Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

BACKGROUND: Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. METHODS: Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO(2 )from (14)C-labelled substrate, and polyamine levels were measured by HPLC. RESULTS: I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G(2)/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. CONCLUSION: While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G(2)/M phase of the cell cycle

Surgical treatment of zygomatic bone fracture using two points fixation versus three point fixation-a randomised prospective clinical trial

<p>Abstract</p> <p>Background</p> <p>The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements which in turn require protocol management and long-term follow up. The preference for open reduction and internal fixation of zygomatic fractures at three points has continued to grow in response to observations of inadequate results from two point and one point fixation techniques.</p> <p>The objectives of this study were to compare the efficacy of zygomatic bone after treatment with ORIF using 2 point fixation and ORIF using 3 point fixation and compare the outcome of two procedures.</p> <p>Methods</p> <p>100 patients were randomly divided equally into two groups. In group A, 50 patients were treated by ORIF using two point fixation by miniplates and in group B, 50 patients were treated by ORIF using three point fixation by miniplates. They were evaluated for their complications during and after surgery with their advantages and disadvantages and the difference between the two groups was observed.</p> <p>Results</p> <p>A total of 100 fractures were sustained. We found that postoperative complication like decreased malar height and vertical dystopia was more common in those patients who were treated by two point fixation than those who were treated with three point fixation.</p> <p>Conclusions</p> <p>Based on this study open reduction and internal fixation using three point fixation by miniplates is the best available method for the treatment zygomatic bone fractures.</p

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Cellular Prion Protein Expression Is Not Regulated by the Alzheimer's Amyloid Precursor Protein Intracellular Domain

There is increasing evidence of molecular and cellular links between Alzheimer's disease (AD) and prion diseases. The cellular prion protein, PrPC, modulates the post-translational processing of the AD amyloid precursor protein (APP), through its inhibition of the β-secretase BACE1, and oligomers of amyloid-β bind to PrPC which may mediate amyloid-β neurotoxicity. In addition, the APP intracellular domain (AICD), which acts as a transcriptional regulator, has been reported to control the expression of PrPC. Through the use of transgenic mice, cell culture models and manipulation of APP expression and processing, this study aimed to clarify the role of AICD in regulating PrPC. Over-expression of the three major isoforms of human APP (APP695, APP751 and APP770) in cultured neuronal and non-neuronal cells had no effect on the level of endogenous PrPC. Furthermore, analysis of brain tissue from transgenic mice over-expressing either wild type or familial AD associated mutant human APP revealed unaltered PrPC levels. Knockdown of endogenous APP expression in cells by siRNA or inhibition of γ-secretase activity also had no effect on PrPC levels. Overall, we did not detect any significant difference in the expression of PrPC in any of the cell or animal-based paradigms considered, indicating that the control of cellular PrPC levels by AICD is not as straightforward as previously suggested

The relationship between body size and mortality in the linked Scottish Health Surveys: cross-sectional surveys with follow-up

Objective: To investigate the relationship between body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) and all-cause mortality or cause-specific mortality. Design: Cross-sectional surveys linked to hospital admissions and death records. Subjects: In total, 20 117 adults (aged 18–86 years) from a nationally representative sample of the Scottish population. Measurements: Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause, or cause-specific, mortality. The three anthropometric measurements BMI, WC and WHR were the main variables of interest. The following were adjustment variables: age, gender, smoking status, alcohol consumption, survey year, social class and area of deprivation. Results: BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with increased risk of mortality (HR=0.93; 95% confidence interval=0.80–1.08), whereas the overweight category (25–&#60;30 kg m−2) was associated with a decreased risk (0.80; 0.70–0.91). In contrast, the HR for a high WC (mengreater than or equal to102 cm, womengreater than or equal to88 cm) was 1.17 (1.02–1.34) and a high WHR (mengreater than or equal to1, women&#8805;0.85) was 1.34 (1.16–1.55). There was an increased risk of cardiovascular disease (CVD) mortality associated with BMI-defined obesity, a high WC and a high WHR categories; the HR estimates for these were 1.36 (1.05–1.77), 1.41 (1.11–1.79) and 1.44 (1.12–1.85), respectively. A low BMI (&#60;18.5 kg m−2) was associated with elevated HR for all-cause mortality (2.66; 1.97–3.60), for chronic respiratory disease mortality (3.17; 1.39–7.21) and for acute respiratory disease mortality (11.68; 5.01–27.21). This pattern was repeated for WC but not for WHR. Conclusions: It might be prudent not to use BMI as the sole measure to summarize body size. The alternatives WC and WHR may more clearly define the health risks associated with excess body fat accumulation. The lack of association between elevated BMI and mortality may reflect the secular decline in CVD mortality.</p

