An orally available compound prevents deficits in memory caused by the Alzheimer amyloid-B oligomers.

Despite progress in defining a pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction. METHODS: Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic function and memory recall. RESULTS: Scyllo-inositol, but not its stereoisomer, chiro-inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human Abeta. Cerebroventricular injection into rats of the soluble Abeta oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo-inositol via the drinking water fully prevented oligomer-induced errors. INTERPRETATION: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity.

Long-term hydroclimatic change and interannual variability in water sources, Apex River (Iqaluit), Baffin Island, Nunavut

The eastern Canadian Arctic is home to Canada’s largest Indigenous population, which depends on local freshwater sources for drinking water. However, small watersheds have rarely been analyzed for long-term hydrologic response to changing climate. This study aims to address this issue by examining the Apex River, a small watershed with a long hydroclimatic record, near Iqaluit, Nunavut. Particular emphasis was placed on the long-term changes in climate and river discharge, and the seasonal variability of water sources between two snapshots in time, 1983 and 2013. Long-term hydrological data were obtained from gauge station 10UH002, operated by Environment and Climate Change Canada, and long-term meteorological data were acquired from Environment Canada–operated stations near Iqaluit Airport. Breakpoint analysis suggested that long-term mean annual surface air temperatures have increased since 1994. In contrast, no long-term total precipitation or annual discharge changes were observed. However, river flow initiation and cessation analyses of the Apex River flow season indicates that flow extended into the autumn since the 2000s. The 2013 flow season lasted 44 days longer than the 1983 flow season. Systematic river sampling was undertaken throughout the 2013 thaw season to determine contributing proportions of event (snowmelt or rainfall) and pre-event (baseflow) water to river runoff. Results from the stable isotope hydrograph separation for 2013 were compared to findings for 1983. Snow was the main source of water to the river during the snowmelt period in 1983 and 2013, however baseflow was still an important contributor. Although there was high similarity of water sources early in the season in 1983 and 2013, the two years differed during the autumn. In 2013 there was a high rainfall runoff response that was not present in 1983, suggesting high release of late-season sub-surface water storage and an increased sensitivity to late-season rainfall events in 2013. This research provides insights into the hydrologic response of the Apex River to long-term climatic change, and highlights the need for high-quality precipitation and discharge data for effective long-term hydrological assessment.

Los grandes sistemas de abastecimiento de agua en el litoral de Alicante

El litoral de Alicante ha sufrido grandes transformaciones territoriales desde las décadas de 1960 y 1970 a raíz de la actividad turística. Uno de los servicios que necesita esta actividad, entre otros, es el abastecimiento de agua potable. En este sentido, por su papel estratégico, el suministro de agua en alta es decisivo para abastecer a los municipios turístico-residenciales. El objetivo de este estudio es conocer y analizar los diferentes sistemas de abastecimiento de agua en alta en la costa de Alicante, sus características, infraestructuras, recursos hídricos disponibles y medidas de gestión llevados a cabo. Algunas de las conclusiones extraídas son el papel estratégico que ejercen en el territorio, especialmente con el agua, un recurso escaso y de vital importancia para la orla costera alicantina, sobre todo en los meses estivales.

Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats.

The extensive clinical experience of angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists as antihypertensive agents provide numerous examples of anecdotal evidence of improvements in cognition and mood. This study aimed to determine the effect of chronic treatment with the angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT(1) receptor antagonist, candesartan, on central neurotransmitter levels in the rat. Perindopril (1.0mg/kg/day) or candesartan (10mg/kg/day) was administered via the drinking water at for 1 week, while controls received water alone. At the end of treatment rats were sacrificed, brains removed and discrete regions dissected and analysed for noradrenaline, dopamine and its major metabolites, and serotonin content. As shown previously we found an increase in striatal dopamine levels after perindopril treatment, though this did not extend to the mesolimbic system with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and frontal cortex. Conversely, candesartan administration produced no change in dopamine, but significant decreases in both DOPAC and HVA in the striatum. In addition chronic candesartan infusion produced a significant increase in the levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin content. These results demonstrate that while angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists act as antihypertensives by affecting the renin-angiotensin system, they have divergent actions on brain neurochemistry.

