Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Use of clinical targets in diabetes patient education: qualitative analysis of the expectations and impact of a structured self-management programme in Type 1 diabetes.

AIMS: To explore the impact of education and target-setting on the life stories of patients with diabetes up to 10 years after they had participated in the Dose Adjustment for Normal Eating programme (DAFNE). METHODS: Qualitative, semi-structured interviews were conducted before and after DAFNE courses to elicit narrative accounts from participants at three UK education centres. Observations of courses also took place. Data were gathered from 21 participants over 32 interviews and 146 h of observations, and analysed using a narrative approach. RESULTS: Findings suggest that patient education can create positive transformations in the lives of people with diabetes in ways that are not fully captured by simple quality-of-life scores. However, a review of evidence from other studies shows that DAFNE-recommended blood glucose results are in fact out of reach of even these most motivated and well-informed patients. This information was not shared with DAFNE attendees, who were expected to aim for near-normal HbA1c levels. After the course, participants sometimes perceived themselves as failing in their efforts, even when they had better than average blood glucose results. CONCLUSIONS: Specific and measurable low HbA1c targets may be desirable for reducing the risk of complications in diabetes, but they are not attainable or realistic even for most DAFNE graduates. It is suggested that setting goals without information about how achievable they really are could be counterproductive in terms of supporting and maintaining patient self-efficacy long-term.

Understanding issues associated with attending a young adult diabetes clinic: a case study.

AIMS: To study the reasons for attendance behaviour from the patient viewpoint at a young adult diabetes outpatient clinic. METHODS: Attendance rates for 231 clinic appointments over 19 months for 102 patients were calculated. Semi-structured interviews were conducted with a purposive sample of 17 of the 102. The interviews encouraged participants to describe routines, thoughts and feelings around clinic appointments. Observations were made of the clinic system. Themes arising from patients' emotional and practical issues around attendance were generated from the data. RESULTS: 'Did not attend' rates for the clinic over the study period were 15.7%. However, bureaucratic problems created many 'missed' appointments; most instances of 'did not attend' investigated were attributable to communication failures. Participants did not divide neatly into 'attenders'/'non-attenders'; many had complex mixed attendance records. Most weighed the value of attendance against immediate obstacles such as incompatible work/clinic hours. Reminders were seen as important, particularly for this age group. Respondents identified fear of being judged for 'poor control' as a major factor in attendance decisions, suggesting that having a high HbA1c level may lead to non-attendance, rather than vice versa. CONCLUSIONS: Health professionals' supportive, non-judgemental attitude is important to patients considering clinic attendance. In this study, improved communication, reminders and flexible hours might reduce 'did not attend' rates.

Setting research priorities for Type 1 diabetes.

AIMS: Research priorities are often set by academic researchers or the pharmaceutical industry. The interests of patients, carers and clinicians may therefore be overlooked and research questions that matter may be neglected. The aims of this study were to collect uncertainties about the treatment of Type 1 diabetes from patients, carers and health professionals, and to collate and prioritize these uncertainties to develop a top 10 list of research priorities, using a structured priority-setting partnership of patients, carers, health professionals and diabetes organizations, as described by the James Lind Alliance. METHODS: A partnership of interested organizations was set up, and from this a steering committee of 10 individuals was formed. An online and paper survey was used to identify uncertainties. These were collated, and the steering group carried out an interim priority-setting exercise with partner organizations. This group of uncertainties was then voted on to give a smaller list that went forward to the final priority-setting workshop. At this meeting, a final list of the top 10 research priorities was agreed. RESULTS: An initial 1141 uncertainties were described. These were reduced to 88 indicative questions, 47 of which went out for voting. Twenty-four were then taken forward to a final priority-setting workshop. This workshop resulted in a list of top 10 research priorities in Type 1 diabetes. CONCLUSION: We have shown that it is possible using the James Lind Alliance process to develop an agreed top 10 list of research priorities for Type 1 diabetes from health professionals, patients and carers.

Immunity to non-cerebral severe malaria is acquired after one or two infections.

