Sleep problems in children with developmental disorders

The first chapter of Volume One contains a meta-analysis of studies comparing sleep in people with and without intellectual disabilities. The key finding was that people with intellectual disabilities slept for, on average, 23 minutes less each night and experienced poorer sleep quality. Chapter Two details an empirical study of sleep in children with Autism Spectrum Disorders (ASD) and a parent-identified sleep problem. Actigraphy and diary measures found no differences between the children with ASD and a typically developing comparison group. Questionnaires identified numerous sleep problems that were more commonly reported in the children with ASD. Chapter Three is a lay summary of the previous chapters

Daytime napping, sleep duration and increased 8-year risk of type 2 diabetes in a British population.

BACKGROUND AND AIMS: Few studies have prospectively examined the relationship between daytime napping and risk of type 2 diabetes. We aimed to study the effects of daytime napping and the joint effects of napping and sleep duration in predicting type 2 diabetes risk in a middle- to older-aged British population. METHODS AND RESULTS: In 1998-2000, 13 465 individuals with no known diabetes participating in the European Prospective Investigation into Cancer-Norfolk study reported daytime napping habit and 24-h sleep duration. Incident type 2 diabetes cases were identified through multiple data sources until 31 July 2006. After adjustment for age and sex, daytime napping was associated with a 58% higher diabetes risk. Further adjustment for education, marital status, smoking, alcohol intake, physical activity, comorbidities and hypnotic drug use had little influence on the association, but additional adjustment for BMI and Waist Circumference attenuated the Odds ratio (OR) (95% CI) to 1.30 (1.01, 1.69). The adjusted ORs (95% CI) associated with short and long sleep duration were 1.46 (1.10, 1.90) and 1.64 (1.16, 2.32), respectively. When sleep duration and daytime napping were examined together, the risk of developing diabetes more than doubled for those who took day naps and had less than 6 h of sleep, compared to those who did not nap and had 6-8 h of sleep. CONCLUSION: Daytime napping was associated with an increased risk of type 2 diabetes, particularly when combined with short sleep duration. Further physiological studies are needed to confirm the interaction between different domains of sleep in relation to diabetes risk.The design and conduct of the EPIC-Norfolk study and collection and management of the data was supported by programme grants from the Medical Research Council UK (G9502233, G0300128) and Cancer Research UK (C865/A2883). Funding sources did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.numecd.2016.06.006

Heat Shock Protein 70 family members interact with Crimean-Congo hemorrhagic fever virus and Hazara virus nucleocapsid proteins and perform a functional role in the nairovirus replication cycle

The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast HAZV is non-pathogenic to humans, and thus represents an excellent model to study aspects of CCHFV biology under more accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N, and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells using small molecule inhibitors significantly reduced HAZV titres, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease

Patients' treatment beliefs in low back pain: development and validation of a questionnaire in primary care

Choosing the most appropriate treatment for individual patients with low back pain (LBP) can be challenging, and clinical guidelines recommend taking into account patients' preferences. However, no tools exist to assess or compare patients' views about LBP treatments. We report the development and validation of the LBP Treatment Beliefs Questionnaire (LBP-TBQ) for use across different treatments in clinical practice and research. Using qualitative data we developed a pool of items assessing perceived credibility, effectiveness, concerns about and individual 'fit' of specific treatments. These items were included in a survey completed by 429 primary care patients with LBP, of whom 115 completed it again 1 to 2 weeks later. We performed psychometric analyses using non-parametric item response theory and classical test theory. The four subscales of the resulting 16-item LBP-TBQ showed good homogeneity (H=.46-.76), internal consistency (α =.73-.94), and stability (r=.63-.83), confirmed most convergent and discriminant validity hypotheses, and had acceptable structural validity for four guideline-recommended treatments: pain medication, exercise, manual therapy and acupuncture. Participants with stronger positive treatment beliefs were more likely to rank that treatment as their first choice, indicating good criterion validity (t values=3.11-9.80, all p<.01, except pain medication effectiveness beliefs, t(339)=1.35; p=.18). A short 4-item version also displayed good homogeneity (H=.43-.66), internal consistency (α=.70-.86), and stability (r=.82-.85), and was significantly related to treatment choice (t values=4.33-9.25, all p<.01). The LBP-TBQ can be used to assess treatment beliefs in primary care patients with LBP and to investigate the effects of treatment beliefs on treatment uptake and adherence.This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivatives 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially

Sailiga tomai ma malamalama’aga fa’a-Pasifika—Seeking Pasifika Knowledge to Support Student Learning: Reflections on Cultural Values Following an Educational Journey to Samoa

Transforming practices in initial teacher education and school and early childhood education contexts to support the success of Pasifika students and children can be challenging. Palagi educators, in particular, may find their practices are constrained by bureaucratic systems, processes and professional norms in ways that limit thinking about and responses to different ways of being and doing. Drawing from the experiences of a diverse group of educators during an educational journey to Samoa led by an esteemed Samoan leader, colleague and mentor, this article argues culturally based pedagogy holds the key to thinking and moving beyond some of these constraints. The article suggests that understanding Pasifika cultural values and integrating these into pedagogy is a critical first step for educators, before concluding with several practice messages. While these messages focus on Pasifika communities, students and children, they can be adapted for other ethnic groups

Rescue of Infectious Recombinant Hazara Nairovirus from cDNA Reveals the Nucleocapsid Protein DQVD Caspase Cleavage Motif Performs an Essential Role other than Cleavage

The Nairoviridae family of the Bunyavirales order comprises tick-borne, trisegmented, negative-strand RNA viruses, with several members being associated with serious or fatal diseases in humans and animals. A notable member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is the most widely distributed tick-borne pathogen and is associated with devastating human disease, with case fatality rates averaging 30%. Hazara virus (HAZV) is closely related to CCHFV, sharing the same serogroup and many structural, biochemical, and cellular properties. To improve understanding of HAZV and nairovirus multiplication cycles, we developed, for the first time, a rescue system permitting efficient recovery of infectious HAZV from cDNA. This system now allows reverse genetic analysis of nairoviruses without the need for high-level biosafety containment, as is required for CCHFV. We used this system to test the importance of a DQVD caspase cleavage site exposed on the apex of the HAZV nucleocapsid protein arm domain that is cleaved during HAZV infection, for which the equivalent DEVD sequence was recently shown to be important for CCHFV growth in tick but not mammalian cells. Infectious HAZV bearing an uncleavable DQVE sequence was rescued and exhibited growth parameters equivalent to those of wild-type virus in both mammalian and tick cells, showing this site was dispensable for virus multiplication. In contrast, substitution of the DQVD motif with the similarly uncleavable AQVA sequence could not be rescued despite repeated efforts. Together, these results highlight the importance of this caspase cleavage site in the HAZV life cycle but reveal the DQVD sequence performs a critical role aside from caspase cleavage

Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples

Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses