Prenatal Prediction of Poor Maternal and Offspring Outcomes: Implications for Selection into Intensive Parent Support Programs

This study examined the predictive ability of mother’s age, antenatal depression, education, financial difficulties, partner status, and smoking for a range of poor maternal and offspring outcomes assessed up to 61 months postnatally. Outcomes obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) were maternal postnatal depression at 8 weeks (n = 10,070), never breastfeeding (n = 7,976), feelings of poor attachment (n = 8,253) and hostility (n = 8,159) at 47 months, and not in employment, education or training (NEET, n = 8,265) at 61 months. Only a small proportion of women with each outcome were aged less than 20 years when they were pregnant. At least half of the women experiencing these outcomes, and up to 74.7% of women with postnatal depression, could be identified if they had at least one of the predictors measured during pregnancy (age < 20, depression, education less than O level, financial difficulties, no partner, or smoking). Model discrimination was poor using maternal age only (area under the receiver operator characteristic (AUROC) curve approximately 0.52), except for never breastfeeding (0.63). Discrimination improved (AUROC: 0.80, 0.69, 0.62, 0.60, 0.66 for depression, never breastfeeding, poor attachment, hostility and NEET, respectively) when all six predictors were included in the model. Calibration improved for all outcomes with the model including all six predictors, except never breastfeeding where even age alone demonstrated good calibration. Factors other than young maternal age, including education, smoking and depression during pregnancy should be considered in identifying women and their offspring likely to benefit from parenting support interventions

Mapping and modelling the geographical distribution and environmental limits of podoconiosis in Ethiopia

BACKGROUND Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues. METHODOLOGY Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008-2010. The integrated mapping used woreda (district) health offices' reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence. PRINCIPAL FINDINGS Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2-51.7) million people (i.e. 43.8%; 95% CI: 25.3-64.8% of Ethiopia's national population) lived in areas environmentally suitable for the occurrence of podoconiosis. CONCLUSIONS Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale

Could sound be used as a strategy for reducing symptoms of perceived motion sickness?

<p>Abstract</p> <p>Background</p> <p>Working while exposed to motions, physically and psychologically affects a person. Traditionally, motion sickness symptom reduction has implied use of medication, which can lead to detrimental effects on performance. Non-pharmaceutical strategies, in turn, often require cognitive and perceptual attention. Hence, for people working in high demand environments where it is impossible to reallocate focus of attention, other strategies are called upon. The aim of the study was to investigate possible impact of a mitigation strategy on perceived motion sickness and psychophysiological responses, based on an artificial sound horizon compared with a non-positioned sound source.</p> <p>Methods</p> <p>Twenty-three healthy subjects were seated on a motion platform in an artificial sound horizon or in non-positioned sound, in random order with one week interval between the trials. Perceived motion sickness (Mal), maximum duration of exposure (ST), skin conductance, blood volume pulse, temperature, respiration rate, eye movements and heart rate were measured continuously throughout the trials.</p> <p>Results</p> <p>Mal scores increased over time in both sound conditions, but the artificial sound horizon, applied as a mitigation strategy for perceived motion sickness, showed no significant effect on Mal scores or ST. The number of fixations increased with time in the non-positioned sound condition. Moreover, fixation time was longer in the non-positioned sound condition compared with sound horizon, indicating that the subjects used more time to fixate and, hence, assumingly made fewer saccades.</p> <p>Conclusion</p> <p>A subliminally presented artificial sound horizon did not significantly affect perceived motion sickness, psychophysiological variables or the time the subjects endured the motion sickness triggering stimuli. The number of fixations and fixation times increased over time in the non-positioned sound condition.</p

Glue ear, hearing loss and IQ:an association moderated by the child's home environment

BACKGROUND: Glue ear or otitis media with effusion (OME) is common in children and may be associated with hearing loss (HL). For most children it has no long lasting effects on cognitive development but it is unclear whether there are subgroups at higher risk of sequelae. OBJECTIVES: To examine the association between a score comprising the number of times a child had OME and HL (OME/HL score) in the first four/five years of life and IQ at age 4 and 8. To examine whether any association between OME/HL and IQ is moderated by socioeconomic, child or family factors. METHODS: Prospective, longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). 1155 children tested using tympanometry on up to nine occasions and hearing for speech (word recognition) on up to three occasions between age 8 months and 5 years. An OME/HL score was created and associations with IQ at ages 4 and 8 were examined. Potential moderators included a measure of the child's cognitive stimulation at home (HOME score). RESULTS: For the whole sample at age 4 the group with the highest 10% OME/HL scores had performance IQ 5 points lower [95% CI -9, -1] and verbal IQ 6 points lower [95% CI -10, -3] than the unaffected group. By age 8 the evidence for group differences was weak. There were significant interactions between OME/HL and the HOME score: those with high OME/HL scores and low 18 month HOME scores had lower IQ at age 4 and 8 than those with high OME/HL scores and high HOME scores. Adjusted mean differences ranged from 5 to 8 IQ points at age 4 and 8. CONCLUSIONS: The cognitive development of children from homes with lower levels of cognitive stimulation is susceptible to the effects of glue ear and hearing loss

Utilizing general human movement models to predict the spread of emerging infectious diseases in resource poor settings.

