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Effective household water treatment can improve drinking water quality and prevent disease if used correctly and consistently over time. One year after completion of a randomized controlled study of water filters among households in Zambia with children < 2 years old and mothers who were human immunodeficiency virus (HIV)-positive, we conducted a follow-up study to assess use and performance of new filters distributed at the conclusion of the study; 90% of participating households met the criteria for current users, and 75% of participating households had stored water with lower levels of fecal contamination than source water. Microbiologically, the filters continued to perform well, removing an average of 99.0% of fecal indicator bacteria. Although this study provides some encouraging evidence about the potential to maintain high uptake and filter performance, even in the absence of regular household visits, additional research is necessary to assess whether these results can be achieved over longer periods and with larger populations.

The Amur leopard is at the point of extinction. At present there are fewer than 35 in the wild. Their natural habitat ranges from China to the North Korean peninsula to Primorsky Krai in Russia. A reintroduction plan has been proposed to increase the population in the wild; however, this proposed plan still has many questions to be answered as to how effective it will be. The main objective is to reintroduce animals from a select group within the Far Eastern leopard programme or the Species Survival programme, which consist of leopards from select populations in the Northern Hemisphere. Zoos are central to the success of this plan, providing suitable breeding pairs to breed animals for reintroduction and also raising much needed funds to finance the project. Zoos are also central in educating the public about the critical status of the Amur leopard and other endangered animals of the world. Veterinary surgeons, by the very nature of their professional skills, are at the forefront of this seemingly endless battle against extinction of thousands of species that are critical to maintaining the balance of our fragile ecosystem. Veterinarians can analyze the health risks and health implications of reintroduction on the animals to be reintroduced and also on the native population. A world without large cats is a world hard to imagine. If we look closer at the implications of extinction, we see the domino effect of their loss and an ecosystem out of control., (© 2013 Published by Elsevier Inc.)

Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P&lt;0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

Background: Schistosomiasis is a major cause of morbidity and mortality, with over 200 million people infected worldwide. Eighty-five percent of cases are in Africa. The hepatosplenic form develops over time by an immune reaction to trapped Schistosoma mansoni eggs in the portal system leading to liver fibrosis, portal hypertension and oesophageal varices. Most patients presenting to the University Teaching Hospital in Lusaka with oesophageal varices, come from Western province, but no formal studies have been carried out in this area assessing the burden of hepatosplenic pathology. We aimed to define the extent of the problem in Kaoma district, western Zambia, and to correlate signs and symptoms with serology., Findings: A symptom questionnaire, demographic survey and physical examination was conducted amongst patients presenting to Kaoma district outpatient clinics. To assess the prevalence of Schistosoma mansoni infections, blood was collected and screened for the presence of Schistosoma antibodies using Enzyme linked immunosorbent assay (ELISA). Of the 110 patients screened, 97 (88%) were ELISA positive. Forty-six percent (51/110) reported haematochezia and 7% experienced haematemesis (8/110). On physical examination 27% (30/110) hepatomegaly and 17% (30/110) splenomegaly was observed amongst participants but there were few correlations between serology and signs/symptoms. On questioning 68% (75/110) of participants knew nothing about schistosomiasis transmission., Conclusions: Our serological and clinical data indicate a very heavy burden of schistosomiasis-related portal hypertension. Our evidence highlights a need for mass treatment in Kaoma to address and prevent extensive pathology of hepatosplenic schistosomiasis. Safe water and health education throughout Western Province are clearly also important.

Aim: To evaluate need for and efficacy of a structured gastroenterology didactic session in expanding awareness and understanding of digestive disorders., Methods: A four-day symposium was developed with didactic sessions (days 1, 2) and practical endoscopy (days 3, 4). Didactic sessions included case presentations highlighting pathophysiology and management. One nurse and four practicing gastroenterologists from the United Kingdom led lectures and supervised workshops with audience participation. Practical endoscopy focused on diagnostic and therapeutic procedures and their application to diagnosis and treatment of ailments of the gastrointestinal tract. Pre- and post-workshop questionnaires were distributed to participants during didactic sessions. A pre-workshop questionnaire gauged expectations and identified objectives to be met at the symposium. Post-workshop questionnaires were administered to assess efficacy of each session. Participants graded sessions from 1 (poor) to 5 (excellent) on quality of case presentations, knowledge, clarity and mode of presentation. We assessed if time allotted to each topic was sufficient, value of sessions, impact on practice and interest in future symposiums., Results: There were 46 attendees on day 1: 41% undergraduates, 41% residents, 11% consultants and 4% unspecified. Day 2 (a Saturday) had 24 participants: 17% undergraduates, 71% residents, 9% consultants, 4% unspecified. Primary pre-workshop symposium expectation was to gain knowledge in: general gastroenterology (55.5%), practical endoscopy (13.8%), pediatric gastroenterology (5%), epidemiology of gastrointestinal disorders specific to Zambia (6%), and interaction with international speakers (6%). The post-symposium questionnaire was answered by 19 participants, of whom 95% felt specific aims were met; all would attend future conferences and recommend to others., Conclusion: The beneficial effect of a structured symposium in developing countries warrants further attention as a mechanism to improve disease awareness in areas where resources are limited.

Background: Gastric cancer is increasingly recognized in Zambia. Although nutritional factors contribute to gastric cancer risk, their effect in Zambia is unknown., Objective: The objective was to investigate the association between intake of dietary antioxidants, urinary 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress, and gastric cancer., Design: This was a case-control study at the University Teaching Hospital in Zambia. Gastric cancer cases were compared with age- and sex-matched controls. Urine 8-iso PGF2α was measured primarily by ELISA, and by gas chromatography-mass spectrometry in a subset, expressed as a ratio to creatinine. Blood was collected for Helicobacter pylori, HIV serology, gastrin-17, and pepsinogen 1 and 2 concentrations. Clinical and dietary data were collected by using questionnaires. Food items were broadly classified into 7 major categories (fruit, vegetables, fish, meat, insects, cereals, and starches)., Results: Fifty cases with gastric cancer (mean age: 61 y; n = 31 males) and 90 controls (mean age: 54 y; n = 41 males) were enrolled. Median urinary 8-iso PGF2α excretion was higher in cases (0.014; IQR: 0.008-0.021) than in controls (0.011; IQR: 0.006-0.018; P = 0.039). On univariate analysis, habitual fruit intake was lower in cases than in controls during the dry season (P = 0.02). On multivariate analysis, smoking (OR: 7.22; IQR: 1.38-37.9) and gastric atrophy (OR: 2.43; IQR: 1.12-5.13) were independently associated with cancer, and higher fruit intake was protective (OR: 0.44; IQR: 0.20-0.95). Isoprostane excretion was inversely correlated with total fruit intake (ρ = -0.23; n = 140; P = 0.006)., Conclusion: Urinary 8-iso PGF2α excretion was associated with the risk of gastric cancer, as were smoking and gastric atrophy, but increased fruit intake conferred protection. This trial was registered at www.pactr.org as ISRCTN52971746.

