Preterm birth and/or factors that lead to preterm delivery: effects on the neonatal kidney

Preterm birth (defined as birth prior to 37 completed weeks of gestation), occurs in approximately 10% of all births and is one of the leading causes of neonatal morbidity and mortality worldwide. Preterm infants are born at a time when kidney development is still ongoing, and consequently can lead to renal impairment (in both the short-term and long-term), as well as severe glomerular abnormalities in some preterm infants. Since the glomerular abnormalities are not present in all preterm kidneys, this suggests that it is not preterm birth per se that leads to the glomerular abnormalities but may relate to factors associated with the etiology of the premature delivery, or factors in neonatal care. In this review, we provide an overview of what is currently known of how prenatal and postnatal factors can potentially impact on the immature kidneys of infants born preterm

What's Digital about Fashion Design? Fashion, Technology and the Digital Economy.

A project report resulting from the RCUK funded NEMODE (New Economic Models in the Digital Economy) Network+ scheme. Project was entitled "Enabling the designer fashion community to understand and adopt technologies that lead to New Economic Models in the Digital Economy", and culminated in a workshop for fashion designers and professionals. held on 27th October 2015 at The Photographers Gallery, London. Project was a collaboration with consultancy AAM Associates, London

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship

Developing stroke specific vocational rehabilitation: a soft systems analysis of current service provision

Purpose: This study aimed to clarify the existing service provision of stroke-specific vocational rehabilitation (VR) in one English county, in order to facilitate future service development. Method: Using soft systems methodology, services in Health, Social Care, Department of Work and Pensions, the voluntary and private sectors, which were identified as supporting return to work after stroke, were mapped using a mixed-methodology approach. Results: A lack of a sanctioned VR pathway meant access to support relied on brokered provision and tacit knowledge. The timing of an intervention was complex and there was a substantial degree of unmet need for mild stroke patients. VR was seen as “non-essential” due to competing commissioning priorities. Service providers from all sectors lacked training and cross-sector partnerships were tenuous and provider roles unclear. Conclusions: Stroke-specific VR should be delivered by an integrated, cross-sector multi-disciplinary team and integrated commissioning between health and other sectors is necessary. Although early intervention is important, support later on in the recovery process is also necessary. Service providers need adequate training to meet the needs of stroke survivors wishing to return to work and better awareness of best practice guidelines. Business cases which demonstrate the efficacy and cost-effectiveness of VR are vital.Implications for Rehabilitation The timeliness of a vocational rehabilitation (VR) intervention is complex; services need to be responsive to the changing needs of the stroke survivor throughout their recovery process and have better mechanisms to ensure re-entry into the stroke pathway is possible. Return to work is a recognised health outcome; health services need to develop better mechanisms for interagency/cross sector working and liaison with employers and not assume that VR is beyond their remit. Therapists and non-health service providers should receive sufficient training to meet the needs of stroke survivors wishing to return to work. Rehabilitation teams must decide how to implement national guidance within existing resources and what training is needed to deploy SSVR. The lack of a sanctioned pathway results in disorganised and patchy provision of VR for stroke survivors; mild stroke patients can fall through the net and receive little or no support. The journey back to work commences at the point of stroke. Mechanisms for identifying acute stroke survivors who were working at onset and for assessing the impact of the stroke on their work need to be put in place. The entire MDT has a role to play. In the absence of a VR specialist, even patients without obvious disability should be referred for ongoing rehabilitation with detailed work assessment and signposted to employment specialists e.g. disability employment advisors EARLY after stroke. Health-based VR interventions can influence work return and job retention. However, therapists must routinely measure work outcomes to inform their business case and be encouraged to demonstrate these outcomes to local commissioners. Commissioners should consider emerging evidence of early VR interventions on reduced length of stay, health and social care resource use and the wider health benefits of maintaining employment

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

Yuri A. Blednov, Jillian M. Benavidez, Mendy Black, Courtney R. Leiter, Elizabeth Osterndorff-Kahanek, David Johnson, Cecilia M. Borghese, R. Adron Harris, Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, United States of AmericaJane R. Hanrahan, Mary Chebib, Faculty of Pharmacy, The University of Sydney, Sydney NSW, AustraliaGraham A. R. Johnston, Department of Pharmacology, The University of Sydney, Sydney NSW, AustraliaGABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.This work was supported by NIH grants AA013520 and AA06399. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Waggoner Center for Alcohol and Addiction ResearchEmail: [email protected]

The Comprehensive Assessment of Neurodegeneration and Dementia: Canadian Cohort Study.

BackgroundThe Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.MethodsThe COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.ResultsThe CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.ConclusionAvailability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years

Returning to work after stroke: perspectives of employer stakeholders, a qualitative study.

Purpose: More than 40 % of working age adults with stroke fail to return to work. The work context is a key factor in return to work, but little is known about the experiences of employers in supporting employees with stroke. The aim of this study was to explore return to work after stroke from the employer perspective, to identify key features associated with success and to seek participants’ views regarding the role of healthcare in return to work. Methods: Data was gathered through 18 semi-structured interviews with employer stakeholders and included small business owners, line managers, human resources and occupational health staff. Data was analysed thematically. Results: The main themes identified were: the impact of stroke on the employer, characteristics of the employee, communication, knowledge and information, experience of other stakeholders, integrating healthcare in return to work. Conclusion: Employers face complex emotional and practical issues when helping an employee return to work after stroke, for which many lack knowledge and experience. The range and quality of support networks that they access is variable and advice and support from clinicians is welcomed. Further research is necessary to investigate how such support could be funded and integrated within existing service provision