Technology for large-scale translation of clinical practice guidelines : a pilot study of the performance of a hybrid human and computer-assisted approach

Background: The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, was initiated in 2011 to optimize quality of care by promoting evidence-based decision-making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL Multiterm termbases) from medical termbases and support from online machine translation. This has resulted in a validated translation memory which is now in use for the translation of new and updated guidelines. Objective: The objective of this study was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods: We conducted a pilot trial in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (a) by certificated junior translators without medical specialization using the hybrid method (b) by an experienced medical translator without this support and (c) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The Human Translation Edit Rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of translation acceptability and adequacy. Results: The average number of words per guideline was 1,195 and the mean total translation time was 100.2 min/1,000 words. No meaningful differences were found in the translation speed for new guidelines. The translation of updated guidelines was 59 min/1,000 words faster (95% CI 2-115; P=.044) in the computer-aided group. Revisions due to terminology accounted for one third of the overall revisions by the medical proofreader. Conclusions: Use of the hybrid human and computer-aided translation by a non-expert translator makes the translation of updates of clinical practice guidelines faster and cheaper because of the benefits of translation memory. For the translation of new guidelines there was no apparent benefit in comparison with the efficiency of translation unsupported by translation memory (whether by an expert or non-expert translator

Toll-like receptor variation in the bottlenecked population of the Seychelles warbler: computer simulations see the ‘ghost of selection past’ and quantify the ‘drift debt’

Balancing selection can maintain immunogenetic variation within host populations, but detecting its signal in a post-bottlenecked population is challenging due to the potentially overriding effects of drift. Toll-like receptor genes (TLRs) play a fundamental role in vertebrate immune defence and are predicted to be under balancing selection. We previously characterised variation at TLR loci in the Seychelles warbler (Acrocephalus sechellensis), an endemic passerine that has undergone a historical bottleneck. Five out of seven TLR loci were polymorphic, which is in sharp contrast to the low genome-wide variation observed. However standard population genetic statistical methods failed to detect a contemporary signature of selection at any TLR loci. We examined whether the observed TLR polymorphism could be explained by neutral evolution, simulating the population's demography in the software DIYABC. This showed that the posterior distributions of mutation rates had to be unrealistically high to explain the observed genetic variation. We then conducted simulations with an agent-based model using typical values for the mutation rate, which indicated that weak balancing selection has acted on the three TLR genes. The model was able to detect evidence of past selection elevating TLR polymorphism in the pre-bottleneck populations, but was unable to discern any effects of balancing selection in the contemporary population. Our results show drift is the overriding evolutionary force that has shaped TLR variation in the contemporary Seychelles warbler population, and the observed TLR polymorphisms might be merely the ‘ghost of selection past’. Forecast models predict immunogenetic variation in this species will continue to be eroded in the absence of contemporary balancing selection. Such ‘drift debt’ occurs when a genepool has not yet reached its new equilibrium level of polymorphism, and this loss could be an important threat to many recently bottlenecked populations

Maternal sleep practices and stillbirth: Findings from an international case‐control study

Background: Late stillbirth, which occurs ≥28 weeks’ gestation, affects 1.3‐8.8 per 1000 births in high‐income countries. Of concern, most occur in women without established risk factors. Identification of potentially modifiable risk factors that relate to maternal behaviors remains a priority in stillbirth prevention research. This study aimed to investigate, in an international cohort, whether maternal sleep practices are related to late stillbirth. Methods: An Internet‐based case‐control study of women who had a stillbirth ≥28 weeks’ gestation within 30 days before completing the survey (n = 153) and women with an ongoing third‐trimester pregnancy or who had delivered a live born child within 30 days (n = 480). Bivariate and multivariate logistic regressions were used to determine unadjusted and adjusted odds ratios (OR and aOR, respectively) with 95% confidence intervals (95% CIs) for stillbirth. Results: Sleeping >9 hours per night in the previous month was associated with stillbirth (aOR 1.75 [95% CI 1.10‐2.79]), as was waking on the right side (2.27 [1.31‐3.92]). Nonrestless sleep in the last month was also found to be associated with stillbirth (1.73 [1.03‐2.99]), with good sleep quality in the last month approaching significance (1.64 [0.98‐2.75]). On the last night of pregnancy, not waking more than one time was associated with stillbirth (2.03 [1.24‐3.34]). No relationship was found with going to sleep position during pregnancy, although very few women reported settling in the supine position (2.4%). Conclusions: Long periods of undisturbed sleep are associated with late stillbirth. Physiological studies of how the neuroendocrine and autonomic system pathways are regulated during sleep in the context of late pregnancy are warranted

