Delivery of small-for-gestational-age neonate and association with early-onset impaired maternal endothelial function

Objective Women who have delivered a small-for-gestational-age (SGA) infant are at an increased risk of developing cardiovascular disease (CVD) in later life. Endothelial dysfunction is a subclinical sign of early CVD. It is unknown whether women who have recently had a pregnancy complicated by SGA, in the absence of other maternal and fetal diseases, have subclinical endothelial dysfunction. Our aim was to assess maternal endothelial function 6 months after a pregnancy complicated by SGA. Methods This was a case–control study conducted in a tertiary referral hospital in London, UK, over a 15-month period. Flow-mediated dilatation (FMD) of the brachial artery was measured in women 6.9 ± 2.5 months after childbirth. Forty-four women were included in the study, of whom 15 had a SGA neonate (mean ± SD customized birth centile of 1.9 ± 2.3) and 29 delivered an appropriately grown baby (mean ± SD customized birth centile of 47.5 ± 26.3). The primary continuous variable, FMD, was assessed in each group and compared using unpaired t-test. Results Women who had a SGA neonate had lower postpartum FMD (6.79 ± 0.95%) than did those who had an appropriately grown offspring (10.26 ± 2.44% (95% CI for difference between groups, −5.37 to −1.57); P = 0.0007). There were no differences in postnatal maternal blood pressure, abdominal circumference, weight and glucose, insulin and lipid profiles between the two groups. Conclusions Women who had a pregnancy affected by SGA, probably due to placental failure in the absence of pre-eclampsia, have evidence of subclinical endothelial dysfunction within 6 months of childbirth. These women may benefit from lifestyle measures focused on the primary prevention of CVD. Further research in larger populations is needed to ascertain if such postpartum maternal endothelial dysfunction is a pregnancy-induced phenomenon or if it is related to the pre-existing maternal phenotype, and whether it persists long term

Agile methods for agile universities

We explore a term, Agile, that is being used in various workplace settings, including the management of universities. The term may have several related but slightly different meanings. Agile is often used in the context of facilitating more creative problem-solving and advocating for the adoption, design, tailoring and continual updating of more innovative organizational processes. We consider a particular set of meanings of the term from the world of software development. Agile methods were created to address certain problems with the software development process. Many of those problems have interesting analogues in the context of universities, so a reflection on agile methods may be a useful heuristic for generating ideas for enabling universities to be more creative

Psychometric evaluation of a visual analog scale for the assessment of anxiety

<p>Abstract</p> <p>Background</p> <p>Fast-acting medications for the management of anxiety are important to patients and society. Measuring early onset, however, requires a sensitive and clinically responsive tool. This study evaluates the psychometric properties of a patient-reported Global Anxiety - Visual Analog Scale (GA-VAS).</p> <p>Methods</p> <p>Data from a double-blind, randomized, placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability, validity, responsiveness, and utility of the GA-VAS. The GA-VAS was completed at clinic visits and at home during the first week of treatment. Targeted psychometric analyses—test-retest reliabilities, validity correlations, responsiveness statistics, and minimum important differences—were conducted.</p> <p>Results</p> <p>The GA-VAS correlates well with other anxiety measures, at Week 4, <it>r </it>= 0.60 (<it>p </it>< 0.0001) with the Hamilton Rating Scale for Anxiety and <it>r </it>= 0.74 (<it>p </it>< 0.0001) with the Hospital Anxiety and Depression Scale - Anxiety subscale. In terms of convergent and divergent validity, the GA-VAS correlated -0.54 (<it>p </it>< 0.0001), -0.48 (<it>p </it>< 0.0001), and -0.68 (<it>p </it>< 0.0001) with the SF-36 Emotional Role, Social Function, and Mental Health subscales, respectively, but correlated much lower with the SF-36 physical functioning subscales. Preliminary minimum important difference estimates cluster between 10 and 15 mm.</p> <p>Conclusions</p> <p>The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose.</p

AMPA receptors in the development and treatment of epilepsy

In this thesis I have determined the effects of seizures on AMPA receptors and examined the effects of AMPA receptor modulation, by medium chain triglycerides and derivatives, on seizures. AMPA receptors play a central role in synaptic transmission in the brain and are critical for the generation of seizure activity. Recent work has indicated that prolonged seizures alter AMPA receptor transmission. Here I determined whether these changes occur in an acute in vitro seizure model, to aid exploration of the underlying mechanisms of these alterations. I demonstrated that, as observed in vivo, seizure activity changes the kinetics of AMPA receptor-mediated currents by increasing the proportion of GluA2-lacking, calcium permeable AMPA receptors. I next showed that this subunit switch is dependent on the activation of NMDA receptors and calcineurin. In a separate set of experiments I determined the effects of a range of novel AMPA receptor antagonists on synaptic transmission and seizure activity. Decanoic acid, a key component of the medium chain triglyceride ketogenic diet used in refractory epilepsy, has recently been shown to act as a non-competitive AMPA receptor antagonist. Here I showed that a range of structurally related compounds which also act as AMPA receptor antagonists are effective in in vitro models of seizure-like activity. I have further explored the mechanisms underlying decanoic acid's action. Decanoic acid is synergistic with the AMPA receptor antagonist, perampanel, and is not use-dependent. Moreover, I have shown that decanoic acid has an action at voltage-gated sodium channels to decrease the intrinsic excitability of neurons. Decanoic acid reduces the persistent sodium current, without altering the transient sodium current. Surprisingly, decanoic acid has minimal effect on in vivo status epilepticus (prolonged seizure activity) possibly because of rapid and extensive metabolism by the liver. Lastly, I undertook preliminary experiments in human neurons. Decanoic acid effectively reduces induced seizure-like activity in slices from surgically-resected human neocortical tissue. It inhibits AMPA receptor-mediated currents but does not alter intrinsic excitability, as in rat CA1, possibly due to regional differences in neuronal properties. My findings indicate that seizure activity rapidly changes the AMPA receptors expressed in the synapse and identify a range of compounds that target AMPA receptors, which are effective against seizure activity