Water requirements as a bottleneck in the reintroduction of European roe deer to the southern edge of its range

Success rates of reintroduction programs are low, often owing to a lack of knowledge of site-specific ecological requirements. A reintroduction program of European roe deer (Capreolus capreolus (L., 1758)) in a dry Mediterranean region in Israel provides an opportunity to study the bottleneck effect of water requirements on a mesic-adapted species. Four does were hand-reared and released in a 10 ha site consisting of an early succession scrubland and a mature oak forest. We measured daily energy expenditure (DEE) and water turnover (WTO) using the doubly labeled water technique during summer and winter. DEE was similar in the summer and winter, but there was a significant difference in WTO and in the source of gained water. In winter, WTO was 3.3 L/day, of which 67% was obtained from vegetation. In summer, WTO dropped to 2.1 L/day, of which only 20% was obtained from the diet and 76% was gained from drinking. When the water source was moved to a nonpreferred habitat, drinking frequency dropped significantly, but water consumption remained constant. In a dry Mediterranean environment, availability of free water is both a physiological contraint and a behavioral constraint for roe deer. This study demonstrates the importance of physiological and behavioral feasibility studies for reintroduction programs.

Presence of arsenic in agricultural products from arsenic-endemic areas and strategies to reduce arsenic intake in rural villages

About 100 million rural people in Asia are exposed to arsenic (As)-polluted drinking water and agricultural products. Total and inorganic arsenic (t-As and i-As) intake mainly depend on the quality of drinking and cooking waters, and amounts of seafood and rice consumed. The main problems occur in countries with poor water quality where the population depends on rice for their diet, and their t-As and i-As intake is high as a result of growing and cooking rice in contaminated water. Workable solutions to remove As from water and breeding rice cultivars with low As accumulation are being sought. In the meantime, simple recommendations for processing and cooking foods will help to reduce As intake. For instance, cooking using high volumes of As-free water may be a cheap way of reducing As exposure in rural populations. It is necessary to consider the effects of cooking and processing on t-As and i-As to obtain a realistic view of the risks associated with intake of As in Asendemic areas.

Habitat for Humanity: Calibrating Best Practice Against the MDGs

Poverty alleviation lies at the heart of contemporary international initiatives on development. The key to development is the creation of an environment in which people can develop their potential, leading productive, creative lives in accordance with their needs, interests and faith. This entails, on the one hand, protecting the vulnerable from things that threaten their survival, such as inadequate nutrition, disease, conflict, natural disasters and the impact of climate change, thereby enhancing the poor’s capabilities to develop resilience in difficult conditions. On the other hand, it also requires a means of empowering the poor to act on their own behalf, as individuals and communities, to secure access to resources and the basic necessities of life such as water, food, shelter, sanitation, health and education. ‘Development’, from this perspective, seeks to address the sources of human insecurity, working towards ‘freedom from want, freedom from fear’ in ways that empower the vulnerable as agents of development (not passive recipients of benefaction).

Recognition of the magnitude of the problems confronted by the poor and failure of past interventions to tackle basic issues of human security led the United Nations (UN) in September 2000 to set out a range of ambitious, but clearly defined, development goals to be achieved by 2015. These are known as the Millennium Development Goals (MDGs). The intention of the UN was to mobilise multilateral international organisations, non-governmental organisations and the wider international community to focus attention on fulfilling earlier promises to combat global poverty. This international framework for development prioritises: the eradication of extreme poverty and hunger; achieving universal primary education; promoting gender equality and empowering women; reducing child mortality; improving maternal health; combating HIV/AIDS, malaria and other diseases; ensuring environmental sustainability; and developing a global partnership for development. These goals have been mapped onto specific targets (18 in total) against which outcomes of associated development initiatives can be measured and the international community held to account. If the world achieves the MDGs, more than 500 million people will be lifted out of poverty. However, the challenges the goals represent are formidable. Interim reports on the initiative indicate a need to scale-up efforts and accelerate progress.
Only MDG 7, Target 11 explicitly identifies shelter as a priority, identifying the need to secure ‘by 2020 a significant improvement in the lives of at least 100 million slum dwellers’. This raises a question over how Habitat for Humanity’s commitment to tackling poverty housing fits within this broader international framework designed to allievate global poverty. From an analysis of HFH case studies, this report argues that the processes by which Habitat for Humanity tackles poverty housing directly engages with the agenda set by the MDGs. This should not be regarded as a beneficial by-product of the delivery of decent, affordable shelter, but rather understood in terms of the ways in which Habitat for Humanity has translated its mission and values into a participatory model that empowers individuals and communities to address the interdependencies between inadequate shelter and other sources of human insecurity. What housing can deliver is as important as what housing itself is.

