Determining the research priorities for emergency care within the Western Cape province of South Africa: A consensus study.

Introduction: Low- and middle-income countries (LMICs) are disproportionally affected by conditions requiring emergency care but there are limited contextually appropriate studies performed within these settings involving the patient population and healthcare systems they aim to benefit. Over the past five years, researchers in the Western Cape of South Africa have produced approximately 20 % of all emergency care publications from Africa, yet no agreed list of research priorities exists. Establishing research priorities, via recognised consensus methods, can ensure that efforts and resources in LMICs are more appropriately targeted to the need. Method: Using a modified Delphi study, we invited a range of public and private representatives from different professional emergency care cadres within the Western Cape to identify current evidence gaps and consensus research priorities across the four areas of the WHO Emergency Care Systems framework: scene care, prehospital care, facility-based care, and the emergency care system itself. We then purposively selected eleven experts holding key academic and management positions to form a panel and perform a nominal group technique process to discuss these identified research priorities and establish a final list of priority research questions. Result: Forty of the sixty-six (61 %) emergency care professionals invited contributed to the Delphi phase of the study, with representation from all professional cadres. After deduplication, 154 research topics were identified in the first round. In the second round, 94 (61 %) topics were considered research priorities by at least 80 % of participants. Following the nominal group technique discussion, 26 questions were established as consensus research priorities having been ranked as a top ten priority by over 50 % of panellists. Conclusion: We were able to successfully collate expert opinion and identify existing emergency care knowledge gaps within the Western Cape province of South Africa. Key topics identified for future work included questions on current health-seeking behaviour, dispatch, interfacility transfer, and staff burnout.

Exploring Flood Response Challenges, Training Needs, and the Impact of Online Flood Training for Lifeguards and Water Safety Professionals in South Africa.

Flooding is a significant cause of human and economic loss in the African region, including in South Africa. Flood mitigation and response in South Africa is challenging due to a range of environmental, infrastructure, and policy constraints. Lifeguards represent a potential additional workforce to bolster flood mitigation and response. This study aimed to explore the feasibility and acceptability of online flood safety training for water safety professionals in South Africa, as well as assess the current flood response capacity and future needs of this group. Online surveys were completed by a convenience sample of South African water safety professionals (including lifeguards) pre-and post a series of four online flood training workshops. Free text responses were thematically coded and flood knowledge was compared between the pre-and post-workshop survey respondents. Sixty-eight responses were analysed (64.7% pre-workshop phase; 63.2% male, 29.4% aged 50-59 years). A range of challenges in flood mitigation and response were identified including equipment, training, and a lack of government support. However, positives were also identified including respondents' willingness to assist in flood emergencies and good cooperation with neighbouring countries and across the region. Opportunities for better cross-municipal and government communication were discussed. In times of crisis, or in resource poor settings, water safety professionals can bolster traditional flood mitigation and response capacity. Opportunities exist to harness this willingness, but also improve cross-governmental and municipal knowledge sharing to improve future flood mitigation and response efforts in South Africa.

Paediatric procedural sedation and analgesia in a South African emergency centre: a single-centre, descriptive study.

BACKGROUND: Procedural sedation and analgesia are considered a core competency in emergency medicine as patients present to the emergency centre on an unscheduled basis, often with complex complaints that necessitate emergent management. Previous evidence has consistently shown that procedural sedation and analgesia in the emergency centre in the paediatric population, even the very young, are safe if appropriate monitoring is performed and appropriate medications are used. The aim of the study was to describe the indications for procedural sedation and analgesia, the fasting status of paediatric patients undergoing procedural sedation and analgesia and the complications observed during procedural sedation and analgesia in the paediatric population at a single emergency centre in Cape Town, South Africa. METHODS: A retrospective, descriptive study was conducted at Mitchells Plain Hospital, a district-level hospital situated in Mitchells Plain, Cape Town. All paediatric patients younger than 13 years of age who presented to the emergency centre and received procedural sedation and analgesia during the study period (December 2020-April 2021) were included in the study. Data was extracted from a standardised form, and simple descriptive statistics were used. RESULTS: A total of 113 patients (69% male) were included: 13 infants (< 1 year of age), 47 young children (1-5 years of age) and 53 older children (5-13 years of age). There was only 1 (0.9%) complication documented, which was vomiting and did not require admission. The majority of patients received ketamine (96.5%). The standardised procedural sedation and analgesia form was completed in 49.1% of cases. Indications included burns debridement (11.5%), suturing (17.7%), fracture reduction (23.9%), lumbar punctures (31.9%) and others (15.0%). The indications for procedural sedation and analgesia varied between the different age groups. The majority of patients in this study did not have their fasting status documented (68.1%), and 18.6% were not appropriately fasted as per American Society of Anaesthesiology guidelines. Despite this, there was an extremely low rate of documented complications of 0.9%. CONCLUSION: The study findings are in accordance with previous international literature reporting low complication rates. Although fasting status was unknown in the majority of patients, there was an extremely low rate of documented complications and no interventions required. Safe, timely procedural sedation and analgesia with minimal pain and unnecessary suffering can become the norm in emergency medicine practice in South Africa.

Application of an in silico approach identifies a genetic locus within ITGB2, and its interactions with HSPG2 and FGF9, to be associated with anterior cruciate ligament rupture risk.

We developed a Biomedical Knowledge Graph model that is phenotype and biological function-aware through integrating knowledge from multiple domains in a Neo4j, graph database. All known human genes were assessed through the model to identify potential new risk genes for anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy (AT). Genes were prioritised and explored in a case-control study comparing participants with ACL ruptures (ACL-R), including a sub-group with non-contact mechanism injuries (ACL-NON), to uninjured control individuals (CON). After gene filtering, 3376 genes, including 411 genes identified through previous whole exome sequencing, were found to be potentially linked to AT and ACL ruptures. Four variants were prioritised: HSPG2:rs2291826A/G, HSPG2:rs2291827G/A, ITGB2:rs2230528C/T and FGF9:rs2274296C/T. The rs2230528 CC genotype was over-represented in the CON group compared to ACL-R (p < 0.001) and ACL-NON (p < 0.001) and the TT genotype and T allele were over-represented in the ACL-R group and ACL-NON compared to CON (p < 0.001) group. Several significant differences in distributions were noted for the gene-gene interactions: (HSPG2:rs2291826, rs2291827 and ITGB2:rs2230528) and (ITGB2:rs2230528 and FGF9:rs2297429). This study substantiates the efficiency of using a prior knowledge-driven in silico approach to identify candidate genes linked to tendon and ACL injuries. Our biomedical knowledge graph identified and, with further testing, highlighted novel associations of the ITGB2 gene which has not been explored in a genetic case control association study, with ACL rupture risk. We thus recommend a multistep approach including bioinformatics in conjunction with next generation sequencing technology to improve the discovery potential of genomics technologies in musculoskeletal soft tissue injuries.HighlightsA biomedical knowledge graph was modelled for musculoskeletal soft tissue injuries to efficiently identify candidate genes for genetic susceptibility analyses.The biomedical knowledge graph and sequencing data identified potential biologically relevant variants to explore susceptibility to common tendon and ligament injuries. Specifically genetic variants within the ITGB2 and FGF9 genes were associated with ACL risk.Novel allele combinations (HSPG2-ITGB2 and ITGB2-FGF9) showcase the potential effect of ITGB2 in influencing risk of ACL rupture.

Factors which affect the application and implementation of a spinal motion restriction protocol by prehospital providers in a low resource setting: A scoping review.

Introduction: The safety and effectiveness of prehospital clinical c-spine clearance or spinal motion restriction (SMR) decision support tools are unclear. The present study aimed to examine the available literature on clinical cervical spine clearance and selective SMR decision support tools to identify possible barriers to implementation, safety, and effectiveness when used by emergency medical service (EMS) practitioners. Method: We performed a focused scoping review of published literature on the prehospital use of clinical c-spine clearance and SMR decision tools in adult blunt trauma patients. The Medline, Embase, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature, Web of Science, Turning Research into Practice and EBSCOhost online databases were searched (February 2021). The type of decision support tool and facilitators and barriers to its use were extracted from each included publication in accordance with a modified descriptive-analytical framework. Extracted data were subjected to thematic analysis. Results: Following screening, forty-two articles were included in this scoping review. No studies conducted specifically in low resource settings were found. The majority of articles (57%) evaluated the use of specific SMR decision support tools, such as the National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian C-spine Rule (CCR). Potential facilitators of safe and effective use were identified in 60%, and potential barriers to safe and effective use in 55% of included articles. Only one study evaluated the CCR when used by EMS practitioners, making it difficult to determine its appropriateness for implementation in the prehospital setting. Conclusion: This is the first scoping review, to our knowledge, that has attempted to identify the possible barriers and facilitators to their implementation, safety, and effectiveness when used by EMS practitioners. Key issues identified included terminology, guideline compliance and implementation, and a lack of context-specific evidence. These may provide important considerations for future guideline development.

