Special study: Legal transition programme review

This study is an evaluation of the European Bank for Reconstruction and Development's Legal Transition Programme’s activities from 2001-2011, through a review of a sample of 30 legal reform projects and advisory projects in Armenia, Hungary, Mongolia, Russia and Serbia. It was conducted by the Evaluation department in conjunction with three external experts: Professor Douglas Arner (University of Hong Kong), Professor Charles Booth (University of Hawaii) and Professor Gordon Walker (LaTrobe University). Overall the programme was found to be successful due to its compatibility with the Bank’s activities and highly relevant due to its support of the Bank’s investments through contributions to legal improvements. The programme’s projects have made a core contribution to the transition process, influencing domestic policy formulation and contributing to stronger free market economies. The transition impact and sustainability of the programme was found to be excellent.published_or_final_versio

Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Hormone replacement therapy and risk of epithelial ovarian cancer

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaig

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data

In vitro assembly of Ebola virus nucleocapsid-like complex expressed in E. coli

Ebola virus (EBOV) harbors an RNA genome encapsidated by nucleoprotein (NP) along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451–739) alone is capable of forming a helical nucleocapsid-like complex (NLC). However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451–739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro

Chronic hepatosplenomegaly in African school children: a common but neglected morbidity associated with schistosomiasis and malaria.

Chronic hepatosplenomegaly, which is known to have a complex aetiology, is common amongst children who reside in rural areas of sub-Saharan Africa. Two of the more common infectious agents of hepatosplenomegaly amongst these children are malarial infections and schistosomiasis. The historical view of hepatosplenomegaly associated with schistosomiasis is that it is caused by gross periportal fibrosis and resulting portal hypertension. The introduction of ultrasound examinations into epidemiology studies, used in tandem with clinical examination, showed a dissociation within endemic communities between presentation with hepatosplenomegaly and ultrasound periportal fibrosis, while immuno-epidemiological studies indicate that rather than the pro-fibrotic Th2 response that is associated with periportal fibrosis, childhood hepatosplenomegaly without ultrasound-detectable fibrosis is associated with a pro-inflammatory response. Correlative analysis has shown that the pro-inflammatory response is also associated with chronic exposure to malarial infections and there is evidence of exacerbation of hepatosplenomegaly when co-exposure to malaria and schistosomiasis occurs. The common presentation with childhood hepatosplenomegaly in rural communities means that it is an important example of a multi-factorial disease and its association with severe and subtle morbidities underlies the need for well-designed public health strategies for tackling common infectious diseases in tandem rather than in isolation

Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto

<p>Abstract</p> <p>Background</p> <p>Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.</p> <p>Methods</p> <p>Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.</p> <p>Results</p> <p>There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.</p> <p>Conclusion</p> <p>Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.</p