The adenine-rich tract in the 5ʹ-end of the hepatitis C virus ORF encodes a peptide regulating the binding of the C protein to RNA

Hepatitis C virus (HCV ) core (C) protein is thought to bind to viral RNA before it undergoes oligomerization leading to RNA encapsidation. Details of these events are so far unknown. The 5ʹ-terminal C protein coding sequence that includes an adenine (A)-rich tract is a part of an internal ribosome entry site(IRES). This nucleotide sequence but not the corresponding protein sequence is needed for proper initiation of translation of viral RNA by an IRES-dependent mechanism. In this study, we examined the importance of this sequence for the ability of the C protein to bind to viral RNA. Serially truncated C proteins with deletions from 10 up to 45 N-terminal amino acids were expressed in Escherichia coli, purified and tested for binding to viral RNA by a gel shift assay. The results showed that truncation of the C protein from its N-terminus by more than 10 amino acids abolished almost completely its expression in E. coli. The latter could be restored by adding a tag to the N-terminus of the protein. The tagged proteins truncated by 15 or more amino acids showed an anomalous migration in SDS-PAGE. Truncation by more than 20 amino acids resulted in a complete loss of ability of tagged C protein to bind to viral RNA. These results provide clues to the early events in the C protein - RNA interactions leading to C protein oligomerization, RNA encapsidation and virion assembly.

Studies on bending limitations for the optimal fit of orthopaedic bone plates

Distal tibial fractures are now commonly treated via intermedullary plate fixation due to higher rates of union and lower rates of postoperative complications. However, patient specific bone morphology demands manual deformation of the plate to ensure appropriate fit along the bone Distal tibial fractures are now commonly treated via intermedullary plate fixation due to higher rates of union and lower rates of postoperative complications. However, patient specific bone morphology demands manual deformation of the plate to ensure appropriate fit along the bone contours, and depending on the material of the plate, different outcomes have been reported along with postoperative complications. A comparative analysis of Stainless Steel 316L and Ti-6Al-4V alloys was carried to estimate the safe bending limit for appropriate fits. The results from the ANSYS FEA simulations were validated with experiments based on ASTM F382-99. It is found that SS316L is better suited for large deformations (up to 16˚ in proximal tip and 7.5˚ in distal end) and Ti for smaller deformation contours (up to 3˚ in proximal tip and 1.8˚ in distal end). The results of this study have profound implications for the choice of plates based on preliminary radiographical fracture examinations to ensure better fixation and higher rates of union of distal tibial fractures.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Depression: an emotional obstacle to seeking medical advice for infertility

Objective: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. Design: Longitudinal cohort study.Setting Population based.Patient(s) Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936).Intervention(s) None.Main Outcome Measure(s) Infertility, not seeking medical advice. Result(s): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. Conclusion(s): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility.

Agreement between self-reported use of in vitro fertilization or ovulation induction, and medical insurance claims in Australian women aged 28–36 years

STUDY QUESTION: What is the self-reported use of in vitro fertilization (IVF) and ovulation induction (OI) in comparison with insurance claims by Australian women aged 28–36 years? SUMMARY ANSWER: The self-reported use of IVF is quite likely to be valid; however, the use of OI is less well reported. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Population-based research often relies on the self-reported use of IVF and OI because access to medical records can be difficult and the data need to include sufficient personal identifying information for linkage to other data sources. There have been few attempts to explore the reliability of the self-reported use of IVF and OI using the linkage to medical insurance claims for either treatment. STUDY DESIGN: This prospective, population-based, longitudinal study included the cohort of women born during 1973–1978 and participating in the Australian Longitudinal Study on Women's Health (ALSWH) (n = 14247). From 1996 to 2009, participants were surveyed up to five times. PARTICIPANTS AND SETTING: Participants self-reported their use of IVF or OI in two mailed surveys when aged 28–33 and 31–36 years (n = 7280), respectively. This study links self-report survey responses and claims for treatment or medication from the universal national health insurance scheme (i.e. Medicare Australia). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between self-reports and claims data were undertaken for all women consenting to the linkage (n = 3375). The self-reported use of IVF was compared with claims for OI for IVF (Kappa, K = 0.83), oocyte collection (K = 0.82), sperm preparation (K = 0.83), intracytoplasmic sperm injection (K = 0.40), fresh embryo transfers (K = 0.82), frozen embryo transfers (K = 0.64) and OI for IVF medication (K = 0.17). The self-reported use of OI was compared with ovulation monitoring (K = 0.52) and OI medication (K = 0.71). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: There is a possibility of selection bias due to the inclusion criteria for participants in this study: (1) completion of the last two surveys in a series of five and (2) consent to the linkage of their responses with Medicare data. GENERALIZABILITY TO OTHER POPULATIONS: The results are relevant to questionnaire-based research studies with infertile women in developed countries. STUDY FUNDING/COMPETING INTEREST(S): ALSWH is funded by the Australian Government Department of Health and Ageing. This research is funded by a National Health and Medical Research Council Centre of Research Excellence grant.