Human mobility is an important driver of geographic spread of infectious pathogens. Detailed information about human movements during outbreaks are, however, difficult to obtain and may not be available during future epidemics. The Ebola virus disease (EVD) outbreak in West Africa between 2014-16 demonstrated how quickly pathogens can spread to large urban centers following one cross-species transmission event. Here we describe a flexible transmission model to test the utility of generalised human movement models in estimating EVD cases and spatial spread over the course of the outbreak. A transmission model that includes a general model of human mobility significantly improves prediction of EVD's incidence compared to models without this component. Human movement plays an important role not only to ignite the epidemic in locations previously disease free, but over the course of the entire epidemic. We also demonstrate important differences between countries in population mixing and the improved prediction attributable to movement metrics. Given their relative rareness, locally derived mobility data are unlikely to exist in advance of future epidemics or pandemics. Our findings show that transmission patterns derived from general human movement models can improve forecasts of spatio-temporal transmission patterns in places where local mobility data is unavailable

A Rapid Flp-In System for Expression of Secreted H5N1 Influenza Hemagglutinin Vaccine Immunogen in Mammalian Cells

Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing.We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine.Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains

Traits Contributing to the Autistic Spectrum

It is increasingly recognised that traits associated with autism reflect a spectrum with no clear boundary between typical and atypical behaviour. Dimensional traits are needed to investigate the broader autism phenotype.Ninety-three individual measures reflecting components of social, communication and repetitive behaviours characterising autistic spectrum disorder (ASD) were identified between the ages of 6 months and 9 years from the ALSPAC database. Using missing value imputation, data for 13,138 children were analysed. Factor analysis suggested the existence of 7 factors explaining 85% of the variance. The factors were labelled: verbal ability, language acquisition, social understanding, semantic-pragmatic skills, repetitive-stereotyped behaviour, articulation and social inhibition. Four factors (1, 3, 5 and 7) were specific to ASD being more strongly associated with this phenotype than other co-morbid conditions while other factors were more associated with learning difficulties and specific language impairment. Nevertheless, all 7 factors contributed independently to the explanation of ASD (p<0.001). Exploration of putative genetic causal factors such as variants in the CNTNAP2 gene showed a varying pattern of associations with these traits. An alternative predictive model of ASD was derived using four individual measures: the coherence subscale of the Children's Communication Checklist (9y), the Social and Communication Disorders Checklist (91 m), repetitive behaviour (69 m) and the sociability subscale of the Emotionality Activity and Sociability measure (38 m). Although univarably these traits performed better than some factors, their combined explanations of ASD were similar (R(2) =  0.48).These results support the fractional nature of ASD with different aetiological origins for these components despite pleiotropic genetic effects being observed. These traits are likely to be useful in the exploration of ASD

Development of a nurse home visitation intervention for intimate partner violence

<p>Abstract</p> <p>Background</p> <p>Despite an increase in knowledge about the epidemiology of intimate partner violence (IPV), much less is known about interventions to reduce IPV and its associated impairment. One program that holds promise in preventing IPV and improving outcomes for women exposed to violence is the Nurse-Family Partnership (NFP), an evidence-based nurse home visitation program for socially disadvantaged first-time mothers. The present study developed an intervention model and modification process to address IPV within the context of the NFP. This included determining the extent to which the NFP curriculum addressed the needs of women at risk for IPV or its recurrence, along with client, nurse and broader stakeholder perspectives on how best to help NFP clients cope with abusive relationships.</p> <p>Methods</p> <p>Following a preliminary needs assessment, an exploratory multiple case study was conducted to identify the core components of the proposed IPV intervention. This included qualitative interviews with purposeful samples of NFP clients and community stakeholders, and focus groups with nurse home visitors recruited from four NFP sites. Conventional content analysis and constant comparison guided data coding and synthesis. A process for developing complex interventions was then implemented.</p> <p>Results</p> <p>Based on data from 69 respondents, an IPV intervention was developed that focused on identifying and responding to IPV; assessing a client's level of safety risk associated with IPV; understanding the process of leaving and resolving an abusive relationship and system navigation. A need was identified for the intervention to include both universal elements of healthy relationships and those tailored to a woman's specific level of readiness to promote change within her life. A clinical pathway guides nurses through the intervention, with a set of facilitators and corresponding instructions for each component.</p> <p>Conclusions</p> <p>NFP clients, nurses and stakeholders identified the need for modifications to the existing NFP program; this led to the development of an intervention that includes universal and targeted components to assist NFP nurses in addressing IPV with their clients. Plans for feasibility testing and evaluation of the effectiveness of the IPV intervention embedded within the NFP, and compared to NFP-only, are discussed.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition