The effect of cleft lip on cognitive development in school-aged children: a paradigm for examining sensitive period effects

Background:  Our previous investigation showed that infants with cleft lip who had undergone late (three-month) surgical repair (but not those with early, neonatal, repair) had significantly poorer cognitive development at 18 months than a group of unaffected control children. These differences were mediated by the quality of early mother–infant interactions. The present study examined whether this pattern persisted into later childhood. Method:  At 7 years, 93 index (44 early, and 49 late repair) and 77 control children were followed up and their cognitive development assessed (IQ, language and school achievements). Results:  Index children (particularly those with late lip repair) scored significantly lower than controls on tests of cognitive development. Group differences in Verbal IQ were mediated by 2 months’ maternal sensitivity; this was associated with 7-year Verbal IQ, even after controlling for later mother–child interactions. Conclusions:  Social interactions in the first few months may be of especial importance for child cognitive development. Interventions for infants with cleft lip should be directed at fostering the best possible parental care in infancy.

Reforming the CDM for sustainable development: lessons learned and policy futures

The Clean Development Mechanism (CDM) has successfully demonstrated that market-based mechanisms can achieve some cost effective emissions reductions in developing countries. However the distribution of CDM projects has been extremely uneven across countries and regions, and a few technologies and sectors have dominated the early stages of CDM experience. This has caused some to question whether the CDM has fallen short of its potential in contributing to sustainable development. We review the broad patterns of CDM project approvals and evaluate 10 CDM projects according to their sustainability benefits. The difficulty of defining “sustainable development” and the process of defining criteria by individual non-Annex 1 governments has meant that sustainable development concerns have been marginalized in some countries. Given these observed limitations, we present possible CDM policy futures, focusing on the main proposals for a post-2012 climate regime. Five options for enhancing the sustainable development benefits in the CDM are discussed, including proactive approaches to favour eligibility of emission reduction projects which ensure such co-benefits.

The longitudinal development of emotion regulation capacities in children at risk for externalizing disorders

The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating: a) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms; and b) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation. Families experiencing high (n=58) and low (n=63) levels of psychosocial adversity were recruited to the study during pregnancy. Direct observational assessments of child emotion regulation capacities and maternal sensitivity were completed in early infancy, at 12 and 18-months, and at 5-years. Key findings were as follows. First, high risk children showed poorer emotion regulation capacities than their low risk counterparts at every stage of assessment. Second, from 12-months onwards, emotion regulation capacities showed a degree of stability, and were associated with behavioral problems, both concurrently and prospectively. Third, maternal sensitivity was related to child emotion regulation capacities throughout development, with poorer emotion regulation in the high risk group being associated with lower maternal sensitivity. The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology, and highlight insensitive parenting as a potentially key developmental influence.

Assessment of cognitive symptoms in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess cognitive symptoms in prHD and early HD individuals.

Assessment of day-to-day functioning in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact in day-to-day activities in prHD and early HD individuals.

Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess Depression, Anxiety and Apathy in prHD and early HD individuals.

Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI-MS peaks

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.

Indian summer monsoon variations could have affected the early Holocene woodland expansion in the Near East

Postglacial expansion of deciduous oak woodlands of the Zagros—Anti-Taurus Mountains, a major biome of the Near East, was delayed until the middle Holocene at ~6300 cal. yr BP. The current hypotheses explain this delay as a consequence of a regional aridity during the early Holocene, slow migration rates of forest trees, and/or a long history of land use and agro-pastoralism in this region. In the present paper, support is given to a hypothesis that suggests different precipitation seasonalities during the early Holocene compared with the late Holocene. The oak species of the Zagros—Anti-Taurus Mts, particularly Quercus brantii Lindl., are strongly dependent on spring precipitation for regeneration and are sensitive to a long dry season. Detailed analysis of modern atmospheric circulation patterns in SW Asia during the late spring suggests that the Indian Summer Monsoon (ISM) intensification can modify the amount of late spring and/or early summer rainfall in western/northwestern Iran and eastern Anatolia, which could in turn have controlled the development of the Zagros—Anti-Taurus deciduous oak woodlands. During the early Holocene, the northwestward shift of the Inter-Tropical Convergence Zone (ITCZ) could have displaced the subtropical anticyclonic belt or associated high pressure ridges to the northwest. The latter could, in turn, have prevented the southeastward penetration of low pressure systems originating from the North Atlantic and Black Sea regions. Such atmospheric configuration could have reduced or eliminated the spring precipitation creating a typical Mediterranean continental climate characterized by winter-dominated precipitation. This scenario highlights the complexity of biome response to climate system interactions in transitional climatic and biogeographical regions.