Correction of step artefact associated with MRI scanning of long bones

3D models of long bones are being utilised for a number of fields including orthopaedic implant design. Accurate reconstruction of 3D models is of utmost importance to design accurate implants to allow achieving a good alignment between two bone fragments. Thus for this purpose, CT scanners are employed to acquire accurate bone data exposing an individual to a high amount of ionising radiation. Magnetic resonance imaging (MRI) has been shown to be a potential alternative to computed tomography (CT) for scanning of volunteers for 3D reconstruction of long bones, essentially avoiding the high radiation dose from CT. In MRI imaging of long bones, the artefacts due to random movements of the skeletal system create challenges for researchers as they generate inaccuracies in the 3D models generated by using data sets containing such artefacts. One of the defects that have been observed during an initial study is the lateral shift artefact occurring in the reconstructed 3D models. This artefact is believed to result from volunteers moving the leg during two successive scanning stages (the lower limb has to be scanned in at least five stages due to the limited scanning length of the scanner). As this artefact creates inaccuracies in the implants designed using these models, it needs to be corrected before the application of 3D models to implant design. Therefore, this study aimed to correct the lateral shift artefact using 3D modelling techniques. The femora of five ovine hind limbs were scanned with a 3T MRI scanner using a 3D vibe based protocol. The scanning was conducted in two halves, while maintaining a good overlap between them. A lateral shift was generated by moving the limb several millimetres between two scanning stages. The 3D models were reconstructed using a multi threshold segmentation method. The correction of the artefact was achieved by aligning the two halves using the robust iterative closest point (ICP) algorithm, with the help of the overlapping region between the two. The models with the corrected artefact were compared with the reference model generated by CT scanning of the same sample. The results indicate that the correction of the artefact was achieved with an average deviation of 0.32 ± 0.02 mm between the corrected model and the reference model. In comparison, the model obtained from a single MRI scan generated an average error of 0.25 ± 0.02 mm when compared with the reference model. An average deviation of 0.34 ± 0.04 mm was seen when the models generated after the table was moved were compared to the reference models; thus, the movement of the table is also a contributing factor to the motion artefacts.

Advances and future directions for management of trauma patients with musculoskeletal injuries

Musculoskeletal injuries are the most common reason for operative procedures in severely injured patients and are major determinants of functional outcomes. In this paper, we summarise advances and future directions for management of multiply injured patients with major musculoskeletal trauma. Improved understanding of fracture healing has created new possibilities for management of particularly challenging problems, such as delayed union and non union of fractures and large bone defects. Optimum timing of major orthopaedic interventions is guided by increased knowledge about the immune response after injury. Individual treatment should be guided by trading off the benefits of early definitive skeletal stabilisation, and the potentially life-threatening risks of systemic complications such as fat embolism, acute lung injury, and multiple organ failure. New methods for measurement of fracture healing and function and quality of life outcomes pave the way for landmark trials that will guide the future management of musculoskeletal injuries.