Objective: To review cases of nosocomial influenza and compare the epidemiology, clinical characteristics and outcomes with community-acquired cases., Design, Setting and Participants: Prospective case series of adults hospitalised with influenza during April - November of 2010 and 2011 using a hospital-based sentinel surveillance system. A nosocomial case was defined as polymerase chain reaction-confirmed influenza where symptom onset was more than 2 15s after admission or, if this was not known, where the date of the positive test was more than 7 15s after admission., Main Outcome Measures: Demographic, clinical and outcome measures for patients with nosocomial influenza compared with patients admitted with community-acquired influenza., Results: In 2010-2011, 598 cases of influenza were detected, of which 26 (4.3%) were nosocomial. All patients with nosocomial influenza had chronic comorbidities, compared with 71.7% of patients (410/572) with community-acquired influenza (P = 0.001). Similar proportions of community-acquired (32.5%) and nosocomial (36.4%) cases occurred in patients vaccinated in the current season. Clinical findings at time of enrollment did not differ between the two groups, with similar rates of fever, cough, chest pain and dyspnoea. Compared with community-acquired cases, a higher proportion of patients with nosocomial influenza received neuraminidase inhibitors within 2 15s of symptom onset (38.5% v 15.9%; P = 0.003). Admission to intensive care took place in 21.3% and 23.1% of community-acquired and nosocomial cases, respectively. One death from nosocomial influenza occurred in a patient with end-stage respiratory disease., Conclusions: Nosocomial influenza is uncommon but may be associated with severe disease. It may be partially preventable as patients frequently have comorbidities for which influenza vaccination is recommended. Patients, particularly those at high risk of complications, and their contacts (including health care workers) should be vaccinated to prevent severe disease.

Background: Active transport can contribute to physical activity accumulation and improved health in adults. The built environment is an established associate of active transport behaviours; however, assessment of environmental features encountered during journeys remains challenging. The purpose of this study was to examine the utility of wearable cameras to objectively audit and quantify environmental features along work-related walking and cycling routes., Methods: A convenience sample of employed adults was recruited in New Zealand, in June 2011. Participants wore a SenseCam for all journeys over three weekdays and completed travel diaries and demographic questionnaires. SenseCam images for work-related active transport journeys were coded for presence of environmental features hypothesised to be related to active transport. Differences in presence of features by transport mode and in participant-reported and SenseCam-derived journey duration were determined using two-sample tests of proportion and an independent samples t-test, respectively., Results: Fifteen adults participated in the study, yielding 1749 SenseCam images from 30 work-related active transport journeys for coding. Significant differences in presence of features were found between walking and cycling journeys. Almost a quarter of images were uncodeable due to being too dark to determine features. There was a non-significant tendency for respondents to under-report their journey duration., Conclusion: This study provides proof of concept for the use of the SenseCam to capture built environment data in real time that may be related to active transportation. Further work is required to test and refine coding methodologies across a range of settings, travel behaviours, and demographic groups.

Technologic advances mean automated, wearable cameras are now feasible for investigating health behaviors in a public health context. This paper attempts to identify and discuss the ethical implications of such research, in relation to existing guidelines for ethical research in traditional visual methodologies. Research using automated, wearable cameras can be very intrusive, generating unprecedented levels of image data, some of it potentially unflattering or unwanted. Participants and third parties they encounter may feel uncomfortable or that their privacy has been affected negatively. This paper attempts to formalize the protection of all according to best ethical principles through the development of an ethical framework. Respect for autonomy, through appropriate approaches to informed consent and adequate privacy and confidentiality controls, allows for ethical research, which has the potential to confer substantial benefits on the field of health behavior research., (Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Studies have shown relationships between important health outcomes and sedentary behavior, independent of physical activity. There are known errors in tools employed to assess sedentary behavior. Studies of accelerometers have been limited to laboratory environments., Purpose: To assess a broad range of sedentary behaviors in free-living adults using accelerometers and a Microsoft SenseCam that can provide an objective observation of sedentary behaviors through first person-view images., Methods: Participants were 40 university employees who wore a SenseCam and Actigraph accelerometer for 3-5 days. Images were coded for sitting and standing posture and 12 activity types. Data were merged and aggregated to a 60-second epoch. Accelerometer counts per minute (cpm) of <100 were compared with coded behaviors. Sensitivity and specificity analyses were performed. Data were collected in June and July 2011 and analyzed in April 2012., Results: TV viewing, other screen use, and administrative activities were correctly classified by the 100-cpm cutpoint. However, standing behaviors also fell under this threshold, and driving behaviors exceeded it. Multiple behaviors occurred simultaneously. A nearly 30-minute per day difference was found in sedentary behavior estimates based on the accelerometer versus the SenseCam., Conclusions: Researchers should be aware of the strengths and weaknesses of the 100-cpm accelerometer cutpoint for identifying sedentary behavior. The SenseCam may be a useful tool in free-living conditions to better understand health behaviors such as sitting., (Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Accelerometers can identify certain physical activity behaviours, but not the context in which they take place. This study investigates the feasibility of wearable cameras to objectively categorise the behaviour type and context of participants' accelerometer-identified episodes of activity., Methods: Adults were given an Actical hip-mounted accelerometer and a SenseCam wearable camera (worn via lanyard). The onboard clocks on both devices were time-synchronised. Participants engaged in free-living activities for 3 days. Actical data were cleaned and episodes of sedentary, lifestyle-light, lifestyle-moderate, and moderate-to-vigorous physical activity (MVPA) were identified. Actical episodes were categorised according to their social and environmental context and Physical Activity (PA) compendium category as identified from time-matched SenseCam images., Results: There were 212 days considered from 49 participants from whom SenseCam images and associated Actical data were captured. Using SenseCam images, behaviour type and context attributes were annotated for 386 (out of 3017) randomly selected episodes (such as walking/transportation, social/not-social, domestic/leisure). Across the episodes, 12 categories that aligned with the PA Compendium were identified, and 114 subcategory types were identified. Nineteen percent of episodes could not have their behaviour type and context categorized; 59% were outdoors versus 39% indoors; 33% of episodes were recorded as leisure time activities, with 33% transport, 18% domestic, and 15% occupational. 33% of the randomly selected episodes contained direct social interaction and 22% were in social situations where the participant wasn't involved in direct engagement., Conclusion: Wearable camera images offer an objective method to capture a spectrum of activity behaviour types and context across 81% of accelerometer-identified episodes of activity. Wearable cameras represent the best objective method currently available to categorise the social and environmental context of accelerometer-defined episodes of activity in free-living conditions.

