The Black Country Education Insight Report 2021

This is the third annual report produced offering an overview of all phases of education in the Black Country. As in 2020, the Covid-19 pandemic and associated lockdowns have dominated all areas of education and society. Therefore, we have concentrated much less on data analysis in this report in favour of capturing the views and first-hand experiences of educational practitioners from the region, gained through snapshot online surveys and opportunistic interviews. The Black Country contains high levels of disadvantage and poverty and early evidence suggests that such areas have been disproportionately affected by the pandemic. As we reported last year, schools, colleges, universities, early years settings and other education providers in the Black Country have worked extremely hard to maintain education and support for all learners, particularly those who are vulnerable, but it is too early to say how successful they have been. However, this report is testament to their efforts and persistence

Against the odds : achieving greater progress for secondary students facing socio-economic disadvantage : June 2021

It has never been more important for all pupils, whatever their background, to be able to make the progress they deserve at school. And yet, in my job as Vice-Principal of a large secondary school, I constantly see how otherwise able pupils are held back by their circumstances of birth. It shouldn’t be this way. While the pupil premium has become a vital part of school funding as part of schools’ strategies to support social mobility, it is also true that most of the successes seen so far are in the primary sector. In this report we provide one of the most thorough investigations to date on the characteristics of secondary schools able to start closing the progress gap and achieve better outcomes for disadvantaged pupils. The blunt truth is that despite schools’ best efforts, this is staggeringly rare. Our research looked closely at the approaches which made a difference, through a survey of 285 schools across England, in-depth fieldwork, and analysis of national Progress 8 data

Axonal BACE1 dynamics and targeting in hippocampal neurons: a role for Rab11 GTPase

BACKGROUND: BACE1 is one of the two enzymes that cleave amyloid precursor protein to generate Alzheimer's disease (AD) beta amyloid peptides. It is widely believed that BACE1 initiates APP processing in endosomes, and in the brain this cleavage is known to occur during axonal transport of APP. In addition, BACE1 accumulates in dystrophic neurites surrounding brain senile plaques in individuals with AD, suggesting that abnormal accumulation of BACE1 at presynaptic terminals contributes to pathogenesis in AD. However, only limited information is available on BACE1 axonal transport and targeting. RESULTS: By visualizing BACE1-YFP dynamics using live imaging, we demonstrate that BACE1 undergoes bi-directional transport in dynamic tubulo-vesicular carriers along axons in cultured hippocampal neurons and in acute hippocampal slices of transgenic mice. In addition, a subset of BACE1 is present in larger stationary structures, which are active presynaptic sites. In cultured neurons, BACE1-YFP is preferentially targeted to axons over time, consistent with predominant in vivo localization of BACE1 in presynaptic terminals. Confocal analysis and dual-color live imaging revealed a localization and dynamic transport of BACE1 along dendrites and axons in Rab11-positive recycling endosomes. Impairment of Rab11 function leads to a diminution of total and endocytosed BACE1 in axons, concomitant with an increase in the soma. Together, these results suggest that BACE1 is sorted to axons in endosomes in a Rab11-dependent manner. CONCLUSION: Our results reveal novel information on dynamic BACE1 transport in neurons, and demonstrate that Rab11-GTPase function is critical for axonal sorting of BACE1. Thus, we suggest that BACE1 transcytosis in endosomes contributes to presynaptic BACE1 localization

‘Sink or Swim’: A Qualitative Study to Understand How and Why Nurses Adapt to Support the Implementation of Integrated Diabetes Care

Background: Integrated care, organising care delivery within and between services, is an approach to improve the quality of care. Existing specialist roles have evolved to work across settings and services to integrate care. However, there is limited insight into how these expanded roles are implemented, including how they may be shaped by context. This paper examines how new diabetes nurse specialists working across care boundaries, together with hospital-based diabetes nurse specialists, adapt to support the implementation of integrated care. Methods: We conducted semi-structured focus groups and interviews with diabetes nurse specialists purposively sampled by work setting and health service region (n = 30). Analysis was data-driven, coding actions or processes to stay closer to the data and using 'In Vivo' codes to preserve meaning. Findings: Community nurse specialists described facing a choice of “sink or swim” when appointed with limited guidance on their role. To ‘swim’ and implement their role, required them to use their initiative and adapt to the local context. When first appointed, both community and hospital nurse specialists actively managed misconceptions of their role by other staff. To establish clinics in general practices, community nurse specialists capitalised on professional contacts to access GPs who might utilise their role. They built GP trust by adopting practice norms and responding to individual needs. They adapted to the lack of a multidisciplinary team “safety net” in the community, by “practicing at a higher level”, working more autonomously. Developing professional links and pursuing on-going education was a way to create an alternative ‘safety net’ so as to feel confident in their clinical decision-making when working in the community. Workarounds facilitated information flow (i.e. patient blood results, treatment, and appointments) between settings in the absence of an electronic record shared between general practices and hospital settings. Conclusions: Flexibility and innovation facilitates a new way of working across boundaries. Successful implementation of nurse specialist-led integrated care requires strategies to address elements in the inner (differences in practice organisation, role acceptance) and outer (information systems) context

Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors

Comparison of gene expression in normal and glaucomatous eyes from Caucasian American and African American donors reveals differences that might reflect different susceptibility to glaucoma

Investigating the role of early low-dose aspirin in diabetes: A phase III multicentre double-blinded placebo-controlled randomised trial of aspirin therapy initiated in the first trimester of diabetes pregnancy

Background: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. Methods: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). Discussion: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks’ gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation

RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair Pathways

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson\u27s disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another section of the nerve fascicles of the distal and pre-degenerated stump of the nerve was dissected and processed for RNA-seq studies. An initial analysis between the pre-lesion status and the postinjury gene expression revealed 3,641 genes that were significantly differentially expressed. In addition, the results support a clear transdifferentiation process that occurred by the end of the 2-wk postinjury. Gene ontology (GO) and hierarchical clustering were used to identify the major signaling pathways affected by the injury. In contrast to previous nonclinical studies, important changes were observed in molecular pathways related to antiapoptotic signaling, neurotrophic factor processes, cell motility, and immune cell chemotactic signaling. The results of our current study provide new insights regarding the essential interactions of different molecular pathways that drive neuronal repair and axonal regeneration in humans