Examples of the ways in which Habitat for Humanity projects engage with the MDG framework include the incorporation of sustainable livelihoods strategies, up-grading of basic infrastructure and promotion of models of good governance. This includes housing projects that have also offered training to young people in skills used in the construction industry, microfinanced loans for women to start up their own home-based businesses, and the provision of food gardens. These play an important role in lifting families out of poverty and ensuring the sustainability of HFH projects. Studies of the impact of improved shelter and security of livelihood upon family life and the welfare of children evidence higher rates of participation in education, more time dedicated to study and greater individual achievement. Habitat for Humanity projects also typically incorporate measures to up-grade the provision of basic sanitation facilities and supplies of safe, potable drinking water. These measures not only directly help reduce mortality rates (e.g. diarrheal diseases account for around 2 million deaths annually in children under 5), but also, when delivered through HFH project-related ‘community funds’, empower the poor to mobilise community resources, develop local leadership capacities and even secure de facto security of tenure from government authorities.

In the process of translating its mission and values into practical measures, HFH has developed a range of innovative practices that deliver much more than housing alone. The organisation’s participatory model enables both direct beneficiaries and the wider community to tackle the insecurities they face, unlocking latent skills and enterprise, building sustainable livelihood capabilities. HFH plays an important role as a catalyst for change, delivering through the vehicle of housing the means to address the primary causes of poverty itself. Its contribution to wider development priorities deserves better recognition. In calibrating the success of HFH projects in terms of units completed or renovated alone, the significance of the process by which HFH realises these outcomes is often not sufficiently acknowledged, both within the organisation and externally. As the case studies developed in the report illustrate, the methodologies Habitat for Humanity employs to address the issue of poverty housing within the developing world, place the organisation at the centre of a global strategic agenda to address the root causes of poverty through community empowerment and the transformation of structures of governance.

Given this, the global network of HFH affiliates constitutes a unique organisational framework to faciliate sharing resources, ideas and practical experience across a diverse range of cultural, political and institutional environments. This said, it is apparent that work needs to be done to better to faciliate the pooling of experience and lessons learnt from across its affiliates. Much is to be gained from learning from less successful projects, sharing innovative practices, identifying strategic partnerships with donors, other NGOs and CBOs, and engaging with the international development community on how housing fits within a broader agenda to alleviate poverty and promote good governance.

Mothers' antenatal depression and their children's antisocial outcomes

Interviews of 120 British adolescents and their parents (80% of a random sample of antenatal patients drawn from a representative urban population and followed longitudinally) revealed that 40 (33%) had been arrested and/or had a diagnosis of DSM-IV conduct disorder by 16 years of age; of those, 18 (45%) had committed violent acts. Depression in pregnancy significantly predicted violence in adolescence, even after controlling for the family environment, the child's later exposure to maternal depression, the mother's smoking and drinking during pregnancy, and parents' antisocial behavior. Mothers with a history of conduct problems were at elevated risk to become depressed in pregnancy, and the offspring of depressed women had a greater chance of becoming violent by age 16.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: The Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Objective: To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France.
Design: Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox's proportional hazards regression analysis.
Setting: One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse).
Participants: 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994.
Main outcome measures: Incident myocardial infarction and coronary death ("hard" coronary events), and incident angina pectoris.
Results: A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country.
Conclusions: Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.

Home curation versus teenage photography: Photo displays in the family home

In this paper we report an empirical study of the photographic portrayal of family members at home. Adopting a social psychological approach and focusing oil intergenerational power dynamics, our research explores the use of domestic photo displays in family representation. Parents and their teenagers from eight families in the south of England were interviewed at home about their interpretations of both stored and displayed photos within the home. Discussions centred on particular photographs found by the participants to portray self and family in different ways. The findings show that public displays of digital photos are still curated by mothers of the households, but with more difficulty and less control all with analogue photos. In addition, teenagers both contribute and comply with this curation within the home, whilst at the same time developing additional ways of presenting their families and themselves online that are 'unsupervised' by the curator. We highlight the conflict of interest that is at play within teen and parent practices and consider the challenges that this presents for supporting the representation of family through the design of photo display technology. (C) 2009 Elsevier Ltd. All rights reserved.

Japan’s Blair Witch: Restraint, Maturity, and Generic Canons in the British Critical Reception of Ring

This essay examines the British critical reception of the Japanese horror ? lm Ring. Critics claimed that Ring was representative of a non-graphic, suggestive tradition in horror, and used the ?lm rhetorically to present a sense of difference from teen horror ?lms such as Scream.