Early onset of behavioural problems has lasting negative effects on a broad range of lifetime outcomes, placing large costs on individuals, families and society. A number of researchers and policy makers have argued that early interventions aimed at supporting the family is the most effective way of tackling child behaviour problems. This study forms the economic component of a randomised evaluation of the Incredible Years programme, a programme aimed at improving the skills and parenting strategies of parents of children with conduct problems. Our results show that the programme provides a cost-effective way of reducing behavioural problems. Furthermore, our cost analysis, when combined with a consideration of the potential long-run benefits, suggests that investment in such programmes may generate favourable long-run economic returns.

A 39-year-old man presented to the emergency department after falling downstairs after he consumed a large quantity of alcohol. On examination, he had altered mental state (GCS 14), central cyanosis and low oxygen saturation of 86%, despite 100% oxygen being administered. His arterial blood gas confirmed diagnosis of methaemoglobinaemia with a methaemoglobin percentage of 14.08. He was treated successfully with methylthioninium chloride. The patient later admitted to use of recreational poppers (amyl nitrates) the previous evening. The emergency physician is challenged by the presentation of a patient with altered mental state and unexplained low oxygen saturation with concurrent alcohol intoxication but must have a high index of suspicion for methaemoglobinaemia particularly with a history of recreational drug ingestion.

Background: To study the role of microRNA (miRNA) in the regulation of Chinese hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS analysis were utilised for simultaneous expression profiling of miRNA, mRNA and protein. The sample set under investigation consisted of clones with variable cellular growth rates derived from the same population. In addition to providing a systems level perspective on cell growth, the integration of multiple profiling datasets can facilitate the identification of non-seed miRNA targets, complement computational prediction tools and reduce false positive and false negative rates., Results: 51 miRNAs were associated with increased growth rate (35 miRNAs upregulated and 16 miRNAs downregulated). Gene ontology (GO) analysis of genes (n=432) and proteins (n=285) found to be differentially expressed (DE) identified biological processes driving proliferation including mRNA processing and translation. To investigate the influence of miRNA on these processes we combined the proteomic and transcriptomic data into two groups. The first set contained candidates where evidence of translational repression was observed (n=158). The second group was a mixture of proteins and mRNAs where evidence of translational repression was less clear (n=515). The TargetScan algorithm was utilised to predict potential targets within these two groups for anti-correlated DE miRNAs., Conclusions: The evidence presented in this study indicates that biological processes such as mRNA processing and protein synthesis are correlated with growth rate in CHO cells. Through the integration of expression data from multiple levels of the biological system a number of proteins central to these processes including several hnRNPs and components of the ribosome were found to be post-transcriptionally regulated. We utilised the expression data in conjunction with in-silico tools to identify potential miRNA-mediated regulation of mRNA/proteins involved in CHO cell growth rate. These data have allowed us to prioritise candidates for cell engineering and/or biomarkers relevant to industrial cell culture. We also expect the knowledge gained from this study to be applicable to other fields investigating the role of miRNAs in mammalian cell growth.

Background: The school journey is often studied in relation to health outcomes in children and adolescents. Self-report is the most common measurement tool., Purpose: To investigate the error on self-reported journey duration in adolescents, using a wearable digital camera (Microsoft SenseCam)., Methods: During March-May 2011, participants (n=17; aged 13-15 years) from four schools wore wearable cameras to and from school for 1 week. The device automatically records time-stamped, first-person point-of-view images, without any action from the wearer. Participants also completed a researcher-administered self-report travel survey over the same period. Analysis took place in November 2011. Within- and between-subjects correlation coefficients and Bland-Altman 95% limits of agreement were derived, accounting for the multiple observations per individual., Results: Self-report data were collected for 150 journey stages and SenseCam data for 135 (90%) of these. The within-subjects correlation coefficient for journey duration was 0.89 (95% CI=0.84, 0.93). The between-subjects correlation coefficient was 0.92 (95% CI=0.79, 0.97). The mean difference (bias) between methods at the whole sample level was small (10 seconds per journey, 95% CI= -33, 53). The wide limits of agreement (± 501 seconds, 95% CI= -491, 511) reveal large random error., Conclusions: Compared to direct observation from images, self-reported journey duration is accurate at the mean group level but imprecise at the level of the individual participant., (Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Current recommendations are that HIV-infected persons should not be given live vaccines. We set out to assess potential toxicity of three live, attenuated oral vaccines (against rotavirus, typhoid and ETEC) in a phase 1 study., Methods: Two commercially available oral vaccines against rotavirus (Rotarix) and typhoid (Vivotif) and one candidate vaccine against Enterotoxigenic Escherichia coli (ACAM2017) were given to HIV seropositive (n=42) and HIV seronegative (n=59) adults. Gastrointestinal symptoms were sought actively by weekly interview up to 1 month of vaccination. In rotavirus vaccine recipients, intestinal biopsies were collected by endoscopy and evaluated for expression of IL-8 and pro-inflammatory cytokines., Results: No difference was observed between symptoms in HIV infected and HIV uninfected vaccinees, except for diarrhoea reported more than 7 days after the last dose of vaccine. If only diarrhoea episodes within 7 days of vaccination are included, diarrhoea was not more frequent in HIV seropositive than in HIV seronegative vaccinees (OR 6.7, 95% CI 1.2-67; P=0.09). However, if later episodes of diarrhoea are included, a significant increase in diarrhoea was demonstrated (OR 5.3, 95% CI 0.98-53; P=0.04). All episodes were mild and transient. IL-8 was slowly up-regulated over the week following vaccination (P=0.02), but IL-β, IFNγ or TNFα were not., Conclusions: No evidence was found of adverse events following administration of these three vaccines, except for late episodes of diarrhoea which may not be attributable to vaccination. Our data do not support the need for a prohibition on oral administration of live, attenuated vaccines to all HIV infected adults, though further work on severely immunocompromised adults and children are required., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: This study aimed to examine the experiences of walking promotion professionals on the range and effectiveness of recruitment strategies used within community based walking programmes within the United Kingdom., Methods: Two researchers recruited and conducted semi-structured interviews with managers and project co-ordinators of community based walking programmes, across the UK, using a purposive sampling frame. Twenty eight interviews were conducted, with community projects targeting participants by age, physical activity status, socio-demographic characteristics (i.e. ethnic group) or by health status. Three case studies were also conducted with programmes aiming to recruit priority groups and also demonstrating innovative recruitment methods. Data analysis adopted an approach using analytic induction., Results: Two types of programmes were identified: those with explicit health aims and those without. Programme aims which required targeting of specific groups adopted more specific recruitment methods. The selection of recruitment method was dependent on the respondent's awareness of 'what works' and the resource capacity at their disposal. Word of mouth was perceived to be the most effective means of recruitment but using this approach took time and effort to build relationships with target groups, usually through a third party. Perceived effectiveness of recruitment was assessed by number of participants rather than numbers of the right participants. Some programmes, particularly those targeting younger adult participants, recruited using new social communication media. Where adopted, social marketing recruitment strategies tended to promote the 'social' rather than the 'health' benefits of walking., Conclusions: Effective walking programme recruitment seems to require trained, strategic, labour intensive, word-of-mouth communication, often in partnerships, in order to understand needs and develop trust and motivation within disengaged sedentary communities. Walking promotion professionals require better training and resources to deliver appropriate recruitment strategies to reach priority groups.

Objectives: Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance., Methods: Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected., Results: Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P < 0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of bla(KPC) had shorter average lengths of stay., Conclusions: Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.

Recent studies delineate substantial genetic components in Parkinson's disease (PD). However, very few studies were performed in Sub-Saharan African populations. Here, we explore the contribution of known PD-causing genes in patients of indigenous Zambian ancestry. We studied thirty-nine Zambian patients, thirty-eight with PD and one with parkinsonian-pyramidal syndrome (18% familial; average onset age 54.9 ± 12.2 years). In the whole group, all SNCA exons and LRRK2 exons 29 to 48 (encoding for important functional domains) were sequenced. In the familial patients and those with onset <55 years (n = 22) the whole LRRK2 coding region was sequenced (51 exons). In the patients with onset <50 years (n = 12), all parkin, PINK1, and DJ-1 exons were sequenced, and dosage analysis of parkin, PINK1, DJ-1, LRRK2, and SNCA was performed. Dosage analysis was also performed in the majority of the late-onset patients. The LRRK2 p.Gly2019Ser mutation was not detected. A novel LRRK2 missense variant (p.Ala1464Gly) of possible pathogenic role was found in one case. Two heterozygous, likely disease-causing deletions of parkin (exon 2 and exon 4) were detected in an early-onset case. Pathogenic mutations were not detected in SNCA, PINK1, or DJ-1. We also report variability at several single nucleotide polymorphisms in the above-mentioned genes. This is the first molecular genetic study in Zambian PD patients, and the first comprehensive analysis of the LRRK2 and SNCA genes in a Sub-Saharan population. Common disease-causing mutations were not detected, suggesting that further investigations in PD patients from these populations might unravel the role of additional, still unknown genes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries.

Multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa have become common in many regions, often requiring therapy with colistin or polymyxin B. An increase in resistance to these agents would render many infections untreatable. We tested the activity of polymyxin B and the novel polymyxin analogue CB-182,804 against over 5,000 recent Gram-negative clinical isolates from New York City, a region with a high prevalence of multiresistant strains. Over 96% of Escherichia coli, K. pneumoniae, A. baumannii, and P. aeruginosa were susceptible to polymyxin B; only 76% of Enterobacter spp. was susceptible. The MICs of CB-182,804 were generally two-fold higher than polymyxin B and cross-resistance was observed. The addition of rifampin resulted in synergistic inhibition and bactericidal activity in time kill studies, and restored activity against all polymyxin-resistant strains. The synergistic effect of the combination with rifampin was most pronounced against A. baumannii strains, and was slightly greater with CB-182,804 than with polymyxin B against K. pneumoniae and Enterobacter spp. Despite considerable usage of polymyxin B and colistin in this region, polymyxin B retains excellent activity against most Gram-negative isolates. CB-182,804 shows similar activity, particularly when combined with rifampin. The clinical utility of CB-182,804 remains to be determined.

