Disease Study
Authors: Jithoo Anamika , Enright Paul L. , Burney Peter , Buist A. Sonia , Bateman Eric D. , Tan Wan C. , Studnicka Michael , Mejza Filip , Gillespie Suzanne , Vollmer William M.
Published: June 2012

This study aimed to compare strategies for chronic obstructive pulmonary disease (COPD) case finding using data from the Burden of Obstructive Lung Disease study.

Population-based samples of adults aged ≥40 yrs (n = 9,390) from 14 countries completed a questionnaire and spirometry. We compared the screening efficiency of differently staged algorithms that used questionnaire data and/or peak expiratory flow (PEF) data to identify persons at risk for COPD and, hence, needing confirmatory spirometry. Separate algorithms were fitted for moderate/severe COPD and for severe COPD. We estimated the cost of each algorithm in 1,000 people.

For moderate/severe COPD, use of questionnaire data alone permitted high sensitivity (97%) but required confirmatory spirometry in 80% of participants. Use of PEF necessitated confirmatory spirometry in only 19–22% of subjects, with 83–84% sensitivity. For severe COPD, use of PEF achieved 91–93% sensitivity, requiring confirmatory spirometry in <9% of participants. Cost analysis suggested that a staged screening algorithm using only PEF initially, followed by confirmatory spirometry as needed, was the most cost-effective case-finding strategy.

Our results support the use of PEF as a simple, cost-effective initial screening tool for conducting COPD case-finding in adults aged ≥40 yrs. These findings should be validated in real-world settings such as the primary care environment.
Sleep apnoea and visceral adiposity in middle-aged male and female subjects
Authors: Kritikou Ilia , Basta Maria , Tappouni Rafel , Pejovic Slobodanha , Fernandez-Mendoza Julio , Nazir Racha , Shaffer Michelle L. , Liao Duanping , Bixler Edward O. , Chrousos George P. , Vgontzas Alexandros N.
Published: June 2012

In obese male subjects, visceral adiposity has been associated with obstructive sleep apnoea (OSA), while studies in overweight males and females are limited. Our goal was to examine the association between OSA and visceral fat in a relatively nonobese population and assess the effects of 2 months placebo-controlled continuous positive airway pressure (CPAP) use on abdominal fat.

81 subjects, 22 middle-aged males and 20 post-menopausal females with OSA, and 19 male and 20 female controls were studied in the sleep laboratory for four nights. Abdominal (visceral (VAT) and subcutaneous (SAT) adipose tissue) and liver fat were assessed with computed tomography. OSA patients were re-assessed post-CPAP and post sham-CPAP.

Apnoeic males had significantly higher VAT than controls, while apnoeic females had higher SAT than controls. In both sexes, OSA was associated with increased liver fat. In males, apnoea was associated with VAT whereas in females it was associated with subcutaneous, visceral and total fat. CPAP did not affect abdominal and liver fat.

In overweight males, visceral adiposity is associated with OSA whereas in females it is associated with global adiposity. In overweight males, our therapeutic goal should be the reduction of visceral adiposity and its metabolic correlates, whereas, in females, weight loss may be sufficient. Short-term CPAP treatment does not affect general, abdominal or intra-hepatic adiposity.
Objective measurement of cough in otherwise healthy volunteers with acute cough
Authors: Sunger Kanchan , Powley William , Kelsall Angela , Sumner Helen , Murdoch Robert , Smith Jaclyn A.
Published: June 2012

Cough is one of the commonest reasons for medical consultation and acute cough associated with upper respiratory tract infections (URTIs) is a global problem. In otherwise healthy volunteers complaining of cough associated with symptoms of URTI, we aimed to assess objective and subjective measures of cough and their repeatability and perform power calculations for the design of future studies to test therapies.

