Gridded birth and pregnancy datasets for Africa, Latin America and the Caribbean.

Understanding the fine scale spatial distribution of births and pregnancies is crucial for informing planning decisions related to public health. This is especially important in lower income countries where infectious disease is a major concern for pregnant women and new-borns, as highlighted by the recent Zika virus epidemic. Despite this, the spatial detail of basic data on the numbers and distribution of births and pregnancies is often of a coarse resolution and difficult to obtain, with no co-ordination between countries and organisations to create one consistent set of subnational estimates. To begin to address this issue, under the framework of the WorldPop program, an open access archive of high resolution gridded birth and pregnancy distribution datasets for all African, Latin America and Caribbean countries has been created. Datasets were produced using the most recent and finest level census and official population estimate data available and are at a resolution of 30 arc seconds (approximately 1 km at the equator). All products are available through WorldPop.

Exploring the high-resolution mapping of gender-disaggregated development indicators.

Improved understanding of geographical variation and inequity in health status, wealth and access to resources within countries is increasingly being recognized as central to meeting development goals. Development and health indicators assessed at national or subnational scale can often conceal important inequities, with the rural poor often least well represented. The ability to target limited resources is fundamental, especially in an international context where funding for health and development comes under pressure. This has recently prompted the exploration of the potential of spatial interpolation methods based on geolocated clusters from national household survey data for the high-resolution mapping of features such as population age structures, vaccination coverage and access to sanitation. It remains unclear, however, how predictable these different factors are across different settings, variables and between demographic groups. Here we test the accuracy of spatial interpolation methods in producing gender-disaggregated high-resolution maps of the rates of literacy, stunting and the use of modern contraceptive methods from a combination of geolocated demographic and health surveys cluster data and geospatial covariates. Bayesian geostatistical and machine learning modelling methods were tested across four low-income countries and varying gridded environmental and socio-economic covariate datasets to build 1×1 km spatial resolution maps with uncertainty estimates. Results show the potential of the approach in producing high-resolution maps of key gender-disaggregated socio-economic indicators, with explained variance through cross-validation being as high as 74-75% for female literacy in Nigeria and Kenya, and in the 50-70% range for many other variables. However, substantial variations by both country and variable were seen, with many variables showing poor mapping accuracies in the range of 2-30% explained variance using both geostatistical and machine learning approaches. The analyses offer a robust basis for the construction of timely maps with levels of detail that support geographically stratified decision-making and the monitoring of progress towards development goals. However, the great variability in results between countries and variables highlights the challenges in applying these interpolation methods universally across multiple countries, and the importance of validation and quantifying uncertainty if this is undertaken.

Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT (1A) receptor antagonist and potential novel antidepressant.

BACKGROUND AND PURPOSE: As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT(1A) receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT(1A) receptor antagonist activities, was evaluated in preclinical models. EXPERIMENTAL APPROACH: Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models. KEY RESULTS: WAY-211612 inhibited 5-HT reuptake (K(i) = 1.5 nmol.L(-1); K(B) = 17.7 nmol.L(-1)) and exhibited full 5-HT(1A) receptor antagonist activity (K(i) = 1.2 nmol.L(-1); K(B) = 6.3 nmol.L(-1); I(max) 100% in adenyl cyclase assays; K(B) = 19.8 nmol.L(-1); I(max) 100% in GTPgammaS). WAY-211612 (3 and 30 mg.kg(-1), po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT(1A) receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3-30 mg.kg(-1), po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg.kg(-1), s.c.) and a 5-HT(1A) antagonist (WAY-100635; 0.3 mg.kg(-1), s.c). WAY-211612 (3.3-30 mg.kg(-1), s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3-30 mg.kg(-1), i.p. and 10-56 mg.kg(-1), po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg.kg(-1), i.p.) in the rat scheduled-induced polydipsia model. CONCLUSIONS AND IMPLICATIONS: These findings suggest that WAY-211612 may represent a novel antidepressant.

Three generations of automatically designed robots.

