Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission.

Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.This study was funded by the Mason Medical Research Trust, the Stanley Medical Research Institute, the GlaxoSmithKlein and the Pinsent Darwin funding.This is the final published version. It first appeared at http://www.nature.com/tp/journal/v5/n3/full/tp201526a.html

Developmental Defects of Enamel in Primary Teeth and Association with Early Life Course Events: A Study of 6--36 Month old Children in Manyara, Tanzania.

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).Focusing 6--36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child's early illness episodes and mothers' perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.22 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania

Field and Laboratory Responses of Male Leaf Roller Moths, Choristoneura rosaceana and Pandemis pyrusana, to Pheromone Concentrations in an Attracticide Paste Formulation

Male leafroller moths, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae) and Pandemis pyrusana (Kearfott), were evaluated for responses to a paste formulation loaded with a range of concentrations of the two species' pheromone blends and evaluated in a laboratory wind tunnel and in the field. Response criteria were flight, flight towards the pheromone source, and contact with the pheromone source for the wind tunnel assays, and capture of moths in traps for the field tests. In the wind tunnel and field, responses of males of both species to the paste generally increased as the pheromone concentration in the paste was increased. There was little response by either species to paste with less than 0.16% pheromone. The relationship between pheromone concentration and response for P. pyrusana was linear and for C. rosaceana was sinusoidal over the range of pheromone concentrations tested. These patterns were seen both in the wind tunnel and in the field. Initial release rates from the paste of (Z)-11-tetradecenyl acetate, the main component of the pheromone blends of both species was 3.6–3.8 ng/h. Inhibitory thresholds for responses were not reached for either species, using pheromone concentrations as high as 16%, in either the wind tunnel or the field. For both species, response of males to rubber septa with one mg pheromone loads was similar to the response to the paste with pheromone at concentrations greater than 3–4%. For C. rosaceana, rates of contact with the paste in the wind tunnel were statistically similar to rates of contact in response to conspecific females, with paste pheromone concentrations above 1.6%. Response rates for males of P. pyrusana were significantly lower to the paste than to conspecific females at all paste pheromone concentrations tested. Overall, the optimum pheromone concentration in the paste for moth attraction to contact was 3.2 % for C. rosaceana and 8% for P. pyrusana

A comparison of photographic, replication and direct clinical examination methods for detecting developmental defects of enamel

Different methods have been used for detecting developmental defects of enamel (DDE). This study aimed to compare photographic and replication methods with the direct clinical examination method for detecting DDE in children's permanent incisors

Life cycle assessment of the sweetness enhancer thaumatin (E957) produced from Thaumatococcus daniellii fruit foraged from West Africa: The SWEET project

Replacing added sugar with non-nutritive sweeteners and sweetness enhancers is of increasing interest due to the negative health effects of excess sugar consumption. Much has been done to understand health and safety of such sweetening additives, but little on their sustainability. This study, part of the Horizon 2020 SWEET project, presents results from the first life cycle assessment of the sweetness enhancer thaumatin, produced from Thaumatococcus daniellii fruit, from forests in West Africa and extracted in the United Kingdom. Thaumatin is used in formulations to increase perceived sweetness of added sugar, allowing some to be removed. Environmental impact is reported for multiple impact categories from the ReCiPe 2016 (H) method, focusing on global warming potential, land use, water consumption, and freshwater eutrophication. Impacts are expressed in terms of product mass and sweetness equivalence. Global warming potential for production of thaumatin is found to be 719.2 kgCO2-eq/kg. When thaumatin replaces 20% of added sugar, environmental impact for a given sweetness is found to reduce by an average of 19.4% across all impact categories. International transport is a major contributor to global warming potential, as is aril removal from the fruit to freshwater eutrophication and water use, and fruit foraging to land use. However, land use is identified as a key area of future research to improve uncertainty in the data. Results show that thaumatin can be used to reduce the environmental impact of providing sweet taste in food and beverage products

‘Nothing about us without us’ : disabled people determining their human rights through the UNCRPD

The human rights and fundamental freedoms of disabled persons are set out in the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). This paper firstly focuses on the importance of the involvement of disabled people at all levels of decision-making. The second part of the paper identifies those aspects of the UNCRPD that reflect the direct involvement of disabled people. Finally, it considers how human rights bodies can best build on this specific aspect of the UNCRPD in order to realize the potential of the Convention as a determining factor in affirming disabled people rights in an effective and meaningful manner.peer-reviewe