In areas of stable transmission, clinical immunity to mild malaria is acquired slowly, so it is not usually effective until early adolescence. Life-threatening disease is, however, restricted to a much younger age group, indicating that resistance to the severe clinical consequences of infection is acquired more quickly. Understanding how rapidly immunity develops to severe malaria is essential, as severe malaria should be the primary target of intervention strategies, and predicting the result of interventions that reduce host exposure will require consideration of these dynamics. Severe disease in childhood is less frequent in areas where transmission is the greatest. One explanation for this is that infants experience increased exposure to infection while they are protected from disease, possibly by maternal antibody. They therefore emerge from this period of clinical protection with considerably more immunity than those who experience lower transmission intensities. Here we use this data, assuming a period of clinical protection, to estimate the number of prior infections needed to reduce the risk of severe disease to negligible levels. Contrary to expectations, one or two successful infective bites seem to be all that is necessary across a broad range of transmission intensities.

The entomological inoculation rate and Plasmodium falciparum infection in African children.

Malaria is an important cause of global morbidity and mortality. The fact that some people are bitten more often than others has a large effect on the relationship between risk factors and prevalence of vector-borne diseases. Here we develop a mathematical framework that allows us to estimate the heterogeneity of infection rates from the relationship between rates of infectious bites and community prevalence. We apply this framework to a large, published data set that combines malaria measurements from more than 90 communities. We find strong evidence that heterogeneous biting or heterogeneous susceptibility to infection are important and pervasive factors determining the prevalence of infection: 20% of people receive 80% of all infections. We also find that individual infections last about six months on average, per infectious bite, and children who clear infections are not immune to new infections. The results have important implications for public health interventions: the success of malaria control will depend heavily on whether efforts are targeted at those who are most at risk of infection.

Are men testing? Sex differentials in HIV testing in Mpumalanga Province, South Africa.

HIV testing is the centerpiece of the national AIDS program in South Africa and many HIV-endemic countries, yet there is surprisingly little published data on who uses testing services. In 2006, we conducted a census of HIV-testing records in all 282 public and non-governmental voluntary counseling and testing (VCT) sites in Mpumalanga (MP), South Africa, the province with the highest HIV prevalence in the country. We secured data on the age and sex of all those tested in 260 sites since the year testing was initiated, as far back as 1998 in some sites. For the year 2006, we also secured data on whether a client came to VCT through self-referral, antenatal services (prevent mother-to-child transmission (PMTCT)), or medical referral. The results characterize the rapid uptake of testing as facilities increased, with the number of people testing in MP more than doubling each year between 2002 and 2006. However, there is a persistent 3:1 differential of females:males testing, with 72.7% of all testing among females. When pregnancy-related testing (via PMTCT) is excluded, females still account for 65.1% of all testing in MP. The data also suggest men are more likely to test at older ages and as a result of medical referral. In summary, females in MP are far more likely to use HIV testing than males, even after accounting for increased access to testing during pregnancy. Sex differentials in HIV testing warrant closer policy attention.

Fever prevalence and management among three rural communities in the North West Zone, Somalia.

Between March and August 2008 we undertook 2 cross-sectional surveys among 1375 residents of 3 randomly selected villages in the district of Gebiley in the North-West Zone, Somalia. We investigated for the presence of malaria infection and the period prevalence of self-reported fever 14 days prior to both surveys. All blood samples examined were negative for both species of Plasmodium. The period prevalence of 14-day fevers was 4.8% in March and 0.6% in August; the majority of fevers (84.4%) were associated with other symptoms including cough, running nose and sore throat; 48/64 cases had resolved by the day of interview (mean duration 5.4 days). Only 18 (37.5%) fever cases were managed at a formal health care facility: 7 within 24 hours and 10 within 24-72 hours of onset. None of the fevers were investigated for malaria; they were treated with antibiotics, antipyretics and vitamins.

Can we use local climate zones for predicting malaria prevalence across sub-Saharan African cities?