Quantifying the relationship between temperature regulation in the ear and floret development stage in wheat (Triticum aestivum L.) under heat and drought stress

Thermal imaging is a valuable tool for the elucidation of gas exchange dynamics between a plant and its environment. The presence of stomata in wheat glumes and awns offers an opportunity to assess photosynthetic activity of ears up to and during flowering. The knowledge of spatial and temporal thermodynamics of the wheat ear may provide insight into interactions between floret developmental stage (FDS), temperature depression (TD) and ambient environment, with potential to be used as a high-throughput screening tool for breeders. A controlled environment study was conducted using six spring wheat (Triticum aestivum L.) genotypes of the elite recombinant inbred line Seri/Babax. Average ear temperature (AET) was recorded using a hand held infrared camera and gas exchange was measured by enclosing ears in a custom built cuvette. FDS was monitored and recorded daily throughout the study. Plants were grown in pots and exposed to a combination of two temperature and two water regimes. In the examined wheat lines, TD varied from 0.1°C to 0.6°C according to the level of stress imposed. The results indicated that TD does not occur at FDS F3, the peak of active flowering, but during the preceding stages prior to pollen release and stigma maturity (F1-F2). These findings suggest that ear temperature during the early stages of anthesis, prior to pollen release and full extension of the stigma, are likely to be the most relevant for identifying heat stress tolerant genotypes.

The central European floods of August 2002: Part 1 - Rainfall periods and flood development

Record-breaking rainfall amounts and intensities were observed at several raingauges in central Europe during the first half of August 2002 (Fig. 1). They produced flash floods in small rivers in the Erz Mountains, the Bohemian Forest and in Lower Austria (see Fig. 2), followed by record-breaking floods of larger rivers fed from these areas. The Vltava submerged parts of the city of Prague on 13± 15 August, and subsequently the Elbe flooded parts of Dresden and further villages and towns located downstream. The gauge level of 9.40m measured at Dresden on 17 August 2002 is the highest level since 1275, exceeding the former maximum level of 8.77m recorded in 1845 (Grollmann and Simon 2002). Parts of the Danube catchment were also affected by severe flooding. There were 100 fatalities connected with the floods in central Europe, and the economic loss is estimated at 9 billion Euros for Germany (German government’s estimate), 3 billion Euros for Austria, and 2.5 billion Euros for the Czech Republic (estimates from Boyle 2002). The event thus replaced the European winter storm Lothar of December 1999 (Ulbrich et al. 2001) as the most expensive weather-related catastrophe in Europe in recent decades (see Cornford 2002). In this study, we give an overview of the exceptional rainfall experienced over wide areas on 12/13 August 2002, and the resulting floods. Further events during early August 2002, in particular the event on 6/7 August in Lower Austria, are briefly mentioned.

Direct experimental evidence that early-life farm environment influences regulation of immune responses

Background: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. Methods: Piglets were nursed by their mother on a commercial farm, while isolatorreared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. Results: There was more CD4+ and CD4+CD25+ effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4+CD25+Foxp3+ regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. Conclusion: Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.

Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

Building climate resilience: lessons of early warning in Africa

Given the high levels of uncertainty and substantial variability in local weather and climate, what constitutes successful adaptation for the 800 million food-insecure people in Africa? In this context there is a need for building climate resilience through effective early warning systems, bringing real-time monitoring and decision-making together with stakeholders. The chapter presents two effective operational early warning systems in Africa: The Radio and Internet (RANET) network and the Rainwatch project. These examples were developed in partnership with local climate scientists and tailored to local development needs, enabled and encouraged with only modest international support. They deliver important lessons about how to prepare for crises using simple real-time monitoring. They also help us identify characteristics of managing for resilience in practice. The chapter concludes that successful adaptation requires adaptive, flexible, linked institutions, together with ground-based collaboration and practical tools. In the context of early warning three features stand out that make these systems successful: effective communication of current weather and climate information, a key individual within a bridging organization with the ability to navigate the governance systems, and sufficient time for innovation development.

Precision placement of fertiliser for optimising the early nutrition of vegetable crops: a review of the implications for the yield and quality of crops, and their nutrient use efficiency

The research outlined in this paper highlights the importance of the early nutrition of vegetable crops, and its long-term effects on their subsequent growth and development. Results are also presented to demonstrate how the nutrient supply during the establishment stages of young seedlings and transplants can be enhanced by targeting fertiliser to a zone close to their developing roots. Three different precision fertiliser placement techniques are compared for this purpose: starter, band or side-injected fertiliser. The use of each of these methods consistently produced the same (or greater) yields at lower application rates than those from conventional broadcast applications, increasing the apparent recovery of N, P and K, and the overall efficiency of nutrient use, while reducing the levels of residual nutrients in the soil. Starter fertilisers also advanced the maturity of some crops, and enhanced produce quality by increasing the proportions of the larger and/or more desirable marketable grades. The benefits of the different placement techniques are illustrated with selected examples from research at Warwick HRI using different vegetable crops, including lettuce, onion and carrot.