The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development.

Ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due to its varied and essential roles, free Ca(2+) is tightly regulated by complex mechanisms. These mechanisms are therefore of interest as putative drug targets. One pathway in Ca(2+) homeostatic control in apicomplexans uses a Ca(2+)/H(+) exchanger (a member of the cation exchanger family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised in asexual blood stage parasites. To determine the physiological importance of apicomplexan CAXs, tagging and knock-out strategies were undertaken in the genetically tractable T. gondii and P. berghei parasites. In addition, a yeast heterologous expression system was used to study the function of apicomplexan CAXs. Tagging of T. gondii and P. berghei CAXs (TgCAX and PbCAX) under control of their endogenous promoters could not demonstrate measureable expression of either CAX in tachyzoites and asexual blood stages, respectively. These results were consistent with the ability of parasites to tolerate knock-outs of the genes for TgCAX and PbCAX at these developmental stages. In contrast, PbCAX expression was detectable during sexual stages of development in female gametocytes/gametes, zygotes and ookinetes, where it was dispersed in membranous networks within the cytosol (with minimal mitochondrial localisation). Furthermore, genetically disrupted parasites failed to develop further from "round" form zygotes, suggesting that PbCAX is essential for ookinete development and differentiation. This impeded phenotype could be rescued by removal of extracellular Ca(2+). Therefore, PbCAX provides a mechanism for free living parasites to multiply within the ionic microenvironment of the mosquito midgut. Ca(2+) homeostasis mediated by PbCAX is critical and suggests plasmodial CAXs may be targeted in approaches designed to block parasite transmission

Exfiltration from sewers - is it a serious problem?

This paper contends that estimates of exfiltration leakage from sewers, and the problems arising from it may be too high due to an underestimation of the “self-repairing” action of sewage and sewage sediments in raw sewage. Two aspects of a continuing programme of research are reported;(i) the measurement of exfiltration rates from a range of defects in a sewer pipe with pipe bedding effects simulated by a dry gravel trench surround to the pipe, and (ii) an assessment of the persistence of pathogens in the gravel and soil beneath the test rig pipe, using coliforms as a biological indicator. The results show that the introduction of a gravel surround resulted in more rapid and effective sealing across the entire range of defects tested compared to previously performed experiments with the defects discharging to air. Complete sealing eventually occurred on every run for a 10 mm x 10 mm defect situated at the invert of the sewer and the lowest recorded levels in each experiment for a 10 mm wide radial defect were of the order 10-3 to 10-4 ls-1. These results have been scaled-up to estimate leakage rates in lengths of sewers and sub-catchments and levels significantly lower than previously estimated are indicated. Additionally, the pilot experiment to investigate the fate of biological contaminants in the exfiltrate suggests rapid reduction in microorganisms levels beneath the sewer pipe

Vulnerability Factors and Pathways Leading to Underage Entry into Sex Work in two Mexican-US Border Cities

The current wave of interest in human trafficking and the commercial sexual exploitation of children has exposed a lack of knowledge about the vulnerabilities leading to underage entry into sex work. This knowledge is necessary for the development of effective prevention programs to identify girls who are most at-risk, especially in Latin America, a region that is believed to be a large source of persons moved across international borders for the purposes of sexual and labor exploitation. The objective of this study was to explore and increase understanding of the vulnerability factors and pathways leading to underage entry into sex work experienced by women currently engaging in sex work in two cities on the northern border of Mexico. From August 2013 to October 2014, 20 female sex workers (FSWs) with a history of entry into sex work prior to age 18 were recruited for in-depth interviews from a larger time-location sample of female sex workers (FSWs) participating in a quantitative survey in Tijuana and Ciudad Juarez. The median age of entry into sex work was 14 (range 10-17); 12/21 participants reported being forced into sex work and, of these, 7 were transported to another city where they began engaging in sex work. Family dysfunction (e.g., domestic violence between parents, parent drug use, neglect, etc.), sexual and physical abuse, and teen pregnancy were among the key themes that emerged as vulnerabilities to underage entry into sex work. Women’s narratives clearly illustrated that the vulnerabilities and pathways leading to underage entry are manifold, complex, and often intersect with each other. Our findings begin to lay the groundwork for understanding the potential vulnerabilities and pathways leading to underage entry into sex, and may have relevance to Latin America in general. This study also provides a foundation for further research to explore what may mitigate these vulnerabilities as well as creating evidence-based interventions to prevent commercial sexual exploitation of minors in the region

The Wicked Machinery of Government: Malta and the Problems of Continuity under the New Model Administration

This is a study focused on the early years of British rule in Malta (1800-1813). It explores the application to the island of the “new model” of colonial government, one based on direct rule from London mediated by the continuation of existing laws and institutions. Systemic deficiencies are identified. These tended to undermine the effectiveness of direct British rule. This study also reveals, in the context of legal and constitutional continuity, unresolved tensions between modernity and tradition. The political stability of the island was damaged and the possibility of continued British possession was threatened

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: Results of the Epilymph European case-control study

Background: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels. Methods: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education. Results: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation. Conclusions: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study

Background: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels. Methods: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education. Results: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation. Conclusions: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation