Frequent burning promotes invasions of alien plants into a mesic African savanna

Fire is both inevitable and necessary for maintaining the structure and functioning of mesic savannas. Without disturbances such as fire and herbivory, tree cover can increase at the expense of grass cover and over time dominate mesic savannas. Consequently, repeated burning is widely used to suppress tree recruitment and control bush encroachment. However, the effect of regular burning on invasion by alien plant species is little understood. Here, vegetation data from a long-term fire experiment, which began in 1953 in a mesic Zimbabwean savanna, were used to test whether the frequency of burning promoted alien plant invasion. The fire treatments consisted of late season fires, lit at 1-, 2-, 3-, and 4-year intervals, and these regularly burnt plots were compared with unburnt plots. Results show that over half a century of frequent burning promoted the invasion by alien plants relative to areas where fire was excluded. More alien plant species became established in plots that had a higher frequency of burning. The proportion of alien species in the species assemblage was highest in the annually burnt plots followed by plots burnt biennially. Alien plant invasion was lowest in plots protected from fire but did not differ significantly between plots burnt triennially and quadrennially. Further, the abundance of five alien forbs increased significantly as the interval (in years) between fires became shorter. On average, the density of these alien forbs in annually burnt plots was at least ten times as high as the density of unburnt plots. Plant diversity was also altered by long-term burning. Total plant species richness was significantly lower in the unburnt plots compared to regularly burnt plots. These findings suggest that frequent burning of mesic savannas enhances invasion by alien plants, with short intervals between fires favouring alien forbs. Therefore, reducing the frequency of burning may be a key to minimising the risk of alien plant spread into mesic savannas, which is important because invasive plants pose a threat to native biodiversity and may alter savanna functioning

Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

<p>Abstract</p> <p>Background</p> <p>The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies.</p> <p>Methods</p> <p>We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells.</p> <p>Results and Discussion</p> <p>Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells.</p> <p>Conclusions</p> <p>Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.</p

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity

T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions

A cost minimisation analysis in teledermatology: model-based approach

<p>Abstract</p> <p>Background</p> <p>Although store-and-forward teledermatology is increasingly becoming popular, evidence on its effects on efficiency and costs is lacking. The aim of this study, performed in addition to a clustered randomised trial, was to investigate to what extent and under which conditions store-and-forward teledermatology can reduce costs from a societal perspective.</p> <p>Methods</p> <p>A cost minimisation study design (a model based approach) was applied to compare teledermatology and conventional process costs per dermatology patient care episode. Regarding the societal perspective, total mean costs of investment, general practitioner, dermatologists, out-of-pocket expenses and employer costs were calculated. Uncertainty analysis was performed using Monte Carlo simulation with 31 distributions in the used cost model. Scenario analysis was performed using one-way and two-way sensitivity analyses with the following variables: the patient travel distance to physician and dermatologist, the duration of teleconsultation activities, and the proportion of preventable consultations.</p> <p>Results</p> <p>Total mean costs of teledermatology process were €387 (95%CI, 281 to 502.5), while the total mean costs of conventional process costs were €354.0 (95%CI, 228.0 to 484.0). The total mean difference between the processes was €32.5 (95%CI, -29.0 to 74.7). Savings by teledermatology can be achieved if the distance to a dermatologist is larger (> = 75 km) or when more consultations (> = 37%) can be prevented due to teledermatology.</p> <p>Conclusions</p> <p>Teledermatology, when applied to all dermatology referrals, has a probability of 0.11 of being cost saving to society.</p> <p>In order to achieve cost savings by teledermatology, teledermatology should be applied in only those cases with a reasonable probability that a live consultation can be prevented.</p> <p>Trail Registration</p> <p>This study is performed partially based on PERFECT D Trial (Current Controlled Trials No.ISRCTN57478950).</p

Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn−/−) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn−/− muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn−/− skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy

Association between Carotid Plaque Characteristics and Cerebral White Matter Lesions: One-Year Follow-Up Study by MRI

Objective: To prospectively assess the relation between carotid plaque characteristics and the development of new cerebral white matter lesions (WMLs) at MRI. Methods: Fifty TIA/stroke patients with ipsilateral 30-69% carotid stenosis underwent MRI of the plaque at baseline. Total plaque volume and markers of vulnerability to thromboembolism (lipid-rich necrotic core [LRNC] volume, fibrous cap [FC] status, and presence of intraplaque hemorrhage [IPH]) were assessed. All patients also underwent brain MRI at baseline and after one year. Ipsilateral cerebral WMLs were quantified with a semiautomatic method. Results: Mean WML volume significantly increased over a one-year period (6.52 vs. 6.97 mm3, P = 0.005). WML volume at baseline and WML progression did not significantly differ (P>0.05) between patients with 30-49% and patients with 50-69% stenosis. There was a significant correlation between total plaque volume and baseline ipsilateral WML volume (Spearman ¿ = 0.393, P = 0.005). There was no significant correlation between total plaque volume and ipsilateral WML progression. There were no significant associations between LRNC volume and WML volume at baseline and WML progression. WML volume at baseline and WML progression did not significantly differ between patients with a thick and intact FC and patients with a thin and/or ruptured FC. WML volume at baseline and WML progression also did not significantly differ between patients with and without IPH. Conclusion: The results of this study indicate that carotid plaque burden is significantly associated with WML severity, but that there is no causal relationship between carotid plaque vulnerability and the occurrence of WMLs. © 2011 Kwee et al