Perpetration of gross human rights violations in South Africa: Association with psychiatric disorders

Background. A nationally representative study of psychiatric disorders in South Africa provided an opportunity to study the association between perpetration of human rights violations (HRVs) during apartheid and psychiatric disorder. Prior work has suggested an association between perpetration and post-traumatic stress disorder (PTSD), but this remains controversial.Methods. Subjects reported on their perpetration of human rights violations, purposeful injury, accidental injury and domestic violence. Lifetime and 12-month prevalence of DSM-IV (Diagnostic and Statistical Manual, 4th edition) disorders were assessed with Version 3.0 of the World Health Organization Composite International Diagnostic Interview (CIDI 3.0). Socio-demographic characteristics of these groups were calculated. Odds ratios for the association between the major categories of psychiatric disorders and perpetrationwere assessed.Results. HRV perpetrators were more likely to be male, black and more educated, while perpetrators of domestic violence ( DV) were more likely to be female, older, married, less educated and with lower income. HRV perpetration was associated with lifetime and 12-month anxiety and substance use disorders, particularly PTSD. Purposeful andDV perpetration were associated with lifetime and 12-month history of all categories of disorders, whereas accidental perpetration was associated most strongly with mood disorders.Conclusion. Socio-demographic profiles of perpetrators of HRV and DV in South Africa differ. While the causal relationship between perpetration and psychiatric disorders deserves further study, it is possible that some HRV and DV perpetrators were themselves once victims. The association between accidental perpetration and mood disorder alsodeserves furher attention

Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair.

It is proposed that an acellular natural osteochondral scaffold will provide a successful repair material for the early intervention treatment of cartilage lesions, to prevent or slow the progression of cartilage deterioration to osteoarthritis. Here, we investigated the efficacy of methods for the decellularisation of bovine osteochondral plugs. The plugs were subject to four freeze/thaw cycles followed by two cycles of washes in hypotonic solution and low concentration (0.1 % w/v) sodium dodecyl sulphate with protease inhibitors. Plugs were treated with nuclease (DNase and RNase) treatment followed by sterilization in peracetic acid. Full tissue decellularisation was achieved as confirmed by histological analysis and DNA quantification, however the resultant acellular matrix had reduced glycosaminoglycan content which led to an increased percent deformation of cartilage. Furthermore, the acellular scaffold was not reproducibly biocompatible. Additional terminal washes were included in the process to improve biocompatibility, however, this led to visible structural damage to the cartilage. This damage was found to be minimised by reducing the cut edge to cartilage area ratio through decellularisation of larger cuts of osteochondral tissue

Mental health service use among South Africans for mood, anxiety and substance use disorders

Background. Europe and North America have low rates of mental health service use despite high rates of mental disorder. Little is known about mental health service use among South Africans.Design. A nationally representative survey of 4 351 adults. Twelve-month DSM-IV (Diagnostic and Statistical Manual, 4th edition) diagnoses, severity, and service utilisation were determined using the World Health Organization Composite International Diagnostic Interview (CIDI). Twelve-month treatment was categorised by sector and province. South Africans in households and hostel quarters were interviewed between 2002 and 2004 in all nine provinces.Outcome measures. 4 317 respondents 18 years and older wereanalysed. Bivariate logistic regression models predicted (i) 12-month treatment use of service sectors by gender, and (ii) 12-month treatment use by race by gender.Results. Of respondents with a mental disorder, 25.2% had sought treatment within the previous 12 months; 5.7% had used any formal mental health service. Mental health service use was highest for adults with mood and anxiety disorders, and among those with a mental disorder it varied by province, from 11.4% (Western Cape) to 2.2% (Mpumalanga). More women received treatment, and this was largelyattributable to higher rates of treatment in women with mood disorders. Age, income, education and marital status were not significantly associated with mental health service use. Race was associated with the treatment sector accessed in those with a mental disorder.Conclusions. There is a substantial burden of untreated mental disorders in the South African population, across all provinces and even in those with substantial impairment. Greater allocation of resources to mental health services and more community awareness initiatives are needed to address the unmet need

Excessive daytime sleepiness and body composition: a population-based study of adults

Excessive daytime sleepiness (EDS) is often associated with increased adiposity, particularly when assessed in the context of samples of sleep-disordered patients; however, it is unclear if this relationship is sustained among non-clinical, population-based cohorts. This study aimed to investigate the relationship between EDS and a number of body composition markers among a population-based sample of men and women

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us