Objective: A community-based randomized controlled trial (RCT) was conducted in urban areas characterized by high levels of disadvantage to test the effectiveness of the Incredible Years BASIC parent training program (IYBP) for children with behavioral problems. Potential moderators of intervention effects on child behavioral outcomes were also explored., Method: Families were included if the child (aged 32-88 months) scored above a clinical cutoff on the Eyberg Child Behavior Inventory (ECBI). Participants (n = 149) were randomly allocated on a 2:1 ratio to an intervention group (n = 103) or a waiting-list control group (n = 46). Child behavior, parenting skills, and parent well-being were assessed at baseline and 6 months later using parent-report and independent observations. An intention-to-treat analysis of covariance was used to examine postintervention differences between groups., Results: Statistically significant differences in child disordered behavior favored the intervention group on the ECBI Intensity (effect size = 0.7, p < .001) and Problem subscales (effect size = 0.75, p < .001). Intervention effects on child hyperactive-inattentive behaviors and social competence, as well as parent competencies and well-being, were also found. Moderator analyses showed that the effects of the IYBP intervention on the primary child outcomes were not moderated by child or family demographic characteristics or risk factors., Conclusion: The results demonstrate the effectiveness of the IYBP in alleviating problem behavior among children and in improving well-being among families living in disadvantaged areas. The findings also highlight the importance of parental intervention in early childhood for parents and children most in need of support., ((PsycINFO Database Record (c) 2012 APA, all rights reserved).)

Objective: To examine the impact of maternity waiting homes on the use of facility-based birthing services for women in two remote districts of Timor-Leste., Methods: A before-and-after study design was used to compare the number of facility-based births in women who lived at different distances (0-5, 6-25, 26-50 and > 50 km) from the health centre before and after implementation of maternity waiting homes. Routine data were collected from health centre records at the end of 2007; they included 249 births in Same, Manufahi district, and 1986 births in Lospalos, Lautem district. Population data were used to estimate the percentage of women in each distance category who were accessing facility-based care., Findings: Most facility-based births in Same (80%) and Lospalos (62%) were among women who lived within 5 km of the health centre. There was no significant increase in the number of facility-based births among women in more remote areas following implementation of the maternity waiting homes. The percentage of births in the population that occurred in a health facility was low for both Manufahi district (9%) and Lautem district (17%), and use decreased markedly as distance between a woman's residence and the health facilities increased., Conclusion: The maternity waiting homes in Timor-Leste did not improve access to facility-based delivery for women in remote areas. The methods for distance analysis presented in this paper provide a framework that could be used by other countries seeking to evaluate maternity waiting homes.

Gastric cancer is a major contributor to mortality worldwide, yet its incidence varies widely around the world in a way which our current understanding of aetiology cannot fully explain. Incidence data from Africa are weak, reflecting poor diagnostic resources, but there are firm data on intestinal metaplasia and gastric atrophy which are important steps in the carcinogenesis pathway. The available registry data suggest that incidence is unlikely to be dramatically different from Europe or North America. Helicobacter pylori infection is an important permissive factor in the development of cancer, but H. pylori seroprevalence is high all over Africa and cannot clearly be correlated with cancer. However, there is evidence that specific bacterial virulence genes, particularly vacA and iceA allele1, do contribute to cancer risk. Intestinal metaplasia and gastric atrophy have been the focus of twelve studies and are common in Africa. Epstein-Barr virus, which causes 10% of cancer worldwide, is the focus of only one African study. Work in other continents demonstrates that other risk factors apply only to one or other of the two major histological types, intestinal and diffuse. Diet, smoking, alcohol and salt intake predispose to the intestinal type of cancer, but genetic factors predispose to the diffuse type. There is a pressing need for information on the histological types occurring in Africa, and their associated risk factors. Most urgently, information on dietary predisposition to cancer is required to inform public health policy with respect to the demographic transition (urbanisation and lifestyle changes) which is occurring all over the continent., (Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Background: Unsafe drinking water presents a particular threat to people living with HIV/AIDS (PLHIV) due to the increased risk of opportunistic infections, diarrhea-associated malabsorption of essential nutrients, and increased exposure to untreated water for children of HIV-positive mothers who use replacement feeding to reduce the risk of HIV transmission. This population may particularly benefit from an intervention to improve water quality in the home., Methods and Findings: We conducted a 12-month randomized, controlled field trial in Zambia among 120 households with children <2 years (100 with HIV-positive mothers and 20 with HIV-negative mothers to reduce stigma of participation) to assess a high-performance water filter and jerry cans for safe storage. Households were followed up monthly to assess use, drinking water quality (thermotolerant coliforms (TTC), an indicator of fecal contamination) and reported diarrhea (7-day recall) among children <2 years and all members of the household. Because previous attempts to blind the filter have been unsuccessful, we also assessed weight-for-age Z-scores (WAZ) as an objective measure of diarrhea impact. Filter use was high, with 96% (596/620) of household visits meeting the criteria for users. The quality of water stored in intervention households was significantly better than in control households (3 vs. 181 TTC/100 mL, respectively, p<0.001). The intervention was associated with reductions in the longitudinal prevalence of reported diarrhea of 53% among children <2 years (LPR=0.47, 95% CI: 0.30-0.73, p=0.001) and 54% among all household members (LPR=0.46, 95% CI: 0.30-0.70, p<0.001). While reduced WAZ was associated with reported diarrhea (-0.26; 95% CI: -0.37 to -0.14, p<0.001), there was no difference in WAZ between intervention and control groups., Conclusion: In this population living with HIV/AIDS, a water filter combined with safe storage was used correctly and consistently, was highly effective in improving drinking water quality, and was protective against diarrhea., Trial Registration: Clinicaltrials.gov NCT01116908.

Walking is a safe, accessible and low cost activity, amenable to change and known to have great potential to increase physical activity levels in sedentary individuals. The objective of this study is to estimate the proportion of the 2009 adult population of England who would attain or exceed vigorous intensity activity (>70% maximum heart rate [HR(max)]) by walking at 3 mph. We conducted predictive impact modelling using participants' (n = 1741, aged 25-64 years) cardiovascular fitness data from treadmill walking tests. We combined this data with English population estimates adjusted for age and sex to estimate the numbers of individuals that would exceed 70% HR(max) (an intensity considered sufficient for fitness gains) when walking at 3 mph (4.8 km · h(-1)). We estimate 1.5 million men (95% confidence interval [CI] 0.9-2.2 million) (from 13.4 million corresponding to 11.6% (95% CI 7.0-16.2%)) and 3.9 million women (95% CI 3.0-4.8 million) (from 13.6 million corresponding to 28.6% (95% CI 22.0-35.1%)) in England aged 25-64 years would benefit from regularly walking at 3 mph. In total, a projected 5.4 million individuals (95% CI 3.9-6.9 million) aged 25-64 (from 26.97 million corresponding to 20.1% (95% CI 14.6-25.7%)) could benefit from walking at 3 mph. Our estimates suggest a considerable number of individuals in the English population could receive fitness and health benefits by walking regularly at 3 mph. Physical activity messages that promote walking at this speed may therefore have the potential to significantly impact national fitness levels and health in England.