We studied 54 otherwise healthy volunteers with acute cough (<3 weeks) (median age 22 yrs (interquartile range 21–26 yrs), 64% female, mean forced expiratory volume in 1 s 97.6±10.5% predicted). All subjects performed 24-h ambulatory cough monitoring and reported cough frequency and severity using visual analogue scales (VAS) on 2 consecutive days. Sample size calculations were performed for crossover and parallel group study designs.

Objective cough frequency was high (session 1: geometric mean 12.1 coughs·h−1(95%CI 9.7–15.2)) and fell significantly (session 2: 9.0 coughs·h−1(95%CI 6.9–11.6); p<0.001). Repeatability was higher for objective cough frequency (intra-class correlation coefficient (ICC)=0.94, p<0.001) than reported cough frequency (daytime VAS ICC=0.784, p<0.001). Crossover/parallel studies require <15 and <41 subjects per arm to detect a 50% reduction in cough frequency with 90% power, respectively.

Acute cough frequency is highly repeatable over any 48-h period, allowing small sample sizes to be used when investigating the effectiveness of novel anti-tussives.
Effects of cigarette smoke condensate on pneumococcal biofilm formation and pneumolysin
Authors: Mutepe N. Daphney , Cockeran Riana , Steel Helen C. , Theron Annette J. , Mitchell Tim J. , Feldman Charles , Anderson Ronald
Published: June 2012

Although the well-recognised predisposition of cigarette smokers to the development of severe pneumococcal disease may be attributable to impairment of local host defences, less is known about the direct effects of smoke exposure on airway pathogens, or their virulence factors. In the current study, we have investigated the effects of cigarette smoke condensate (CSC) on biofilm formation byStreptococcus pneumoniae, and on the pore-forming activity of its major toxin, pneumolysin.

Biofilm formation following exposure of the pneumococcus to CSC (20–160 μg·mL−1) was measured using a crystal violet-based spectrophotometric procedure, while the pore-forming activity of recombinant pneumolysin was determined by a fura-2/acetoxymethyl ester-based spectrofluorimetric procedure to monitor the uptake of extracellular Ca2+by isolated human neutrophils.

Exposure of the pneumococcus or pneumolysin to CSC resulted in significant dose-related augmentation of biofilm formation (p≤0.05 at 80 and 160 μg·mL−1) and substantial attenuation of the pore-forming interactions of pneumolysin, respectively.

Augmentation of biofilm formation and inactivation of pneumolysin as a consequence of smoking are likely to favour microbial colonisation and persistence, both being essential precursors of pneumococcal disease.
A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma
Authors: Piper Edward , Brightling Christopher , Niven Robert , Oh Chad , Faggioni Raffaella , Poon Kwai , She Dewei , Kell Chris , May Richard D. , Geba Gregory P. , Molfino Nestor A.
Published: June 2012

Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies.

194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β2-agonist use and safety. Numerical end-points are reported as mean±sd.

At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumabversus-0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV1) were 0.21±0.38 Lversus0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β2-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45versusplacebo -0.10±1.49 (p=0.020). The increase in FEV1following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab.

No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.
Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism
Authors: Moores Lisa , Zamarro Celia , Gómez Vicente , Aujesky Drahomir , García Leticia , Nieto Rosa , Yusen Roger , Jiménez David
Published: June 2012

Although the Pulmonary Embolism Severity Index (PESI) accurately identifies 35% of patients with acute pulmonary embolism (PE) as being low risk, some patients deemed high risk by the PESI on admission might be treated safely in the outpatient environment.

This retrospective cohort study included a total of 304 consecutive patients with acute PE, classified at the time of hospital admission into PESI class III. The PESI was recalculated 48 h after admission (PESI48) and each patient reclassified into the corresponding risk category. The primary outcome of the study was all-cause mortality between day 2 and day 30 after PE diagnosis.