The ethical considerations for emergency care research in low- and middle-income countries: A scoping review of the published literature.

INTRODUCTION: Research studies on emergency care in low- and middle-income countries (LMICs) face many ethical considerations, including obtaining valid informed consent from vulnerable patients. This study aims to describe the body of literature related to the ethical considerations associated with emergency care research in low- and middle-income settings. METHODS: A scoping review was conducted to identify literature published between 2000 and 2020 related to ethical considerations associated with emergency care research in the LMIC setting. Titles and abstracts were screened in duplicate, and full texts were reviewed and extracted by the principal author. RESULTS: In total, 1087 articles were identified and 17 articles were included. Major themes identified in the literature included risk versus benefit assessments, patient vulnerabilities, consent, community engagement, clinical roles, ancillary care provision, and regulation of research. Alternative models of consent are often used in emergency care research, including surrogate consent, community consent, and waiver of consent. Challenges and best practices with these alternative models of consent in LMICs are discussed. DISCUSSION: Gaps remain in the literature describing the ethics of emergency care research in LMICs, including clear guidelines for protecting vulnerable patients and designing ethical consent processes. Best practices identified include community engagement for designing research studies, identifying acceptable risk profiles, and allocating benefits. Continuous and rigorous assessment of the quality of consent is also needed.

A COVID-19 field hospital in a conference centre - The Cape Town, South Africa experience.

BACKGROUND: The coronavirus pandemic has put extreme pressure on health care services in South Africa. AIM: To describe the design, patients and outcomes of a field hospital during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. SETTING: The Cape Town International Convention Centre was the first location in Cape Town to be commissioned as a field hospital that would serve as an intermediate care bed facility. METHODS: This was a retrospective descriptive study of patients admitted to this facility between 8th June 2020 and 14th August 2020 using deidentified data extracted from patient records. RESULTS: There were 1502 patients admitted, 56.4% female, with a mean age of 58.6 years (standard deviation [s.d.]: 14.2). The majority of patients (82.9%) had at least one comorbidity, whilst 15.4% had three or more. Nearly 80.0% (79.8%) of patients required oxygen and 63.5% received steroids, and only 5.7% of patients were required to be transferred for escalation of care. The mean length of stay was 6 days (s.d.: 4.8) with an overall mortality of 5.7%. CONCLUSION: This study highlights the role of a field hospital in providing surge capacity. Its use halved the predicted duration of stay at acute care hospitals, allowing them the capacity to manage more unstable and critical patients. Adaptability and responsivity as well as adequate referral platforms proved to be crucial. Daily communication with the whole health care service platform was a critical success factor. This study provides information to assist future health planning and strategy development in the current pandemic and future disease outbreaks.

Social media and the modern scientist: a research primer for low- and middle-income countries.

Social media has changed the way we communicate. Wherever you are in the world, various forms of social media are being used by individuals to share information and connect without borders. Due to its ubiquity, social media holds great promise in linking clinicians, scientists, investigators, and the public to change the way we conduct scientific discourse. In this paper, we present a step-by-step guide on optimizing your social media strategy with regards to: research/scholarly practice (discourse, collaboration, recruitment), knowledge translation, dissemination, and education. This guide also highlights key readings that provide guidance to those interested in incorporating social media into their scholarly practice.

An analysis of the descriptors of acute myocardial infarction used by South Africans when calling for an ambulance from a private emergency call centre.

INTRODUCTION: Acute myocardial infarction (AMI) is a time sensitive emergency. In resource limited settings, prompt identification and management of patients experiencing AMI in the pre-hospital setting may minimise the negative consequences associated with overburdened emergency medical and hospital services. Expedited care thus, in part, relies on the dispatch of appropriate pre-hospital medical providers by emergency medical dispatchers. Identification of these patients in call centres is challenging due to a highly diverse South African society, with multiple languages, cultures, and levels of education. The aim of this study was therefore, to describe the terms used by members of the South African public when calling for an ambulance for patients suffering an AMI. METHODS: In this qualitative study, we performed content analysis to identify keywords and phrases that callers used to describe patients who were experiencing an advanced life support (ALS) paramedic-diagnosed AMI. Using the unique case reference number of randomly selected AMI cases, original voice recordings between the caller and emergency medical dispatcher at the time of the emergency were extracted and transcribed verbatim. Descriptors of AMI were identified, coded and categorised using content analysis, and quantified. RESULTS: Of the 50 randomly selected calls analysed, 5 were not conducted in English. The descriptors used by callers were found to fall into three categories; Pain: Thorax, No pain: Thorax and Ill- health. The code that occurred most often was no pain, heart related (n = 16; 23.2%), followed by the code describing pain in the chest (n = 15; 21.7%). CONCLUSION: South African callers use a consistent set of descriptors when requesting an ambulance for a patient experiencing an AMI. The most common of these are non-pain descriptors related to the heart. These descriptors may ultimately be used in developing validated algorithms to assist dispatch decisions. In this way, we hope to expedite the correct level of care to these time- critical patients and prevent the unnecessary dispatch of limitedly available ALS paramedics to inappropriate cases.

