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The difficulties in establishing and delivering reliable clinical hematology and laboratory services in resource-limited settings are well recognized. However, much can be achieved by better use of existing resources through a concerted quality improvement approach. The recommendations of this chapter are based in part upon work in the thalassemias, inherited disorders of hemoglobin that are widely prevalent in Asia, which may serve as a model that is applicable to other common, chronic disorders in resource-poor settings. Resources are highlighted and recommendations made regarding approaches to improving services. Over the last few years, a number of low and middle-income countries, obtaining support from appropriate governmental sources, have assessed and overcome difficulties and significantly improved clinical services for patients with thalassemia.

This paper critiques the two-dimensional (hierarchical–spatial) focus on scales evident in management and organizational studies, and the capitalist ecological modernization (CEM) paradigm that dominates current corporate and governmental approaches to sustainability. Our contribution is to propose a more complex and nuanced understanding of scale, which incorporates social, political, temporal and material dimensions. We propose a heuristic framework from Harvey, in order to evaluate different paradigms of socio-ecological organizing: specifically, the dominant paradigm of CEM against a social ecology (SE) alternative. We explore the divergent conceptions of, and relative importance placed upon, concepts of scale, grain, level and field in these two contrasting paradigms. Our analysis highlights the limitations and contradictions of the CEM expression of scale, namely its predominant focus on measurement and expansion through 'economies of scale'. By offering an alternative conception of the links between scales, grains, levels and social fields, we show how this enriches the conceptualization of potential forms of socio-ecological organizing and opens up the potential for alternative modes of organizing socio-ecological sustainability.

This Handbook provides an authoritative and comprehensive analysis of the concept of jurisdiction in international law. The authors undertake a thematic analysis of its history, its contemporary application, and how it needs to adapt to encompass future developments in international law.

This handbook provides an authoritative and comprehensive analysis of the concept of jurisdiction in international law. The authors undertake a thematic analysis of its history, its contemporary application, and how it needs to adapt to encompass future developments in international law.

In most industrialized countries, the buildings sector is the largest contributor to energy consumption and associated carbon emissions. These emissions can be reduced by a combination of energy efficiency and the use of building integrated renewables. Additionally, either singularly or as a group, buildings can provide energy network services by timing their use and production of energy. Such grid-aware or grid-responsive buildings have been termed Active Buildings. The recent UK Government investment of £36m in the Active Building Centre is a demonstration that such buildings are of considerable interest. One problem with the concept, however, is that there is no clear definition of Active Buildings, nor a building code to design or research against. Here we develop and test an initial novel code, called ABCode1. It is based on the need to encourage: (i) the minimisation of energy consumption; (ii) building-integrated generation; (iii) the provision of grid services; and (iv) the minimisation of embodied carbon. For grid services, we find that a lack of a precise, quantifiable measure, or definition, of such services means that for the time being, theoretical hours of autonomy of the building is the most reasonable proxy for these services within such a code.

BACKGROUND In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. METHODS AND FINDINGS This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. CONCLUSIONS Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria. TRIAL REGISTRATION ClinicalTrials.gov NCT03201770.