28 years of vegetation change (1978 – 2006) in a calcareous coastal dune system

Changes in vegetation structure and composition over a 28 year period (1978–2006) following removal of human-induced disturbances, were examined in a calcareous coastal dune system in Point Nepean National Park (380 19’S, 1440 41’E) in south-eastern Victoria, Australia. In the early 1980s human habitation of Point Nepean was abandoned and disturbance regimes such as burning, slashing and land clearing were altered or removed, providing an opportunity to study the recovery of disturbed coastal vegetation. Broad-scale and community-level vegetation changes were assessed by comparing quadrat and GIS mapping data from 1978 with data collected in 2006. Results indicate a change in broad vegetation patterns; shrubland vegetation has replaced hind dune grasslands and disturbed areas and there has been a decrease in exposed coastal areas (such as blowouts, dunes and cliffs), and an increase in woody native species and highly invasive woody weeds. The changes highlight the importance of incorporating vegetation states in planning management actions in dynamic coastal vegetation

Persistent Barriers to Implementing Efficacious Mosquito Control Activities in the Continental United States: Insights from Vector Control Experts

Many barriers undermine vector surveillance and control efforts in the United States. Experts warn that such barriers, including funding, threaten the capacity of public-health surveillance systems to detect emerging mosquito-borne disease and respond appropriately, timely and effectively. This chapter explores the status, barriers, and corrective strategies to effective mosquito surveillance and control in the US based on experiences and insights of the 35 interviewed representatives of diverse mosquito-control programs selected from 18 U.S. states. Although our interest is in mosquito-borne diseases, we focus on the 2016 Zika outbreak. For the most part, this chapter will outline issues relating to mosquito control and surveillance that have persistent among state, county and municipal programs as a result of insufficient and unreliable funding, inadequate trained personnel, poor facilities, and inadequate political support. At the community level, we will discuss issues that hinder mosquito control efforts including apathy and low public awareness, and provide examples of how mosquito control agencies have adapted to “readily” respond to changing vector-borne disease environments, demands and constrained funding

The vegetation of the Nepean Peninsula, Victoria : an historical perspective

We use historical information and extensive contemporary surveys to describe the pre-European vegetation of the Nepean Peninsula, an extensive area of calcareous sand dunes at the tip of the Mornington Peninsula, south of Melbourne, Victoria (38º19’S 144º43’E). We conclude that much of the area was once covered by open, grassy woodlands, variously dominated by Allocasuarina verticillata (Drooping Sheoak), Banksia integrifolia subsp. integrifolia (Coast Banksia), Acacia species (Wattles), and Melaleuca lanceolata subsp. lanceolata (Moonah), along with a range of other species. Some areas supported shrublands, woodlands, forests, grasslands and wetlands. This area was markedly distinct from most other nearby areas, and has ecological affinities with areas in western Victoria. Over 200 years of ‘European’ land use have left this landscape remarkably different today – even in places where native vegetation persists. We review and discuss the environmental factors that have influenced the pattern and structure of the vegetation

Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study

Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson’s disease, and Alzheimer’s disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected by clinical teams after clinical examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also in only participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2·40, 95% CI 2·14–2·70; p=1·05 × 10–⁴⁸), SNCA (rs7681440; OR 0·73, 0·66–0·81; p=6·39 × 10–¹⁰), and GBA (rs35749011; OR 2·55, 1·88–3·46; p=1·78 × 10–⁹). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1·51, 1·27–1·79; p=2·21 × 10–⁶); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease

Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

A comprehensive screening of copy number variability in dementia with Lewy bodies

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk. (C) 2019 Elsevier Inc. All rights reserved.Peer reviewe

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

“Older-wiser-lesbians” and “baby-dykes”: mediating age and generation in New Queer Cinema

Representations of intersections of gender, age, and sexuality can reveal deep-rooted cultural anxieties about older women and sexuality. Images of lesbian ageing are of particular interest in terms of alterity, as the old/er queer woman can combine layers of otherness—not only is she the cultural “other” within heteronormativity, but she can also appear as the opposite of popular culture’s lesbian chic. In this article, a cultural analysis of a range of films—If These Walls Could Talk 2 (dir. Anderson, Coolidge, and Heche 2000), Itty Bitty Titty Committee (dir. Babbit 2007), The Owls (dir. Dunye 2010), Hannah Free (dir. Carlton 2009), and Cloudburst (dir. Fitzgerald 2011)—considers diverse dramatisations of lesbian generations. This article interrogates to what extent alternative cinemas deconstruct normative conceptualisations of ageing. Drawing on recent critiques of post-feminist culture, and a range of feminist and age/ing studies scholarship, it suggests that a linear understanding of ageing and the generational underlies dominant depictions of oppositional binaries of young versus old, of generational segregation or rivalry, and the othering of age. It concludes that non-linear understandings of temporality and ageing contain the potential for New Queer Cinema to counteract such idealisations of youthfulness, which, it argues, is one of the most deep-rooted manifestations of (hetero)normativity

Increase in Obesity Among Women of Reproductive Age in Zambia, 2002-2014

To describe trends in obesity in Zambian women of reproductive age and to identify factors that may have contributed to changes in trends and nutrition outcomes. We obtained data on body mass index and individual factors of women from the Zambia Demographic and Health Survey for the period 2002 to 2014. From these data, we calculated descriptive statistics and examined the extent to which factors link to the odds of obesity over time. We also reviewed primary and secondary data sources, such as government documents, theses, and search engines to identify factors that may have contributed to trends and changes in nutrition outcomes. The proportion of obesity doubled from 2002 (12.5%) to 2014 (22.3%). The odds were higher among educated, currently married and wealthy women, and it increased with age. Rural residence and working in agricultural-related jobs were linked to lower odds for obesity. This disparity varies by province. In addition, despite the presence of many nutrition policies and strategies, the increase in obesity occurred within the past two decades when urbanization and other factors ( , sedentary work, a proliferation of fast food restaurants, and advertisements) may have affected changes in nutrition outcomes for women. We identified increasing trends in obesity in women of reproductive age over time. The rapid urbanization and other factors that occurred in Zambia during this period are significant risk factors for obesity in Zambian women. The findings will be of interest to countries that are undergoing a nutrition transition