As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine ...production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals. We demonstrate a strong impact of genetic heritability on cytokine production capacity after challenge with bacterial, fungal, viral, and non-microbial stimuli. In addition to 17 novel genome-wide significant cytokine QTLs (cQTLs), our study provides a comprehensive picture of the genetic variants that influence six different cytokines in whole blood, blood mononuclear cells, and macrophages. Important biological pathways that contain cytokine QTLs map to pattern recognition receptors (TLR1-6-10 cluster), cytokine and complement inhibitors, and the kallikrein system. The cytokine QTLs show enrichment for monocyte-specific enhancers, are more often located in regions under positive selection, and are significantly enriched among SNPs associated with infections and immune-mediated diseases.
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•Host genetics play a major role in inter-individual variability in cytokine responses•Identification of 17 novel genome-wide significant cytokine QTLs (cQTLs)•cQTLs generally overlap with genomic regions under positive selection•Many cQTLs overlap with loci associated with infectious and immune-mediated diseases
As part of the Human Functional Genomics Project, examination of millions of human genetic variants demonstrates that host genetics plays a significant role in inter-individual variability of cytokine production in response to different types of microbial stimuli.
A search for charge-parity (CP) violation in D^{0}→K^{-}K^{+} and D^{0}→π^{-}π^{+} decays is reported, using pp collision data corresponding to an integrated luminosity of 5.9 fb^{-1} collected at a ...center-of-mass energy of 13 TeV with the LHCb detector. The flavor of the charm meson is inferred from the charge of the pion in D^{*}(2010)^{+}→D^{0}π^{+} decays or from the charge of the muon in Bover ¯→D^{0}μ^{-}νover ¯_{μ}X decays. The difference between the CP asymmetries in D^{0}→K^{-}K^{+} and D^{0}→π^{-}π^{+} decays is measured to be ΔA_{CP}=-18.2±3.2(stat)±0.9(syst)×10^{-4} for π-tagged and ΔA_{CP}=-9±8(stat)±5(syst)×10^{-4} for μ-tagged D^{0} mesons. Combining these with previous LHCb results leads to ΔA_{CP}=(-15.4±2.9)×10^{-4}, where the uncertainty includes both statistical and systematic contributions. The measured value differs from zero by more than 5 standard deviations. This is the first observation of CP violation in the decay of charm hadrons.
Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens ...and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens.
A measurement of the ratio of branching fractions of the decays B^{+}→K^{+}μ^{+}μ^{-} and B^{+}→K^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated ...luminosity of 5.0 fb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0 GeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations.
National cancer incidence trends are presented for eight Asian American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese, Kampucheans, Koreans, Laotians, and Vietnamese.
Cancer ...incidence data from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End Results (SEER) registries. Incidence rates from 1990 through 2008 and average percentage change were computed using SEER*Stat and Joinpoint software. The annual percentage change (APC) in incidence rates was estimated with 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Rates for non-Hispanic whites are presented for comparison.
Prostate cancer was the most common malignancy among most groups, followed by lung, colorectal, liver, and stomach cancers. Breast cancer was generally the most common cancer in women, followed by colorectal and lung cancers; liver, cervix, thyroid, and stomach cancers also ranked highly. Among men, increasing trends were observed for prostate (Asian Indians and Pakistanis: APC 1990-2003 = 2.2, 95% CI = 0.3 to 4.1; Filipinos: APC 1990-1994 = 19.0, 95% CI = 4.5 to 35.4; Koreans: APC 1990-2008 = 2.9, 95% CI = 1.8 to 4.0), colorectal (Koreans: APC 1990-2008 = 2.2, 95% CI = 0.9 to 3.5), and liver cancers (Filipinos: APC 1990-2008 = 1.6, 95% CI = 0.4 to 2.7; Koreans: APC 1990-2006 = 2.1, 95% CI = 0.4 to 3.7; Vietnamese: APC 1990-2008 = 1.6, 95% CI = 0.3 to 2.8), whereas lung and stomach cancers generally remained stable or decreased. Among women, increases were observed for uterine cancer (Asian Indians: APC 1990-2008 = 3.0, 95% CI = 0.3 to 5.8; Chinese: APC 2004-2008 = 7.0, 95% CI = 1.4 to 12.9; Filipina: APC 1990-2008 = 3.0, 95% CI = 2.4 to 3.7; Japanese: APC 1990-2008 = 1.1, 95% CI = 0.1 to 2.0), colorectal cancer (Koreans: APC 1990-2008 = 2.8, 95% CI = 1.7 to 3.9; Laotians: APC: 1990-2008 = 5.9, 95% CI = 4.0 to 7.7), lung cancer (Filipinas: APC 1990-2008 = 2.1, 95% CI = 1.4 to 2.8; Koreans: APC 1990-2008 = 2.1, 95% CI = 0.6 to 3.6), thyroid cancer (Filipinas: APC 1990-2008 = 2.5, 95% CI = 1.7 to 3.3), and breast cancer in most groups (APC 1990-2008 from 1.2 among Vietnamese and Chinese to 4.7 among Koreans). Decreases were observed for stomach (Chinese and Japanese), colorectal (Chinese), and cervical cancers (Laotians and Vietnamese).
