Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

An appraisal of students' awareness of "self-reflection" in a first-year pathology course of undergraduate medical/dental education

<p>Abstract</p> <p>Background</p> <p>Self-reflection and reflective practice are increasingly considered as essential attributes of competent professionals functioning in complex and ever-changing healthcare systems of the 21^stcentury. The aim of this study was to determine the extent of students' awareness and understanding of the reflective process and the meaning of 'self-reflection' within the contextual framework of their learning environment in the first-year of their medical/dental education. We endorse that the introduction of such explicit educational tasks at this early stage enhances and promotes students' awareness, understanding, and proficiency of this skill in their continuing life-long health professional learning.</p> <p>Methods</p> <p>Over two years, students registered in first-year pathology at the University of Saskatchewan were introduced to a self-reflection assignment which comprised in the submission of a one-page reflective document to a template of reflective questions provided in the given context of their learning environment. This was a mandatory but ungraded component at the midterm and final examinations. These documents were individually analyzed and thematically categorized to a "5 levels-of-reflection-awareness" scale using a specially-designed rubric based on the accepted major theories of reflection that included students' identification of: 1) personal abilities, 2) personal learning styles 3) relationships between course material and student history 4) emotional responses and 5) future applications.</p> <p>Results</p> <p>410 self-reflection documents were analyzed. The student self-awareness on personal learning style (72.7% level 3+) and course content (55.2% level 3+) were well-reflected. Reflections at a level 1 awareness included identification of a) specific teaching strategies utilized to enhance learning (58.4%), b) personal strengths/weaknesses (53%), and c) emotional responses, values, and beliefs (71.5%). Students' abilities to connect information to life experiences and to future events with understanding were more evenly distributed across all 5 levels of reflection-awareness.</p> <p>Conclusions</p> <p>Exposure to self-reflection assignments in the early years of undergraduate medical education increases student awareness and promotes the creation of personal meaning of one's reactions, values, and premises in the context of student learning environments. Early introduction with repetition to such cognitive processes as practice tools increases engagement in reflection that may facilitate proficiency in mastering this competency leading to the creation of future reflective health professionals.</p

Teaching Engineering Ethics using BLOCKS Game

The aim of this study was to investigate the use of a newly developed design game called BLOCKS to stimulate awareness of ethical responsibilities amongst engineering students. The design game was played by seventeen teams of chemical engineering students, with each team having to arrange pieces of colored paper to produce two letters each. Before the end of the game, additional constraints were introduced to the teams such that they faced similar ambiguity in the technical facts that the engineers involved in the Challenger disaster had faced prior to the space shuttle launch. At this stage, the teams had to decide whether to continue with their original design or to develop alternative solutions. After the teams had made their decisions, a video of the Challenger explosion was shown followed by a post-game discussion. The students’ opinion on five Statements on ethics was tracked via a Five-Item Likert survey which was administered three times, before and after the ethical scenario was introduced, and after the video and post-game discussion. The results from this study indicated that the combination of the game and the real-life incident from the video had generally strengthened the students’ opinions of the Statements

Retained Surgical Items and Minimally Invasive Surgery

A retained surgical item is a surgical patient safety problem. Early reports have focused on the epidemiology of retained-item cases and the identification of patient risk factors for retention. We now know that retention has very little to do with patient characteristics and everything to do with operating room culture. It is a perception that minimally invasive procedures are safer with regard to the risk of retention. Minimally invasive surgery is still an operation where an incision is made and surgical tools are placed inside of patients, so these cases are not immune to the problem of inadvertent retention. Retained surgical items occur because of problems with multi-stakeholder operating room practices and problems in communication. The prevention of retained surgical items will therefore require practice change, knowledge, and shared information between all perioperative personnel

Gene fusions and gene duplications: relevance to genomic annotation and functional analysis

BACKGROUND: Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular) proteins consist of two or more components (modules) encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. RESULTS: Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused) proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. CONCLUSION: The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes it possible to generate protein groups related by both sequence and function, avoiding mixing of unrelated sequences. Organisms differ in sizes of groups of sequence-related proteins. A sample comparison of orthologs to selected E. coli paralogous groups correlates with known physiological and taxonomic relationships between the organisms

