A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

The Cow: Discovery of a Luminous, Hot, and Rapidly Evolving Transient

We present the ATLAS discovery and initial analysis of the first 18 days of the unusual transient event, ATLAS18qqn/AT2018cow. It is characterized by a high peak luminosity (~1.7 × 1044 erg s−1), rapidly evolving light curves (>5 mag rise to peak in ~3.5 days), and hot blackbody spectra, peaking at ~27,000 K that are relatively featureless and unchanging over the first two weeks. The bolometric light curve cannot be powered by radioactive decay under realistic assumptions. The detection of high-energy emission may suggest a central engine as the powering source. Using a magnetar model, we estimated an ejected mass of 0.1–0.4 M ${}_{\odot }$, which lies between that of low-energy core-collapse events and the kilonova, AT2017gfo. The spectra cooled rapidly from 27,000 to 15,000 K in just over two weeks but remained smooth and featureless. Broad and shallow emission lines appear after about 20 days, and we tentatively identify them as He i although they would be redshifted from their rest wavelengths. We rule out that there are any features in the spectra due to intermediate mass elements up to and including the Fe group. The presence of r-process elements cannot be ruled out. If these lines are due to He, then we suggest a low-mass star with residual He as a potential progenitor. Alternatively, models of magnetars formed in neutron star mergers, or accretion onto a central compact object, give plausible matches to the data

Medical student and academic staff perceptions of role models: an analytical cross-sectional study

BACKGROUND: This study explored the associations between the perceptions of students and the perceptions of academic staff about the characteristics of clinical lecturers at the Department of Internal Medicine at Kerman University of Medical Sciences (KUMS). It also assessed what characteristics constitute a 'role model' from the point of view of students and staff. METHODS: Staff and students were questioned about the characteristics of their colleagues and lecturers, respectively. They were asked about 15 characteristics under four headings: personality, teaching skill, group working and overall performance as a role model. Associations between lecturers' characteristics were explored using Pearson correlation and characteristics were allocated into groups by partition cluster method. In addition, predictors of being a valuable lecturer were assessed using logistic regression analysis. RESULTS: Based on staff responses, the strongest association observed was between honesty and being respectful (r = 0.93, p < 0.0001). Based on student responses, the strongest association observed was between being professional and honesty (r = 0.98, p < 0.0001). None of the correlations between student and staff perceptions were significant for any characteristic. Two groups were recognized among the characteristics. group one contained those characteristics which were related to the lecturer's activity; while the second group contained characteristics that were related to the personality or teaching performance of the lecturer. The predictors of lecturer as 'role model' (i.e., perceptions of students) consisted mostly of characteristics from the first group, while the predictors of a 'role model' by fellow academic staff consisted of characteristics that were in both groups. CONCLUSION: These findings showed considerable differences between the perceptions of students about their lecturers when compared with perceptions of staff about their colleagues. Students were more concerned with the personality of their lecturers, while staff also considered their ideas and behaviors. This suggests that a more comprehensive assessment of a lecturer's performance could be obtained by taking into account feedback from both students and colleagues

Interventional radiology virtual simulator for liver biopsy

Purpose Training in Interventional Radiology currently uses the apprenticeship model, where clinical and technical skills of invasive procedures are learnt during practice in patients. This apprenticeship training method is increasingly limited by regulatory restrictions on working hours, concerns over patient risk through trainees’ inexperience and the variable exposure to case mix and emergencies during training. To address this, we have developed a computer-based simulation of visceral needle puncture procedures. Methods A real-time framework has been built that includes: segmentation, physically based modelling, haptics rendering, pseudo-ultrasound generation and the concept of a physical mannequin. It is the result of a close collaboration between different universities, involving computer scientists, clinicians, clinical engineers and occupational psychologists. Results The technical implementation of the framework is a robust and real-time simulation environment combining a physical platform and an immersive computerized virtual environment. The face, content and construct validation have been previously assessed, showing the reliability and effectiveness of this framework, as well as its potential for teaching visceral needle puncture. Conclusion A simulator for ultrasound-guided liver biopsy has been developed. It includes functionalities and metrics extracted from cognitive task analysis. This framework can be useful during training, particularly given the known difficulties in gaining significant practice of core skills in patients

A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition

Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level

Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness?

Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2x180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS. Methods: Seventeen healthy non-smoking females (age 20.4 +/- 2.1 years, height 161.2 +/- 8.3cm and mass 61.48 +/- 7.4kg) were randomly assigned to either placebo (N = 10) or EPA (N = 7). Serum IL-6, isometric and isokinetic (concentric and eccentric) strength, and rating of perceived exertion (RPE) were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects), iii-48 hours following a single bout of resistance exercise (acute training response effects), and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects). Results: There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 +/- 60% increment in IL-6 levels whereas the placebo group only had 80 +/- 26% incremented IL-6 levels (P = 0.020). We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. Conclusion: The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to exercise. In a context where previous in vitro work has shown EPA to decrease the effects of inflammatory cytokines, it may in fact be that the doses required in vivo is much larger than current recommended amounts. An attempt to dampen the exercise-induced cytokine flux in fact results in an over-compensatory response of this system

Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes

Background Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with 24,072 gene probe sets representing more than 23,000 gene transcripts. Results Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of gene transcripts showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity® Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. Conclusions This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.This work was supported by Investigator Grants from Science Foundation Ireland (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038), a Research Stimulus Grant from the Department of Agriculture, Fisheries and Food (No: RSF 06 405) and a European Union Framework 7 Project Grant (No: KBBE-211602-MACROSYS). KEK is supported by the Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and Systems Biology PhD Programme http://bioinfo-casl.ucd.ie/PhD

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

BACKGROUND: For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. METHODS: The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. RESULTS: Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. CONCLUSIONS: For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review