Childhood vulnerability to drowning in the Western Cape, South Africa: Risk differences across age and sex.

INTRODUCTION: Drowning is amongst the leading causes of death of children and young people worldwide, with high concentrations in Southeast Asia and Sub-Saharan Africa. In the Western Cape province in South Africa, drowning mortality rates for children were reported at 3.8 per 100,000 population. Internationally, evidence suggests that unimpeded access to water bodies and containers and lapses in supervision together with the child's limited developmental capacities, place children at greater risk of drowning. This study examined the risk for fatal drowning by age cohort and sex in child and adolescent (0-19 years old) in the Western Cape. METHOD: Demographic and descriptive data for child drowning fatalities from 2010 to 2016 were obtained from the Western Cape Forensic Pathology Service. Descriptive variables included location of drowning incident by body of water, time of day, day of week and season. Data were analysed by age cohorts aligned to child psychosocial developmental stages. Descriptive statistics reported fatality frequencies by age cohort and sex, and logistic regression was conducted to detect differences in drowning risk across these categories. RESULTS: A total of 538 childhood drowning fatalities were analysed, with the highest proportion occurring in children aged 13-19 years (29.6%) and the majority occurring in males (75.8%). Sex, location of drowning incident and season were significant predictors of drowning across the age cohorts. Relative to females, males between ages 0-1 and 2-3 years were less likely to drown when compared with older children. CONCLUSION: This study confirms existing evidence that children younger than five are most at risk of drowning. In contrast to international and local research findings that have indicated a similar or higher risk for drowning amongst boys compared with girls aged 3 years and younger, this study identified that males were less likely to drown between the ages of 0 and 3 years compared with girls.

Exploring new genetic variants within COL5A1 intron 4-exon 5 region and TGF-ß family with risk of anterior cruciate ligament ruptures.

Variants within genes encoding structural and regulatory elements of ligaments have been associated with musculoskeletal soft tissue injury risk. The role of intron 4-exon 5 variants within the α1 chain of type V collagen (COL5A1) gene and genes of the transforming growth factor-ß (TGF-ß) family, TGFBR3 and TGFBI, was investigated on the risk of anterior cruciate ligament (ACL) ruptures. A case-control genetic association study was performed on 210 control (CON) and 249 participants with surgically diagnosed ruptures (ACL), of which 147 reported a noncontact mechanism of injury (NON). Whole-exome sequencing data were used to prioritize variants of potential functional relevance. Genotyping for COL5A1 (rs3922912 G>A, rs4841926 C>T, and rs3124299 C>T), TGFBR3 (rs1805113 G>A and rs1805117 T>C), and TGFBI (rs1442 G>C) was performed using Taqman SNP genotyping assays. Significant overrepresentation of the G allele of TGFBR3 rs1805113 was observed in CON vs ACL (P = .014) and NON groups (P = .021). Similar results were obtained in a female with the G allele (CON vs ACL: P = .029; CON vs NON: P = .016). The TGFBI rs1442 CC genotype was overrepresented in the female ACL vs CON (P = .013). Associations of inferred allele combinations were observed in line with the above results. COL5A1 intron 4-exon 5 genomic interval was not associated with the risk of ACL ruptures. Instead, this novel study is the first to use this approach to identify variants within the TGF-ß signaling pathway to be implicated in the risk of ACL ruptures. A genetic susceptibility interval was identified to be explored in the context of extracellular matrix remodeling.

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence - a retrospective study.

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post-transplant follow-up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post-transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Fatal drowning in the Western Cape, South Africa: a 7-year retrospective, epidemiological study.