26 (8.5%) patients (95% CI 5.4–11.7%) died between day 2 and day 30 after PE diagnosis. Investigators reclassified 83 (27.3%) patients (95% CI 22.3–32.3%) as low risk (classes I and II) at 48 h. 30-day mortality in these patients was 1.2% (95% CI 0–3.5%) as opposed to 11.3% (95% CI 7.1–15.5%) in those who remained high risk. The net improvement in reclassification was estimated at 54% (p<0.001).

In a cohort of intermediate-risk patients with acute PE, calculation of the PESI48allows identification of those patients at very low risk of dying during the first month of follow-up.
Stage-specific embryonic antigen-4is expressed in basaloid lung cancer and associated with poor prognosis
Authors: Gottschling Sandra , Jensen Katrin , Warth Arne , Herth Felix J.F. , Thomas Michael , Schnabel Philipp A. , Herpel Esther
Published: June 2012

Basaloid carcinoma represents a rare variant of nonsmall cell lung cancer (NSCLC), which has shown a poor prognosis in a number of studies. Although it is considered to derive from a pluri- or multipotent pulmonary stem cells, little is known about the expression and clinical significance of stem cell antigens in this variant.

Stage-specific embryonic antigen-4(SSEA-4) was analysed by immunohistochemistry in 38 patients with resected early-stage basaloid NSCLC who had a median follow-up of 72.9 months. The expression ofSSEA-4was related to clinico-pathological characteristics, to the expression of the adult stem cell antigens CD117, CD133 andbreast cancer resistance protein 1(BCRP1), and to prognosis.

SSEA-4was positive in 37% of the specimens and showed no association with clinico-pathological characteristics or the expression of adult stem cell antigens. Cox proportional hazards regression analysis revealed a 6.0-fold increased risk of relapse (p = 0.001) and a 4.2-fold increased risk of disease-related mortality (p = 0.017) inSSEA-4-positive patients, whileSSEA-4-negative patients showed a prognosis comparable with that of other early-stage NSCLC.

SSEA-4is expressed in a fraction of basaloid NSCLC and is associated with poor prognosis.
MarVis: a tool for clustering and visualization of metabolic biomarkers
Authors: Kaever Alexander , Lingner Thomas , Feussner Kirstin , Göbel Cornelia , Feussner Ivo , Meinicke Peter
Published: June 2012

Background

A central goal of experimental studies in systems biology is to identify meaningful markers that are hidden within a diffuse background of data originating from large-scale analytical intensity measurements as obtained from metabolomic experiments. Intensity-based clustering is an unsupervised approach to the identification of metabolic markers based on the grouping of similar intensity profiles. A major problem of this basic approach is that in general there is no prior information about an adequate number of biologically relevant clusters.

Results

We present the tool MarVis (Marker Visualization) for data mining on intensity-based profiles using one-dimensional self-organizing maps (1D-SOMs). MarVis can import and export customizable CSV (Comma Separated Values) files and provides aggregation and normalization routines for preprocessing of intensity profiles that contain repeated measurements for a number of different experimental conditions. Robust clustering is then achieved by training of an 1D-SOM model, which introduces a similarity-based ordering of the intensity profiles. The ordering allows a convenient visualization of the intensity variations within the data and facilitates an interactive aggregation of clusters into larger blocks. The intensity-based visualization is combined with the presentation of additional data attributes, which can further support the analysis of experimental data.

Conclusion

MarVis is a user-friendly and interactive tool for exploration of complex pattern variation in a large set of experimental intensity profiles. The application of 1D-SOMs gives a convenient overview on relevant profiles and groups of profiles. The specialized visualization effectively supports researchers in analyzing a large number of putative clusters, even though the true number of biologically meaningful groups is unknown. Although MarVis has been developed for the analysis of metabolomic data, the tool may be applied to gene expression data as well.
Origin of a novel protein-coding gene family with similar signal sequence in Schistosoma japonicum
Authors: Mbanefo Evaristus Chibunna , Chuanxin Yu , Kikuchi Mihoko , Shuaibu Mohammed Nasir , Boamah Daniel , Kirinoki Masashi , Hayashi Naoko , Chigusa Yuichi , Osada Yoshio , Hamano Shinjiro , Hirayama Kenji
Published: June 2012