Physical activity interventions to improve daily walking activity in cancer survivors

Background Cancer patients may benefit from physical exercise programs. It is unclear, however, how sustained levels of physical activity are best achieved in this population. A systematic review was performed to summarize the current evidence of the effect of physical activity interventions on daily walking activity enhancement in cancer survivors, and to review the literature for its methodological quality. Methods A search in Medline, PEDro and the Cochrane databases was performed for English literature citations (randomized controlled trials; `RCTs`). In a first step, one reviewer abstracted data from the included studies on patients, physical activity interventions and outcomes. Two independent reviewers reviewed the methodological quality of these studies. Data were pooled using random-effects calculations. Results Our search identified 201 citations. Five RCTs that reported changes in daily step activity over time were identified, and were reviewed for methodological quality and substantive results. The median score across studies for methodological quality based on the PEDro criteria was 8. These 5 RCTs evaluated 660 participants with a mean age of 53.6 (SD 4.2) years. The mean change in daily step activity for patients with a physical exercise intervention was 526 daily steps (SD 537), with a range from -92 to 1299 daily steps. The data of three studies reporting the effect of combined physical activity and counseling on daily walking activity in breast cancer survivors were pooled, however; the I2 was 79%, indicating statistical heterogeneity between the three trials. Conclusion The 5 RCTs reviewed were of good methodological quality. Together they suggest that combined physical activity and counseling improves daily step activity in (breast) cancer survivors. Studies that define a step goal appear to be more effective in improving daily walking activity than studies that do not do so. However, the current results should be interpreted with caution because of the observed clinical and statistical heterogeneity. Future studies are warranted to evaluate the effects of goal targeted physical activity, with or without counseling, on daily walking in various cancer populations

Contrast in Edge Vegetation Structure Modifies the Predation Risk of Natural Ground Nests in an Agricultural Landscape

Nest predation risk generally increases nearer forest-field edges in agricultural landscapes. However, few studies test whether differences in edge contrast (i.e. hard versus soft edges based on vegetation structure and height) affect edge-related predation patterns and if such patterns are related to changes in nest conspicuousness between incubation and nestling feeding. Using data on 923 nesting attempts we analyse factors influencing nest predation risk at different edge types in an agricultural landscape of a ground-cavity breeding bird species, the Northern Wheatear (Oenanthe oenanthe). As for many other bird species, nest predation is a major determinant of reproductive success in this migratory passerine. Nest predation risk was higher closer to woodland and crop field edges, but only when these were hard edges in terms of ground vegetation structure (clear contrast between tall vs short ground vegetation). No such edge effect was observed at soft edges where adjacent habitats had tall ground vegetation (crop, ungrazed grassland). This edge effect on nest predation risk was evident during the incubation stage but not the nestling feeding stage. Since wheatear nests are depredated by ground-living animals our results demonstrate: (i) that edge effects depend on edge contrast, (ii) that edge-related nest predation patterns vary across the breeding period probably resulting from changes in parental activity at the nest between the incubation and nestling feeding stage. Edge effects should be put in the context of the nest predator community as illustrated by the elevated nest predation risk at hard but not soft habitat edges when an edge is defined in terms of ground vegetation. These results thus can potentially explain previously observed variations in edge-related nest predation risk

Using Basic Science to Design a Clinical Trial: Baseline Characteristics of Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

Observational and epidemiological studies suggest that menopausal hormone therapy (MHT) reduces cardiovascular disease (CVD) risk. However, results from prospective trials showed neutral or adverse effects most likely due to differences in participant demographics, such as age, timing of initiation of treatment, and preexisting cardiovascular disease, which reflected in part the lack of basic science information on mechanisms of action of hormones on the vasculature at the time clinical trials were designed. The Kronos Early Estrogen Replacement Study (KEEPS) is a prospective, randomized, controlled trial designed, using findings from basic science studies, to test the hypothesis that MHT when initiated early in menopause reduces progression of atherosclerosis. KEEPS participants are younger, healthier, and within 3 years of menopause thus matching more closely demographics of women in prior observational and epidemiological studies than women in the Women’s Health Initiative hormone trials. KEEPS will provide information relevant to the critical timing hypothesis for MHT use in reducing risk for CVD