INTRODUCTION: Drowning is a neglected public health threat in low-income and middle-income countries where the greatest drowning burden is observed. There is a paucity of drowning surveillance data from low-resource settings, particularly in Africa. Understanding local epidemiological factors will enable the development of context-specific drowning prevention initiatives and the appropriate allocation of resources. AIM: The primary aim of this study was to describe the epidemiology of fatal drowning in the Western Cape, South Africa. METHOD: This retrospective study describes fatal drowning incidents captured in the Western Cape vital registration system between 2010 and 2016. Data were obtained from the Forensic Pathology Services of the Western Cape Government. One-way analysis of variance was performed to detect a trend in mean drowning mortality rates between 2010 and 2016. χ2 tests for independence were performed to detect differences in the distribution of variables between groups. RESULTS: A total of 1391 fatal drownings occurred in the Western Cape between 2010 and 2016, with an age-adjusted drowning mortality rate of 3.2 per 100 000 population. Rates were fourfold higher in men compared with women. Children, particularly young children aged 0-4 years, and young adult men between 20 and 34 years of age were identified to be at high risk of fatal drowning. Drowning occurred predominantly in large, open bodies of water with concentrations in summer and public holidays. CONCLUSIONS: The Western Cape drowning prevention strategy should prioritise interventions to reduce drowning in children and young adult men, with a targeted focus on festive periods such as public holidays.

Defining the molecular signatures of Achilles tendinopathy and anterior cruciate ligament ruptures: A whole-exome sequencing approach.

Musculoskeletal soft tissue injuries are complex phenotypes with genetics being one of many proposed risk factors. Case-control association studies using the candidate gene approach have predominately been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to further define the genetic profile of these injuries using an integrated omics approach involving whole exome sequencing and a customised analyses pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. Approximately 200 000 variants were identified in the sequenced samples. Previous research was used to guide a targeted analysis of the genes encoding the tenascin-C (TNC) glycoprotein and the α1 chain of type XXVII collagen (COL27A1) located on chromosome 9. Selection of variants within these genes were; however, not predetermined but based on a tiered filtering strategy. Four variants in TNC (rs1061494, rs1138545, rs2104772 and rs1061495) and three variants in the upstream COL27A1 gene (rs2567706, rs2241671 and rs2567705) were genotyped in larger Achilles tendinopathy and anterior cruciate ligament (ACL) rupture sample groups. The CC genotype of TNC rs1061494 (C/T) was associated with the risk of Achilles tendinopathy (p = 0.018, OR: 2.5 95% CI: 1.2-5.1). Furthermore, the AA genotype of the TNC rs2104772 (A/T) variant was significantly associated with ACL ruptures in the female subgroup (p = 0.035, OR: 2.3 95% CI: 1.1-5.5). An inferred haplotype in the TNC gene was also associated with the risk of Achilles tendinopathy. These results provide a proof of concept for the use of a customised pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.

The interaction of polymorphisms in extracellular matrix genes and underlying miRNA motifs that modulate susceptibility to anterior cruciate ligament rupture.

OBJECTIVES: Variants within genes that encode proteins regulating fibrillogenesis such as BGN (rs1126499 C>T, rs1042103 C>T), COL5A1 (rs12722 C>T) and DCN (rs516115 C>T) have been associated with susceptibility to anterior cruciate ligament (ACL) ruptures. A miRNA mediated transcript instability was proposed for the COL5A1 association. The study aims were: (i) to investigate the association of inferred allele combinations across the COL5A1 3'-UTR, BGN and DCN genes with susceptibility to ACL rupture; and (ii) to use an in silico approach to identify miRNA binding sites common to these risk associated allele combinations. DESIGN: Case-control association study METHODS: Allele combinations were generated from the genotype data of the BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) loci for 227 participants with surgically diagnosed ACL ruptures and 234 asymptomatic controls. Statistical analyses between the CON and ACL groups as well as sex-specific interactions were investigated. Significance was accepted at p<0.05. miRNA binding sites within these genes were identified using DIANA tools. RESULTS: Several sex-specific inferred allele combinations were associated with altered susceptibility and miRNA (miR-22, miR-27b, miR-140, miR-199a, miR-199b, miR-299, miR-338 and miR-484) recognition motifs were identified in range of these susceptibility loci. CONCLUSIONS: In conclusion, this study has implicated inferred allele combinations across BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) as well as eight miRNA recognition sequences in susceptibility to ACL rupture. The biological significance of these genomic signatures needs to be explored to understand their effect on the ligaments functional capacity.

Designing a course model for distance-based online bioinformatics training in Africa: The H3ABioNet experience.