The difficulties associated with designing, building, and controlling robots have led their development to a stasis: Applications are limited mostly to repetitive tasks with predefined behavior. Over the last few years we have been trying to address this challenge through an alternative approach: Rather than trying to control an existing machine or create a general-purpose robot, we propose that both the morphology and the controller should evolve at the same time. This process can lead to the automatic design of special-purpose mechanisms and controllers for specific short-term objectives. Here we provide a brief review of three generations of our recent research, which underlies the robots shown on the cover of this issue: Automatically designed static structures, automatically designed and manufactured dynamic electromechanical systems, and modular robots automatically designed through a generative DNA-like encoding.

Probing the ligand-binding domain of the mGluR4 subtype of metabotropic glutamate receptor.

Metabotropic glutamate receptors (mGluRs) are G-protein-coupled glutamate receptors that subserve a number of diverse functions in the central nervous system. The large extracellular amino-terminal domains (ATDs) of mGluRs are homologous to the periplasmic binding proteins in bacteria. In this study, a region in the ATD of the mGluR4 subtype of mGluR postulated to contain the ligand-binding pocket was explored by site-directed mutagenesis using a molecular model of the tertiary structure of the ATD as a guiding tool. Although the conversion of Arg(78), Ser(159), or Thr(182) to Ala did not affect the level of protein expression or cell-surface expression, all three mutations severely impaired the ability of the receptor to bind the agonist L-[(3)H]amino-4-phosphonobutyric acid. Mutation of other residues within or in close proximity to the proposed binding pocket produced either no effect (Ser(157) and Ser(160)) or a relatively modest effect (Ser(181)) on ligand affinity compared with the Arg(78), Ser(159), and Thr(182) mutations. Based on these experimental findings, together with information obtained from the model in which the glutamate analog L-serine O-phosphate (L-SOP) was "docked" into the binding pocket, we suggest that the hydroxyl groups on the side chains of Ser(159) and Thr(182) of mGluR4 form hydrogen bonds with the alpha-carboxyl and alpha-amino groups on L-SOP, respectively, whereas Arg(78) forms an electrostatic interaction with the acidic side chains of L-SOP or glutamate. The conservation of Arg(78), Ser(159), and Thr(182) in all members of the mGluR family indicates that these amino acids may be fundamental recognition motifs for the binding of agonists to this class of receptors.

Establishing a Parent to Parent service.

A Parent to Parent service has been established in Auckland to provide assistance to parents of children with disabilities. Parents who themselves have children with special needs undergo training to prepare them to support other parents. The Auckland scheme is a telephone counselling service which has been set up through cooperation between parents and professionals in the field of special education. Steps in the establishment of the scheme are described, the training course is outlined and various issues regarding the scheme are discussed. After 3 years of operation the Auckland Parent to Parent Service is well established and has developed a model of operation which has been used to set up similar schemes in various other centres around New Zealand. It is intended that this article be of assistance to other groups considering setting up Parent to Parent schemes.

Behavioural group training with parents of mentally retarded children.

Seven parents of moderately mentally retarded children participated in a behavioural group training programme. Parents were taught to apply behavioural procedures to the specific problems presented by their children. A pre-test and post-test experimental design was used. A battery of outcome measures was employed, including observations of the parent-child interaction in the home environment. Although the results were somewhat mixed, in general the parents indicated that the programme was helpful and improved their knowledge of behavioural principles. Some positive changes in parent-child interaction at home were also observed.

Group training for parents of mentally retarded children: a review and methodological analysis of behavioural studies.

Behavioural group training studies with parents of mentally retarded children were reviewed, with a special emphasis on methodology. While all studies reported favourable training outcome, the lack of certain methodological controls demands that the results of these studies be interpreted with caution. Several methodological refinements are proposed in this paper and it is suggested that the group training modality offers a more economical and practical approach than individual parent training.

Group programmes for parents of children with various handicaps.

Programmes were conducted with groups of parents of school-aged, physically handicapped, hearing impaired, and, mildly and moderately mentally handicapped children. In this paper the salient features of the organization of these parent programmes are discussed. Programmes have involved six to eight weekly 2 hour sessions. The format of each session included both lecture presentation and discussion in small groups. Discussions were led by educational psychologists using a combination of reflective and behavioural procedures. Evaluation, by means of post-programme questionnaires and attendance checks, has shown that parents have found programmes to be valuable. An integral part of the parent programmes has been the training of special education teachers in the attitudes and skills necessary for working with parents of handicapped children. The introduction of group programmes is considered to complement the individual training and counselling services already available to such parents in New Zealand.