Effects of demand-side financing on utilisation, experiences and outcomes of maternity care in low- and middle-income countries: a systematic review.

Demand-side financing, where funds for specific services are channelled through, or to, prospective users, is now employed in health and education sectors in many low- and middle-income countries. This systematic review aimed to critically examine the evidence on application of this approach to promote maternal health in these settings. Five modes were considered: unconditional cash transfers, conditional cash transfers, short-term payments to offset costs of accessing maternity services, vouchers for maternity services, and vouchers for merit goods. We sought to assess the effects of these interventions on utilisation of maternity services and on maternal health outcomes and infant health, the situation of underprivileged women and the healthcare system

Co-Development of Technology for Measuring Faecal Contamination of Drinking Water

Participatory approaches to innovation aim to address persistent failures of technology to respond to end-user needs and context. Here, we present the results of a transdisciplinary project aimed at co-developing new technologies for water quality monitoring in remote locations in developing countries. Drawing from critical social science, we developed and implemented a suite of approaches to engage community members and other regional stakeholders in an innovation process that is simultaneously social and technical. Part of our community engagement activities involved the sampling and molecular analysis of drinking water sources from two communities on the island of Efate in Vanuatu. The results revealed evidence for temporal variations in the extent of faecal contamination from different sources. This analysis was used to help frame discussions about microbial contamination, water quality and health, which, along with other structured conversations, led to technical and institutional specifications for water quality sensing. These co-developed specifications were striking, contradicting widely assumed requirements for handheld, rapid, mobile devices. Informed by these specifications, a device for monitoring colorimetric changes in response to microbial growth was designed and built. This device was able to quantify growth of faecal coliform indicator species Escherichia coli inoculated into sterile media. Subsequently, we showed the device could detect E. coli inoculated into sterilised river water. The limit of detection was as low as a single E. coli cell in 100 mL of liquid. Detection at this low concentration was achieved in 16 hours, meeting a specification requirement established through the co-design process

PER-TIM Interactions with the Photoreceptor Cryptochrome Mediate Circadian Temperature Responses in Drosophila

Drosophila cryptochrome (CRY) is a key circadian photoreceptor that interacts with the period and timeless proteins (PER and TIM) in a light-dependent manner. We show here that a heat pulse also mediates this interaction, and heat-induced phase shifts are severely reduced in the cryptochrome loss-of-function mutant cryb. The period mutant perL manifests a comparable CRY dependence and dramatically enhanced temperature sensitivity of biochemical interactions and behavioral phase shifting. Remarkably, CRY is also critical for most of the abnormal temperature compensation of perL flies, because a perL; cryb strain manifests nearly normal temperature compensation. Finally, light and temperature act together to affect rhythms in wild-type flies. The results indicate a role for CRY in circadian temperature as well as light regulation and suggest that these two features of the external 24-h cycle normally act together to dictate circadian phase

A Symmetric Dual Feedback System Provides a Robust and Entrainable Oscillator

Many organisms have evolved molecular clocks to anticipate daily changes in their environment. The molecular mechanisms by which the circadian clock network produces sustained cycles have extensively been studied and transcriptional-translational feedback loops are common structures to many organisms. Although a simple or single feedback loop is sufficient for sustained oscillations, circadian clocks implement multiple, complicated feedback loops. In general, different types of feedback loops are suggested to affect the robustness and entrainment of circadian rhythms

Why don't some women attend antenatal and postnatal care services?: a qualitative study of community members' perspectives in Garut, Sukabumi and Ciamis districts of West Java Province, Indonesia

<p>Abstract</p> <p>Background</p> <p>Antenatal, delivery and postnatal care services are amongst the recommended interventions aimed at preventing maternal and newborn deaths worldwide. West Java is one of the provinces of Java Island in Indonesia with a high proportion of home deliveries, a low attendance of four antenatal services and a low postnatal care uptake. This paper aims to explore community members' perspectives on antenatal and postnatal care services, including reasons for using or not using these services, the services received during antenatal and postnatal care, and cultural practices during antenatal and postnatal periods in Garut, Sukabumi and Ciamis districts of West Java province.</p> <p>Methods</p> <p>A qualitative study was conducted from March to July 2009 in six villages in three districts of West Java province. Twenty focus group discussions (FGDs) and 165 in-depth interviews were carried out involving a total of 295 respondents. The guidelines for FGDs and in-depth interviews included the topics of community experiences with antenatal and postnatal care services, reasons for not attending the services, and cultural practices during antenatal and postnatal periods.</p> <p>Results</p> <p>Our study found that the main reason women attended antenatal and postnatal care services was to ensure the safe health of both mother and infant. Financial difficulty emerged as the major issue among women who did not fulfil the minimum requirements of four antenatal care services or two postnatal care services within the first month after delivery. This was related to the cost of health services, transportation costs, or both. In remote areas, the limited availability of health services was also a problem, especially if the village midwife frequently travelled out of the village. The distances from health facilities, in addition to poor road conditions were major concerns, particularly for those living in remote areas. Lack of community awareness about the importance of these services was also found, as some community members perceived health services to be necessary only if obstetric complications occurred. The services of traditional birth attendants for antenatal, delivery, and postnatal care were widely used, and their roles in maternal and child care were considered vital by some community members.</p> <p>Conclusions</p> <p>It is important that public health strategies take into account the availability, affordability and accessibility of health services. Poverty alleviation strategies will help financially deprived communities to use antenatal and postnatal health services. This study also demonstrated the importance of health promotion programs for increasing community awareness about the necessity of antenatal and postnatal services.</p

