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Biomedical subjects

Patrick Sullivan

Publications and source records attributed to Patrick Sullivan.

At least 19 recordsLinked to original sources
PubMed2026

A spatially resolved genomic-molecular atlas of human white-matter microstructure.

Human white matter has been linked to inherited variation, circulating molecular state and brain disease, but these layers have rarely been mapped onto the same tract anatomy. Here we measured genetic effects along 6,090 atlas-aligned fiber pathways sampled at 609,000 locations in 72,185 UK Biobank participants, and integrated proteomic and metabolomic profiles within the same anatomical frame. Genetic effects were not whole-tract properties: each locus formed a spatial footprint along fiber trajectories, ranging from single locations to broad multi-tract patterns and reflecting regional polygenicity rather than tract heritability. This map identified 258, 186 and 298 previously unreported loci for fractional anisotropy, mean diffusivity and axial diffusivity; spatial patterns replicated in adults and 157 of 315 FA loci replicated in adolescence in ABCD. Mendelian randomization linked localized genetic effects to neurodegenerative and psychiatric traits, with Alzheimer's disease showing directional effects across 12 of 17 tracts. Multi-omic analyses identified 97 proteomic and 161 metabolomic associations, with the broadest signals from lipid metabolites including linoleic acid and phosphatidylcholines. The strongest lipid-metabolite and genetic signals converged in the corpus callosum, placing inherited variation, disease risk and systemic lipid metabolism on the same localized tract segments.

Journal Article↗
PubMed2026

Risk of subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm episode among young people: a population-based cohort study.

BACKGROUND: Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. OBJECTIVE: To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. METHODS: This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10-24 years during 1973-2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. FINDINGS: Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10-12. CONCLUSIONS: The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. CLINICAL IMPLICATIONS: These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10-12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.

Humans↗
PubMed2006

HIV-related risk behaviors, perceptions of risk, HIV testing, and exposure to prevention messages and methods among urban American Indians and Alaska Natives.

The goal of this study was to describe HIV risk behaviors, perceptions, testing, and prevention exposure among urban American Indians and Alaska Natives (AI/AN). Interviewers administered a questionnaire to participants recruited through anonymous peer-referral sampling. Chi-square tests and multiple logistic regression were used to compare HIV testing by perception of risk and risk behavior status. Of 218 respondents with seronegative or unknown HIV status, 156 (72%, 95% confidence interval [CI]: 66-78%) reported some HIV risk behavior: 57 (26%, 95% CI: 20-32%) high-risk behavior, and 99 (45%, 95% CI: 39-52%), potentially high-risk. Among respondents reporting high-risk behavior, 44% rated themselves at no or low risk for HIV infection. Overall, 180 respondents (83%, 95% CI: 78-88%) had ever received an HIV test, 79 (36%, 95% CI: 31-57%) in the past year. HIV risk behaviors and perception of risk were independently associated with recent HIV testing after adjustment for gender, income, and homelessness (odds ratio [OR] = 3.6; 95% CI: 1.5-9.0 for high-risk behavior vs. no reported risk behavior, and OR: 3.2; 95% CI: 1.3-7.6, for high vs. no perceived risk). Addressing inaccurate perception of risk may be a key to improving uptake of HIV testing among high-risk urban AI/AN.

Adult↗
PubMed2005

Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.

Both impaired nicotinic neurotransmission and the inheritance of apoE4 are associated with increased risk for Alzheimer disease (AD) as well as other deficiencies in memory-related behavior. Long-term potentiation (LTP), a cellular model of memory, is known to be altered by nicotinic agents. Recent studies also support an emergent role for apoE in LTP. We compared the effects of mecamylamine, a nonspecific antagonist of nicotinic acetylcholine receptors (nAChRs), on basal synaptic transmission and LTP in hippocampal slices from wild-type (wt) mice and targeted replacement mice expressing human apoE4 (apoE4-TR). Field excitatory postsynaptic potentials (EPSPs) were recorded in the dentate gyrus (DG) in response to medial perforant path activation, and theta burst stimulation was used to induce LTP. Bath application of mecamylamine (3 microM) did not alter input-output relationships or paired pulse depression in either mouse strain. Under control conditions, apoE4-TR mice showed significantly less LTP than wt mice (17.5% +/- 3.2%, n = 9, vs. 30.1% +/- 3.9%, n = 11, P < 0.02). Mecamylamine reduced LTP in wt mice to a level that was similar to control levels for apoE4-TR mice (15.7% +/- 3.4%, n = 9), whereas apoE4-TR showed no further reduction of LTP (16.6% +/- 3.7%, n = 8) by mecamylamine. Thus mice expressing human apoE4 differ from wt mice both in their capacity for LTP and in the effect on LTP of nicotinic cholinergic blockade. It is possible that nicotinic neurotransmission is already compromised in apoE4-TR mice and, hence, that interference with the integrity of this cholinergic system represents a mechanism by which inheritance of the apoE4 allele contributes to cognitive risk.