Environmental life cycle assessment of production of the high intensity sweetener steviol glycosides from Stevia rebaudiana leaf grown in Europe: The SWEET project

Purpose There is an increasing interest in the use of non-nutritive sweeteners to replace added sugar in food and beverage products for reasons of improving consumer health. Much work has been done to understand safety of sweeteners, but very little on sustainability. To address that gap, this study presents the results of a life cycle assessment (LCA) of production of rebaudioside A 60%, 95% pure (RA60) steviol glycoside mix from Stevia rebaudiana leaf grown in Europe. Methods An attributional cradle-to-factory-gate life cycle assessment was conducted on growing of stevia leaves and extraction of steviol glycosides in Europe. Primary data were used from a case study supply chain. Results are reported in impact categories from the ReCiPe 2016 (H) method, with focus given to global warming potential, freshwater eutrophication, water consumption, and land use. Impacts are expressed both in terms of production mass and sweetness equivalence, a common metric for understanding high intensity sweetener potency. Sweetness equivalence of RA60 is typically 200 to 300 times that of sugar. Comparison of environmental impact is made to sugar (sucrose) produced from both cane and beets. The research is part of the EU project SWEET (sweeteners and sweetness enhancers: impact on health, obesity, safety, and sustainability). Results and discussion Global warming potential for production of RA60 was found to be 20.25 kgCO2-eq/kgRA60 on a mass basis and 0.081 kgCO2-eq/kgSE on a sweetness equivalence basis. Field production of stevia leaves was found to be the main source of impact for most impact categories, and for all four focus categories. Extraction of the RA60 was the main source of impact for the others. Leaf processing and seedling propagation were minor contributors to life cycle impact. Removal of international transport from the supply chain reduced global warming potential by 18.8%. Compared with sugar on a sweetness equivalence basis, RA60 has approximately 5.7% to 10.2% the impact for global warming potential, 5.6% to 7.2% the impact for land use, and is lower across most other impact categories. Conclusion This is the first LCA of steviol glycoside mix RA60 produced from leaf in Europe. The results indicate that RA60 can be used to reduce environmental impact of providing a sweet taste by replacing sugar across all impact categories. However, it is important to note that specific formulations in which RA60 is used will have a bearing on the final environmental impact of any food or beverage products. For solid foods, this requires further research

An Iterative Jackknife Approach for Assessing Reliability and Power of fMRI Group Analyses

For functional magnetic resonance imaging (fMRI) group activation maps, so-called second-level random effect approaches are commonly used, which are intended to be generalizable to the population as a whole. However, reliability of a certain activation focus as a function of group composition or group size cannot directly be deduced from such maps. This question is of particular relevance when examining smaller groups (<20–27 subjects). The approach presented here tries to address this issue by iteratively excluding each subject from a group study and presenting the overlap of the resulting (reduced) second-level maps in a group percent overlap map. This allows to judge where activation is reliable even upon excluding one, two, or three (or more) subjects, thereby also demonstrating the inherent variability that is still present in second-level analyses. Moreover, when progressively decreasing group size, foci of activation will become smaller and/or disappear; hence, the group size at which a given activation disappears can be considered to reflect the power necessary to detect this particular activation. Systematically exploiting this effect allows to rank clusters according to their observable effect size. The approach is tested using different scenarios from a recent fMRI study (children performing a “dual-use” fMRI task, n = 39), and the implications of this approach are discussed

Improvement for detection of microcalcifications through clustering algorithms and artificial neural networks

A new method for detecting microcalcifications in regions of interest (ROIs) extracted from digitized mammograms is proposed. The top-hat transform is a technique based on mathematical morphology operations and, in this paper, is used to perform contrast enhancement of the mi-crocalcifications. To improve microcalcification detection, a novel image sub-segmentation approach based on the possibilistic fuzzy c-means algorithm is used. From the original ROIs, window-based features, such as the mean and standard deviation, were extracted; these features were used as an input vector in a classifier. The classifier is based on an artificial neural network to identify patterns belonging to microcalcifications and healthy tissue. Our results show that the proposed method is a good alternative for automatically detecting microcalcifications, because this stage is an important part of early breast cancer detectio