Background

Evolution of novel protein-coding genes is the bedrock of adaptive evolution. Recently, we identified six protein-coding genes with similar signal sequence from Schistosoma japonicum egg stage mRNA using signal sequence trap (SST). To find the mechanism underlying the origination of these genes with similar core promoter regions and signal sequence, we adopted an integrated approach utilizing whole genome, transcriptome and proteome database BLAST queries, other bioinformatics tools, and molecular analyses.

Results

Our data, in combination with database analyses showed evidences of expression of these genes both at the mRNA and protein levels exclusively in all developmental stages of S. japonicum. The signal sequence motif was identified in 27 distinct S. japonicum UniGene entries with multiple mRNA transcripts, and in 34 genome contigs distributed within 18 scaffolds with evidence of genome-wide dispersion. No homolog of these genes or similar domain was found in deposited data from any other organism. We observed preponderance of flanking repetitive elements (REs), albeit partial copies, especially of the RTE-like and Perere class at either side of the duplication source locus. The role of REs as major mediators of DNA-level recombination leading to dispersive duplication is discussed with evidence from our analyses. We also identified a stepwise pathway towards functional selection in evolving genes by alternative splicing. Equally, the possible transcription models of some protein-coding representatives of the duplicons are presented with evidence of expression in vitro.

Conclusion

Our findings contribute to the accumulating evidence of the role of REs in the generation of evolutionary novelties in organisms’ genomes.
The immune gene repertoire of an important viral reservoir, the Australian black flying fox
Authors: Papenfuss Anthony T , Baker Michelle L , Feng Zhi-Ping , Tachedjian Mary , Crameri Gary , Cowled Chris , Ng Justin , Janardhana Vijaya , Field Hume E , Wang Lin-Fa
Published: June 2012

Background

Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity.

Results

Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts.

Conclusions

This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection.
Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report
Authors: Diserens Esther-Amélie , Bodenmann Patrick , N'Garambe Chantal , Ansermet-Pagot Anne , Vannotti Marco , Masserey Eric , Cavassini Matthias
Published: June 2012

Background

Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries.

Method

This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic.

Result

We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing.

Conclusion

This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.
Statin therapy in critical illness: an international survey of intensive care physicians’ opinions, attitudes and practice
Authors: Shankar-Hari Manu , Kruger Peter S , Di Gangi Stefania , Scales Damon C , Perkins Gavin D , McAuley Danny F , Terblanche Marius
Published: June 2012

Background

Pleotropic effects of statins on inflammation are hypothesised to attenuate the severity of and possibly prevent the occurrence of the host inflammatory response to pathogen and infection-related acute organ failure. We conducted an international survey of intensive care physicians in Australia, New Zealand (ANZ) and United Kingdom (UK). The aims of the survey were to assess the current prescribing practice patterns, attitudes towards prescribing statin therapy in critically ill patients and opinions on the need for an interventional trial of statin therapy in critically ill patients.

Methods

Survey questions were developed through an iterative process. An expert group reviewed the resulting 26 items for face and content validity and clarity. The questions were further refined following pilot testing by ICU physicians from Australia, Canada and the UK. We used the online Smart SurveyTM software to administer the survey.

Results

Of 239 respondents (62 from ANZ and 177 from UK) 58% worked in teaching hospitals; most (78.2%) practised in ‘closed’ units with a mixed medical and surgical case mix (71.0%). The most frequently prescribed statins were simvastatin (77.6%) in the UK and atorvastatin (66.1%) in ANZ. The main reasons cited to explain the choice of statin were preadmission prescription and pharmacy availability. Most respondents reported never starting statins to prevent (65.3%) or treat (89.1%) organ dysfunction. Only a minority (10%) disagreed with a statement that the risks of major side effects of statins when prescribed in critically ill patients were low. The majority (84.5%) of respondents strongly agreed that a clinical trial of statins for prevention is needed. More than half (56.5%) favoured rates of organ failure as the primary outcome for such a trial, while a minority (40.6%) favoured mortality.