Meiotic Transmission of Drosophila pseudoobscura Chromosomal Arrangements

Drosophila pseudoobscura harbors a rich gene arrangement polymorphism on the third chromosome generated by a series of overlapping paracentric inversions. The arrangements suppress recombination in heterokaryotypic individuals, which allows for the selective maintenance of coadapted gene complexes. Previous mapping experiments used to determine the degree to which recombination is suppressed in gene arrangement heterozygotes produced non-recombinant progeny in non-Mendelian ratios. The deviations from Mendelian expectations could be the result of viability differences between wild and mutant chromosomes, meiotic drive because of achiasmate pairing of homologues in heterokaryotypic females during meiosis, or a combination of both mechanisms. The possibility that the frequencies of the chromosomal arrangements in natural populations are affected by mechanisms other than adaptive selection led us to consider these hypotheses. We performed reciprocal crosses involving both heterozygous males and females to determine if the frequency of the non-recombinant progeny deviates significantly from Mendelian expectations and if the frequencies deviate between reciprocal crosses. We failed to observe non-Mendelian ratios in multiple crosses, and the frequency of the non-recombinant classes differed in only one of five pairs of reciprocal crosses despite sufficient power to detect these differences in all crosses. Our results indicate that deviations from Mendelian expectations in recombination experiments involving the D. pseudoobscura inversion system are most likely due to fitness differences of gene arrangement karyotypes in different environments

Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review

BACKGROUND: Vancomycin resistant enterococcus (VRE) is a major cause of nosocomial infections in the United States and may be associated with greater morbidity, mortality, and healthcare costs than vancomycin-susceptible enterococcus. Current guidelines for the control of VRE include prudent use of vancomycin. While vancomycin exposure appears to be a risk factor for VRE acquisition in individual patients, the effect of vancomycin usage at the population level is not known. We conducted a systematic review to determine the impact of reducing vancomycin use through prescribing interventions on the prevalence and incidence of VRE colonization and infection in hospitals within the United States. METHODS: To identify relevant studies, we searched three electronic databases, and hand searched selected journals. Thirteen studies from 12 articles met our inclusion criteria. Data were extracted and summarized for study setting, design, patient characteristics, types of intervention(s), and outcome measures. The relative risk, 95% confidence interval, and p-value associated with change in VRE acquisition pre- and post-vancomycin prescription interventions were calculated and compared. Heterogeneity in study results was formally explored by stratified analysis. RESULTS: No randomized clinical trials on this topic were found. Each of the 13 included studies used a quasi-experimental design of low hierarchy. Seven of the 13 studies reported statistically significant reductions in VRE acquisition following interventions, three studies reported no significant change, and three studies reported increases in VRE acquisition, one of which reported statistical significance. Results ranged from a reduction of 82.5% to an increase of 475%. Studies of specific wards, which included sicker patients, were more likely to report positive results than studies of an entire hospital including general inpatients (Fisher's exact test 0.029). The type of intervention, endemicity status, type of study design, and the duration of intervention were not found to significantly modify the results. Among the six studies that implemented vancomycin reduction strategies as the sole intervention, two of six (33%) found a significant reduction in VRE colonization and/or infection. In contrast, among studies implementing additional VRE control measures, five of seven (71%) reported a significant reduction. CONCLUSION: It was not possible to conclusively determine a potential role for vancomycin usage reductions in controlling VRE colonization and infection in hospitals in the United States. The effectiveness of such interventions and their sustainability remains poorly defined because of the heterogeneity and quality of studies. Future research using high-quality study designs and implementing vancomycin as the sole intervention are needed to answer this question

Controlling epidemic spread by social distancing: Do it well or not at all

BACKGROUND: Existing epidemiological models have largely tended to neglect the impact of individual behaviour on the dynamics of diseases. However, awareness of the presence of illness can cause people to change their behaviour by, for example, staying at home and avoiding social contacts. Such changes can be used to control epidemics but they exact an economic cost. Our aim is to study the costs and benefits of using individual-based social distancing undertaken by healthy individuals as a form of control.METHODS: Our model is a standard SIR model superimposed on a spatial network, without and with addition of small-world interactions. Disease spread is controlled by allowing susceptible individuals to temporarily reduce their social contacts in response to the presence of infection within their local neighbourhood. We ascribe an economic cost to the loss of social contacts, and weigh this against the economic benefit gained by reducing the impact of the epidemic. We study the sensitivity of the results to two key parameters, the individuals' attitude to risk and the size of the awareness neighbourhood.RESULTS: Depending on the characteristics of the epidemic and on the relative economic importance of making contacts versus avoiding infection, the optimal control is one of two extremes: either to adopt a highly cautious control, thereby suppressing the epidemic quickly by drastically reducing contacts as soon as disease is detected; or else to forego control and allow the epidemic to run its course. The worst outcome arises when control is attempted, but not cautiously enough to cause the epidemic to be suppressed. The next main result comes from comparing the size of the neighbourhood of which individuals are aware to that of the neighbourhood within which transmission can occur. The control works best when these sizes match and is particularly ineffective when the awareness neighbourhood is smaller than the infection neighbourhood. The results are robust with respect to inclusion of long-range, small-world links which destroy the spatial structure, regardless of whether individuals can or cannot control them. However, addition of many non-local links eventually makes control ineffective.CONCLUSIONS: These results have implications for the design of control strategies using social distancing: a control that is too weak or based upon inaccurate knowledge, may give a worse outcome than doing nothing