Africa is not unique in its need for basic bioinformatics training for individuals from a diverse range of academic backgrounds. However, particular logistical challenges in Africa, most notably access to bioinformatics expertise and internet stability, must be addressed in order to meet this need on the continent. H3ABioNet (www.h3abionet.org), the Pan African Bioinformatics Network for H3Africa, has therefore developed an innovative, free-of-charge "Introduction to Bioinformatics" course, taking these challenges into account as part of its educational efforts to provide on-site training and develop local expertise inside its network. A multiple-delivery-mode learning model was selected for this 3-month course in order to increase access to (mostly) African, expert bioinformatics trainers. The content of the course was developed to include a range of fundamental bioinformatics topics at the introductory level. For the first iteration of the course (2016), classrooms with a total of 364 enrolled participants were hosted at 20 institutions across 10 African countries. To ensure that classroom success did not depend on stable internet, trainers pre-recorded their lectures, and classrooms downloaded and watched these locally during biweekly contact sessions. The trainers were available via video conferencing to take questions during contact sessions, as well as via online "question and discussion" forums outside of contact session time. This learning model, developed for a resource-limited setting, could easily be adapted to other settings.

Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes.

Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation of human genes and identify candidate genes by ontology-seeded queries capturing the features of tendinopathy. Our BioOntological Relationship Graph database (BORG) integrates multiple sources of genomic and biomedical knowledge into an on-disk semantic network where human genes and their orthologs in mouse and rat are central concepts mapped to ontology terms. The BORG was used to screen all human genes for potential links to tendinopathy. Following further prioritisation, four strong candidate genes (COL11A2, ELN, ITGB3, LOX) were identified. These genes are differentially expressed in tendinopathy, functionally linked to features of tendinopathy and previously implicated in other connective tissue diseases. In conclusion, cross-domain semantic integration of multiple sources of biomedical knowledge, and interrogation of phenotypes and gene functions associated with disease, may significantly increase the probability of identifying strong and unobvious candidate genes in genetic association studies.

Extracellular matrix proteins interact with cell-signaling pathways in modifying risk of achilles tendinopathy.

The aim of this study was to investigate interactions between variants within genes encoding components of the collagen fibril and components of cell-signaling pathways within the extracellular matrix, and determine the relative contribution of these variants to Achilles tendinopathy risk in a polygenic model. A total of 339 asymptomatic control participants and 179 participants clinically diagnosed with Achilles tendinopathy were genotyped for variants within six genes encoding components of the collagen fibril and three genes encoding components of cell-signaling pathways. Logistic regression, stepwise selection, and receiver operating characteristic curve (ROC) analysis was used to select and evaluate genetic interactions and determine the relative contribution of these variants to overall genetic risk. The strongest, best fit polygenic risk model included the variables sex, three COL27A1 variants (rs4143245; rs1249744; rs946053), COL5A1 rs12722, CASP8 rs1045485, and CASP8 rs2824129 with an area under the ROC curve of 0.737 and the maximum sum of sensitivity and specificity indicators equal to 134%. Significant interactions between genes encoding components of the collagen fibril and genes encoding components of the cell-signaling pathways modify risk of Achilles tendinopathy.

A variant within the AQP1 3'-untranslated region is associated with running performance, but not weight changes, during an Ironman Triathlon.

The objective of this study was to test the association of the rs1049305 (G > C) variant within the 3'-untranslated region of the aquaporin 1 gene, AQP1, with changes in body weight, post-race serum sodium concentration and performance in Ironman triathletes. Five hundred and four male Ironman triathletes were genotyped for the rs1049305 variant within the AQP1 gene. Change in pre- and post-race body weight was calculated for 470 triathletes and used as a proxy for changes in body fluid during the race, as well as to divide triathletes into biologically relevant weight-loss groups (0-3%, 3-5% and >5%). There were no rs1049305 genotype effects on post-race serum sodium concentrations (P = 0.647), pre-race weight (P = 0.610) nor relative weight change during the Ironman Triathlons (P = 0.705). In addition, there were no significant differences in genotype (P = 0.640) nor allele (P = 0.643) distributions between the weight loss groups. However, triathletes who carry a C-allele were found to complete the 42.2-km run stage faster (mean 286, s = 49 min) than triathletes with a GG genotype (mean 296, s = 47 min; P = 0.032). The AQP1 rs1049305 variant is associated with running performance, but not relative body weight change, during the 2000, 2001 and 2006 South African Ironman Triathlons.

Variants within the COMP and THBS2 genes are not associated with Achilles tendinopathy in a case-control study of South African and Australian populations.

Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.