So-called ectopic prostatic tissue in the cervix and vaginal tubulosquamous polyps are rare morphologically similar lesions that may show positive immunohistochemical staining with prostatic markers. It has been suggested that they are related to paraurethral Skene's glands that are the female equivalent of prostatic glands in the male. We report a large series of lesions in women aged 23 to 81 years, found within the cervix (n=24), vagina (n=10), and vulva (n=2), which we believe to be a part of a spectrum of lesions derived from Skene's glands, either eutopic or more commonly misplaced during embryonic development. In all cervical cases, the lesion was predominantly situated in the ectocervix and was an incidental finding in specimens procured for a variety of reasons. In the vagina, the lesions usually presented themselves as polyps or cysts, although occasionally they were an incidental finding. The 2 vulval cases were incidental findings in punch biopsies. The basic morphological features were of epithelial elements of both glandular and squamous type; in some cases, the glandular elements formed a double cell layer. Uncommon findings included the presence of sebaceous glands in 2 cases (1 cervix, 1 vagina), basaloid formations resembling hair follicle structures in 4 (2 cervix, 2 vagina), and a microglandular proliferation resembling nephrogenic adenoma in 1 vaginal case. Prostate-specific antigen was positive in 13 of 26 cases and prostatic acid phosphatase in 16 of 26 tested. Six cases were negative with both markers. We propose that these benign lesions in the cervix, vagina, and vulva are derived from eutopic or misplaced Skene's glands.

Background: Tissue MicroArrays (TMAs) are a valuable platform for tissue based translational research and the discovery of tissue biomarkers. The digitised TMA slides or TMA Virtual Slides, are ultra-large digital images, and can contain several hundred samples. The processing of such slides is time-consuming, bottlenecking a potentially high throughput platform., Methods: A High Performance Computing (HPC) platform for the rapid analysis of TMA virtual slides is presented in this study. Using an HP high performance cluster and a centralised dynamic load balancing approach, the simultaneous analysis of multiple tissue-cores were established. This was evaluated on Non-Small Cell Lung Cancer TMAs for complex analysis of tissue pattern and immunohistochemical positivity., Results: The automated processing of a single TMA virtual slide containing 230 patient samples can be significantly speeded up by a factor of circa 22, bringing the analysis time to one minute. Over 90 TMAs could also be analysed simultaneously, speeding up multiplex biomarker experiments enormously., Conclusions: The methodologies developed in this paper provide for the first time a genuine high throughput analysis platform for TMA biomarker discovery that will significantly enhance the reliability and speed for biomarker research. This will have widespread implications in translational tissue based research.

Cryptosporidiosis is a major infection of humans, leading to diarrhoea and growth failure in children, diarrhoea and malnutrition in immunocompromised adults, and is associated with increased mortality in all age groups. Using the country of Zambia as an example, I review the possible approaches to treatment and prevention in a tropical setting. The current optimal therapy for cryptosporidiosis is nitazoxanide which works well in HIV uninfected children, but treatment in patients with HIV infection remains remarkably difficult. No single drug has demonstrated efficacy in a randomised trial. No vaccine is available, so the best option for prevention for the moment is filtration and clean storage of drinking water. This would be expected to reduce cryptosporidiosis dramatically, but this needs to be demonstrated directly. Water filtration would have the added benefit of protection against many other pathogens, but the paucity of alternative approaches highlights the need for a better understanding of this important human pathogen.

Background: The family unit may be an important mechanism for increasing physical activity levels, yet little is known about what types of family-based interventions are effective. This study involved a formative evaluation of a 12 week intervention to encourage walking as a family based activity. The intervention consisted of several key elements including led walks and tailored resources, as well as remote support provided via the telephone. The project aimed to explore factors associated with successful delivery of the programme and to identify areas of improvement for future implementation., Methods: A total of nine interviews were undertaken with programme staff who were involved in either the set up or delivery of the intervention. In addition, four interviews and two focus groups were undertaken with participants to explore their experiences of the programme. The analysis involved both deductive and inductive reasoning., Results: In total, 114 people participated in the programme, which included 36 adults, 10 adolescents and 68 children (≤ 10 years of age). Adult participants reported several barriers to walking including concerns over their children's behaviour and their ability to maintain 'control' of their children. Walking in a group with other families gave parents confidence to go out walking with their children and provided a valuable opportunity for social interaction for parents and children alike. The most successful walks incorporated specific destinations and an activity to undertake upon reaching the destination. Incorporating other activities along the way also helped to keep the children engaged., Conclusions: The results of this study have highlighted the important contribution that formative research can make in informing and refining a programme to increase appropriateness and effectiveness. The study has helped to highlight the key characteristics associated with delivering a successful walking intervention to young families. It is recommended that practitioners undertake formative research when developing novel health promotion initiatives to help refine the programme protocols.

In low-income settings, human immunodeficiency virus (HIV)-positive mothers must choose between breastfeeding their infants and risking transmission of HIV or replacement feeding their infants and risking diarrheal disease from contaminated water. We conducted a cross-sectional study of children < 2 years of age of 254 HIV-positive mothers in peri-urban Zambia to assess their exposure to waterborne fecal contamination. Fecal indicators were found in 70% of household drinking water samples. In a multivariable analysis, factors associated with diarrhea prevalence in children < 2 years were mother having diarrhea (adjusted odds ratio [aOR] = 5.18, 95% confidence interval [CI] = 1.65-16.28), child given water in the past 2 days (aOR = 4.08, 95% CI = 1.07-15.52), child never being breastfed (aOR = 2.67, 95% CI = 1.06-6.72), and rainy (versus dry) season (aOR = 4.60, 95% CI = 1.29-16.42). Children born to HIV-positive mothers were exposed to contaminated water through direct intake of drinking water, indicating the need for interventions to ensure microbiological water quality.

