A difficult case. Childhood onset insulin dependent diabetes presenting with severe hyperlipidaemia.

Confronted with a child deteriorating during treatment of diabetic ketoacidosis, Godfrey Nyamugunduru and Helen Roper describe how the child''s management was complicated by gross hyperlipidaemia. At the point where the child''s condition was deteriorating despite conventional management we invited two experts-Gilbert R Thompson and J I Mann-to suggest a course of action. The original authors then describe how they did manage the case, and our experts comment again.     

How do disordered regions achieve comparable functions to structured domains?

The traditional structure to function paradigm conceives of a protein''s function as emerging from its structure. In recent years, it has been established that unstructured, intrinsically disordered regions (IDRs) in proteins are equally crucial elements for protein function, regulation and homeostasis. In this review, we provide a brief overview of how IDRs can perform similar functions to structured proteins, focusing especially on the formation of protein complexes and assemblies and the mediation of regulated conformational changes. In addition to highlighting instances of such functional equivalence, we explain how differences in the biological and physicochemical properties of IDRs allow them to expand the functional and regulatory repertoire of proteins. We also discuss studies that provide insights into how mutations within functional regions of IDRs can lead to human diseases.     

The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks

Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely been studied as a cause. Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person. Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads, how drug use behavior spreads, and how a friend''s sleep behavior influences one''s own drug use. We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation (to one''s friends'' friends'' friends'' friends) in the social network. Prospective regression models show that being central in the network negatively influences future sleep outcomes, but not vice versa. Moreover, if a friend sleeps ≤7 hours, it increases the likelihood a person sleeps ≤7 hours by 11%. If a friend uses marijuana, it increases the likelihood of marijuana use by 110%. Finally, the likelihood that an individual uses drugs increases by 19% when a friend sleeps ≤7 hours, and a mediation analysis shows that 20% of this effect results from the spread of sleep behavior from one person to another. This is the first study to suggest that the spread of one behavior in social networks influences the spread of another. The results indicate that interventions should focus on healthy sleep to prevent drug use and targeting specific individuals may improve outcomes across the entire social network.     

Causal mediation analysis in nested case-control studies using conditional logistic regression

The paper proposes an approach to causal mediation analysis in nested case-control study designs, often incorporated with countermatching schemes using conditional likelihood, and we compare the method's performance to that of mediation analysis using the Cox model for the full cohort with a continuous or dichotomous mediator. Simulation studies are conducted to assess our proposed method and investigate the efficiency relative to the cohort. We illustrate the method using actual data from two studies of potential mediation of radiation risk conducted within the Adult Health Study cohort of atomic-bomb survivors. The performance becomes comparable to that based on the full cohort, illustrating the potential for valid mediation analysis based on the reduced data obtained through the nested case-control design.     

Population differences in spatial learning in three-spined sticklebacks

In a changing environment, learning and memory are essential for an animal''s survival and reproduction. The role played by the environment in shaping learning and memory is now attracting considerable attention. Until now, studies have tended to compare the behaviour of two, or at best a few species but interspecific comparisons can be misleading as many life history variables other than environment may differ between species. Here we report on an experiment designed to determine how learning varies between different populations of the same species, the three-spined stickleback. We found differences between the populations in their ability to solve a spatial task and also in the spatial strategies they used. A second simple learning task showed that these differences were not the result of gross differences in learning ability or adaptation to laboratory conditions. We discuss these results and suggest that the behavioural differences may relate to features of the respective habitats from which the fish were sampled.     

