Short-Term Effects of Air Pollution on Wheeze in Asthmatic Children in Fresno, California

BACKGROUND: Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy. OBJECTIVE: This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution. METHODS: A cohort of 315 children with asthma, 6-11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter <= 2.5 mu m in aerodynamic diameter, particulate matter between 2.5 and 10 mu m in aerodynamic diameter (PM(10-2.5)), elemental carbon, nitrogen dioxide (NO(2)), nitrate, and O(3). RESULTS: For the group as a whole, wheeze was significantly associated with short-term exposures to NO(2) [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02-1.20] and PM(10-2.5) (OR = 1.11 for 14.7-mu g/m(3) increase; 95% CI, 1.01-1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma. CONCLUSION: A pollutant associated with traffic emissions, NO(2), and a pollutant with bioactive constituents, PM(10-2.5), were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations

Global Genotype-Phenotype Correlations in Pseudomonas aeruginosa

Once the genome sequence of an organism is obtained, attention turns from identifying genes to understanding their function, their organization and control of metabolic pathways and networks that determine its physiology. Recent technical advances in acquiring genome-wide data have led to substantial progress in identifying gene functions. However, we still do not know the function of a large number of genes and, even when a gene product has been assigned to a functional class, we cannot normally predict its contribution to the phenotypic behaviour of the cell or organism - the phenome. In this study, we assessed bacterial growth parameters of 4030 non-redundant PA14 transposon mutants in the pathogenic bacterium Pseudomonas aeruginosa. The genome-wide simultaneous analysis of 119 distinct growth-related phenotypes uncovered a comprehensive phenome and provided evidence that most genotypes are not phenotypically isolated but rather define specific complex phenotypic clusters of genotypes. Since phenotypic overlap was demonstrated to reflect the relatedness of genotypes on a global scale, knowledge of an organism's phenome might significantly contribute to the advancement of functional genomics

Systematic Identification of Balanced Transposition Polymorphisms in Saccharomyces cerevisiae

High-throughput techniques for detecting DNA polymorphisms generally do not identify changes in which the genomic position of a sequence, but not its copy number, varies among individuals. To explore such balanced structural polymorphisms, we used array-based Comparative Genomic Hybridization (aCGH) to conduct a genome-wide screen for single-copy genomic segments that occupy different genomic positions in the standard laboratory strain of Saccharomyces cerevisiae (S90) and a polymorphic wild isolate (Y101) through analysis of six tetrads from a cross of these two strains. Paired-end high-throughput sequencing of Y101 validated four of the predicted rearrangements. The transposed segments contained one to four annotated genes each, yet crosses between S90 and Y101 yielded mostly viable tetrads. The longest segment comprised 13.5 kb near the telomere of chromosome XV in the S288C reference strain and Southern blotting confirmed its predicted location on chromosome IX in Y101. Interestingly, inter-locus crossover events between copies of this segment occurred at a detectable rate. The presence of low-copy repetitive sequences at the junctions of this segment suggests that it may have arisen through ectopic recombination. Our methodology and findings provide a starting point for exploring the origins, phenotypic consequences, and evolutionary fate of this largely unexplored form of genomic polymorphism

Protein Kinase C Iota Regulates Pancreatic Acinar-to-Ductal Metaplasia

Pancreatic acinar-to-ductal metaplasia (ADM) is associated with an increased risk of pancreatic cancer and is considered a precursor of pancreatic ductal adenocarcinoma. Transgenic expression of transforming growth factor alpha (TGF-α) or K-rasG12D in mouse pancreatic epithelium induces ADM in vivo. Protein kinase C iota (PKCι) is highly expressed in human pancreatic cancer and is required for the transformed growth and tumorigenesis of pancreatic cancer cells. In this study, PKCι expression was assessed in a mouse model of K-rasG12D-induced pancreatic ADM and pancreatic cancer. The ability of K-rasG12D to induce pancreatic ADM in explant culture, and the requirement for PKCι, was investigated. PKCι is elevated in human and mouse pancreatic ADM and intraepithelial neoplastic lesions in vivo. We demonstrate that K-rasG12D is sufficient to induce pancreatic ADM in explant culture, exhibiting many of the same morphologic and biochemical alterations observed in TGF-α-induced ADM, including a dependence on Notch activation. PKCι is highly expressed in both TGF-α- and K-rasG12D-induced pancreatic ADM and inhibition of PKCι significantly reduces TGF-α- and K-rasG12D-mediated ADM. Inhibition of PKCι suppresses K-rasG12D–induced MMP-7 expression and Notch activation, and exogenous MMP-7 restores K-rasG12D–mediated ADM in PKCι-depleted cells, implicating a K-rasG12D-PKCι-MMP-7 signaling axis that likely induces ADM through Notch activation. Our results indicate that PKCι is an early marker of pancreatic neoplasia and suggest that PKCι is a potential downstream target of K-rasG12D in pancreatic ductal metaplasia in vivo

Design of the BRISC study: a multicentre controlled clinical trial to optimize the communication of breast cancer risks in genetic counselling

Background: Understanding risks is considered to be crucial for informed decision-making. Inaccurate risk perception is a common finding in women with a family history of breast cancer attending genetic counseling. As yet, it is unclear how risks should best be communicated in clinical practice. This study protocol describes the design and methods of the BRISC (Breast cancer RISk Communication) study evaluating the effect of different formats of risk communication on the counsellee's risk perception, psychological well-being and decision-making regarding preventive options for breast cancer. Methods and design: The BRISC study is designed as a pre-post-test controlled group intervention trial with repeated measurements using questionnaires. The intervention-an additional risk consultation-consists of one of 5 conditions that differ in the way counsellee's breast cancer risk is communicated: 1) lifetime risk in numerical format (natural frequencies, i.e. X out of 100), 2) lifetime risk in both numerical format and graphical format (population figures), 3) lifetime risk and age-related risk in numerical format, 4) lifetime risk and age-related risk in both numerical format and graphical format, and 5) lifetime risk in percentages. Condition 6 is the control condition in which no intervention is given (usual care). Participants are unaffected women with a family history of breast cancer attending one of three participating clinical genetic centres in the Netherlands. Discussion: The BRISC study allows for an evaluation of the effects of different formats of communicating breast cancer risks to counsellees. The results can be used to optimize risk communication in order to improve informed decision-making among women with a family history of breast cancer. They may also be useful for risk communication in other health-related services. Trial registration: Current Controlled Trials ISRCTNI4566836

Race and the Legacy of the First World War in French Anti-Colonial Politics of the 1920s

There has been relatively little historical research on the small number of African veterans who stayed on in France after the First World War and became militants in the radical anti-colonial movements created in the 1920s. From his entry onto the political stage in late 1924 until his early death three years later, the most celebrated and feared of these anti-colonial militants was Lamine Senghor, a decorated war veteran from Senegal. This chapter will chart Senghor’s brief career as an activist, focusing primarily on the ways in which he projected his identity as a veteran in his speeches and writings, as well as exploring, more generally, how France’s “blood debt” to its colonial subjects became a key theme of anti-colonial discourse in the interwar period

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BackgroundWhile revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR.PurposeTo report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR.Study designCase-control study; Level of evidence, 3.MethodsA total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation.ResultsOf the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate.ConclusionThere was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR