Quantifying microglial morphology: an insight into function.

Microglia are specialized immune cells unique to the central nervous system (CNS). Microglia have a highly plastic morphology that changes rapidly in response to injury or infection. Qualitative and quantitative measurements of ever-changing microglial morphology are considered a cornerstone of many microglia-centric research studies. The distinctive morphological variations seen in microglia are a useful marker of inflammation and severity of tissue damage. Although a wide array of damage-associated microglial morphologies has been documented, the exact functions of these distinct morphologies are not fully understood. In this review, we discuss how microglia morphology is not synonymous with microglia function, however, morphological outcomes can be used to make inferences about microglial function. For a comprehensive examination of the reactive status of a microglial cell, both histological and genetic approaches should be combined. However, the importance of quality immunohistochemistry-based analyses should not be overlooked as they can succinctly answer many research questions.

Postpartum haemorrhage and risk of cardiovascular disease in later life: A population-based record linkage cohort study.

OBJECTIVE: To investigate the association between postpartum haemorrhage (PPH) and subsequent cardiovascular disease. DESIGN: Population-based retrospective cohort study, using record linkage between Aberdeen Maternity and Neonatal Databank (AMND) and Scottish healthcare data sets. SETTING: Grampian region, Scotland. POPULATION: A cohort of 70 904 women who gave birth after 24 weeks of gestation in the period 1986-2016. METHODS: We used extended Cox regression models to investigate the association between having had one or more occurrences of PPH in any (first or subsequent) births (exposure) and subsequent cardiovascular disease, adjusted for sociodemographic, medical, and pregnancy and birth-related factors. MAIN OUTCOME MEASURES: Cardiovascular disease identified from the prescription of selected cardiovascular medications, hospital discharge records or death from cardiovascular disease. RESULTS: In our cohort of 70 904 women (with 124 795 birth records), 25 177 women (36%) had at least one PPH. Compared with not having a PPH, having at least one PPH was associated with an increased risk of developing cardiovascular disease, as defined above, in the first year after birth (adjusted hazard ratio, aHR 1.96; 95% confidence interval, 95% CI 1.51-2.53; p < 0.001). The association was attenuated over time, but strong evidence of increased risk remained at 2-5 years (aHR 1.19, 95% CI 1.11-1.30, P < 0.001) and at 6-15 years after giving birth (aHR 1.17, 95% CI 1.05-1.30, p = 0.005). CONCLUSIONS: Compared with women who have never had a PPH, women who have had at least one episode of PPH are twice as likely to develop cardiovascular disease in the first year after birth, and some increased risk persists for up to 15 years.

The carbon footprint of different modes of birth in the UK and the Netherlands: An exploratory study using life cycle assessment.

OBJECTIVE: To compare the carbon footprint of caesarean and vaginal birth. DESIGN: Life cycle assessment (LCA). SETTING: Tertiary maternity units and home births in the UK and the Netherlands. POPULATION: Birthing women. METHODS: A cradle-to-grave LCA using openLCA software to model the carbon footprint of different modes of delivery in the UK and the Netherlands. MAIN OUTCOME MEASURES: 'Carbon footprint' (in kgCO2 equivalents [kgCO2 e]). RESULTS: Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO2 e, compared with 12.47 kgCO2 e for vaginal birth in hospital and 7.63 kgCO2 e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO2 e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO2 e, respectively). Emissions associated with analgesia for vaginal birth ranged from 0.08 kgCO2 e (with opioid analgesia) to 237.33 kgCO2 e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 versus 193.26 kgCO2 e). CONCLUSION: The carbon footprint of a caesarean is higher than for a vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25-fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.

Tobacco cessation experiences and needs: perspectives from Arabic-speaking communities.