A knowledge-based system for discovering ecological interactions in biodiversity data-stores of heterogeneous specimen-records: A case-study of flower-visiting ecology

We modeled expert knowledge of arthropod flower-visiting behavioral ecology and represented this in an event-centric domain ontology, which we describe along with the ontology construction process. Two smaller domain ontologies were created to represent expert knowledge of known flower-visiting insect groups and expert knowledge of the flower-visiting behavioral ecology of Rediviva bees. Two application ontologies were designed, which, together with the domain ontologies, constituted the ontology framework of a prototype semantic enrichment and mediation system that we designed and implemented to improve semantic interoperability between flower-visiting data-stores. We describe and evaluate the system implementation in a case-study of three flower-visiting data-stores, and we discuss the system's scalability, extension and potential impact. We demonstrate how the system is able to dynamically extract complex ecological interactions from heterogeneous specimen data-stores. The conceptual stance and modeling approach are potentially of general use in representing knowledge of animal behavior and ecological interactions, and in engineering semantic interoperability between data-stores containing behavioral ecology data.     

Granger mediation analysis of multiple time series with an application to functional magnetic resonance imaging

This paper presents Granger mediation analysis, a new framework for causal mediation analysis of multiple time series. This framework is motivated by a functional magnetic resonance imaging (fMRI) experiment where we are interested in estimating the mediation effects between a randomized stimulus time series and brain activity time series from two brain regions. The independent observation assumption is thus unrealistic for this type of time‐series data. To address this challenge, our framework integrates two types of models: causal mediation analysis across the mediation variables, and vector autoregressive (VAR) models across the temporal observations. We use “Granger” to refer to VAR correlations modeled in this paper. We further extend this framework to handle multilevel data, in order to model individual variability and correlated errors between the mediator and the outcome variables. Using Rubin's potential outcome framework, we show that the causal mediation effects are identifiable under our time‐series model. We further develop computationally efficient algorithms to maximize our likelihood‐based estimation criteria. Simulation studies show that our method reduces the estimation bias and improves statistical power, compared with existing approaches. On a real fMRI data set, our approach quantifies the causal effects through a brain pathway, while capturing the dynamic dependence between two brain regions.     

Besonderheiten bei der Ermittlung der Primärproduktion in der Elbe aus Sauerstoff-Ganglinien. Some Particularities in Estimating Primary Productivity in the River Elbe Using Oxygen Time Curves

The phytoplanktonic primary production was estimated in the River Elbe (average flow 325 m³/s) by ODUM 's twin and single curve analysis of changes in the oxygen content (1- and 2- SGA). The results were affected by the severe and varying waste water load and the non-uniform conditions along the upstream river stretch. It is shown how the gross primary productivity was corrected by using the photosynthesis-light-relationship. At favourable measuring sites, single curve analysis gives similar values as ODUM 's twin curve method. But they scatter more when applied to establish the photsynthesis-light-relationship.     

The Links Between Parent Behaviors and Boys' and Girls' Science Achievement Beliefs

This study examined whether parental involvement in children's science schoolwork (i.e., discussions about science, homework helping and encouragement of science interest) varies for boys and girls, and how these behaviors relate to children's science achievement beliefs (i.e., ability perceptions and task-value) at the end of a school year. We analyzed these links both for fathers and mothers and examined whether child gender moderates how parental behaviors relate to children's beliefs over time. Data were gathered over a span of a school year from 114 middle-school students (50% girls, 81% European American) and their parents (mothers: n = 103, fathers: n = 90). We found support for the moderating effect of gender. Specifically, the findings indicated that only parents' encouragement of science interest varied by child gender; mothers' encouragement positively predicted girls' self-assessments of science ability at the end of the year, but was a negative estimator of boys' self-assessments. Additionally, mothers' discussions about science showed similar findings with respect to girls' and boys' utility beliefs about science.     

When Domestic Environmental Policy Meets International Trade Policy: Venezuela's Challenge to the U.S. Gasoline Rule

The role of the World Trade Organization (WTO) in the setting and enforcement of international and domestic environmental policy continues to evolve. This paper reviews the first case that focused clearly on environmental issues that involved WTO mediation: the case of Venezuela's challenge of the legality of United States restrictions on the importation of gasoline based on requirements to reduce health risks under the Clean Air Act. In this case, the WTO deemed the U.S. Environmental Protection Agency's policy as a barrier to free trade and this has important implications for future policies. We explore the underlying issues of the decision and its implications for future cases that focus on environmental risks.     