Conclusions

Despite differences in type of statins prescribed, critical care physicians in the UK and ANZ reported similar prescription practices. Respondents from both communities agreed that a trial is needed to test whether statins can prevent the onset of new organ failure in patients with sepsis.
Reflections of students graduating from a transforming medical curriculum in South Africa: a qualitative study
Authors: Green-Thompson Lionel Patrick , McInerney Patricia , Manning Dianne Mary , Mapukata-Sondzaba Ntsiki , Chipamaunga Shalote , Maswanganyi Tlangelani
Published: June 2012

Background

The six year medical programme at the University of the Witwatersrand admits students into the programme through two routes – school entrants and graduate entrants. Graduates join the school entrants in the third year of study in a transformed curriculum called the Graduate Entry Medical Programme (GEMP). In years I and 2 of the GEMP, the curriculum is structured into system based blocks. Problem-based learning, using a three session format, is applied in these two years. The curriculum adopts a biopsychosocial approach to health care, which is implemented through spiral teaching and learning in four main themes – basic and clinical sciences, patient-doctor, community- doctor and personal and professional development. In 2010 this programme produced its fifth cohort of graduates.

Methods

We undertook a qualitative, descriptive and contextual study to explore the graduating students’ perceptions of the programme. Interviews were conducted with a total of 35 participants who volunteered to participate in the study. The majority of the participants interviewed participated in focus group discussions. The interviews were transcribed verbatim and analysed thematically, using Tesch’s eight steps. Ethics approval for the study was obtained from the Human Research Ethics Committee of the University of the Witwatersrand. Participants provided written consent to participate in the interviews and for the interviews to be audio-taped.

Results

Six themes were identified. These were: two separate programmes, problem-based learning and Garmins® (navigation system), see patients for real, being seen as doctors, assessment: of mice and MCQ’s, a cry for support and personal growth and pride. Participants were vocal in their reflections of experiences encountered during the programme and made several insightful suggestions for curriculum transformation. The findings suggest that graduates are exiting the programme confident and ready to begin their internships.

Conclusions

The findings of this study have identified a number of areas which need attention in the curriculum. Specifically attention needs to be given to ensuring that assessment is standardized; student support structures and appropriate levels of teaching. The study demonstrated the value of qualitative methods in obtaining students’ perceptions of a curriculum.
Computational synchronization of microarray data with application to Plasmodium falciparum
Authors: Zhao Wei , Dauwels Justin , Niles Jacquin C , Cao Jianshu
Published: June 2012

Background

Microarrays are widely used to investigate the blood stage ofPlasmodium falciparuminfection. Starting with synchronized cells, gene expression levels are continually measured over the 48-hour intra-erythrocytic cycle (IDC). However, the cell population gradually loses synchrony during the experiment. As a result, the microarray measurements are blurred. In this paper, we propose a generalized deconvolution approach to reconstruct the intrinsic expression pattern, and apply it toP. falciparumIDC microarray data.

Methods

We develop a statistical model for the decay of synchrony among cells, and reconstruct the expression pattern through statistical inference. The proposed method can handle microarray measurements with noise and missing data. The original gene expression patterns become more apparent in the reconstructed profiles, making it easier to analyze and interpret the data. We hypothesize that reconstructed gene expression patterns represent better temporally resolved expression profiles that can be probabilistically modeled to match changes in expression level to IDC transitions. In particular, we identify transcriptionally regulated protein kinases putatively involved in regulating theP. falciparumIDC.

