Protective effects of peri-menopausal oestrogen replacement: A test of the critical period hypothesis

New director of studies: Prof Jackie AndradeFull version unavailable due to 3rd party copyright restrictions.Oestrogen decline during the menopause leads to decline in cognitive performance because oestrogen receptor sites are found in the prefrontal cortex and hippocampus of the female brain, areas associated with memory and attention functions. Extensive research over the past two decades has tested the effects of administering Hormone Replacement Therapy (HRT) to maintain oestrogen levels. MRI studies have shown improvements in hippocampal volume and frontal functions with HRT, but evidence for associated improvements in verbal memory performance has been mixed. Some studies have even found detrimental effects of HRT, leading to the suggestion of a critical period for HRT administration relative to menopause. Oestrogen receptor sites are found in frontal brain regions associated with working memory (WM) functions including attention. These functions have been researched less than verbal memory, but with similarly mixed findings. The research reported in this thesis tested the critical period hypothesis in relation to WM. Study one tested the prediction that HRT will benefit WM if the therapy is initiated during the peri-menopause, and will harm it if initiated post-menopause. A naturalistic sample of 121 women were recruited, comprising women who varied in the time they had begun taking HRT, and menopausal status-matched controls who had never taken HRT. Participants completed three tests of WM span and the Sustained Attention to Response Task (SART) on two occasions 12 months apart. WM performance supported the critical period hypothesis, with women who had begun the therapy after the menopause displayed worsened WM capacity when compared to peri-menopausal initiators and post-menopausal women with no history of HRT use. At one year follow up, postmenopausal HRT users were still underperforming compared to peri-HRT initiators and those in the post-menopausal stage with no history of HRT use. No significant differences were identified between groups on the SART. The effects of natural supplements on physical symptoms of the menopause have been researched, but there is little research on their effects on cognitive symptoms and none specifically testing the critical period hypothesis. Study two tested the effects of soya isoflavones on WM during peri- and post-menopausal stages. One hundred and twelve peri- and post-menopausal women were randomly allocated to receive either placebo or 100mg soya supplement in capsules daily for three months. Participants and researcher were blind to this allocation. Participants completed two tests of WM span and two Sustained Attention (SA) tasks at baseline, after three months of soya/placebo, and after a further three months without supplement. There was no effect of isoflavones on cognition, regardless of time of initiation of the supplement. This thesis offers a unique contribution to the literature, by establishing empirically that HRT may have long-lasting benefits for WM if administered in the peri-menopause period, and detriments if taken post-menopause. There was no evidence that administration of soya-based phytoestrogens for three months peri- or post-menopause replicated these effects of HRT on cognition

Selected factors contributing to preservice teachers' perceptions of the social and cognitive competence of preschool children

As increasing numbers of poor children enter child care programs due to changes in work requirements under the Welfare Reform Act, there is a critical need to examine factors that may affect the quality of care that these children receive. One factor that has received limited attention in the literature is how preservice teachers' perceptions of young children may vary according to characteristics of the child and the context in which the child exists. The current study employed an ecological person-process-context model to examine differences in preservice teachers' perceptions of children's social and cognitive competence. The sample for this study consisted of 68 children and 28 preservice teachers enrolled at a university-based preschool in Oregon. The preschool was the only site in the state featuring an integrated program in which Head Start children were enrolled with non-Head Start children under an Oregon Prekindergarten Program (OPP) grant. Hierarchical regression was used to determine if the contextual factor of enrollment in OPP would be a more significant contributor to preservice teachers' perceptions of children's social and cognitive competence than the person factors of child age, sex, race/ethnicity, temperament and actual child competence. Qualitative data was also collected through focus group discussions with preservice teachers. Sex was the most important contributor to preservice teachers' perceptions of children's social competence, followed by enrollment in OPP, actual social competence, and age. For preservice teachers' perceptions of children's cognitive competence, age was the most significant contributor, followed by actual cognitive competence, enrollment in OPP, and sex. While enrollment in OPP was not the most significant contributor to preservice teachers' perceptions of children's social and cognitive competence, it was still a significant contributor, beyond other person variables. For both social and cognitive competence, preservice teachers rated children enrolled in OPP lower than their non-OPP peers, girls higher than boys, and older children higher than younger children, even when the unique contribution of children's actual competence was included. Qualitative data generally supported these findings. Implications for research, policy, and practice are discussed

Reported changes in cycling habits among older adults during the early months of the COVID-19 pandemic, New South Wales, Australia

