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13 recordsLinked to original sources
PubMed2003

Quantifying biases in causal models: classical confounding vs collider-stratification bias.

It has long been known that stratifying on variables affected by the study exposure can create selection bias. More recently it has been shown that stratifying on a variable that precedes exposure and disease can induce confounding, even if there is no confounding in the unstratified (crude) estimate. This paper examines the relative magnitudes of these biases under some simple causal models in which the stratification variable is graphically depicted as a collider (a variable directly affected by two or more other variables in the graph). The results suggest that bias from stratifying on variables affected by exposure and disease may often be comparable in size with bias from classical confounding (bias from failing to stratify on a common cause of exposure and disease), whereas other biases from collider stratification may tend to be much smaller.

Bias↗
PubMed2025

No More Free Lunch: Challenges to Mendelian Randomization Due to Sample Selection and Complex Methods.

Mendelian randomization (MR) is increasingly used in epidemiological studies to investigate causal relationships. MR depends on 3 fundamental instrumental variable assumptions: relevance, independence, and exclusion restriction. Studies often assume that MR mitigates bias from confounding due to the random allocation of genetic variants at conception. In this perspective, using causal directed acyclic graphs, we discuss several scenarios where biases in MR analyses may arise due to the nature of the data or methods being used. These include (1) collider bias due to the nonrandom selection of participants into study populations used for conducting genome-wide association studies (GWAS), (2) indirect genetic effects arising from population-based GWAS rather than within-family studies, and (3) collider bias due to gene-environment interaction effects on the exposure in nonlinear MR analyses. We provide practical considerations for examining and reducing these biases in MR analyses.

Humans↗
PubMed2026

Assessment of Methodological Bias in Studies Reporting Racial Differences in Retinopathy of Prematurity in the United States.

PURPOSE: To assess methodological biases in studies reporting racial and ethnic differences in retinopathy of prematurity (ROP). METHODS: Systematic review of peer-reviewed studies published between 2014 and 2024 that reported on ROP outcome measures by race, ethnicity, or social determinants of health (SDOH). Three reviewers independently assessed each observation for selection and collider bias using definitions derived from perinatal epidemiology literature. Findings were also compared using a structured comparative synthesis between studies with and without identified methodological bias. RESULTS: A structured PubMed search identified 78 articles; 13 met inclusion criteria, with one study contributing two distinct analytical approaches, yielding 14 total observations. Survivorship bias was identified in 6 of 14 observations (42.9%), primarily due to the exclusion of infants who died prior to ROP screening. Potential collider bias was most common, found in 9 of 14 observations (64.3%), and was introduced through adjustment or stratification by gestational age and/or birthweight. Three studies did not exhibit either assessed biases. Among studies with identified bias, 8 of 10 observations reported lower ROP risk among Black versus White infants, whereas 3 of 4 observations without identified bias reported higher ROP risk or incidence among Black infants. CONCLUSION: Methodological biases in ROP studies investigating race or ethnicity are prevalent. Adjustment for gestational age or birthweight may introduce spurious race-ROP associations and contribute to paradoxical findings. Further exploration of the impact of SDOH on disease outcomes may reduce the misattribution of race as a biological risk factor and improve the interpretation of ROP disparities.

Collider bias↗
PubMed2026

Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.

BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases. RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude. CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.

Humans↗
PubMed2026

Genetically Proxied Inhibition of Cholesterol-Lowering Drug Targets and Survival in HPV-Positive and Non-HPV-Driven Head and Neck Cancer: A Multicentre MR Study.