Results

By analyzing publicly available microarray data sets for theP. falciparumIDC, protein kinases are ranked in terms of their likelihood to be involved in regulating transitions between the ring, trophozoite and schizont developmental stages of theP. falciparumIDC. In our theoretical framework, a few protein kinases have high probability rankings, and could potentially be involved in regulating these developmental transitions.

Conclusions

This study proposes a new methodology for extracting intrinsic expression patterns from microarray data. By applying this method toP. falciparummicroarray data, several protein kinases are predicted to play a significant role in theP. falciparumIDC. Earlier experiments have indeed confirmed that several of these kinases are involved in this process. Overall, these results indicate that further functional analysis of these additional putative protein kinases may reveal new insights into how theP. falciparumIDC is regulated.
Ion annotation-assisted analysis of LC-MS based metabolomic experiment
Authors: Varghese Rency S , Zhou Bin , Nezami Ranjbar Mohammad R , Zhao Yi , Ressom Habtom W
Published: June 2012

Background

Analysis of multiple LC-MS based metabolomic studies is carried out to determine overlaps and differences among various experiments. For example, in large metabolic biomarker discovery studies involving hundreds of samples, it may be necessary to conduct multiple experiments, each involving a subset of the samples due to technical limitations. The ions selected from each experiment are analyzed to determine overlapping ions. One of the challenges in comparing the ion lists is the presence of a large number of derivative ions such as isotopes, adducts, and fragments. These derivative ions and the retention time drifts need to be taken into account during comparison.

Results

We implemented an ion annotation-assisted method to determine overlapping ions in the presence of derivative ions. Following this, each ion is represented by the monoisotopic mass of its cluster. This mass is then used to determine overlaps among the ions selected across multiple experiments.

Conclusion

The resulting ion list provides better coverage and more accurate identification of metabolites compared to the traditional method in which overlapping ions are selected on the basis of individual ion mass.
EMG-based simultaneous and proportional estimation of wrist/hand kinematics in uni-lateral trans-radial amputees
Authors: Jiang Ning , Vest-Nielsen Johnny LG , Muceli Silvia , Farina Dario
Published: June 2012

We propose a method for estimating wrist kinematics during dynamic wrist contractions from multi-channel surface electromyography (EMG). The algorithm extracts features from the surface EMG and uses dedicated multi-layer perceptron networks to estimate individual joint angles of the 3 degrees of freedom (DoFs) of the wrist. The method was designed with the aim of proportional and simultaneous control of multiple DoFs of active prostheses by unilateral amputees. Therefore, the proposed approach was tested in both unilateral transradial amputees and in intact-limbed control subjects. It was shown that the joint angles at the 3 DoFs of amputees can be estimated from surface EMG recordings , during mirrored bi-lateral contractions that simultaneously and proportionally articulated the 3 DoFs. The estimation accuracies of amputee subjects with long stumps were 62.5% ± 8.50% across all 3 DoFs, while accuracies of the intact-limbed control subjects were 72.0% ± 8.29%. The estimation results from intact-limbed subjects were consistent with earlier studies. The results from the current study demonstrated the feasibility of the proposed myoelectric control approach to provide a more intuitive myoelectric control strategy for unilateral transradial amputees.
Gastrointestinal lymphomas in a North American population: clinicopathologic features from one major Central-Midwestern United States tertiary care medical center
Authors: Warrick Joshua , Luo Jingqin , Robirds Diane , Branson Julie , Frater John L , Kreisel Friederike , Hassan Anjum , Nguyen TuDung T
Published: June 2012

Background

Gastrointestinal (GI) lymphomas are very common types of extranodal lymphomas, and we hypothesize there are regional differences in subtype, distribution in the GI tract, and epidemiological features among the different populations.

Methods

We retrospectively evaluated the clinical, molecular and histologic features of North American primary and secondary GI lymphomas diagnosed from 2000–2009 seen at our institution. We utilized immunohistochemistry and fluorescence in situ hybridization to further evaluate a subset of the gastric lymphomas.