Analysis of Variance↗
PubMed2005

ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.

Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42.

Alzheimer Disease↗
PubMed2005

Developing an administrative plan for transfusion medicine--a global perspective.

Throughout the world blood services aim to provide a life-saving service by ensuring an adequate supply of safe blood. However, across the world blood services are at very different levels of development. Consequently, the actions taken in one country or region would not be appropriate in another. This paper aims to identify how suitable solutions can be developed to match the different prevailing circumstances of an individual country or region. In trying to do this it is important to look at the whole of the supply chain within a blood service and identify the part where a change could make the biggest impact. Four key areas are identified that are integral to this. These are the donor, testing of blood, hemovigilance, and overall management arrangements. Whilst the first two have largely been addressed in highly developed countries, there is still much work that could be done in these areas in developing countries. In particular, a move to voluntary nonremunerated donors worldwide would significantly improve overall safety. Hemovigilance systems are identified as a powerful tool to influence policy development, yet these are largely under developed throughout the world. In order to make high impact and sustainable changes it is important that those in the blood industry across the world work together to improve education and training, to share experience of best practice, and to move to develop agreed standards in transfusion medicine. It is imperative that developed countries recognize the importance of working with developing countries if the safety of the global blood supply is to be maintained and improved.

Blood Banks↗
PubMed2004

Translating emerging research on the genetics of smoking into clinical practice: ethical and social considerations.

Despite decades of research aimed at improving the effectiveness of smoking treatment, available treatments are only modestly effective, and smoking remains the leading cause of preventable deaths in the United States. Recent research on genetic factors related to smoking behavior eventually may lead to the design of new tobacco dependence treatments and to the individualization of treatment based on genetic factors. Although this research is in its infancy, and data on the analytic and clinical validity of genetic tests to tailor smoking treatment are not yet available, it is not too soon to begin identifying and addressing key ethical issues associated with genetic testing in the context of tobacco dependence treatment. Key concerns include (a) potential harm (e.g., stigmatization, discrimination) to patients related to inappropriate use of genetic information, (b) implications of pleiotropic associations, (c) differential prevalence of risk-conferring genotypes among racial or ethnic subpopulations, (d) preparedness of primary care physicians to incorporate genetic testing into smoking treatment, (e) informed consent, and (f) ensuring an appropriate balance between individually tailored treatment by genotype and broad-based interventions that focus on social and environmental factors affecting smoking behavior. Additional research on these ethical and social issues must be conducted simultaneously with the scientific work currently under way. Failure to address these concerns will likely undermine efforts to translate knowledge emerging from the United States' substantial investment in genetic research on smoking into clinical practice and improved patient outcomes.

Adult↗
PubMed2004

An anatomic and histologic analysis of the alar-facial crease and the lateral crus.

The key to achieving an excellent result following rhinoplasty lies in a strong fundamental knowledge of nasal anatomy. The purpose of this study was to analyze the anatomic and histologic relationship of the nose to the alar-facial crease. Fifteen cadaver noses were dissected and a total of thirty lower lateral cartilages were measured. Two fresh cadaver noses were fixed in neutral buffer formalin and embedded in paraffin. They were then sectioned into 6-mu coronal and sagittal sections and stained with hematoxylin and eosin, Eosin von Geison, and safranin to evaluate for collagen, elastin and muscle, respectively. Measurements of the lower lateral cartilages showed the average lateral crural height was 23.5 mm (+/- 2.5 mm), lateral crus width was 11.7 mm (+/- 1.5 mm), lateral domal width was 5.7 mm (+/- 0.9 mm), and intercrural distance was 20.2 mm (+/- 3.2 mm). No statistical differences were noted between male and female cadaver measurements. Histologic sections showed the area of the alar-facial crease to have a greater quantity of elastin fibers compared with muscle, collagen, or cartilage. These elastin fibers were predominantly orientated vertically (anterior-posterior) rather than horizontally (cephalo-caudad). This study demonstrates a higher ratio of elastin to collagen fibers in the region of the alar-facial crease.

Body Weights and Measures↗