BACKGROUND: Cholesterol pathways may influence head and neck squamous cell carcinoma (HNSCC) progression, but evidence on prognosis is inconsistent. We used Mendelian randomization (MR) to test whether genetically proxied inhibition of major low-density lipoprotein cholesterol (LDL-C)-lowering drug targets and circulating lipid traits affects overall survival (OS) in HPV-positive and non-HPV-driven HNSCCs. METHODS: We proxied lifelong LDL-C lowering using 55 cis-acting single-nucleotide polymorphisms in HMGCR, NPC1L1, PCSK9, and LDL-receptor (LDLR) from the updated 2021 Global Lipids Genetics Consortium and instrumented circulating lipid traits. Two-sample MR estimated effects on OS in 4,869 multicentre HNSCC cases (1,291 HPV-positive; 3,578 non-HPV-driven) using minimally adjusted Cox models. Sensitivity analyses additionally adjusted for tumor stage and treatment, assessed collider bias using an external HNSCC incidence genome-wide association study, and examined between-center heterogeneity and colocalization. RESULTS: Using the updated Global Lipids Genetic Consortium 2021 instruments, genetically proxied HMGCR inhibition showed a directionally protective but nonsignificant association with OS in HPV-positive oropharyngeal HNSCC in the primary analysis [inverse variance weighted (IVW) HR = 0.19; 95% confidence interval (CI), 0.03-1.18; P = 0.08], with directionally concordant weighted median results. No corresponding protective association was observed for HMGCR in non-HPV-driven disease (IVW HR = 1.68; 95% CI, 0.78-3.63; P = 0.19). No clear evidence of association was observed for NPC1L1, PCSK9, LDLR, or circulating lipid traits in either HPV stratum. Colocalization did not support a shared causal variant. CONCLUSIONS: These analyses provide suggestive evidence that genetically proxied HMGCR inhibition may influence survival in HPV-positive oropharyngeal HNSCC. IMPACT: HMGCR-related pathways may be relevant to prognosis in HPV-positive oropharyngeal HNSCC, whereas clear survival effects of other cholesterol-lowering targets were not supported.

Humans↗
PubMed2006

Things that go bump in the right: the effect of unimanual activity on rightward collisions.

Patients with right parietal damage and spatial neglect ignore the leftward features of their environment - causing them to bump into the left-side of doorways. In contrast, the normal population shows a mild attentional bias towards the left. Self-report measures show more collisions to the right in everyday settings. We sought to obtain a quantitative measure of lateralised bumping in a laboratory setting. Participants (n=276) walked through a narrow doorway and the experimenter recorded collisions. To investigate the association between bumping and paper-and-pencil tests of pseudoneglect, a line bisection task was administered. Unilateral activation of the hemispheres has been found to ameliorate the effects of spatial neglect. We investigated the effect of activation by asking participants to move their left-, right- or both-hands as they walked. In the both hands condition, which acted as a baseline, there were more right bumps than left bumps. The rightward bias was exasperated when the left hand moved, presumably because this movement activated the right hemisphere. In contrast, there were more left bumps when the right hand moved. The results demonstrate that bumping is not random and that we collide with the right side more often. Biases in bumping, however, were not related to biases in line bisection. The effect of hand-movement demonstrates that bumping is brought about by an imbalance of activation between the hemispheres.

Adult↗
PubMed2005

Centrality dependence of charged-particle pseudorapidity distributions from d + Au collisions at sqrt[sNN] = 200 GeV.

Charged-particle pseudorapidity densities are presented for the d + Au reaction at sqrt[s(NN)] = 200 GeV with -4.2 < or = eta < or = 4.2. The results, from the BRAHMS experiment at BNL Relativistic Heavy-Ion Collider, are shown for minimum-bias events and 0%-30%, 30%-60%, and 60%-80% centrality classes. Models incorporating both soft physics and hard, perturbative QCD-based scattering physics agree well with the experimental results. The data do not support predictions based on strong-coupling, semiclassical QCD. In the deuteron-fragmentation region the central 200 GeV data show behavior similar to full-overlap d+Au results at sqrt[s(NN)] = 19.4 GeV.

Journal Article↗
PubMed2002

Measurement of Lambda and Lambda(macro) particles in Au+Au collisions at the square root of S(NN) = 130 GeV.

We present results on the measurement of Lambda and Lambda(macro) production in Au+Au collisions at square root of (S (NN) = 130 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider. The transverse momentum spectra were measured for minimum bias and for the 5% most central events. The Lambda;/Lambda ratios are constant as a function of p(T) and the number of participants. The measured net Lambda density is significantly larger than predicted by models based on hadronic strings (e.g., HIJING) but in approximate agreement with models which include the gluon-junction mechanism.