Objective: Obesity levels are rising in almost all parts of the world, including the UK. School food offers children in Great Britain between 25 % and 33 % of their total daily energy, with vending typically offering products high in fat, salt or sugar. Government legislation of 2007 to improve the quality of school food now restricts what English schools can vend. In assessing the effect of this legislation on the quality of English secondary-school vending provision, the response of schools to these effects is explored through qualitative data., Design: A longitudinal postal and visit-based inventory survey of schools collected vending data during the academic year 2006-2007 (pre-legislation), 2007-2008 and 2008-2009 (both post-legislation). Interviews with school staff explored issues of compliance. Product categorisation and analysis were carried out by product type, nutrient profiling and by categories of foods allowed or prohibited by the legislation., Setting: English secondary schools., Subjects: A representative sample of 279 schools including sixty-two researcher-visited inventory schools participated in the research., Results: School vending seems to have moved towards compliance with the new standards - now drinks vending predominates and is largely compliant, whereas food vending is significantly reduced and is mostly non-compliant. Sixth form vending takes a disproportionate share of non-compliance. Vending has declined overall, as some schools now perceive food vending as uneconomic. Schools adopting a 'whole-school' approach appeared the most successful in implementing the new standards., Conclusions: Government legislation has achieved significant change towards improving the quality of English school vending, with the unintended consequence of reducing provision.

Boiling is the most common method of disinfecting water in the home and the benchmark against which other point-of-use water treatment is measured. In a six-week study in peri-urban Zambia, we assessed the microbiological effectiveness and potential cost of boiling among 49 households without a water connection who reported "always" or "almost always" boiling their water before drinking it. Source and household drinking water samples were compared weekly for thermotolerant coliforms (TTC), an indicator of fecal contamination. Demographics, costs, and other information were collected through surveys and structured observations. Drinking water samples taken at the household (geometric mean 7.2 TTC/100 mL, 95% CI, 5.4-9.7) were actually worse in microbiological quality than source water (geometric mean 4.0 TTC/100 mL, 95% CI, 3.1-5.1) (p < 0.001), although both are relatively low levels of contamination. Only 60% of drinking water samples were reported to have actually been boiled at the time of collection from the home, suggesting over-reporting and inconsistent compliance. However, these samples were of no higher microbiological quality. Evidence suggests that water quality deteriorated after boiling due to lack of residual protection and unsafe storage and handling. The potential cost of fuel or electricity for boiling was estimated at 5% and 7% of income, respectively. In this setting where microbiological water quality was relatively good at the source, safe-storage practices that minimize recontamination may be more effective in managing the risk of disease from drinking water at a fraction of the cost of boiling.

Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region., (© 2011 Wiley-Liss, Inc.)

Background: Active travel such as walking and cycling has potential to increase physical activity levels in sedentary individuals. Motorised car travel is a sedentary behaviour that contributes to carbon emissions. There have been recent calls for technology that will improve our ability to measure these travel behaviours, and in particular evaluate modes and volumes of active versus sedentary travel. The purpose of this pilot study is to investigate the potential efficacy of a new electronic measurement device, a wearable digital camera called SenseCam, in travel research., Methods: Participants (n = 20) were required to wear the SenseCam device for one full day of travel. The device automatically records approximately 3,600 time-stamped, first-person point-of-view images per day, without any action required by the wearer. Participants also completed a self-report travel diary over the same period for comparison, and were interviewed afterwards to assess user burden and experience., Results: There were a total of 105 confirmed journeys in this pilot. The new SenseCam device recorded more journeys than the travel diary (99 vs. 94). Although the two measures demonstrated an acceptable correlation for journey duration (r = 0.92, p < 0.001) self-reported journey duration was over-reported (mean difference 154 s per journey; 95% CI = 89 to 218 s; 95% limits of agreement = 154 ± 598 s (-444 to 752 s)). The device also provided visual data that was used for directed interviews about sources of error., Conclusions: Direct observation of travel behaviour from time-stamped images shows considerable potential in the field of travel research. Journey duration derived from direct observation of travel behaviour from time-stamped images appears to suggest over-reporting of self-reported journey duration.

Background: Intestinal helminthiasis modulates immune responses to vaccines and environmental allergens. To explore the impact on intestinal host defense, we assessed expression of antimicrobial peptide genes, together with T cell subset markers and cytokines, in patients with ascariasis before and after treatment., Methods: Case patients (n = 27) and control subjects (n = 44) underwent enteroscopy for collection of jejunal biopsy specimens, which were used in quantitative, real-time reverse-transcription polymerase chain reaction for a range of host defense genes; blood samples were also analyzed simultaneously., Results: The level of gene expression (mRNA) of HD5, hBD1, and LL-37 was lower in case patients than in control subjects, and the level of expression of HD6 was increased. However, after successful eradication, there was no trend to values seen in control subjects. Helminthiasis was associated with increased intestinal expression of the Th1 genes T-bet and interferon-γ. In peripheral blood mononuclear cells (PBMCs), a mixed profile of T cell markers and cytokines was increased. Ascaris-induced down-regulation of HD5 was observed in individuals with higher RORγt expression in PBMCs, but we found no evidence that this was mediated by circulating interleukin-22., Conclusions: Human ascariasis was associated with changes in antimicrobial peptide gene expression and immunological markers. Such changes may have implications for susceptibility to infectious disease and responsiveness to oral vaccines in tropical populations.

The authors report a case of hypertensive emergency (defined as systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg with end organ damage) following brachial plexus blockade in a hypertensive lady with unstable angina. The authors describe blocking of baroreceptor reflexes by the local anaesthetic as a putative mechanism and suggest that this potentially serious complication should be considered when planning this particular anaesthetic technique.