Deletion of RAGE Causes Hyperactivity and Increased Sensitivity to Auditory Stimuli in Mice

The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor that belongs to the immunoglobulin superfamily of cell surface receptors. In diabetes and Alzheimer''s disease, pathological progression is accelerated by activation of RAGE. However, how RAGE influences gross behavioral activity patterns in basal condition has not been addressed to date. In search for a functional role of RAGE in normal mice, a series of standard behavioral tests were performed on adult RAGE knockout (KO) mice. We observed a solid increase of home cage activity in RAGE KO. In addition, auditory startle response assessment resulted in a higher sensitivity to auditory signal and increased prepulse inhibition in KO mice. There were no significant differences between KO and wild types in behavioral tests for spatial memory and anxiety, as tested by Morris water maze, classical fear conditioning, and elevated plus maze. Our results raise a possibility that systemic therapeutic treatments to occlude RAGE activation may have adverse effects on general activity levels or sensitivity to auditory stimuli.     

Psychological Implications of Cystic Fibrosis

A psychological and psychiatric study of 11 children with cystic fibrosis revealed major psychological problems in all of them. Among the parents of the majority of these children, marked psychopathology and gross marital discord were noted. Popular literature concerning cystic fibrosis had a negative effect on the child''s attitude toward the disease. Virtually all of these patients showed a preoccupation with death. In this study, the necessity of psychiatric consultation as an integral part of current intensive treatment programs in cystic fibrosis clinics was demonstrated.     

Jural relations of middle‐class marriage and women as legal subjects in the imaginary of ‘new India’

In India's capital New Delhi, four Family Courts were set up between 2009 and 2012, and 12 mediation institutions known as Crime Against Women Cells (CAW cells) were established during the same period. The Indian state has also endorsed gender‐equalising family legislation, mutual‐consent divorce and introduced new language of and for mediation. Together with India's projection of a rising global economy, these recent legal changes have engendered perceptions of a dramatic upturn in formal divorce and of women as liberal legal subjects. In the anthropology of Asia, marital practices have crucially informed our comprehension of modernisation, family formations and moral panics. This article explores the impact of new forms of legal availability on marriage, family and kinship among the metropolitan middle classes. It ethnographically engages with important structural shifts reflected in the intimate lives of Hindu couples, but also foregrounds a cautious narrative of newly imagined jural relations.     

Potential Mechanisms for Imperfect Synchronization in Parkinsonian Basal Ganglia

Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe) neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Earlier studies showed how the strengthening of dopamine-modulated coupling may lead to transitions from non-synchronized to partially synchronized dynamics, typical in Parkinson''s disease. However, dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson''s disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson''s disease.     

Carbon budgets of wetland ecosystems in China

Wetlands contain a large proportion of carbon (C) in the biosphere and partly affect climate by regulating C cycles of terrestrial ecosystems. China contains Asia's largest wetlands, accounting for about 10% of the global wetland area. Although previous studies attempted to estimate C budget in China's wetlands, uncertainties remain. We conducted a synthesis to estimate C uptake and emission of wetland ecosystems in China using a dataset compiled from published literature. The dataset comprised 193 studies, including 370 sites representing coastal, river, lake and marsh wetlands across China. In addition, C stocks of different wetlands in China were estimated using unbiased data from the China Second Wetlands Survey. The results showed that China's wetlands sequestered 16.87 Pg C (315.76 Mg C/ha), accounting for about 3.8% of C stocks in global wetlands. Net ecosystem productivity, jointly determined by gross primary productivity and ecosystem respiration, exhibited annual C sequestration of 120.23 Tg C. China's wetlands had a total gaseous C loss of 173.20 Tg C per year from soils, including 154.26 Tg CO₂‐C and 18.94 Tg CH₄‐C emissions. Moreover, C stocks, uptakes and gaseous losses varied with wetland types, and were affected by geographic location and climatic factors (precipitation and temperature). Our results provide better estimation of the C budget in China's wetlands and improve understanding of their contribution to the global C cycle in the context of global climate change.     