Use of tobacco products is higher in Arabic-speaking communities in Australia, compared to other populations. 70 persons identifying as being from Arabic-speaking communities in Western Sydney participated in focus group discussions to explore experiences and needs relating to tobacco, alcohol and other drug treatment. Tobacco was rated as the substance of highest concern in this sample, however a pattern of change was observed. Widespread cigarette use supported by gendered norms that particularly encouraged smoking among men was shifting, with some decline in the social acceptability of cigarette smoking linked to experience of health impacts and the financial cost to families. In contrast, waterpipe tobacco smoking was described as a common and acceptable practice across age and gender cohorts, despite some participants challenging the cultural and health rationales of this practice. Preventing tobacco-related harm among younger populations was highly valued among study participants, drawing on strong support for families as key influencer of health behaviors. Cessation strategies viewed as effective among community members spoken with commonly centered upon the notion of individual willpower, and appreciated the disincentivising impacts of high taxation on cigarettes. This study prioritizes community-informed perspectives for reducing tobacco related harms amongst Arabic-speaking populations in Australia and offers direction to health promoters, public health workers and policymakers. Results indicate opportunities exist to improve tobacco control outcomes through strategies that align prevention and treatment options with relevant community beliefs and norms, and build on existing harm reduction behaviors and support seeking behaviors.

Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease-specific changes in sleep and incongruous peripheral inflammation.

Elderly populations (≥65 years old) have the highest risk of developing Alzheimer's disease (AD) and/or obtaining a traumatic brain injury (TBI). Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16-month-old wild-type (WT Aged) and 3xTg-AD mice, as well as a 2-month-old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre- and post-TBI) and 3xTg-AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed-effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre-TBI and compared with AD mice. However, differences between WT Aged and 3xTg-AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, although both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease-specific treatments in clinical settings.

Acute peripheral inflammation and post-traumatic sleep differ between sexes after experimental diffuse brain injury.

Identifying differential responses between sexes following traumatic brain injury (TBI) can elucidate the mechanisms behind disease pathology. Peripheral and central inflammation in the pathophysiology of TBI can increase sleep in male rodents, but this remains untested in females. We hypothesized that diffuse TBI would increase inflammation and sleep in males more so than in females. Diffuse TBI was induced in C57BL/6J mice and serial blood samples were collected (baseline, 1, 5, 7 days post-injury [DPI]) to quantify peripheral immune cell populations and sleep regulatory cytokines. Brains and spleens were harvested at 7DPI to quantify central and peripheral immune cells, respectively. Mixed-effects regression models were used for data analysis. Female TBI mice had 77%-124% higher IL-6 levels than male TBI mice at 1 and 5DPI, whereas IL-1ß and TNF-α levels were similar between sexes at all timepoints. Despite baseline sex differences in blood-measured Ly6Chigh monocytes (females had 40% more than males), TBI reduced monocytes by 67% in TBI mice at 1DPI. Male TBI mice had 31%-33% more blood-measured and 31% more spleen-measured Ly6G+ neutrophils than female TBI mice at 1 and 5DPI, and 7DPI, respectively. Compared with sham, TBI increased sleep in both sexes during the first light and dark cycles. Male TBI mice slept 11%-17% more than female TBI mice, depending on the cycle. Thus, sex and TBI interactions may alter the peripheral inflammation profile and sleep patterns, which might explain discrepancies in disease progression based on sex.

What is the alcohol, tobacco, and other drug prevalence among culturally and linguistically diverse groups in the Australian population? A national study of prevalence, harms, and attitudes.

In Australia, one in three people are born overseas, and one in five households speak languages other than English. This study explores substance use prevalence, related harms, and attitudes among these large groups in the population. Analysis was conducted using cross-sectional data (N = 22, 696) from the 2013 National Drug Strategy Household Survey. General linear model and binary logistic regression were used to assess substance use and harms, using stabilized inverse propensity score weighting to control for potential confounding variables. Between culturally and linguistically diverse populations and the population born in Australia, United Kingdom, or New Zealand who speak only English at home, there is no statistically significant variation in the likelihood of current smoking; using analgesics, tranquilizers, or sleeping pills; or administering drugs via injection. Culturally diverse populations are less likely to drink alcohol or use cannabis or methamphetamines. No difference between these two major groups in the population is observed in substance-related abuse from strangers; but culturally diverse respondents are less likely to report substance-related abuse from known persons. Lower substance use prevalence is not observed among people from culturally diverse backgrounds who have mental health issues. Australian-, UK-, or New Zealand-born respondents who speak only English at home are more likely to oppose drug and tobacco policies, including a range of harm reduction policies. We discuss the practical and ethical limitations of this major Australian data set for examining the burden of drug-related harms experienced by specific migrant populations. Avenues for potential future research are outlined.

Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation.

Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod-shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse-chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI-induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll-like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI-induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.

Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel TNF receptor (TNF-R) inhibitors could be screened using post-traumatic sleep and that these novel compounds would improve functional recovery following diffuse TBI in the mouse. METHODS: Three inhibitors of TNF-R activation were synthesized based on the structure of previously reported TNF CIAM inhibitor F002, which lodges into a defined TNFR1 cavity at the TNF-binding interface, and screened for in vitro efficacy of TNF pathway inhibition (IκB phosphorylation). Compounds were screened for in vivo efficacy in modulating post-traumatic sleep. Compounds were then tested for efficacy in improving functional recovery and verification of cellular mechanism. RESULTS: Brain-injured mice treated with Compound 7 (C7) or SGT11 slept significantly less than those treated with vehicle, suggesting a therapeutic potential to target neuroinflammation. SGT11 restored cognitive, sensorimotor, and neurological function. C7 and SGT11 significantly decreased cortical inflammatory cytokines 3 h post-TBI. CONCLUSIONS: Using sleep as a bio-indicator of TNF-R-dependent neuroinflammation, we identified C7 and SGT11 as potential therapeutic candidates for TBI.

Birthplace choices: what are the information needs of women when choosing where to give birth in England? A qualitative study using online and face to face focus groups.

BACKGROUND: Current clinical guidelines and national policy in England support offering 'low risk' women a choice of birth setting. Options include: home, free-standing midwifery unit (FMU), alongside midwifery unit (AMU) or obstetric unit (OU). This study, which is part of a broader project designed to inform policy on 'choice' in relation to childbirth, aimed to provide evidence on UK women's experiences of choice and decision-making in the period since the publication of the Birthplace findings (2011) and new NICE guidelines (2014). This paper reports on findings relating to women's information needs when making decisions about where to give birth. METHODS: A qualitative focus group study including 69 women in the last trimester of pregnancy in England in 2015-16. Seven focus groups were conducted online via a bespoke web portal, and one was face-to-face. To explore different aspects of women's experience, each group included women with specific characteristics or options; planning a home birth, living in areas with lots of choice, living in areas with limited choice, first time mothers, living close to a FMU, living in opt-out AMU areas, living in socioeconomically disadvantaged areas and planning to give birth in an OU. Focus group transcripts were analysed thematically. RESULTS: Women drew on multiple sources when making choices about where to give birth. Sources included; the Internet, friends' recommendations and experiences, antenatal classes and their own personal experiences. Their midwife was not the main source of information. Women wanted the option to discuss and consider their birth preferences throughout their pregnancy, not at a fixed point. CONCLUSIONS: Birthplace choice is informed by many factors. Women may encounter fewer overt obstacles to exercising choice than in the past, but women do not consistently receive information about birthplace options from their midwife at a time and in a manner that they find helpful. Introducing options early in pregnancy, but deferring decision-making about birthplace until a woman has had time to consider and explore options and discuss these with her midwife, might facilitate choice.

Blood-brainbarrier disruption dictates nanoparticle accumulation following experimental brain injury.