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies.

Previous meta-analyses of intervention studies have come to different conclusions about effects of consumption of low-calorie sweeteners (LCS) on body weight. The present review included 60 articles reporting 88 parallel-groups and cross-over studies ≥1 week in duration that reported either body weight (BW), BMI and/or energy intake (EI) outcomes. Studies were analysed according to whether they compared (1) LCS with sugar, (2) LCS with water or nothing, or (3) LCS capsules with placebo capsules. Results showed an effect in favour of LCS vs sugar for BW (29 parallel-groups studies, 2267 participants: BW change, -1.06 kg, 95% CI -1.50 to -0.62, I2 = 51%), BMI and EI. Effect on BW change increased with 'dose' of sugar replaced by LCS, whereas there were no differences in study outcome as a function of duration of the intervention or participant blinding. Overall, results showed no difference in effects of LCS vs water/nothing for BW (11 parallel-groups studies, 1068 participants: BW change, 0.10 kg, 95% CI -0.87 to 1.07, I2 = 82%), BMI and EI; and inconsistent effects for LCS consumed in capsules (BW change: -0.28 kg, 95% CI -0.80 to 0.25, I2 = 0%; BMI change: 0.20 kg/m2, 95% CI 0.04 to 0.36, I2 = 0%). Occurrence of adverse events was not affected by the consumption of LCS. The studies available did not permit robust analysis of effects by LCS type. In summary, outcomes were not clearly affected when the treatments differed in sweetness, nor when LCS were consumed in capsules without tasting; however, when treatments differed in energy value (LCS vs sugar), there were consistent effects in favour of LCS. The evidence from human intervention studies supports the use of LCS in weight management, constrained primarily by the amount of added sugar that LCS can displace in the diet

Fundamental properties of the circadian clock in Drosophila melanogaster: A molecular, behavioral, and genetic analysis

Virtually all organisms exhibit rhythmic behaviors that occur with a period of approximately twenty four hours, about the length of a day. Circadian behaviors are the product of an endogenous biological clock. Circadian rhythms in Drosophila depend on the appropriate regulation of at least two genes, period (per) and timeless (tim). Levels of per and tim RNA cycle with the same phase, and the two proteins interact directly. In addition the two proteins inhibit their own transcription, thus generating a regulatory loop. Work described in this thesis (1) addresses the mechanisms that generate the feedback loop and (2) explains how the endogenous clock synchronizes to a light/dark cycle. The first part of the thesis describes the partial characterization of one conserved domain of per that participates in the per feedback loop. Deletion of this domain disrupts the expression of behavioral and molecular rhythms in Drosophila. The effects of this deletion on molecular rhythms suggest that the deletion perturbs PER\u27s ability to negatively regulate its own transcription, possibly by compromising PER\u27s ability to bind and repress a transcriptional activator. Feedback loops are a common mechanism used by many diverse organisms to generate circadian behaviors. Insights gained into the generation of the per feedback loop may suggest conserved mechanisms used to generate circadian behaviors in higher organisms as well. The second part of the thesis demonstrates that TIM mediates light-induced resetting of the circadian clock. TIM is degraded in response to light, and that this acute response resets the clock. Characterizing tim\u27s role in light resetting may advance our understanding of phototransduction and circadian clock function

Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by Light

AbstractCircadian behavioral rhythms in Drosophila depend on the appropriate regulation of at least two genes, period (per) and timeless (tim). Previous studies demonstrated that levels of PER and TIM RNA cycle with the same phase and that the PER and TIM proteins interact directly. Here we show the cyclic expression of TIM protein in adult heads and report that it lags behind peak levels of TIM RNA by several hours. We also show that nuclear expression of TIM depends upon the expression of PER protein. Finally, we report that the expression of TIM, but not PER, is rapidly reduced by light, suggesting that TIM mediates light-induced resetting of the circadian clock. Since both PER and TIM RNA are unaffected by light treatment, the effects of light on TIM appear to be posttranscriptional