Malaria burden is increasing in sub-Saharan cities because of rapid and uncontrolled urbanization. Yet very few studies have studied the interactions between urban environments and malaria. Additionally, no standardized urban land-use/land-cover has been defined for urban malaria studies. Here, we demonstrate the potential of local climate zones (LCZs) for modeling malaria prevalence rate (Pf PR2-10) and studying malaria prevalence in urban settings across nine sub-Saharan African cities. Using a random forest classification algorithm over a set of 365 malaria surveys we: (i) identify a suitable set of covariates derived from open-source earth observations; and (ii) depict the best buffer size at which to aggregate them for modeling Pf PR2-10. Our results demonstrate that geographical models can learn from LCZ over a set of cities and be transferred over a city of choice that has few or no malaria surveys. In particular, we find that urban areas systematically have lower Pf PR2-10 (5%-30%) than rural areas (15%-40%). The Pf PR2-10 urban-to-rural gradient is dependent on the climatic environment in which the city is located. Further, LCZs show that more open urban environments located close to wetlands have higher Pf PR2-10. Informal settlements-represented by the LCZ 7 (lightweight lowrise)-have higher malaria prevalence than other densely built-up residential areas with a mean prevalence of 11.11%. Overall, we suggest the applicability of LCZs for more exploratory modeling in urban malaria studies.

Advances in process control.

Advances in electronics and computers have enabled industries to attain better control of their processes with resulting increases in quality, productivity, profitability, and compliance with government regulations. With a hierarchy of computers, distributed data acquisition, and information processing and control, it is possible to achieve overall optimum performance of a plant. While further advances in microprocessors and large-scale integration will be useful to the process engineer, major improvements in process control await advances in sensor technology and software.

Risk Associated with Malaria Infection in Tihama Qahtan, Aseer Region, Kingdom of Saudi Arabia: 2006-2007.

INTRODUCTION: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region. METHODS: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons. RESULTS: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods. CONCLUSION: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area's elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region.

Translation of artemether-lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya.

OBJECTIVE: To describe the quality of outpatient paediatric malaria case-management approximately 4-6 months after artemether-lumefantrine (AL) replaced sulfadoxine-pyrimethamine (SP) as the nationally recommended first-line therapy in Kenya. METHODS: Cross-sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under-fives. RESULTS: We evaluated 193 facilities, 227 health workers and 1533 sick-child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in-service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight-specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker's cadre, in-service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. CONCLUSIONS: Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost-effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin-based combination therapy in Africa.

Effects of revised diagnostic recommendations on malaria treatment practices across age groups in Kenya.

OBJECTIVE: The recent change of treatment policy for uncomplicated malaria from sulfadoxine-pyrime-thamine to artemether-lumefantrine (AL) in Kenya was accompanied by revised malaria diagnosis recommendations promoting presumptive antimalarial treatment in young children and parasitological diagnosis in patients 5 years and older. We evaluated the impact of these age-specific recommendations on routine malaria treatment practices 4-6 months after AL treatment was implemented. METHODS: Cross-sectional, cluster sample survey using quality-of-care assessment methods in all government facilities in four Kenyan districts. Analysis was restricted to the 64 facilities with malaria diagnostics and AL available on the survey day. Main outcome measures were antimalarial treatment practices for febrile patients stratified by age, use of malaria diagnostic tests, and test result. RESULTS: Treatment practices for 706 febrile patients (401 young children and 305 patients > or =5 years) were evaluated. 43.0% of patients > or =5 years and 25.9% of children underwent parasitological malaria testing (87% by microscopy). AL was prescribed for 79.7% of patients > or =5 years with positive test results, for 9.7% with negative results and for 10.9% without a test. 84.6% of children with positive tests, 19.2% with negative tests, and 21.6% without tests were treated with AL. At least one antimalarial drug was prescribed for 75.0% of children and for 61.3% of patients > or =5 years with a negative test result. CONCLUSIONS: Despite different recommendations for patients below and above 5 years of age, malaria diagnosis and treatment practices were similar in the two age groups. Parasitological diagnosis was under-used in older children and adults, and young children were still tested. Use of AL was low overall and alternative antimalarials were commonly prescribed; but AL prescribing largely followed the results of malaria tests. Malaria diagnosis recommendations differing between age groups appear complex to implement; further strengthening of diagnosis and treatment practices under AL policy is required.

Muscle Na+-K+-ATPase activity and isoform adaptations to intense interval exercise and training in well-trained athletes.