Clinically, traumatic brain injury (TBI) results in complex heterogeneous pathology that cannot be recapitulated in single pre-clinical animal model. Therefore, we focused on evaluating utility of nanoparticle (NP)-based therapeutics following three diffuse-TBI models: mildclosed-head injury (mCHI), repetitive-mCHI and midline-fluid percussion injury (FPI). We hypothesized that NP accumulation after diffuse TBI correlates directly with blood-brainbarrier permeability. Mice received PEGylated-NP cocktail (20-500 nm) (intravenously) after single- or repetitive-(1 impact/day, 5 consecutive days) CHI (immediately) and midline-FPI (1 h, 3 h and 6 h). NPs circulated for 1 h before perfusion/brain extraction. NP accumulation was analyzed using fluorescent microscopy in brain regions vulnerable to neuropathology. Minimal/no NP accumulation after mCHI/RmCHI was observed. In contrast, midlineFPI resulted in significant peak accumulation of up to 500 nm NP at 3 h post-injury compared to sham, 1 h, and 6 h groups in the cortex. Therefore, our study provides the groundwork for feasibility of NP-delivery based on NPinjection time and NPsize after mCHI/RmCHI and midline-FPI.

Aging with a traumatic brain injury: Could behavioral morbidities and endocrine symptoms be influenced by microglial priming?

A myriad of factors influence the developmental and aging process and impact health and life span. Mounting evidence indicates that brain injury, even moderate injury, can lead to lifetime of physical and mental health symptoms. Therefore, the purpose of this mini-review is to discuss how recovery from traumatic brain injury (TBI) depends on age-at-injury and how aging with a TBI affects long-term recovery. TBI initiates pathophysiological processes that dismantle circuits in the brain. In response, reparative and restorative processes reorganize circuits to overcome the injury-induced damage. The extent of circuit dismantling and subsequent reorganization depends as much on the initial injury parameters as other contributing factors, such as genetics and age. Age-at-injury influences the way the brain is able to repair itself, as a result of developmental status, extent of cellular senescence, and injury-induced inflammation. Moreover, endocrine dysfunction can occur with TBI. Depending on the age of the individual at the time of injury, endocrine dysfunction may disrupt growth, puberty, influence social behaviors, and possibly alter the inflammatory response. In turn, activation of microglia, the brain's immune cells, after injury may continue to fuel endocrine dysfunction. With age, the immune system develops and microglia become primed to subsequent challenges. Sustained inflammation and microglial activation can continue for weeks to months post-injury. This prolonged inflammation can influence developmental processes, behavioral performance and age-related decline. Overall, brain injury may influence the aging process and expedite glial and neuronal alterations that impact mental health.

What influences birth place preferences, choices and decision-making amongst healthy women with straightforward pregnancies in the UK? A qualitative evidence synthesis using a 'best fit' framework approach.

BACKGROUND: English maternity care policy has supported offering women choice of birth setting for over twenty years, but only 13% of women in England currently give birth in settings other than obstetric units (OUs). It is unclear why uptake of non-OU settings for birth remains relatively low. This paper presents a synthesis of qualitative evidence which explores influences on women's experiences of birth place choice, preference and decision-making from the perspectives of women using maternity services. METHODS: Qualitative evidence synthesis of UK research published January 1992-March 2015, using a 'best-fit' framework approach. Searches were run in seven electronic data bases applying a comprehensive search strategy. Thematic framework analysis was used to synthesise extracted data from included studies. RESULTS: Twenty-four papers drawing on twenty studies met the inclusion criteria. The synthesis identified support for the key framework themes. Women's experiences of choosing or deciding where to give birth were influenced by whether they received information about available options and about the right to choose, women's preferences for different services and their attributes, previous birth experiences, views of family, friends and health care professionals and women's beliefs about risk and safety. The synthesis additionally identified that women's access to choice of place of birth during the antenatal period varied. Planning to give birth in OU was straightforward, but although women considering birth in a setting other than hospital OU were sometimes well-supported, they also encountered obstacles and described needing to 'counter the negativity' surrounding home birth or birth in midwife-led settings. CONCLUSIONS: Over the period covered by the review, it was straightforward for low risk women to opt for hospital birth in the UK. Accessing home birth was more complex and contested. The evidence on freestanding midwifery units (FMUs) is more limited, but suggests that women wanting to opt for an FMU birth experienced similar barriers. The extent to which women experienced similar problems accessing alongside midwifery units (AMUs) is unclear. Women's preferences for different birth options, particularly for 'hospital' vs non-hospital settings, are shaped by their pre-existing values, beliefs and experience, and not all women are open to all birth settings.