Chronic fatigue syndrome in an ethnically diverse population: the influence of psychosocial adversity and physical inactivity

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) is a complex multifactorial disorder. This paper reports the prevalence of chronic fatigue (CF) and CFS in an ethnically diverse population sample and tests whether prevalence varies by social adversity, social support, physical inactivity, anxiety and depression.</p> <p>Methods</p> <p>Analysis of survey data linking the Health Survey for England (1998 and 1999) and the Ethnic Minority Psychiatric Illness Rates in the Community (EMPIRIC) study undertaken in 2000. The study population comprised a national population sample of 4,281 people ages 16 to 74 years. CF and CFS were operationally defined on the basis of an interview in the EMPIRIC study, alongside questions about psychosocial risk factors. Previous illnesses were reported in the Health Survey for England during 1998 and 1999, as was physical inactivity.</p> <p>Results</p> <p>All ethnic minority groups had a higher prevalence of CFS than the White group. The lowest prevalence was 0.8% in the White group, and it was highest at 3.5% in the Pakistani group (odds ratio (OR), 4.1; 95% confidence interval (95% CI), 1.6 to 10.4). Anxiety (OR, 1.8; 95% CI, 1.4 to 2.2), depression (OR, 1.4; 95% CI, 1.1 to 1.8), physical inactivity (OR, 2.0; 95% CI, 1.1 to 3.8), social strain (OR, 1.24; 95% CI, 1.04 to 1.48) and negative aspects of social support (OR, 2.12; 95% CI, 1.4 to 3.3) were independent risk factors for CFS in the overall sample. Together these risk factors explained ethnic differences in the prevalence of CFS, but no single risk factor could explain a higher prevalence in all ethnic groups.</p> <p>Conclusions</p> <p>The prevalence of CFS, but not CF, varies by ethnic group. Anxiety, depression, physical inactivity, social strain and negative aspects of social support together accounted for prevalence differences of CFS in the overall sample.</p

Perceived need for mental health care and barriers to care in the Netherlands and Australia

This study of Australian and Dutch people with anxiety or depressive disorder aims to examine people's perceived needs and barriers to care, and to identify possible similarities and differences. Data from the Australian National Survey of Mental Health and Well-Being and the Netherlands Study of Depression and Anxiety were combined into one data set. The Perceived Need for Care Questionnaire was taken in both studies. Logistic regression analyses were performed to check if similarities or differences between Australia and the Netherlands could be observed. In both countries, a large proportion had unfulfilled needs and self-reliance was the most frequently named barrier to receive care. People from the Australian sample (N = 372) were more likely to perceive a need for medication (OR 1.8; 95% CI 1.3-2.5), counselling (OR 1.4; 95% CI 1.0-2.0) and practical support (OR 1.8; 95% CI 1.2-2.7), and people's overall needs in Australia were more often fully met compared with those of the Dutch sample (N = 610). Australians were more often pessimistic about the helpfulness of medication (OR 3.8; 95% CI 1.4-10.7) and skills training (OR 3.0; 95% CI 1.1-8.2) and reported more often financial barriers for not having received (enough) information (OR 2.4; 95% CI 1.1-5.5) or counselling (OR 5.9; 95% CI 2.9-11.9). In both countries, the vast majority of mental health care needs are not fulfilled. Solutions could be found in improving professionals' skills or better collaboration. Possible explanations for the found differences in perceived need and barriers to care are discussed; these illustrate the value of examining perceived need across nations and suggest substantial commonalities of experience across the two countries

An evaluation of three DoE-guided meta-heuristic-based solution methods for a three-echelon sustainable distribution network

This article evaluates the efficiency of three meta-heuristic optimiser (viz. MOGA-II, MOPSO and NSGA-II)-based solution methods for designing a sustainable three-echelon distribution network. The distribution network employs a bi-objective location-routing model. Due to the mathematically NP-hard nature of the model a multi-disciplinary optimisation commercial platform, modeFRONTIER®, is adopted to utilise the solution methods. The proposed Design of Experiment (DoE)-guided solution methods are of two phased that solve the NP-hard model to attain minimal total costs and total CO2 emission from transportation. Convergence of the optimisers are tested and compared. Ranking of the realistic results are examined using Pareto frontiers and the Technique for Order Preference by Similarity to Ideal Solution approach, followed by determination of the optimal transportation routes. A case of an Irish dairy processing industry’s three-echelon logistics network is considered to validate the solution methods. The results obtained through the proposed methods provide information on open/closed distribution centres (DCs), vehicle routing patterns connecting plants to DCs, open DCs to retailers and retailers to retailers, and number of trucks required in each route to transport the products. It is found that the DoE-guided NSGA-II optimiser based solution is more efficient when compared with the DoE-guided MOGA-II and MOPSO optimiser based solution methods in solving the bi-objective NP-hard three-echelon sustainable model. This efficient solution method enable managers to structure the physical distribution network on the demand side of a logistics network, minimising total cost and total CO2 emission from transportation while satisfying all operational constraints