The role of polycyclic frameworks in modulating P2X<inf>7</inf> receptor function

Herein we describe our recent attempts to target the P2X7 receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X7 receptor

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

An international internet survey of the experiences of 1,714 mothers with a late stillbirth: The STARS cohort study

Background: Stillbirth occurring after 28 weeks gestation affects between 1.5-4.5 per 1,000 births in high-income countries. The majority of stillbirths in this setting occur in women without risk factors. In addition, many established risk factors such as nulliparity and maternal age are not amenable to modification during pregnancy. Identification of other risk factors which could be amenable to change in pregnancy should be a priority in stillbirth prevention research. Therefore, this study aimed to utilise an online survey asking women who had a stillbirth about their pregnancy in order to identify any common symptoms and experiences. Methods: A web-based survey. Results: A total of 1,714 women who had experienced a stillbirth >3 weeks prior to enrolment completed the survey. Common experiences identified were: perception of changes in fetal movement (63 % of respondents), reports of a "gut instinct" that something was wrong (68 %), and perceived time of death occurring overnight (56 %). A quarter of participants believed that their baby's death was due to a cord issue and another 18 % indicated that they did not know the reason why their baby died. In many cases (55 %) the mother believed the cause of death was different to that told by clinicians. Conclusions: This study confirms the association between altered fetal movements and stillbirth and highlights novel associations that merit closer scrutiny including a maternal gut instinct that something was wrong. The potential importance of maternal sleep is highlighted by the finding of more than half the mothers believing their baby died during the night. This study supports the importance of listening to mothers' concerns and symptoms during pregnancy and highlights the need for thorough investigation of stillbirth and appropriate explanation being given to parents

Control of Mycobacterium bovis infection in two sika deer herds in Ireland

In a number of countries, tuberculosis (due to infection with Mycobacterium bovis) is a significant health problem of captive deer. This paper describes outbreaks of bovine tuberculosis in sika deer (Cervus nippon) on two farms in Ireland and the methods used to control the disease. On Farm A, infection was first detected during 1993. The infection was eradicated using a programme of test and removal, in association with segregation of young animals. A second outbreak (also due to infection with M. bovis, but a different RFLP profile) was detected in 2002. In the latter outbreak, infection was particularly prevalent in two groups of young deer. M. bovis with the same RFLP profile was also isolated in a badger found dead on the farm. Control was achieved by test and removal in association with herd management changes. In Herd B, infection was first detected in 1995, and subsequently eradicated using test and removal alone. In Herd A, re-infection remains an ongoing risk. Control rather than eradication of infection may more realistic in the short-to medium-term

Insulin trafficking in a glucose responsive engineered human liver cell line is regulated by the interaction of ATP-sensitive potassium channels and voltage- gated calcium channels

Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions

False positive HIV diagnoses in resource limited settings: operational lessons learned for HIV programmes

Access to HIV diagnosis is life-saving; however the use of rapid diagnostic tests in combination is vulnerable to wrongly diagnosing HIV infection when both screening tests give a false positive result. Misclassification of HIV patients can also occur due to poor quality control, administrative errors and lack of supervision and training of staff. Médecins Sans Frontières discovered in 2004 that HIV negative individuals were enrolled in some HIV programmes. This paper describes the result of an audit of three sites to review testing practices, implement improved testing algorithms and offer re-testing to clients enrolled in the HIV clinic