Diffuse traumatic brain injury induces prolonged immune dysregulation and potentiates hyperalgesia following a peripheral immune challenge.

BACKGROUND: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. RESULTS: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1-9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). CONCLUSIONS: We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for therapeutic rebalancing of peripheral immune homeostasis to improve functional outcome and decrease the incidence of peripheral inflammatory pain following traumatic brain injury.

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats.

Development and aging are influenced by external factors with the potential to impact health throughout the life span. Traumatic brain injury (TBI) can initiate and sustain a lifetime of physical and mental health symptoms. Over 1.7 million TBIs occur annually in the USA alone, with epidemiology suggesting a higher incidence for young age groups. Additionally, increasing life spans mean more years to age with TBI. While there is ongoing research of experimental pediatric and adult TBI, few studies to date have incorporated animal models of pediatric, adolescent, and adult TBI to understand the role of age at injury across the life span. Here, we explore repeated behavioral performance between rats exposed to diffuse TBI at five different ages. Our aim was to follow neurological morbidities across the rodent life span with respect to age at injury. A single cohort of male Sprague-Dawley rats (n = 69) was received at postnatal day (PND) 10. Subgroups of this cohort (n = 11-12/group) were subjected to a single moderate midline fluid percussion injury at age PND 17, PND 35, 2 months, 4 months, or 6 months. A control group of naïve rats (n = 12) was assembled from this cohort. The entire cohort was assessed for motor function by beam walk at 1.5, 3, 5, and 7 months of age. Anxiety-like behavior was assessed with the open field test at 8 months of age. Cognitive performance was assessed using the novel object location task at 8, 9, and 10 months of age. Depression-like behavior was assessed using the forced swim test at 10 months of age. Age at injury and time since injury differentially influenced motor, cognitive, and affective behavioral outcomes. Motor and cognitive deficits occurred in rats injured at earlier developmental time points, but not in rats injured in adulthood. In contrast, rats injured during adulthood showed increased anxiety-like behavior compared to uninjured control rats. A single diffuse TBI did not result in chronic depression-like behaviors or changes in body weight among any groups. The interplay of age at injury and aging with an injury are translationally important factors that influence behavioral performance as a quality of life metric. More complete understanding of these factors can direct rehabilitative efforts and personalized medicine for TBI survivors.

The UK Midwifery Study System (UKMidSS): a programme of work to establish a research infrastructure to carry out national studies of uncommon conditions and events in midwifery units.

BACKGROUND: Midwifery-led care during labour and birth in the UK is increasingly important given national commitments to choice of place of birth, reduction of unnecessary intervention and improving women's experience of care, and evidence on safety and benefits for 'low risk' women. Further evidence is needed on safety and potential benefits of midwifery-led care for some groups of 'higher risk' women and about uncommon adverse outcomes or 'near-miss' events. Uncommon obstetric events and conditions have been investigated since 2005 using the UK Obstetric Surveillance System. This programme of research will establish the UK Midwifery Study System (UKMidSS) in all UK alongside midwifery units (AMUs) and carry out the first two UKMidSS studies investigating: (i) outcomes in severely obese women admitted to AMUs, and (ii) risk factors for neonatal unit admission following birth in an AMU. METHODS: We will carry out national cohort and case-control studies using UKMidSS, a national data collection platform which we will establish to collect anonymised information from all UK AMUs. Reporting midwives in each AMU will actively report cases or nil returns in response to monthly notification emails. Denominator data on the number of women admitted to and giving birth in each AMU will also be collected. Anonymised data on risk factors, management and outcomes for cases and controls/comparators as appropriate for each study, will be collected electronically using information from medical records. We will calculate incidence and prevalence with 95% confidence intervals (CIs), tabulate descriptive data using frequencies and proportions, and use logistic regression to estimate odds ratios with 95% CIs comparing specific outcomes in case and comparison women and to investigate risk factors for conditions or outcomes. DISCUSSION: As the first national infrastructure facilitating research into uncommon events and conditions in women starting labour in midwifery-led settings, UKMidSS builds on the success of other national research systems. UKMidSS studies will extend the evidence base regarding the quality and safety of midwifery-led intrapartum care and investigate extending the benefits of midwifery-led care to more women. As a national collaboration of midwives contributing to high quality research, UKMidSS will provide an infrastructure to support midwifery research capacity development.

