Improvement in serological diagnosis of pertussis by external quality assessment

Purpose. Serological analysis is an essential tool for the diagnosis of pertussis or whooping cough, disease surveillance and the evaluation of vaccine effectiveness against Bordetella pertussis. Accurate measurement of anti-pertussis toxin (anti-PT) IgG antibody levels in sera is essential. These measurements are usually performed using immunological methods such as ELISA and multiplex immunoassays. However, there are a large number of different assay systems available, and therefore standardization and harmonization between the methods are needed to obtain comparable data.Methodology. In collaboration with ECDC, the EUPert-LabNet network has organized three External Quality Assessment (EQA) schemes (2010, 2012 and 2016), which initially identified the diverse range of techniques and reagents being used throughout Europe. This manuscript discusses the findings of each of the EQA rounds and their impact on the participating laboratories.Results. The studies have shown an increasing number of laboratories (from 65% to 92%) using only the recommended coating antigen, purified PT, in immunoassays, as this allows exact quantification of serum anti-PT IgG and since PT is only produced by Bordetella pertussis this prevents cross-reactivity with other species. There has also been an increase in the numbers of laboratories (from 59% to 92%), including a WHO reference serum in their assays, which allows anti-PT IgG concentrations to be measured in International Units, thus enabling the comparison of results from different methods and laboratories. In addition, manufacturers have also considered these recommendations when they produce commercial ELISA kits.Conclusion. The three EQA rounds have resulted in greater harmonization in methods among different laboratories, showing a significant improvement of the ELISA methods used for serodiagnosis of pertussis

Financing intersectoral action for health: a systematic review of co-financing models.

BACKGROUND: Addressing the social and other non-biological determinants of health largely depends on policies and programmes implemented outside the health sector. While there is growing evidence on the effectiveness of interventions that tackle these upstream determinants, the health sector does not typically prioritise them. From a health perspective, they may not be cost-effective because their non-health outcomes tend to be ignored. Non-health sectors may, in turn, undervalue interventions with important co-benefits for population health, given their focus on their own sectoral objectives. The societal value of win-win interventions with impacts on multiple development goals may, therefore, be under-valued and under-resourced, as a result of siloed resource allocation mechanisms. Pooling budgets across sectors could ensure the total multi-sectoral value of these interventions is captured, and sectors' shared goals are achieved more efficiently. Under such a co-financing approach, the cost of interventions with multi-sectoral outcomes would be shared by benefiting sectors, stimulating mutually beneficial cross-sectoral investments. Leveraging funding in other sectors could off-set flat-lining global development assistance for health and optimise public spending. Although there have been experiments with such cross-sectoral co-financing in several settings, there has been limited analysis to examine these models, their performance and their institutional feasibility. AIM: This study aimed to identify and characterise cross-sectoral co-financing models, their operational modalities, effectiveness, and institutional enablers and barriers. METHODS: We conducted a systematic review of peer-reviewed and grey literature, following PRISMA guidelines. Studies were included if data was provided on interventions funded across two or more sectors, or multiple budgets. Extracted data were categorised and qualitatively coded. RESULTS: Of 2751 publications screened, 81 cases of co-financing were identified. Most were from high-income countries (93%), but six innovative models were found in Uganda, Brazil, El Salvador, Mozambique, Zambia, and Kenya that also included non-public and international payers. The highest number of cases involved the health (93%), social care (64%) and education (22%) sectors. Co-financing models were most often implemented with the intention of integrating services across sectors for defined target populations, although models were also found aimed at health promotion activities outside the health sector and cross-sectoral financial rewards. Interventions were either implemented and governed by a single sector or delivered in an integrated manner with cross-sectoral accountability. Resource constraints and political relevance emerged as key enablers of co-financing, while lack of clarity around the roles of different sectoral players and the objectives of the pooling were found to be barriers to success. Although rigorous impact or economic evaluations were scarce, positive process measures were frequently reported with some evidence suggesting co-financing contributed to improved outcomes. CONCLUSION: Co-financing remains in an exploratory phase, with diverse models having been implemented across sectors and settings. By incentivising intersectoral action on structural inequities and barriers to health interventions, such a novel financing mechanism could contribute to more effective engagement of non-health sectors; to efficiency gains in the financing of universal health coverage; and to simultaneously achieving health and other well-being related sustainable development goals