α1-肾上腺素受体介导交感神经对机体调节及针灸效应的研究情况分析

为明确近30年α_1-AR(a1-Adrenoceptor)介导交感神经对机体生理病理变化及针灸效应的研究情况,本文查阅CNKI数据库及Pubmed数据库,对近30年关于α_1-AR介导的交感神经对机体生理病理影响及针灸效应的研究情况进行系统回顾。发现α_1-AR不但介导交感神经对心脏的变力变时效应,以及血管平滑肌、膀胱括约肌和子宫平滑肌的收缩等生理效应的调节,还介导了心律失常、心肌肥大等病理过程,此外,α_1-AR还介导了针刺信号的传导,而且针刺还可以调节交感神经张力。说明机体的许多生理病理改变与α_1-AR及亚型的变化有密切关系,因此,深入研究α_1-AR将有助于阐释机体的生理病理机制,也为有效药物提供理论依据和相应的药理模型;对经脉穴位上α_1-AR的深入研究,有助于经络实质的探讨及针刺效应物质基础研究。     

Socioeconomic assessment of the relevance of a community-based goat breeding project in smallholding systems

In the last decade, community-based animal breeding programs have gained attention for the genetic improvement of small ruminants in the tropics. Nevertheless, implementing such programs remains challenged by the issue of smallholders' participation. To shed light on this issue of participation, a goat genetic improvement project has been assessed for its socioeconomic relevance through participatory methods, taking account of goat multifunctionality. We quantified the gross margins per flock and per animal as indicators of viability. We assessed then the correspondence between the goat functions defined through a proportional piling tool with the relative share of these functions in the gross revenue. For that purpose, 160 smallholders were surveyed and 77 among them were monitored for one year. A cluster analysis of factors linked to the dynamic of goat farming identified three groups of farmers. The first group gathered farmers with the smallest goat flocks, who were goat oriented in the future. Their sustainable participation in goat breeding project was impeded by the excessive sales of goats. The second group involved farmers with the highest farm size, who planned to buy cattle to replace part of their goats. The third group included farmers who were members of the project with the largest goat flocks. This group emphasized the importance of goat for their future but showed weak abilities to manage large flocks. The gross margin per animal was the highest in the third group. The relative importance of goat functions as defined through participatory tools did not correspond to the relative share of these functions in the composition of the gross revenue from goats. Participatory tools and economic calculation then appear as complementary to understand farmers' priorities. Consolidating breeders' associations and supporting farmers to diversify their sources of income are two ways proposed here to ensure an enabling environment to goat husbandry and farmers' well-being.     

Wind Speed Perception and Risk

Background

How accurately do people perceive extreme wind speeds and how does that perception affect the perceived risk? Prior research on human–wind interaction has focused on comfort levels in urban settings or knock-down thresholds. No systematic experimental research has attempted to assess people''s ability to estimate extreme wind speeds and perceptions of their associated risks.

Method

We exposed 76 people to 10, 20, 30, 40, 50, and 60 mph (4.5, 8.9, 13.4, 17.9, 22.3, and 26.8 m/s) winds in randomized orders and asked them to estimate wind speed and the corresponding risk they felt.

Results

Multilevel modeling showed that people were accurate at lower wind speeds but overestimated wind speeds at higher levels. Wind speed perceptions mediated the direct relationship between actual wind speeds and perceptions of risk (i.e., the greater the perceived wind speed, the greater the perceived risk). The number of tropical cyclones people had experienced moderated the strength of the actual–perceived wind speed relationship; consequently, mediation was stronger for people who had experienced fewer storms.

Conclusion

These findings provide a clearer understanding of wind and risk perception, which can aid development of public policy solutions toward communicating the severity and risks associated with natural disasters.