Survival in pulmonary fibrosis combined with emphysema: likely defined by characteristics of specific patient subpopulations

Authors' Reply to letter from Cottin et al

The Public Health Leadership and Implementation Academy for Noncommunicable Diseases.

PURPOSE AND OBJECTIVES: Low- and middle-income countries (LMICs) have a large burden of noncommunicable diseases and confront leadership capacity challenges and gaps in implementation of proven interventions. To address these issues, we designed the Public Health Leadership and Implementation Academy (PH-LEADER) for noncommunicable diseases. The objective of this program evaluation was to assess the quality and effectiveness of PH-LEADER. INTERVENTION APPROACH: PH-LEADER was directed at midcareer public health professionals, researchers, and government public health workers from LMICs who were involved in prevention and control of noncommunicable diseases. The 1-year program focused on building implementation research and leadership capacity to address noncommunicable diseases and included 3 complementary components: a 2-month online preparation period, a 2-week summer course in the United States, and a 9-month, in-country, mentored project. EVALUATION METHODS: Four trainee groups participated from 2013 through 2016. We collected demographic information on all trainees and monitored project and program outputs. Among the 2015 and 2016 trainees, we assessed program satisfaction and pre-post program changes in leadership practices and the perceived competence of trainees for performing implementation research. RESULTS: Ninety professionals (mean age 38.8 years; 57% male) from 12 countries were trained over 4 years. Of these trainees, 50% were from India and 29% from Mexico. Trainees developed 53 projects and 9 publications. Among 2015 and 2016 trainees who completed evaluation surveys (n = 46 of 55), we saw pre-post training improvements in the frequency with which they acted as role models (Cohen's d = 0.62, P <.001), inspired a shared vision (d = 0.43, P =.005), challenged current processes (d = 0.60, P <.001), enabled others to act (d = 0.51, P =.001), and encouraged others by recognizing or celebrating their contributions and accomplishments (d = 0.49, P =.002). Through short on-site evaluation forms (scale of 1-10), trainees rated summer course sessions as useful (mean, 7.5; SD = 0.2), with very good content (mean, 8.5; SD = 0.6) and delivered by very good professors (mean, 8.6; SD = 0.6), though they highlighted areas for improvement. IMPLICATIONS FOR PUBLIC HEALTH: The PH-LEADER program is a promising strategy to build implementation research and leadership capacity to address noncommunicable diseases in LMICs

Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

<p>Abstract</p> <p>Background</p> <p>Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring.</p> <p>Methods</p> <p>From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion.</p> <p>Results</p> <p>The adjusted ORs and 95% confidence intervals (CI) were 1.69 (0.98, 2.92) during the preconception period; 1.98 (1.13, 3.45) during the index pregnancy; 2.11 (1.17, 3.78) during breastfeeding period; 2.17 (1.28, 3.66) after birth; and 2.06 (1.24, 3.42) for global exposure.</p> <p>Conclusion</p> <p>This is the first study in which an OEI was used to assess a father's occupational exposure to carcinogenic agents as a risk factor for the development of childhood AL in his offspring. From our results, we conclude that children whose fathers have been exposed to a high level of carcinogenic agents seem to have a greater risk of developing acute leukemia. However, confounding factors cannot be disregarded due to an incomplete control for confounding.</p

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.

BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. RESULTS: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. CONCLUSIONS: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts

Whole-genome genotyping of grape using a panel of microsatellite

The use of microsatellite markers in large-scale genetic studies is limited by its low throughput and high cost and labor requirements. Here, we provide a panel of 45 multiplex PCRs for fast and cost-efficient genome-wide fluorescence-based microsatellite analysis in grapevine. The developed multiplex PCRs panel (with up to 15-plex) enables the scoring of 270 loci covering all the grapevine genome (9 to 20 loci/chromosome) using only 45 PCRs and sequencer runs. The 45 multiplex PCRs were validated using a diverse grapevine collection of 207 accessions, selected to represent most of the cultivated Vitis vinifera genetic diversity. Particular attention was paid to quality control throughout the whole process (assay replication, null allele detection, ease of scoring). Genetic diversity summary statistics and features of electrophoretic profiles for each studied marker are provided, as are the genotypes of 25 common cultivars that could be used as references in other studies