Journal Article↗
PubMed2004

Effect of particle bombardment on the orientation and the residual stress of sputtered AlN films for SAW devices.

We present a study of the effect of particle bombardment on the preferred orientation and the residual stress of polycrystalline aluminum nitride (AlN) thin films for surface acoustic wave (SAW) applications. Films were deposited on silicon (100) substrates by radio frequency (RF) sputtering of an aluminum target in an argon and nitrogen gas mixture. The main deposition parameters were changed as follows: the total pressure from 4 mTorr to 11 mTorr, the N2 content in the gas mixture from 20% to 80%, and the substrate self-bias voltage from -10 V to -30 V. If a sufficiently high negative substrate self-bias voltage is induced, (00.2)-oriented films are obtained over the full ranges of pressure and N2 content. Such films have values of residual stress ranging from -3 GPa to +1 GPa, depending on the deposition conditions. Our results suggest that the energy of the Ar ions colliding with the substrate controls the preferred orientation of the films, whereas the directionality of the ions (for the same energy) is the main factor determining the residual stress. To demonstrate the suitability of our material for the intended application, SAW filters with good electroacoustic response have been fabricated using AlN thin films with optimized (00.2) orientation and controlled residual stress.

Journal Article↗
PubMed2003

Central pseudorapidity gaps in events with a leading antiproton at the fermilab tevatron pp collider.

We report a measurement of the fraction of events with a large pseudorapidity gap deltaeta within the pseudorapidity region available to the proton dissociation products X in p+p-->p+X. For a final state p of fractional momentum loss xi(p) and 4-momentum transfer squared t(p) within 0.06 3 is found to be 0.246+/-0.001 (stat)+/-0.042 (syst) [0.184+/-0.001 (stat)+/-0.043 (syst)]. Our results are compared with gap fractions measured in minimum bias pp collisions and with theoretical expectations.

Journal Article↗
PubMed2002

Allocation concealment in randomised trials: defending against deciphering.

Proper randomisation rests on adequate allocation concealment. An allocation concealment process keeps clinicians and participants unaware of upcoming assignments. Without it, even properly developed random allocation sequences can be subverted. Within this concealment process, the crucial unbiased nature of randomised controlled trials collides with their most vexing implementation problems. Proper allocation concealment frequently frustrates clinical inclinations, which annoys those who do the trials. Randomised controlled trials are anathema to clinicians. Many involved with trials will be tempted to decipher assignments, which subverts randomisation. For some implementing a trial, deciphering the allocation scheme might frequently become too great an intellectual challenge to resist. Whether their motives indicate innocent or pernicious intents, such tampering undermines the validity of a trial. Indeed, inadequate allocation concealment leads to exaggerated estimates of treatment effect, on average, but with scope for bias in either direction. Trial investigators will be crafty in any potential efforts to decipher the allocation sequence, so trial designers must be just as clever in their design efforts to prevent deciphering. Investigators must effectively immunise trials against selection and confounding biases with proper allocation concealment. Furthermore, investigators should report baseline comparisons on important prognostic variables. Hypothesis tests of baseline characteristics, however, are superfluous and could be harmful if they lead investigators to suppress reporting any baseline imbalances.

Adult↗
PubMed2005

Multistrange Baryon elliptic flow in Au+Au collisions at square root of sNN=200 GeV.

We report on the first measurement of elliptic flow v2(pT) of multistrange baryons Xi- +Xi+ and Omega- + Omega+ in heavy-ion collisions. In minimum-bias Au+Au collisions at square root of s(NN)=200 GeV, a significant amount of elliptic flow, comparable to other nonstrange baryons, is observed for multistrange baryons which are expected to be particularly sensitive to the dynamics of the partonic stage of heavy-ion collisions. The pT dependence of v2 of the multistrange baryons confirms the number of constituent quark scaling previously observed for lighter hadrons. These results support the idea that a substantial fraction of the observed collective motion is developed at the early partonic stage in ultrarelativistic nuclear collisions at the Relativistic Heavy Ion Collider.

Journal Article↗