115 research outputs found
Monitoring Poverty Trends in Ireland: Results from the 2001 Living in Ireland Survey. ESRI Policy Series No. 51. December 2003
This study uses data gathered as part of the 2001 Living in Ireland Survey (LIIS) to monitor the evolution of poverty in Ireland. The study is the fourth in a line of reports from The Economic and Social Research Institute which have examined poverty in Ireland using the LIIS data and like previous reports in the series, inter alia, provides information on progress toward achieving the targets set
out in the National Anti-Poverty Strategy
Unraveling the consecutive recombination events in the human IGK locus
In addition to the classical Vkappa-Jkappa, Vkappa-kappa deleting element
(Kde), and intron-Kde gene rearrangements, atypical recombinations
involving Jkappa recombination signal sequence (RSS) or intronRSS elements
can occur in the Igkappa (IGK) locus, as observed in human B cell
malignancies. In-depth analysis revealed that atypical
JkappaRSS-intronRSS, Vkappa-intronRSS, and JkappaRSS-Kde recombinations
not only occur in B cell malignancies, but rather reflect physiological
gene rearrangements present in normal human B cells as well. Excision
circle analysis and recombination substrate assays can discriminate
between single-step vs multistep rearrangements. Using this combined
approach, we unraveled that the atypical Vkappa-intronRSS and
JkappaRSS-Kde pseudohybrid joints most probably result from ongoing
recombination following an initial aberrant JkappaRSS-intronRSS signal
joint formation. Based on our observations in normal and malignant human B
cells, a model is presented to describe the sequential (classical and
atypical) recombination events in the human IGK locus and their estimated
relative frequencies (0.2-1.0 vs < 0.03). The initial JkappaRSS-intronRSS
signal joint formation (except for Jkappa1RSS-intronRSS) might be a side
event of an active V(D)J recombination mechanism, but the subsequent
formation of Vkappa-intronRSS and JkappaRSS-Kde pseudohybrid joints can
represent an alternative pathway for IGK allele inactivation and allelic
exclusion, in addition to classical Ckappa deletions. Although usage of
this alternative pathway is limited, it seems essential for inactivation
of those IGK alleles that have undergone initial aberrant recombinations,
which might otherwise hamper selection of functional Ig L chain proteins
A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses\u27 Health Study (NHS) and Health Professionals Follow-up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T-NHL), B cell NHL (B-NHL) and three individual B-NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B-NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0, and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T-NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B-NHLs other than CLL/SLL and for VLCSFA and MUFA with T-NHL suggest an influence of fatty acid metabolism on lymphomagenesis
KLF4-Induced Connexin40 Expression Contributes to Arterial Endothelial Quiescence
Shear stress, a blood flow-induced frictional force, is essential in the control of endothelial cell (EC) homeostasis. High laminar shear stress (HLSS), as observed in straight parts of arteries, assures a quiescent non-activated endothelium through the induction of KrĂĽppel-like transcription factors (KLFs). Connexin40 (Cx40)-mediated gap junctional communication is known to contribute to a healthy endothelium by propagating anti-inflammatory signals between ECs, however, the molecular basis of the transcriptional regulation of Cx40 as well as its downstream effectors remain poorly understood. Here, we show that flow-induced KLF4 regulated Cx40 expression in a mouse EC line. Chromatin immunoprecipitation in ECs revealed that KLF4 bound to three predicted KLF consensus binding sites in the Cx40 promoter. HLSS-dependent induction of Cx40 expression was confirmed in primary human ECs. The downstream effects of Cx40 modulation in ECs exposed to HLSS were elucidated by an unbiased transcriptomics approach. Cell cycle progression was identified as an important downstream target of Cx40 under HLSS. In agreement, an increase in the proportion of proliferating cell nuclear antigen (PCNA)-positive ECs and a decrease in the proportion of ECs in the G0/G1 phase were observed under HLSS after Cx40 silencing. Transfection of communication-incompetent HeLa cells with Cx40 demonstrated that the regulation of proliferation by Cx40 was not limited to ECs. Using a zebrafish model, we finally showed faster intersegmental vessel growth and branching into the dorsal longitudinal anastomotic vessel in embryos knock-out for the Cx40 orthologs Cx41.8 and Cx45.6. Most significant effects were observed in embryos with a mutant Cx41.8 encoding for a channel with reduced gap junctional function. Faster intersegmental vessel growth in Cx41.8 mutant embryos was associated with increased EC proliferation as assessed by PH3 immunostaining. Our data shows a novel evolutionary-conserved role of flow-driven KLF4-dependent Cx40 expression in endothelial quiescence that may be relevant for the control of atherosclerosis and diseases involving sprouting angiogenesis
Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies
Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses\u27 Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years ( \u3c 5, 5 to \u3c 10, \u3e /=10) after blood draw. Soluble interleukin-2 receptor-alpha, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (odds ratio: 95% confidence interval: 0.51, 0.43-0.62) persisted more than 10 years after blood draw (odds ratio: 0.70; 95% confidence interval: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis
The relationship between hourly energy balance and fat mass in female collegiate soccer players
Introduction: Soccer athletes have better performance if they maintain low fat mass (FM) relative to fat-free mass. Recent evidence suggests that maintenance of energy balance (EB) is associated with lower FM in athletes. Prior studies have used daily EB rather than hourly, but this approach does not consider duration of time athletes spend in EB versus surplus or deficit. Objective: Test the hypotheses that (1) time spent in EB is inversely associated with FM, and (2) athletes with mean hourly EB in the deficit range have lower FM than those in balance or surplus. Methods: Collegiate female soccer players (n=20) were enrolled in this cross-sectional study. A 3-day diet/activity record was obtained and analysed to estimate EB in hourly increments. Hourly EB was categorized as: Surplus, >400 kcal EB; Balance, between ±400 kcal EB; Deficit, <-400 kcal EB. Total hours spent in each category and mean EB (kcals) was calculated from the 3-day period. Bioelectrical Impedance Analysis was used to derive indices of FM (total FM in kg, % fat, fat mass index). Pearson correlations evaluated associations between FM measures and time spent in each EB category. One-way ANOVA with Tukey post-hoc testing was used to assess differences in FM among athletes stratified into surplus, balance, or deficit based on mean hourly EB. Results: Hourly energy deficit was associated with higher FM compared to energy surplus or balance. Conclusion: Female collegiate soccer players who sustain EB during the day, and limit time spent in energy deficit, had lower FM measures.CEB is supported by Grant Number (T32HL105349) from The National Heart, Lung, and Blood Institute. Additional support was provided by Award Number (P30DK056336) from The National Institute of Diabetes and Digestive and Kidney Diseases
Realizing the therapeutic potential of novel cardioprotective therapies: The EU-CARDIOPROTECTION COST Action - CA16225
Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE
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