Results

Extranodal marginal zone lymphomas of mucosal associated lymphoid tissue (MALTs) and diffuse large B cell lymphomas (DLBCLs) were the most common subtypes of GI lymphomas. Select gastric DLBCLs (N = 6) and MALTs (N = 13) were further examined for API2-MALT1 and IGH translocations, and P16 and P53 protein expression. Gastric MALTs showed frequent API2-MALT1 (38%) but not IGH translocations (0%), and the DLBCLs showed neither translocation. Expression of P16 and P53 proteins and the proliferative index were compared between high grade gastric lymphomas (gastric DLBCLs) and low grade gastric lymphomas (gastric MALTs). P53 overexpression (P = 0.008) and a high proliferation index [Ki-67] (P = 0.00042) were significantly associated with gastric DLBCL, but no statistically significant difference was observed in P16 expression (p = 0.108) between gastric DLBCL and gastric MALT.

Conclusion

Our study revealed that GI lymphomas from a Central-Midwestern North American population showed differences and similarities to non-North American cohorts. In addition, API2-MALT1, P16 and P53 abnormalities occurred frequently in gastric lymphomas from this North American population.

Virtual slides

The virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1415505838687793
Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum
Authors: Beisser Daniela , Grohme Markus A , Kopka Joachim , Frohme Marcus , Schill Ralph O , Hengherr Steffen , Dandekar Thomas , Klau Gunnar W , Dittrich Marcus , Müller Tobias
Published: June 2012

Background

Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress.

Results

In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration.

Conclusions

The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.
Thrombocytopenia and absent radii (TAR) syndrome associated with bilateral congenital cataract: a case report
Authors: Omran Ahmed , Sahmoud Shaimaa , Peng Jing , Ashhab Usman , Yin Fei
Published: June 2012

Introduction

Thrombocytopenia with absent radii is a rare congenital defect with hypomegakaryocytic thrombocytopenia and bilateral radial aplasia that may have additional anomalies. We report the case of a girl baby with thrombocytopenia and absent radii syndrome and bilateral congenital cataract. This anomaly has not been previously reported in the children of a non- consanguineous marriage.

Case presentation

This case report describes a two-day-old girl baby of Arab origin with thrombocytopenia and absent radii syndrome and bilateral congenital cataract.

Conclusions

This report describes a finding of bilateral congenital cataract associated with thrombocytopenia and absent radii syndrome that has been reported only once before in the literature. This case report highlights a new ocular manifestation in one of the bone marrow failure syndromes.
The computational-based structure of Dwarf14 provides evidence for its role as potential strigolactone receptor in plants
Authors: Gaiji Noura , Cardinale Francesca , Prandi Cristina , Bonfante Paola , Ranghino Graziella
Published: June 2012

Background

Strigolactones (SLs) are recently identified plant hormones modulating root and shoot branching. Besides their endogenous role within the producing organism, SLs are also key molecules in the communication of plants with arbuscular mycorrhizal (AM) fungi and parasitic weeds. In fact SLs are exuded into the rhizosphere where they act as a host-derived signal, stimulating the germination of the seeds of parasitic plants which would not survive in the absence of a host root to colonize. Similarly, their perception by AM fungi causes extensive hyphal branching; this is a prerequisite for effective root colonization, since it increases the number of potential contact points with the host surface. In spite of the crucial and multifaceted biological role of SLs, there is no information on the receptor(s) which bind(s) such active molecules, neither in the producing plants, or in parasitic weeds or AM fungi.

Results

In this work, we applied homology modelling techniques to investigate the structure of the protein encoded by the gene Dwarf14, which was first identified in rice as conferring SLs insensitivity when mutated. The best sequence identity was with bacterial RsbQ. Both proteins belong to the superfamily of alpha/beta-fold hydrolases, some members of which play a role in the metabolism or signalling of plant hormones. The Dwarf14 (D14) structure was refined by means of molecular dynamics simulations. In order to support the hypothesis that D14 could be an endogenous SLs receptor, we performed docking experiments with a natural ligand.

Conclusions

It is suggested that D14 interacts with and thereby may act as a receptor for SLs in plants. This hypothesis offers a starting point to experimentally study the mechanism of its activity in vivo by means of structural, molecular and genetic approaches. Lastly, knowledge of the putative receptor structure will boost the research on analogues of the natural substrates as required for agricultural applications.
Blastocystis sp.: waterborne zoonotic organism, a possibility?
Authors: Lee Li Ii , Chye Tan Tian , Karmacharya Biraj Man , Govind Suresh Kumar
Published: June 2012

Background

Blastocystis sp. is a common intestinal parasite found in faecal sample surveys. Several studies have implicated human-to-human, zoonotic and waterborne transmissions by Blastocystis sp. However, there has been no study providing evidence interlinking these three transmissions in a community. We have previously shown a high prevalence of Blastocystis sp. subtype 4 amongst village dwellers in Bahunipati, Nepal, and the present study extends the observation to assess if the same subtype of Blastocystis sp. occurs in animals they rear and rivers they frequent.

Methods

Faecal samples were collected from 65 animals. Four river water samples were collected from two rivers. Faecal samples were examined using in vitro cultivation. Blastocystis sp. from animal faecal and river samples were genotyped using seven subtype-specific sequence tagged site (STS) primer-polymerase chain reaction (PCR).

Results

Blastocystis sp. infected 15.4% animals with subtype 4 being the predominant genotype (40.0%). Both rivers were contaminated with Blastocystis sp. subtype 1 and subtype 4, which were also detected in humans living in the same village in our previous study. Blastocystis sp. subtype 4 that was detected in buffalo and pigs was also found in the respective family members that reared these animals.

Conclusions

This unusually high prevalence of Blastocystis subtype 4 found in village dwellers was also found to be pervasive in the animals they reared and the rivers they frequented implying a strong possibility of waterborne zoonosis for Blastocystis sp.
Inter‐assessor reliability of practice based biomechanical assessment of the foot and ankle
Authors: Jarvis Hannah L , Nester Christopher J , Jones Richard K , Williams Anita , Bowden Peter D
Published: June 2012

Background

There is no consensus on which protocols should be used to assess foot and lower limb biomechanics in clinical practice. The reliability of many assessments has been questioned by previous research. The aim of this investigation was to (i) identify (through consensus) what biomechanical examinations are used in clinical practice and (ii) evaluate the inter‐assessor reliability of some of these examinations.

Methods

Part1: Using a modified Delphi technique 12 podiatrists derived consensus on the biomechanical examinations used in clinical practice. Part 2: Eleven podiatrists assessed 6 participants using a subset of the assessment protocol derived in Part 1. Examinations were compared between assessors.

Results

Clinicians choose to estimate rather than quantitatively measure foot position and motion. Poor inter‐assessor reliability was recorded for all examinations. Intra‐class correlation coefficient values (ICC) for relaxed calcaneal stance position were less than 0.23 and were less than 0.14 for neutral calcaneal stance position. For the examination of ankle joint dorsiflexion, ICC values suggest moderate reliability (less than 0.61). The results of a random effects ANOVA highlight that participant (up to 5.7°), assessor (up to 5.8°) and random (up to 5.7°) error all contribute to the total error (up to 9.5° for relaxed calcaneal stance position, up to 10.7° for the examination of ankle joint dorsiflexion). Kappa Fleiss values for categorisation of first ray position and mobility were less than 0.05 and for limb length assessment less than 0.02, indicating slight agreement.

Conclusion

Static biomechanical assessment of the foot, leg and lower limb is an important protocol in clinical practice, but the key examinations used to make inferences about dynamic foot function and to determine orthotic prescription are unreliable.