Ability of modal analysis to detect osseointegration of implants in transfemoral amputees : a physical model study

Owing to the successful use of non-invasive vibration analysis to monitor the progression of dental implant healing and stabilization, it is now being considered as a method to monitor femoral implants in transfemoral amputees. This study uses composite femur-implant physical models to investigate the ability of modal analysis to detect changes at the interface between the implant and bone simulating those that occur during osseointegration. Using electromagnetic shaker excitation, differences were detected in the resonant frequencies and mode shapes of the model when the implant fit in the bone was altered to simulate the two interface cases considered: firm and loose fixation. The study showed that it is beneficial to examine higher resonant frequencies and their mode shapes (rather than the fundamental frequency only) when assessing fixation. The influence of the model boundary conditions on the modal parameters was also demonstrated. Further work is required to more accurately model the mechanical changes occurring at the bone-implant interface in vivo, as well as further refinement of the model boundary conditions to appropriately represent the in vivo conditions. Nevertheless, the ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.

Mastering medical terminology : Australia and New Zealand

Mastering Medical Terminology: Australia and New Zealand is medical terminology book of relevance to an audience in Australia and New Zealand. Australian terminology, perspectives, examples and spelling have been included and Australian pronunciation specified. The textbook is accompanied by a self-help workbook, an online workbook and a Smartphone app. Throughout Mastering Medical Terminology, review of medical terminology as it is used in clinical practice is highlighted. Features of the textbook, workbook and electronic product include: • Simple, non-technical explanations of medical terms • Workbook format with ample spaces to write answers • Explanations of clinical procedures, laboratory tests and abbreviations used in Australian clinical practice, as they apply to each body system and speciality area • Pronunciation of terms and spaces to write meanings of terms • Practical applications sections • Exercises that test understanding of terminology as students work through the text chapter by chapter • Review activities that pull together terminology to help students study • Comprehensive glossary and appendices for reference • Links to other useful references, such as websites and textbooks.

Exploiting medical hierarchies for concept-based information retrieval

Search technologies are critical to enable clinical sta to rapidly and e ectively access patient information contained in free-text medical records. Medical search is challenging as terms in the query are often general but those in rel- evant documents are very speci c, leading to granularity mismatch. In this paper we propose to tackle granularity mismatch by exploiting subsumption relationships de ned in formal medical domain knowledge resources. In symbolic reasoning, a subsumption (or `is-a') relationship is a parent-child rela- tionship where one concept is a subset of another concept. Subsumed concepts are included in the retrieval function. In addition, we investigate a number of initial methods for combining weights of query concepts and those of subsumed concepts. Subsumption relationships were found to provide strong indication of relevant information; their inclusion in retrieval functions yields performance improvements. This result motivates the development of formal models of rela- tionships between medical concepts for retrieval purposes.

Exploiting SNOMED CT concepts and relationships for clinical information retrieval : Australian e-Health Research Centre and Queensland University of Technology at the TREC 2012 Medical Track

The Australian e-Health Research Centre and Queensland University of Technology recently participated in the TREC 2012 Medical Records Track. This paper reports on our methods, results and experience using an approach that exploits the concept and inter-concept relationships defined in the SNOMED CT medical ontology. Our concept-based approach is intended to overcome specific challenges in searching medical records, namely vocabulary mismatch and granularity mismatch. Queries and documents are transformed from their term-based originals into medical concepts as defined by the SNOMED CT ontology, this is done to tackle vocabulary mismatch. In addition, we make use of the SNOMED CT parent-child `is-a' relationships between concepts to weight documents that contained concept subsumed by the query concepts; this is done to tackle the problem of granularity mismatch. Finally, we experiment with other SNOMED CT relationships besides the is-a relationship to weight concepts related to query concepts. Results show our concept-based approach performed significantly above the median in all four performance metrics. Further improvements are achieved by the incorporation of weighting subsumed concepts, overall leading to improvement above the median of 28% infAP, 10% infNDCG, 12% R-prec and 7% Prec@10. The incorporation of other relations besides is-a demonstrated mixed results, more research is required to determined which SNOMED CT relationships are best employed when weighting related concepts.

