SLC25A22 is a novel gene for migrating partial seizures in infancy

Objective To identify a genetic cause for migrating partial seizures in infancy (MPSI). Methods We characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22. Results In a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport. Interpretation We have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22. Ann Neurol 2013;74:873-882 © 2013 American Neurological Association

Continuity of midwifery care and gestational weight gain in obese women: a randomised controlled trial

Background: The increased prevalence of obesity in pregnant women in Australia and other developed countries is a significant public health concern. Obese women are at increased risk of serious perinatal complications and guidelines recommend weight gain restriction and additional care. There is limited evidence to support the effectiveness of dietary and physical activity lifestyle interventions in preventing adverse perinatal outcomes and new strategies need to be evaluated. The primary aim of this project is to evaluate the effect of continuity of midwifery care on restricting gestational weight gain in obese women to the recommended range. The secondary aims of the study are to assess the impact of continuity of midwifery care on: women&rsquo;s experience of pregnancy care; women&rsquo;s satisfaction with care and a range of psychological factors.Methods/Design: A two arm randomised controlled trial (RCT) will be conducted with primigravid women recruited from maternity services in Victoria, Australia. Participants will be primigravid women, with a BMI&ge;30 who are less than 17 weeks gestation. Women allocated to the intervention arm will be cared for in a midwifery continuity of care model and receive an informational leaflet on managing weight gain in pregnancy. Women allocated to the control group will receive routine care in addition to the same informational leaflet. Weight gain during pregnancy, standards of care, medical and obstetric information will be extracted from medical records. Data collected at recruitment (self administered survey) and at 36 weeks by postal survey will include sociodemographic information and the use of validated scales to measure secondary outcomes.Discussion: Continuity of midwifery care models are well aligned with current Victorian, Australian and many international government policies on maternity care. Increasingly, midwifery continuity models of care are being introduced in low risk maternity care, and information on their application in high risk populations is required. There is an identified need to trial alternative antenatal interventions to reduce perinatal risk factors for women who are obese and the findings from this project may have application in other maternity services. In addition this study will inform a larger trial that will focus on birth and postnatal outcomes.<br /

Young patients', parents', and survivors' communication preferences in paediatric oncology: Results of online focus groups

Contains fulltext : 51596.pdf ( ) (Open Access)BACKGROUND: Guidelines in paediatric oncology encourage health care providers to share relevant information with young patients and parents to enable their active participation in decision making. It is not clear to what extent this mirrors patients' and parents' preferences. This study investigated communication preferences of childhood cancer patients, parents, and survivors of childhood cancer. METHODS: Communication preferences were examined by means of online focus groups. Seven patients (aged 8-17), 11 parents, and 18 survivors (aged 8-17 at diagnosis) participated. Recruitment took place by consecutive inclusion in two Dutch university oncological wards. Questions concerned preferences regarding interpersonal relationships, information exchange and participation in decision making. RESULTS: Participants expressed detailed and multi-faceted views regarding their needs and preferences in communication in paediatric oncology. They agreed on the importance of several interpersonal and informational aspects of communication, such as honesty, support, and the need to be fully informed. Participants generally preferred a collaborative role in medical decision making. Differences in views were found regarding the desirability of the patient's presence during consultations. Patients differed in their satisfaction with their parents' role as managers of the communication. CONCLUSION: Young patients' preferences mainly concur with current guidelines of providing them with medical information and enabling their participation in medical decision making. Still, some variation in preferences was found, which faces health care providers with the task of balancing between the sometimes conflicting preferences of young cancer patients and their parents

Litter Decomposition as an Indicator of Stream Ecosystem Functioning at Local-to-Continental Scales