Speculating on health: public health meets finance in 'health impact bonds'.

Where modern public health developed techniques to calculate probability, potentiality, risk and uncertainty, contemporary finance introduces instruments that redeploy these. This article traces possibilities for interrogating the connection between health and financialisation as it is arising in one particular example - the health impact bond. It locates the development of this very recent financial innovation in an account of public health's role within governance strategies over the 20th century to the present. We examine how social impact bonds for chronic disease prevention programmes bring two previously distinct ways of thinking about and addressing risk into the same domain. Exploring the derivative-type properties of health impact bonds elucidates the financial processes of exchange, hedging, bundling and leveraging. As tools for speculation, the functions of health impact bonds can be delinked from any particular outcome for participants in health interventions. How public health techniques for knowing and acting on risks to population health will contest, rework or be subsumed within finance's speculative response to risk, is to be seen.

Clinical relevance of midline fluid percussion brain injury: Acute deficits, chronic morbidities and the utility of biomarkers.

BACKGROUND: After 30 years of characterisation and implementation, fluid percussion injury (FPI) is firmly recognised as one of the best-characterised reproducible and clinically relevant models of TBI, encompassing concussion through diffuse axonal injury (DAI). Depending on the specific injury parameters (e.g. injury site, mechanical force), FPI can model diffuse TBI with or without a focal component and may be designated as mild-to-severe according to the chosen mechanical forces and resulting acute neurological responses. Among FPI models, midline FPI may best represent clinical diffuse TBI, because of the acute behavioural deficits, the transition to late-onset behavioural morbidities and the absence of gross histopathology. REVIEW: The goal here was to review acute and chronic physiological and behavioural deficits and morbidities associated with diffuse TBI induced by midline FPI. In the absence of neurodegenerative sequelae associated with focal injury, there is a need for biomarkers in the diagnostic, prognostic, predictive and therapeutic approaches to evaluate outcomes from TBI. CONCLUSIONS: The current literature suggests that midline FPI offers a clinically-relevant, validated model of diffuse TBI to investigators wishing to evaluate novel therapeutic strategies in the treatment of TBI and the utility of biomarkers in the delivery of healthcare to patients with brain injury.

Experimental diffuse brain injury results in regional alteration of gross vascular morphology independent of neuropathology.

PRIMARY OBJECTIVE: A dynamic relationship exists between diffuse traumatic brain injury and changes to the neurovascular unit. The purpose of this study was to evaluate vascular changes during the first week following diffuse TBI. It was hypothesized that pathology is associated with modification of the vasculature. METHODS: Male Sprague-Dawley rats underwent either midline fluid percussion injury or sham-injury. Brain tissue was collected 1, 2 or 7 days post-injury or sham-injury (n = 3/time point). Tissue was collected and stained by de Olmos amino-cupric silver technique to visualize neuropathology or animals were perfused with AltaBlue casting resin before high-resolution vascular imaging. The average volume, surface area, radius, branching and tortuosity of the vessels were evaluated across three regions of interest. RESULTS: In M2, average vessel volume (p < 0.01) and surface area (p < 0.05) were significantly larger at 1 day relative to 2 days, 7 days and sham. In S1BF and VPM, no significant differences in the average vessel volume or surface area at any of the post-injury time points were observed. No significant changes in average radius, branching or tortuosity were observed. CONCLUSIONS: Preliminary findings suggest gross morphological changes within the vascular network likely represent an acute response to mechanical forces of injury, rather than delayed or chronic pathological processes.