Battle and Beating, Water and Waste: Micro-Level Impact Evaluation in Developing and Emerging Economies

Die Dissertation mit dem Titel “Battle and Beating, Water and Waste: Micro-Level Impact Evaluation in Developing and Emerging Economies” beinhaltet die Ergebnisse ökonometrischer Wirkungsevaluierungen, die innerhalb zwei verschiedener Themengebieten des täglichen Lebens in Entwicklungs- und Schwellenländern durchgeführt wurden: Gewalt und Wasser. Im ersten dieser Themengebiete konzentriert sich die Analyse auf die Verhaltens-Reaktionen der Bevölkerung, die in räumlicher Nähe zu gewaltsamem Konflikt lebt. Detailliert die Wirkung solcher Exponierung auf das Auftreten häuslicher Gewalt untersuchend, trägt das erste Kapitel – gemeinsam verfasst mit Dominik Noe – dazu bei, die gesellschaftlichen Kosten kriegsähnlicher Auseinandersetzungen abzuschätzen. Insbesondere die Nachwirkungen auf zwischenmenschliche Beziehungen und soziales Verhalten gegenüber Familie und Freunden werden betrachtet. Wir formulieren die Theorie, dass das Leben in Haushalten in der Nähe zu Orten von extrem gewaltsamen Zwischenfällen die Wahrscheinlichkeit von Frauen in diesen Haushalten erhöht, Opfer häuslicher Gewalt zu werden. Diese Theorie überprüfen wir dann anhand von Daten aus Kolumbien; einem Land, in dem sowohl reichhaltige Daten zu Gefechten als auch zu häuslicher Gewalt vorliegen. Die Kernerkenntnis lautet, dass eine höhere Intensität der gewaltsamen Konflikte mutmaßlich die Wahrscheinlichkeit der Frauen, Opfer häuslicher Gewalt zu werden, deutlich erhöht. Das zweite und dritte Kapitel dieser Dissertation sind dem zweiten Themengebiet gewidmet, und hier insbesondere Aspekten des Anschlusses von Haushalten an Leitungswasser und moderne Abwasser-Entsorgung. Das zweite Kapitel – gemeinsam verfasst mit Stephan Klasen, Tobias Lechtenfeld und Kristina Meier – untersucht die Wirkung des Anschlusses von Haushalten an Leitungswasser und Abwasser-entsorgung auf Gesundheit sowie Schul- und Arbeitsplatz-Anwesenheit. Es trägt zu der derzeit noch überschaubaren Anzahl von Wirkungsevaluierungen im Wasser- und Abwasserbereich bei, und ist nach Kenntnis der Autoren die erste rigorose Wirkungsevaluierung im städtischen Umfeld. Quasi-experimentelle Methoden und Wasserqualitäts-Tests unter Berücksichtigung von ungleichmäßiger Infrastruktur-Ausbreitung erlauben es, die Wirkungen separat einerseits für Anschluss lediglich an Leitungswasser, als auch andererseits für zusätzlichen Anschluss an Abwasserentsorgung, zu schätzen. Die Kernerkenntnis lautet, dass Anschluss an Leitungswasser in jemenitischen Städten schädlich sein kann, wenn die Wasserversorgung unregelmäßig ist; und die Wirkung bei regelmäßiger Versorgung im Vergleich zu traditionellen und alternativen Wasserquellen sehr gering ist. Anschluss an Abwasserentsorgung scheint dagegen bei regelmäßiger Wasserversorgung zu gesundheitlichem Nutzen zu führen. Es ist regelmäßig zu beobachten, dass in Aufbereitungsanlagen entkeimtes Leitungswasser innerhalb des Haushaltes rekontaminiert wird. Wasserqualitäts-Tests an Testpunkten entlang der Versorgungskette innerhalb des Haushaltes erlaubt Rückschlüsse auf Ort und Quelle der Kontaminierung. Der Löwenanteil dieser Verschlechterung der Wasserqualität ist auf Verhalten im Zusammenhang mit Wasser-Handhabung und Hygiene zurückzuführen. Das in Alleinautorschaft verfasste dritte Kapitel baut auf dem zweiten auf und untersucht, welche treibenden Faktoren hinter Verhaltensaspekten stehen, die Rekontaminierung verhindern würden. Spezifisch die Determinanten von Wasserbehandlung und Hygiene werden untersucht, und vor dem Hintergrund der Erkenntnisse aus dem zweiten Kapitel interpretiert. Die Kernerkenntnis lautet, dass Hygiene-Training, Zugang zu Informations- und Kommunikations-Technologie sowie Schulbildung mutmaßlich zu den relevanten, beeinflussbaren Determinanten zählen. Anschluss an Leitungswasser und Abwasserentsorgung – welche üblicherweise bestenfalls mittelfristig ausgebaut werden können – haben scheinbar ebenfalls wünschenswerte Effekte, allerdings in geringerem Maße, und in höherem Maße bei Leitungswasser als bei zusätzlicher Abwasserentsorgung

‘More than scaling-up’: Sustainability contexts, competencies, and consequences - a critical inquiry

To identify and problematise the key issues characterising the relationship between global sustainability contexts and the limited response of HE to date - with the purpose of unlocking the potential for innovative, replicable efforts to develop sustainability competencies through innovation in curriculum policy and practice, through addressing these sub-aims: How far does HE policy accommodate and reflect the need for sustainability competencies? How can capacity for teaching for competency be built and supported through new policies? How can curricula and pedagogy be better aligned to facilitate the building of sustainability competency in learners and teachers? What effect and influence does education for sustainability competency have in terms of facilitating transformative social learning, supporting systems structure change, and cultivating informed responsibility (in terms of policy and everyday decision making)?PedRI

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS

Background Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods MOG35-55 induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results EAE disease course was slightly attenuated in male apoE-deficient (apoE −/− ) mice compared to wildtype mice (cumulative median score: apoE −/−  = 2 [IQR 0.0–4.5]; wildtype = 4 [IQR 1.0–5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE −/− mice compared to wildtype mice (cumulative median score: apoE −/−  = 3 [IQR 2.0–4.5]; wildtype = 3 [IQR 0.0–4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease

Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial

The efficacy of chloroquine in the treatment of Plasmodium vivax malaria is declining on the Northwestern border of Thailand. This randomized controlled trial in 500 adults and children shows that dihydroartemisinin-piperaquine is a safe and effective alternative treatment

Functional classification of memory CD8(+) T cells by CX(3)CR1 expression

Localization of memory CD8(+) T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX(3)CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX(3)CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8(+) T cells with effector function. We find CD62L(hi)CX(3)CR1(+) memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX(3)CR1(+) memory CD8(+) T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX3CR1-based functional classification will help to resolve the principles of protective CD8(+) T-cell memory

A protocol for a randomised double-blind placebo-controlled feasibility study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing and remitting multiple sclerosis (RRMS)

Background: Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis. Methods: Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (< 10 years) of relapsing and remitting MS (RRMS) and who are over 18 years of age will be recruited from neurology clinics and throughout the Thames Valley community. During a 6-week nutrition intervention period, participants will consume the cocoa beverage, high flavonoid or low flavonoid content, at breakfast daily. At baseline, demographic factors and disease-related factors will be assessed. Fatigue, activity and quality of life, in addition to other measures, will be taken at three visits (baseline, week 3 and week 6) in a university setting by a researcher blinded to group membership. Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial.We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. Discussion: We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. Trial registration: Registered with ISRCTN Registry. Trial registration No: ISRCTN69897291; Date April 2016