The im.pact of the 2020 COVID-19 pandemic and the associated public health measures enacted by governments globally bad a significant impact on all aspects of human life including economic activity and mobility. One of the main public health measures designed to reduce the transmission of the SAR-Co V-2 vims have been the implementation ofvarious levels of lockdowns that limited mobility and resulted in almost half of the world's population UD.der som.e form of confinement. Many govemm.ents, including in Australia, UK, and Norway, enacted flexible forms oflockdowns that allowed daily outdoor exercise, while adhering to safe physical distancing, in recognition of the role of physical activity in reducing the mental and physical consequences of confinement. Australia saw first strict lockdown restrictions over March/April 2020 with progressive easing of restrictions during May and Ju.ne 2020. Emerging evidence from these countries has indicated that physical activity, particularly cycling, increased over the lockdown period and the following months as some restrictions were eased. However, many have wamed of a decline in physical activity with serious health consequences among older adults who were at a high.er risk: of m.orbidity and fatality associated with COVID-19 and were m.ore likely tobe confined to their homes for longer periods compared to younger age groups. The aim ofthis stu.dy was to investigate the impact ofCOVID-19 pandemic on cycling activity among older adults aged 50 years and over in New South Wales (NSW), Australia during the early months of the COVID-19 pandemic

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Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

ABSTRACT Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa , a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC ( fT >MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2-compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance ( r = 0.71, P MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of ≥90% at MICs up to 4 and 8 μg/ml, respectively. Ceftolozane-tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.

Automatic detection and quantification of abdominal aortic calcification in dual energy X-ray absorptiometry

Cardiovascular disease (CVD) is a major cause of mortality and the main cause of morbidity worldwide. CVD may lead to heart attacks and strokes and most of these are caused by atherosclerosis; this is a medical condition in which the arteries become narrowed and hardened due to an excessive build-up of plaque on the inner artery wall. Arterial calcification and, in particular, abdominal aortic calcification (AAC) is a manifestation of atherosclerosis and a prognostic indicator of CVD. In this paper, a two-stage automatic method to detect and quantify the severity of AAC is described; it is based on the analysis of lateral vertebral fracture assessment (VFA) images. These images were obtained on a dual energy x-ray absorptiometry (DXA) scanner used in single energy mode. First, an active appearance model was used to segment the lumbar vertebrae L1-L4 and the aorta on VFA images; the segmentation of the aorta was based on its position with respect to the vertebrae. In the second stage, feature vectors representing calcified regions in the aorta were extracted to quantify the severity of AAC. The presence and severity of AAC was also determined using an established visual scoring system (AC24). The abdominal aorta was divided into four parts immediately anterior to each vertebra, and the severity of calcification in the anterior and posterior walls was graded separately for each part on a 0-3 scale. The results were summed to give a composite severity score ranging from 0 to 24. This severity score was classified as follows: mild AAC (score 0-4), moderate AAC (score 5-12) and severe AAC (score 12-24). Two classification algorithms (k-nearest neighbour and support vector machine) were trained and tested to assign the automatically extracted feature vectors into the three classes. There was good agreement between the automatic and visual AC24 methods and the accuracy of the automated technique relative to visual classification indicated that it is capable of identifying and quantifying AAC over a range of severit

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis

OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. METHODS: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. CONCLUSIONS: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule

Environmental change: prospects for conservation and agriculture in a southwest Australia biodiversity hotspot

Accelerating environmental change is perhaps the greatest challenge for natural resource management; successful strategies need to be effective for decades to come. Our objective is to identify opportunities that new environmental conditions may provide for conservation, restoration, and resource use in a globally recognized biodiversity hotspot in southwestern Australia. We describe a variety of changes to key taxonomic groups and system-scale characteristics as a consequence of environmental change (climate and land use), and outline strategies for conserving and restoring important ecological and agricultural characteristics. Opportunities for conservation and economic adaptation are substantial because of gradients in rainfall, temperature, and land use, extensive areas of remnant native vegetation, the ability to reduce and ameliorate areas affected by secondary salinization, and the existence of large national parks and an extensive network of nature reserves. Opportunities presented by the predicted environmental changes encompass agricultural as well as natural ecosystems. These may include expansion of aquaculture, transformation of agricultural systems to adapt to drier autumns and winters, and potential increases in spring and summer rain, carbon-offset plantings, and improving the network of conservation reserves. A central management dilemma is whether restoration/preservation efforts should have a commercial or biodiversity focus, and how they could be integrated. Although the grand challenge is conserving, protecting, restoring, and managing for a future environment, one that balances economic, social, and environmental values, the ultimate goal is to establish a regional culture that values the unique regional environment and balances the utilization of natural resources against protecting remaining natural ecosystems