Monoclonal antibody development for acrylamide-adducted human haemoglobin; A biomarker of dietary acrylamide exposure

The spontaneous formation of the neurotoxic carcinogen acrylamide in a wide range of cooked foods has recently been discovered, leading to dietary exposure estimates of 30.8 mu g of acrylamide day(-1) for an average 77 kg human male. This is considerably higher than the European legal limit of acrylamide in drinking water, which is approximately 0.2 mu g of acrylamide person(-1) day(-1). A recent study of 62,573 women over 11.3 years has observed an increased risk of postmenopausal endometrial and ovarian cancer (but not breast cancer) with increasing dietary acrylamide intake, demonstrating significant risk to human health. As individual acrylamide exposure is affected by dietary habits, cooking methods, and cigarette consumption; accurate extrapolation from estimated dietary exposure is extremely difficult. Quantifying biomarkers of acrylamide exposure therefore remains the most effective means of rapidly determining individual exposure to acrylamide, and correlating exposure with lifestyle choices. Current methodologies for the analysis of blood biomarkers of acrylamide are focused on expensive, slower chromatographic techniques such as GC and LC coupled to mass spectrometry. This paper describes the first successful development of two monoclonal antibodies specific to acrylamide-adducted haemoglobin (IC50 of 94 ng ml(-1) and 198 ng ml(-1)), that are suitable for use in a high-throughput biomarker immunoassay to determine individual acrylamide exposure. Further development of acrylamide-haemoglobin standards with defined levels of acrylamide adduction will enable a fully quantitative assay, and allow sensitivity comparisons with alternative chromatographic methods of analysis. (C) 2008 Elsevier B.V. All rights reserved.

Vitamin C supplementation decreases insulin glycation and improves glucose homeostasis in obese hyperglycemic (ob/ob) mice

The effects of dietary vitamin C supplementation on glucose homeostasis and insulin glycation were examined in adult lean and obese hyperglycemic (ob/ob) mice. In lean mice, supplementation of the drinking water with vitamin C (25 g/L) for 14 days did not affect food intake, fluid intake, glycated hemoglobin, plasma glucose, or plasma insulin concentrations. Total pancreatic insulin content and the percentage of glycated pancreatic insulin were also similar to control lean mice. In ob/ob mice, vitamin C supplementation caused significant reductions by 26% to 48% in food intake and fluid intake, glycated hemoglobin, plasma glucose, and insulin concentrations compared with untreated control ob/ob mice. The total insulin content and the extent of insulin glycation in the pancreas of ob/ob mice were also significantly decreased by 42% to 45% after vitamin C supplementation. This change was accompanied by a significant 80% decrease in the percentage of glycated insulin in the circulation of vitamin C- supplemented ob/ob mice. These data demonstrate that vitamin C supplementation can decrease insulin glycation and ameliorate aspects of the obesity-diabetes syndrome in ob/ob mice. Copyright 2002, Elsevier Science (USA). All rights reserved.

The extent and nature of family alcohol and drug use: Findings from the Belfast Youth Development Study

Using data from an ongoing longitudinal study of adolescent drug use, this study examines the proportion of teenagers living with parents who are problem alcohol or drug users. Around two percent of parents report high levels of problem drinking and one per cent report problem drug use. If a broader definition of hazardous drinking is used, the proportion of teenagers exposed increases to over 15 per cent. When substance use is examined at a family level (taking account of alcohol and drug use amongst dependent children in addition to that of parents), the proportion of families experiencing some form of substance use is considerable. These findings add further support to the call for increased recognition of the needs of dependent children within adult treatment services when working with parents. Likewise, the reduction of harm to children as a result of parent substance use should be an increasingly important priority for family support services. This is likely to be achieved through the closer integration of addiction and family services.

The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes

We examined the ability of pyridoxamine (PM), an inhibitor of formation of advanced glycation end products (AGEs) and lipoxidation end products (ALEs), to protect against diabetes-induced retinal vascular lesions. The effects of PM were compared with the antioxidants vitamin E (VE) and R-alpha-lipoic acid (LA) in streptozotocin-induced diabetic rats. Animals were given either PM (1 g/l drinking water), VE (2,000 IU/kg diet), or LA (0.05%/kg diet). After 29 weeks of diabetes, retinas were examined for pathogenic changes, alterations in extracellular matrix (ECM) gene expression, and accumulation of the immunoreactive AGE/ALE N-epsilon-(carboxymethyl)lysine (CML). Acellular capillaries were increased more than threefold, accompanied by significant upregulation of laminin immunoreactivity in the retinal microvasculature. Diabetes also increased mRNA expression for fibronectin (2-fold), collagen IV (1.6-fold), and laminin beta chain (2.6-fold) in untreated diabetic rats compared with nondiabetic rats. PM treatment protected against capillary drop-out and limited laminin protein upregulation and ECM mRNA expression and the increase in CML in the retinal vasculature. VE and LA failed to protect against retinal capillary closure and had inconsistent effects on diabetes-related upregulation of ECM mRNAs. These results indicate that the AGE/ALE inhibitor PM protected against a range of pathological changes in the diabetic retina and may be useful for treating diabetic retinopathy.