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

An application of the Household Food Insecurity Access Scale to assess food security in rural communities of Nepal

Abstract The state of food (in)security in rural communities of different ecological zones of the Kaligandaki Basin, Nepal, is assessed using a Household Food Insecurity Access Scale (HFIAS). The data were collected from 360 households using face‐to‐face interviews. The results show poor availability of food from subsistence production in the Middle‐Mountains and Trans‐Himalaya, whereas most households with sufficient purchasing power are able to access additional food from the market. Net food security is poor, with the highest level of insecurity in the Middle‐Mountains, followed by the Trans‐Himalaya and the Tarai. Although weaknesses were found in application of the HFIAS method due to respondent bias in subjective assessments of food insecurity in producer–consumer rural households, the method was found to be effective for rapidly incorporating utilization and stability elements into appraisals. Although not comprehensive, this approach has the potential to complement other forms of knowledge for designing targeted food policy in Nepal

Assessing vulnerability and framing adaptive options of two Mediterranean wine growing regions facing climate change : Roussillon (France) and cLaren Vale (Australia)

International audienceUne hausse des températures et une baisse des précipitations pourraient être préjudiciables au maintien d’une viticulture de qualité dans les régions de climat méditerranéen. Cet article propose d’étudier l’exposition récente et future de deux régions viticoles méditerranéennes à de tels changements : le Roussillon (France) et McLaren Vale (Australie) ; ainsi que de cerner les éléments concourant à augmenter leur vulnérabilité face à ces changements, et en retour les éléments qui permettraient d’améliorer leur capacité d’adaptation. Une étude de données de température et de précipitations observées (1956-2010) à Perpignan et Adelaïde, et simulées (2001-2060) par ARPEGE-RETIC-V4 et CSIRO Mk3.5, a été complétée par soixante-et-un entretiens avec des acteurs-clés de la filière viti-vinicole dans les deux régions. Les résultats montrent que les producteurs ont dû faire face ces dix dernières années à une augmentation de la température et à une baisse des précipitations, et que cela est, selon les modèles, amené à se répéter d’ici 2060, malgré une grande part d’incertitude. Ces conditions ont des impacts négatifs sur la maturation du raisin, qui ne pourront pas forcement être gérés avec les techniques actuelles. La mise en place de stratégies d’adaptation à l’incertitude du climat, couplées à celle des marchés, s’appuie sur : un capital financier suffisant, une gestion durable des ressources en eau, et une souplesse de la législation. Pour cela, la diversification et l’entreprenariat des producteurs sont particulièrement importants

Transforming society to govern planned retreat: responding to "The contested nature of coastal climate change"

Douglas K. Bardsley, Rhiannon J. Nive

The viticultural system and climate change: coping with long-term trends in temperature and rainfall in Roussillon, France

International audienceClimate change could put at risk viticultural areas situated at the hotter margins of Vitis vinifera growth climatic range. We focus on two such regions with a Mediterranean climate (CSb type in Köppen classification): Côtes-du-Roussillon in southern France and McLaren Vale in South Australia. They share a relatively similar recent climate evolution. Based on data from two synoptic weather stations, Perpignan (France) and Adelaide (Australia), with daily time series running from 1956 to 2010, we identified changes in temperatures and precipitation patterns, especially an increase of maximum temperatures, of the Huglin Index and Cool Night Index. According to climate models (data from DRIAS project in France, CSIRO Mk3.5 model in Australia) this tendency is likely to continue in the future. In these two regions, two red varieties are mainly grown: Grenache and Shiraz, as they are relatively well suited to Mediterranean climate and to market demand in volatile global markets. Based on twenty in-depth semi-structured interviews in both regions, we identified that vineyard management practices -current and planned for a near future, are based in their vast majority on economical considerations. Concerns of producers include: maintaining income and market position by producing optimal yields, a constant wine style and quality and a diversified offer. In addition, producers feel they have to deal with an increasing uncertainty regarding climate variability, confirmed by climate data. Adaptation strategies of producers to various types of changes, including climate change, take into account a multiplicity of factors, in which climate change is often not the main concern. Two opposite systems of legislation and cultural traditions in the two regions also make the choice and implementation of adaptation strategies very different. Thus the sensitivity of viticultural systems to climate change depends strongly on non-climatic factors