Semantic judgement of medical concepts : combining syntagmatic and paradigmatic information with the tensor encoding model

This paper outlines a novel approach for modelling semantic relationships within medical documents. Medical terminologies contain a rich source of semantic information critical to a number of techniques in medical informatics, including medical information retrieval. Recent research suggests that corpus-driven approaches are effective at automatically capturing semantic similarities between medical concepts, thus making them an attractive option for accessing semantic information. Most previous corpus-driven methods only considered syntagmatic associations. In this paper, we adapt a recent approach that explicitly models both syntagmatic and paradigmatic associations. We show that the implicit similarity between certain medical concepts can only be modelled using paradigmatic associations. In addition, the inclusion of both types of associations overcomes the sensitivity to the training corpus experienced by previous approaches, making our method both more effective and more robust. This finding may have implications for researchers in the area of medical information retrieval.

Encouraging, assisting and time to EAT : improved nutritional intake for older medical patients receiving Protected Mealtimes and/or additional nursing feeding assistance

Background & Aims: Inadequate feeding assistance and mealtime interruptions during hospitalisation may contribute to malnutrition and poor nutritional intake in older people. This study aimed to implement and compare three interventions designed to specifically address mealtime barriers and improve energy intakes of medical inpatients aged ≥65 years. Methods: Pre-post study compared three mealtime assistance interventions: PM: Protected Mealtimes with multidisciplinary education; AIN: additional assistant-in-nursing (AIN) with dedicated meal role; PM+AIN: combined intervention. Dietary intake of 254 patients (pre: n=115, post: n=141; mean age 80±8) was visually estimated on a single day in the first week of hospitalisation and compared with estimated energy requirements. Assistance activities were observed and recorded. Results: Mealtime assistance levels significantly increased in all interventions (p<0.01). Post-intervention participants were more likely to achieve adequate energy intake (OR=3.4, p=0.01), with no difference noted between interventions (p=0.29). Patients with cognitive impairment or feeding dependency appeared to gain substantial benefit from mealtime assistance interventions. Conclusions: Protected Mealtimes and additional AIN assistance (implemented alone or in combination) may produce modest improvements in nutritional intake. Targeted feeding assistance for certain patient groups holds promise; however, alternative strategies are required to address the complex problem of malnutrition in this population.

More is not necessarily better. A biomechanical study on distal screw numbers in volar locking distal radius plates

INTRODUCTION: Currently available volar locking plates for the treatment of distal radius fractures incorporate at least two distal screw rows for fixation of the metaphyseal fragment and have a variable-angle locking mechanism which allows placement of the screws in various directions There is, however no evidence that these plates translate into better outcomes or have superior biomechanical properties to first generation plates, which had a single distal screw row and fixed-angle locking. The aim of our biomechanical study was to compare fixed-angle single-row plates with variable-angle multi-row plates to clarify the optimal number of locking screws. MATERIALS AND METHODS: Five different plate-screw combinations of three different manufacturers were tested, each group consisting of five synthetic fourth generation distal radius bones. An AO type C2 fracture was created and the fractures were plated according to each manufacturer's recommendations. The specimens then underwent cyclic and load-to-failure testing. An optical motion analysis system was used to detect displacement of fragments. RESULTS: No significant differences were detected after cyclic loading as well as after load-to-failure testing, neither in regard to axial deformation, implant rigidity or maximum displacement. The fixed-angle single-row plate showed the highest pre-test rigidity, least increase in post-testing rigidity and highest load-to-failure rigidity and least radial shortening. The radial shortening of plates with two distal screw rows was 3.1 and 4.3 times higher, respectively, than that of the fixed-angle single-row plate. CONCLUSION: The results of our study indicate that two distal screw rows do not add to construct rigidity and resistance against loss of reduction. Well conducted clinical studies based on the findings of biomechanical studies are necessary to determine the optimal number of screws necessary to achieve reproducibly good results in the treatment of distal radius fractures.