These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are needed-in particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampuchean, and Vietnamese men.
Abstract
Background
Paranoia is higher in minority group individuals, especially those reporting intersecting aspects of difference. High negative and low positive self and other beliefs, and low ...social rank, are predictive of paranoia overtime; however, data are typically from majority group participants. This study examined whether social defeat or healthy cultural mistrust best characterizes paranoia in minority groups.
Study Design
Using cross-sectional, survey design, with a large (n = 2510) international sample, moderation analyses (PROCESS) examined whether self and other beliefs, and perceived social rank, operate similarly or differently in minority vs majority group participants. Specifically, we tested whether beliefs moderated the influence of minority group, and intersecting aspects of difference, on paranoia.
Study Results
Paranoia was consistently higher in participants from minority vs majority groups and level of paranoid thinking was significantly higher at each level of the intersectionality index. Negative self/other beliefs were associated with elevated paranoia in all participants. However, in support of the notion of healthy cultural mistrust, low social rank, and low positive self/other beliefs were significantly associated with paranoia in majority group participants but unrelated to paranoia in respective minority group members.
Conclusions
Although mixed, our findings signal the need to consider healthy cultural mistrust when examining paranoia in minority groups and bring into question whether “paranoia” accurately describes the experiences of marginalized individuals, at least at low levels of severity. Further research on paranoia in minority groups is crucial to developing culturally appropriate ways of understanding people’s experiences in the context of victimization, discrimination, and difference.
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Using proton-proton collision data at centre-of-mass energies of s=7,8 and 13TeV recorded by the LHCb experiment at the Large Hadron Collider, corresponding to an integrated ...luminosity of 9fb-1, the invariant mass spectrum of J/ψ pairs is studied. A narrow structure around 6.9GeV/c2 matching the lineshape of a resonance and a broad structure just above twice the J/ψ mass are observed. The deviation of the data from nonresonant J/ψ-pair production is above five standard deviations in the mass region between 6.2 and 7.4GeV/c2, covering predicted masses of states composed of four charm quarks. The mass and natural width of the narrow X(6900) structure are measured assuming a Breit-Wigner lineshape.
Background: Adequate lymph node evaluation is required for proper staging of colorectal cancer, and the number of lymph nodes examined is associated with survival. According to current guidelines, ...the recommended minimum number of lymph nodes examined to ensure adequate sampling is 12. We used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program to determine the proportion of colorectal cancer patients in the United States who receive adequate lymph node evaluation. Methods: For 116 995 adults with colorectal adenocarcinoma, diagnosed from 1988 through 2001, who underwent radical surgery and did not receive neoadjuvant radiation, we evaluated the number of lymph nodes, the likelihood of receiving adequate lymph node evaluation (i.e., at least 12 lymph nodes examined), and the influence of tumor and patient factors on lymph node evaluation. All statistical tests were two-sided. Results: Among all patients, the median number of lymph nodes examined was nine. Only 37% of all patients received adequate lymph node evaluation. The proportion of patients receiving adequate lymph node evaluation increased from 32% in 1988 to 44% in 2001 (Ptrend<.001, Cochran–Armitage test). Advanced tumor stage was statistically significantly associated with adequate lymph node evaluation (odds ratio OR of receiving adequate lymph node evaluation=2.27, 95% confidence interval CI = 2.18 to 2.35). Older patients (≥71 years, OR = 0.45, 95% CI = 0.44 to 0.47) were less likely to receive adequate lymph node evaluation than younger patients, and those with left-sided (OR = 0.45, 95% CI = 0.44 to 0.47) or rectal (OR = 0.52, 95% CI = 0.50 to 0.54) cancers were less likely to receive adequate lymph node evaluation than patients with right-sided cancers. In all analyses, geographic location was an important predictor of adequate lymph node evaluation, which ranged from 33% to 53%, depending on geographic location. Conclusions: In 2001, the majority of patients with colorectal cancer still received inadequate lymph node evaluation. The association of demographic variables, particularly patient age and geographic location, with adequate lymph node evaluation indicates that local surgical and pathology practice patterns may affect adequacy of lymph node evaluation.
Somatic variants of the β-catenin gene were found in aldosterone-producing adenomas in two pregnant women. These adenomas expressed very high levels of two hormone receptors, which were presumably ...engaged by high levels of circulating cognate hormones.
Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with treatment-resistant hypertension.
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A unilateral aldosterone-producing adenoma is the most common potentially curable cause of hypertension in such cases.
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Early detection of a unilateral aldosterone-producing adenoma is important both to maximize the likelihood of a complete cure of hypertension by means of adenoma removal and to prevent the onset of resistant hypertension and the risk of long-term cardiovascular complications.
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The Wnt pathway, through β-catenin signaling, is critical for normal adrenocortical development and maintenance, in particular the zona glomerulosa of . . .
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