Initiating antiretrovirals during tuberculosis treatment: a drug safety review

Introduction: Integrating HIV and tuberculosis (TB) treatment can reduce mortality substantially. Practical barriers to treatment integration still exist and include safety concerns related to concomitant drug use because of drug interactions and additive toxicities. Altered therapeutic concentrations may influence the chances of treatment success or toxicity. Areas covered: The available data on drug-drug interactions between the rifamycin class of anti-mycobacterials and the non-nucleoside reverse transcriptase inhibitor and the protease inhibitor classes of antiretrovirals are discussed with recommendations for integrated use. Additive drug toxicities, the impact of immune reconstitution inflammatory syndrome (IRIS) and the latest data on survival benefits of integrating treatment are elucidated. Expert opinion: Deferring treatment of HIV to avoid drug interactions with TB treatment or the occurrence of IRIS is not necessary. In the integrated management of TB-HIV co-infection, rational drug combinations aimed at reducing toxicities while effecting TB cure and suppressing HIV viral load are possible

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients

<p>Abstract</p> <p>Background</p> <p>Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients.</p> <p>Methods</p> <p>Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m²) and docetaxel (80 mg/m²); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol.</p> <p>Results</p> <p>Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage.</p> <p>Conclusion</p> <p>The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.</p

Conservation implications of the mating system of the Pampa Hermosa landrace of peach palm analyzed with microsatellite markers

Peach palm (Bactris gasipaes) is cultivated by many indigenous and traditional communities from Amazonia to Central America for its edible fruits, and is currently important for its heart-of-palm. The objective of this study was to investigate the mating system of peach palm, as this is important for conservation and breeding. Eight microsatellite loci were used to genotype 24 open-pollinated progenies from three populations of the Pampa Hermosa landrace maintained in a progeny trial for genetic improvement. Both the multi-locus outcrossing rates (0.95 to 0.99) and the progeny level multi-locus outcrossing rates (0.9 to 1.0) were high, indicating that peach palm is predominantly allogamous. The outcrossing rates among relatives were significantly different from zero (0.101 to 0.202), providing evidence for considerable biparental inbreeding within populations, probably due to farmers planting seeds of a small number of open-pollinated progenies in the same plot. The correlations of paternity estimates were low (0.051 to 0.112), suggesting a large number of pollen sources (9 to 20) participating in pollination of individual fruit bunches. Effective population size estimates suggest that current germplasm collections are insufficient for long-term ex situ conservation. As with most underutilized crops, on farm conservation is the most important component of an integrated conservation strategy

Politicising government engagement with corporate social responsibility: “CSR” as an empty signifier

Governments are widely viewed by academics and practitioners (and society more generally) as the key societal actors who are capable of compelling businesses to practice corporate social responsibility (CSR). Arguably, such government involvement could be seen as a technocratic device for encouraging ethical business behaviour. In this paper, we offer a more politicised interpretation of government engagement with CSR where “CSR” is not a desired form of business conduct but an element of discourse that governments can deploy in structuring their relationships with other social actors. We build our argument through a historical analysis of government CSR discourse in the Russian Federation. Laclau and Mouffe's (Hegemony and socialist strategy: Towards a radical democratic politics,Verso Books, London, 1985) social theory of hegemony underpins our research. We find that “CSR” in the Russian government’s discourse served to legitimise its power over large businesses. Using this case, we contribute to wider academic debates by providing fresh empirical evidence that allows the development of critical evaluation tools in relation to governments’ engagement with “CSR”. We find that governments are capable of hijacking CSR for their own self-interested gain. We close the paper by reflecting on the merit of exploring the case of the Russian Federation. As a “non-core”, non-western exemplar, it provides a useful “mirror” with which to reflect on the more widely used test-bed of Western industrial democracies when scrutinising CSR. Based on our findings, we invite other scholars to adopt a more critical, politicised stance when researching the role of governments in relation to CSR in other parts of the world

Fine-Scale Genetic Structure Arises during Range Expansion of an Invasive Gecko

Processes of range expansion are increasingly important in light of current concerns about invasive species and range shifts due to climate change. Theoretical studies suggest that genetic structuring may occur during range expansion. Ephemeral genetic structure can have important evolutionary implications, such as propagating genetic changes along the wave front of expansion, yet few studies have shown evidence of such structure. We tested the hypothesis that genetic structure arises during range expansion in Hemidactylus mabouia, a nocturnal African gecko recently introduced to Florida, USA. Twelve highly variable microsatellite loci were used to screen 418 individuals collected from 43 locations from four sampling sites across Florida, representing a gradient from earlier (∼1990s) to very recent colonization. We found earlier colonized locations had little detectable genetic structure and higher allelic richness than more recently colonized locations. Genetic structuring was pronounced among locations at spatial scales of tens to hundreds of meters near the leading edge of range expansion. Despite the rapid pace of range expansion in this introduced gecko, dispersal is limited among many suitable habitat patches. Fine-scale genetic structure is likely the result of founder effects during colonization of suitable habitat patches. It may be obscured over time and by scale-dependent modes of dispersal. Further studies are needed to determine if such genetic structure affects adaptation and trait evolution in range expansions and range shifts

How do firms comply with international sustainability standards? Processes and consequences of adopting the global reporting initiative