RivFunction is a pan-European initiative that started in 2002 and was aimed at esta- blishing a novel functional-based approach to assessing the ecological status of rivers. Litter decomposition was chosen as the focal process because it plays a central role in stream ecosystems and is easy to study in the field. Impacts of two stressors that occur across the continent, nutrient pollution and modified riparian vegetation, were exam- ined at >200 paired sites in nine European ecoregions. In response to the former, decomposition was dramatically slowed at both extremes of a 1000-fold nutrient gra- dient, indicating nutrient limitation in unpolluted sites, highly variable responses across Europe in moderately impacted streams, and inhibition via associated toxic and addi- tional stressors in highly polluted streams. Riparian forest modification by clear cutting or replacement of natural vegetation by plantations (e.g. conifers, eucalyptus) or pasture produced similarly complex responses. Clear effects caused by specific riparian distur- bances were observed in regionally focused studies, but general trends across different types of riparian modifications were not apparent, in part possibly because of important indirect effects. Complementary field and laboratory experiments were undertaken to tease apart the mechanistic drivers of the continental scale field bioassays by addressing the influence of litter, fungal and detritivore diversity. These revealed generally weak and context-dependent effects on decomposition, suggesting high levels of redundancy (and hence potential insurance mechanisms that can mitigate a degree of species loss) within the food web. Reduced species richness consistently increased decomposition variability, if not the absolute rate. Further field studies were aimed at identifying impor- tant sources of this variability (e.g. litter quality, temporal variability) to help constrain ranges of predicted decomposition rates in different field situations. Thus, although many details still need to be resolved, litter decomposition holds considerable potential in some circumstances to capture impairment of stream ecosystem functioning. For instance, species traits associated with the body size and metabolic capacity of the con- sumers were often the main driver at local scales, and these were often translated into important determinants of otherwise apparently contingent effects at larger scales. Key insights gained from conducting continental scale studies included resolving the appar- ent paradox of inconsistent relationships between nutrients and decomposition rates, as the full complex multidimensional picture emerged from the large-scale dataset, of which only seemingly contradictory fragments had been seen previously

Understanding the Multidimensionality of Group Development

This article presents a three-dimensional definition space of the group development literature that differentiates group development models on three dimensions: content, population, and path dependency. The multidimensional conceptualization structures and integrates the vast group development literature, enabling direct comparison of competing theories. The utility of this definition space is demonstrated by using the relative positioning of two seemingly competing group development models—the punctuated equilibrium model and the integrative model—to demonstrate their complementarity. The authors also show how organizational researchers and practitioners can use the three-dimensional definition space to select an appropriate theoretical model for the group or group process with which they are working

Cancer Patients' Self-Reported Attitudes About the Internet

BACKGROUND: Increasing numbers of cancer patients are using the Internet, but little is known about their attitudes toward online health care. OBJECTIVE: The purpose of this substudy was to analyze cancer patients' attitudes toward online health care. METHODS: This was a substudy of 41 persons with cancer who used the Internet for health care information and support and who completed the Attitudes Toward Online Health Care (ATOHC) survey. RESULTS: The majority of study participants were married, held graduate degrees, and had high incomes. Using a five-point Likert scale, means for the five dimensions of the ATOHC survey were as follows: community and news 3.22 (SD = 1.01), outcomes 3.20 (SD = 1.08), trusted information and advice 2.73 (SD = 0.66), self-efficacy in evaluating information and intention 3.46 (SD = 0.65), and disclosure 3.15 (SD = 1.06). The average response fell between “About half the time” and “Usually.” Favorite websites for content were Medscape and WebMD, while favorite sites for support were WebMD and Mediconsult. CONCLUSIONS: Respondents were generally eager to obtain and offer cancer information and support online, but they were skeptical of unknown sources. They were comfortable both giving and receiving information and support. Respondents were interested in the experiences of other patients and benefited by their direct and indirect interactions with them. Respondents felt that they coped better with their illness and experienced less uncertainty and anxiety as a result of their online experiences. They reported a certain level of trust, primarily for established reputable sources of information, and they were confident in their ability to evaluate the information, including research reports. In addition, cancer patients displayed a healthy skepticism when presented with the option of divulging their personal health information; however, they were willing to provide personal details if, as a result, a website provided them with individualized information