Objectives: Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa have become a global problem, often leaving the polymyxins as therapeutic agents of last resort. ACHN-490, a next-generation aminoglycoside with activity against a broad range of Gram-positive and Gram-negative pathogens, was examined against clinical isolates of A. baumannii and P. aeruginosa., Methods: The activity of aminoglycosides and ACHN-490 was determined against a contemporary collection of A. baumannii and P. aeruginosa. Selected aminoglycoside-resistant isolates were screened for the presence of genes encoding common aminoglycoside-modifying enzymes and methylases., Results: Resistance to the traditional aminoglycosides was common in the collection of A. baumannii. ACHN-490 possessed superior activity against these isolates, with an MIC(50) value of 8 mg/L. In P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin (MIC(50) value of 8 mg/L for both agents). For both A. baumannii and P. aeruginosa, the MICs of ACHN-490 did not correlate with the presence of commonly encountered aminoglycoside-modifying enzymes., Conclusions: For A. baumannii, the MICs of ACHN-490 were lower than those of traditional aminoglycosides. For P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin.

Background: Active travel to school (ATS) has been identified as an important source of physical activity for youth. However, the relationship between ATS and health-related fitness (HRF) among youth remains unclear., Methods: A systematic search of seven electronic databases (EMBASE, OVID MEDLINE, PsycINFO, PubMed, Scopus, SPORTDiscus and TRIS on line) was conducted in December 2009 and studies published since 1980 were considered for inclusion., Results: Twenty seven articles were identified that explored the relationship between ATS and the following aspects of HRF: weight status/body composition, cardiorespiratory fitness, muscular fitness and flexibility. Forty-eight percent of the studies that examined the relationship between ATS and weight status/body composition reported significant associations, this increased to 55% once poor quality studies were removed. Furthermore, the findings from five studies, including one longitudinal study, indicate that ATS is positively associated with cardiorespiratory fitness in youth. However, the evidence for the relationships between ATS and muscular fitness or flexibility is equivocal and limited by low study numbers., Conclusions: There is some evidence to suggest that ATS is associated with a healthier body composition and level of cardiorespiratory fitness among youth. Strategies to increase ATS are warranted and should be included in whole-of-school approaches to the promotion of physical activity., (© 2011 Lubans et al; licensee BioMed Central Ltd.)

The ability of microRNAs to influence gene expression is now recognized as a fundamental layer of regulation within the cell. MicroRNAs have a major impact on most biological processes and have generated considerable interest as potential biomarkers as well as therapeutic or engineering targets. In this review we provide a brief overview of their biogenesis, genomic organization and mode of action, followed by a description of the methods and approaches to studying their expression. We go on to consider some of the approaches to utilizing them as tools and their potential application in the bioprocessing area, with particular emphasis on Chinese hamster ovary cell engineering.

In 2007, an extensive contact screening investigation into onward transmission of tuberculosis was instigated at a hospital in Northern Ireland following diagnosis of pulmonary multi-drug resistant TB in a healthcare worker. Interferon gamma release assays (IGRAs) were used to test 333 patients and 98 staff. We investigated for evidence of onward transmission and recent infection based on analysis of clinical, demographic and IGRA data. We also described within-patient variability of IGRA results. Among patients and staff, increasing age of patients was the only factor associated with IGRA positivity. Greatest within-subject variability of IU/mL in serially-tested patients/staff was seen in those with a positive IGRA test and this did not correlate with increased exposure to the index case. IGRA positivity being largely explained by increasing age in patients and previous TB contact in staff lends weight to the conclusion that IGRA positivity reflected previous infection rather than recent transmission.

The high rate of maternal mortality in Timor-Leste is a persistent problem which has been exacerbated by the long history of military occupation and ongoing political crises since independence in 1999. It is similar to other developing countries where there have been slow declines in maternal mortality despite 20 years of Safe Motherhood interventions. The national Ministry of Health, United Nations (UN) agencies and non-government organisations (NGOs) have attempted to reduce maternal mortality by enacting policies and interventions to increase the number of births in health centres and hospitals. Despite considerable effort in promoting facility-based delivery, most Timorese women birth at home and the lack of midwives means few women have access to a skilled birth attendant. This paper investigates factors influencing access to and use of maternal health services in rural areas of Timor-Leste. It draws on 21 interviews and 11 group discussions with Timorese women and their families collected over two periods of fieldwork, one month in September 2006 and five months from July to December 2007. Theoretical concepts from anthropology and health social science are used to explore individual, social, political and health system issues which affect the way in which maternal health services are utilised. In drawing together a range of theories this paper aims to extend explanations around access to maternal health services in developing countries. An empirically informed framework is proposed which illustrates the complex factors that influence women's birth choices. This framework can be used by policy-makers, practitioners, donors and researchers to think critically about policy decisions and where investments can have the most impact for improving maternal health in Timor-Leste and elsewhere., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background & Aims: Studies have shown that the circulating citrulline concentration is decreased in patients with proximal small bowel villous atrophy from coeliac disease and more so in patients with extensive damage to the intestinal mucosa, but there have been few data on HIV enteritis and tropical enteropathy (TE). Our primary aim was to correlate serum citrulline with the degree of reduction of the enterocyte mass in HIV-infected patients with TE., Methods: Postabsorptive fasting serum citrulline was measured in 150 TE pts, 44 of whom had HIV infection, using reverse phase, high performance liquid chromatography. Absorptive capacity and permeability were measured after intrajejunal instillation of 4 sugars (5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O methyl D glucose) with assay by thin-layer chromatography. Morphometric analysis was carried out on jejunal biopsies., Results: In HIV positive patients, the median serum citrulline was significantly lower (median 19, interquartile range (IQR) 17-24 μmol/L) than in HIV negative patients (median 27, IQR 23-33 μmol/L; p < 0.001). There were statistically significant correlations (p < 0.005) between citrulline and: crypt depth; villous height/crypt depth ratio; Shenk-Klipstein score; and xylose absoption, only in the HIV positive., Conclusions: Serum citrulline concentration appears to be a quantitative biomarker of small bowel mass integrity in HIV positive enteropathy and deserves assessment as a surrogate for monitoring anti-retroviral therapy., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The detection of Enterobacteriaceae carrying the carbapenemase KPC has been problematic. Thirty isolates of KPC-possessing Escherichia coli were gathered from hospitals in New York City and Connecticut. The imipenem, meropenem, doripenem, and ertapenem MIC50 values were 4, 2, 1, and 4 μg/ml, respectively. Over half of the isolates belonged to a single ribotype. Using an ertapenem breakpoint of 0.25 μg/ml would efficiently detect these isolates.