The Na+ -K+ -ATPase enzyme is vital in skeletal muscle function. We investigated the effects of acute high-intensity interval exercise, before and following high-intensity training (HIT), on muscle Na+ -K+ -ATPase maximal activity, content, and isoform mRNA expression and protein abundance. Twelve endurance-trained athletes were tested at baseline, pretrain, and after 3 wk of HIT (posttrain), which comprised seven sessions of 8 x 5-min interval cycling at 80% peak power output. Vastus lateralis muscle was biopsied at rest (baseline) and both at rest and immediately postexercise during the first (pretrain) and seventh (posttrain) training sessions. Muscle was analyzed for Na+ -K+ -ATPase maximal activity (3-O-MFPase), content ([3H]ouabain binding), isoform mRNA expression (RT-PCR), and protein abundance (Western blotting). All baseline-to-pretrain measures were stable. Pretrain, acute exercise decreased 3-O-MFPase activity [12.7% (SD 5.1), P < 0.05], increased alpha1, alpha2, and alpha3 mRNA expression (1.4-, 2.8-, and 3.4-fold, respectively, P < 0.05) with unchanged beta-isoform mRNA or protein abundance of any isoform. In resting muscle, HIT increased (P < 0.05) 3-O-MFPase activity by 5.5% (SD 2.9), and alpha3 and beta3 mRNA expression by 3.0- and 0.5-fold, respectively, with unchanged Na+ -K+ -ATPase content or isoform protein abundance. Posttrain, the acute exercise induced decline in 3-O-MFPase activity and increase in alpha1 and alpha3 mRNA each persisted (P < 0.05); the postexercise 3-O-MFPase activity was also higher after HIT (P < 0.05). Thus HIT augmented Na+ -K+ -ATPase maximal activity despite unchanged total content and isoform protein abundance. Elevated Na+ -K+ -ATPase activity postexercise may contribute to reduced fatigue after training. The Na+ -K+ -ATPase mRNA response to interval exercise of increased alpha- but not beta-mRNA was largely preserved posttrain, suggesting a functional role of alpha mRNA upregulation.

Determinants of HIV counselling and testing participation in a prevention of mother-to-child transmission programme in rural Burkina Faso.

OBJECTIVES: To analyse the factors associated with the uptake of HIV counselling, HIV testing and returning for test results in a rural hospital setting in Nouna, Burkina Faso. METHODS: Cross sectional survey of 435 pregnant women who visited the district hospital for antenatal care, from July to December 2004. Separate multivariate logistic regression analyses including analysis of reported reasons were performed to identify the factors associated with accepting HIV counselling and testing. RESULTS: HIV testing participation was related to discussing HIV screening with the partner (OR 8.36), and the number of antenatal care (ANC) visits already accomplished (OR 2.23). The quality of pre-test counselling was very poor as 42% did not understand the process. The absence of doctors and mismanagement of time for post-test counselling were the main reasons why women did not receive test results. Analysis of participants by discussion status, counselling and test participation revealed that fewer women dropped out at every stage who discussed HIV testing with their partner. CONCLUSION: Communication with the partner plays a vital role in the uptake of HIV testing. Encouraging women to engage in a discussion about testing with their partners may be a viable intervention to improve participation. Quality of service needs to be better.

Genetic Evidence for Interaction between Nonhomologous Proteins in Yeast and a Case of Suppression at the HIS1 Locus.

The HIS1 and THR4 loci are the structural genes for phosphoribosyl-ATP pyrophosphorylase and threonine synthetase, respectively. The allele his1-1S has no enzyme activity at 30 degrees , but does have activity at 15 degrees provided the cell contains the wild-type THR4 allele or a suppressing allele at another locus, designated SUP(his1-1S). Under these conditions, cells with the his1-1S mutation are capable of growth on minimal medium at 15 degrees . Three kinds of reversions of a his1-1S thr4 sup(his1-1S) strain to histidine prototrophy have been obtained: (1) his1-1S locus reversions to HIS1 that restore growth without added histidine at 30 degrees , (2) thr4 reversions to THR4 that simultaneously eliminate the requirement for threonine and restore the low-temperature effect on the his1-1S allele, and (3) mutations from sup to SUP. The SUP allele is not an ochre suppressor, and it is not linked to either HIS1, THR4 or a centromere. It may represent a missense suppressor. It is proposed that the effect of THR4 is caused by aggregation of the wild-type threonine synthetase with defective his1-1S monomers, causing a favorable conformational change in the histidine protein that restores limited enzymatic activity. This can be regarded as a case of complementation between nonhomologous proteins.