This paper addresses the issue of the influence of global governance institutions, particularly international sustainability standards, on a firm’s intra-organizational practices. More precisely, we provide an exploratory empirical view of the impact of the Global Reporting Initiative (GRI) on a multinational corporation’s (MNC) corporate social responsibility (CSR) management practices. We investigate standard compliance by comparing the stated intention of the use of the GRI with its actual use and the consequent effects within the firm. Based on an in-depth case study, our findings illustrate the processes and consequences of the translation of the GRI within the organization. We show that substantive standard adoption can lead to unintended consequences on CSR management practices, specifically it can influence the management structure and CSR committee function; the choice of CSR activities, the relationships between subsidiaries, the temporal dimension of CSR management, and the interpretation of CSR performance. We also highlight the need to look at the relationship dynamics (or lack of) between standards. Finally we illustrate and discuss the role of reporting and its influence on management in order to better understand the internal issues arising from compliance with standards

Global Phylogeography with Mixed-Marker Analysis Reveals Male-Mediated Dispersal in the Endangered Scalloped Hammerhead Shark (Sphyrna lewini)

Background: The scalloped hammerhead shark, Sphyrna lewini, is a large endangered predator with a circumglobal distribution, observed in the open ocean but linked ontogenetically to coastal embayments for parturition and juvenile development. A previous survey of maternal (mtDNA) markers demonstrated strong genetic partitioning overall (global W ST = 0.749) and significant population separations across oceans and between discontinuous continental coastlines. Methodology/Principal Findings: We surveyed the same global range with increased sample coverage (N = 403) and 13 microsatellite loci to assess the male contribution to dispersal and population structure. Biparentally inherited microsatellites reveal low or absent genetic structure across ocean basins and global genetic differentiation (FST = 0.035) over an order of magnitude lower than the corresponding measures for maternal mtDNA lineages (W ST = 0.749). Nuclear allelic richness and heterozygosity are high throughout the Indo-Pacific, while genetic structure is low. In contrast, allelic diversity is low while population structure is higher for populations at the ends of the range in the West Atlantic and East Pacific. Conclusions/Significance: These data are consistent with the proposed Indo-Pacific center of origin for S. lewini, and indicate that females are philopatric or adhere to coastal habitats while males facilitate gene flow across oceanic expanses. This study includes the largest sampling effort and the most molecular loci ever used to survey the complete range of

Contrasting patterns of population structure and gene flow facilitate exploration of connectivity in two widely distributed temperate octocorals

This is the final version of the article. Available from Springer Nature via the DOI in this record.Connectivity is an important component of metapopulation dynamics in marine systems and can influence population persistence, migration rates and conservation decisions associated with Marine Protected Areas (MPAs). In this study, we compared the genetic diversity, gene flow and population structure of two octocoral species, Eunicella verrucosa and Alcyonium digitatum, in the northeast Atlantic (ranging from the northwest of Ireland and the southern North Sea, to southern Portugal), using two panels of thirteen and eight microsatellite loci, respectively. Our results identified regional genetic structure in E. verrucosa partitioned between populations from southern Portugal, northwest Ireland, and Britain/France; subsequent hierarchical analysis of population structure also indicated reduced gene flow between southwest Britain and northwest France. However, over a similar geographical area, A. digitatum showed little evidence of population structure, suggesting high gene flow and/or a large effective population size; indeed, the only significant genetic differentiation detected in A. digitatum occurred between North Sea samples and those from the English Channel/northeast Atlantic. In both species the vast majority of gene flow originated from sample sites within regions, with populations in southwest Britain being the predominant source of contemporary exogenous genetic variants for the populations studied. Unsurprisingly, historical patterns of gene flow appeared more complex, though again southwest Britain appeared an important source of genetic variation for both species. Our findings have major conservation implications, particularly for E. verrucosa, a protected species in UK waters and listed by the IUCN as ‘Vulnerable’, and for the designation and management of European MPAs.We thank Natural England (project No. RP0286, contract No. SAE 03-02-146), the NERC (grant No. NE/L002434/1) and the University of Exeter for funding this research. Additional funding for sample collection, travel and microsatellite development was provided by the EU Framework 7 ASSEMBLE programme, agreement no. 227799, and NERC grant No. NBAF-362

Genetic and ecological outcomes of Inga vera subsp. affinis (leguminosae) tree plantations in a fragmented tropical landscape

Planting of native trees for habitat restoration is a widespread practice, but the consequences for the retention and transmission of genetic diversity in planted and natural populations are unclear. Using Inga vera subsp. affinis as a model species, we genotyped five natural and five planted populations in the Atlantic forest of northeastern Brazil at polymorphic microsatellite loci. We studied the breeding system and population structure to test how much genetic diversity is retained in planted relative to natural populations. We then genotyped seedlings from these populations to test whether genetic diversity in planted populations is restored by outcrossing to natural populations of I. vera. The breeding system of natural I. vera populations was confirmed to be highly outcrossing (t = 0.92; FIS = -0.061, P = 0.04), with populations showing weak population substructure (FST = 0.028). Genetic diversity in planted populations was 50% less than that of natural populations (planted: AR = 14.9, HO = 0.865 and natural: AR = 30.8, HO = 0.655). However, seedlings from planted populations showed a 30% higher allelic richness relative to their parents (seedlings AR = 10.5, parents AR = 7.6). Understanding the processes and interactions that shape this system are necessary to provide ecologically sensible goals and successfully restore hyper-fragmented habitats. Future restoration plans for I. vera must consider the genetic diversity of planted populations and the potential for gene flow between natural populations in the landscape, in order to preserve ecological interactions (i.e. pollination), and promote opportunities for outcrossing