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Biomedical subjects

A Marshall

Publications and source records attributed to A Marshall.

At least 19 recordsLinked to original sources
PubMed2025

Multi-Polygenic prediction of Frailty and its Trajectories highlights Chronic Pain, Rheumatoid Arthritis, and Educational Attainment pathways.

Frailty is a complex ageing-related trait with a growing evidence base for genetic influence. While a single polygenic score (PGS) for frailty has shown predictive value, few studies have examined the joint effect of multiple genetic risks. This study used a multi-polygenic score (MPS) approach to evaluate the combined and relative contributions of 26 PGSs to frailty, measured via the Frailty Index (FI), in two UK cohorts aged 65 and older: the English Longitudinal Study of Ageing (ELSA) and the Lothian Birth Cohort 1936 (LBC1936). Using elastic net regression with repeated cross-validation, we identified chronic pain and depressive symptoms PGSs as the strongest risk predictors of cross-sectional frailty status, while educational attainment, parental longevity, and rheumatoid arthritis PGSs were protective. Compared to single PGS models, MPS models provided improved prediction of frailty levels, explaining up to 4.7% of variance in frailty status - an improvement over the best single PGS (2.5%). To assess whether PGSs also predicted longitudinal frailty progression, we applied generalized additive mixed models (GAMMs) to model age-related trajectories. In ELSA, five PGSs (chronic pain, depressive symptoms, rheumatoid arthritis, educational attainment, and parental death) significantly interacted with age, influencing the rate of frailty change. In LBC1936, consistent though weaker effects were observed for chronic pain and education PGSs. These findings show that polygenic liability shapes both frailty levels and trajectories in later life. Our results support the use of multi-trait genomic models to improve risk prediction and understanding of frailty's complex aetiology.

Journal Article↗
PubMed2005

Determinants of HAART discontinuation among injection drug users.

The objective of this study was to identify psychosocial determinants of, and self-reported reasons for, HAART discontinuation among HIV-positive injection drug users (IDUs). We examined correlates between sociodemographic characteristics, drug use and risk behaviors, outcome expectations, adherence self-efficacy, social support and HAART discontinuation among 160 HIV-positive participants in the Vancouver Injection Drug Users' Study (VIDUS). Logistic regression was used to identify the factors independently associated with discontinuation of HAART. Seventy-one (44%) study participants discontinued HAART during the study period. Factors independently associated with discontinuation of HAART included recent incarceration (OR = 4.84, p = 0.022), negative outcome expectations (OR = 1.41, p = 0.001), adherence efficacy expectations (OR = 0.70, p = 0.003) and self-regulatory efficacy (OR = 0.86, p = 0.050). The most frequently cited reasons provided for discontinuing HAART were being in jail (44%) and medication side effects (41%). The results of this study suggest that psychological constructs derived from self-efficacy theory are highly germane to the understanding of HAART discontinuation behavior and interventions that may change it. Incarceration may result in interruptions in HAART among IDUs, and programmatic changes may be needed to promote optimal retention on HAART among incarcerated HIV-infected IDUs.

Adult↗
PubMed2005

Androgen-binding protein is co-expressed with oxytocin in the male reproductive tract.

Androgen-binding protein (ABP) and the posterior lobe hormone oxytocin (OT) were co-localized in male rat reproductive organs. Immunostaining of serial semi-thin sections revealed a high rate of coexistence of both antigens in Sertoli cells and in the epithelial cells of the prostate. There was a considerably less co-localization of OT and ABP in epithelial cells of the epididymis, and in the different tissues of the ductus deferens. In situ hybridization with synthetic oligonucleotides complementary to a fragment of ABP mRNA showed specific staining in the same sites that were immunostained for ABP. ABP was isolated by affinity chromatography from homogenates of testis, epididymis, prostate and the content of the prostate lumen. Identical protein patterns could be shown with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in all samples except for the epididymis indicating that ABP structure is similar in all these tissues. ABP seems to be expressed in specified cells throughout the male rat reproductive tract. Most of these cells appear to be oxytocinergic. ABP and OT have previously been detected in the ejaculate. The observed epithelial cells are likely to be their source.

Androgen-Binding Protein↗
PubMed2004

Childhood autism spectrum disorder in the Barwon region: a community based study.

OBJECTIVE: To establish a community database for children with autism spectrum disorder (ASD) to determine prevalence and identify subgroups based on key intellectual, clinical and family parameters. METHODS: Data were collected for children previously diagnosed with an ASD in the Barwon region using parental interview and review of the child's paediatric and psychological records. Preschool diagnoses were typically made by specialist psychologists and school-age diagnoses made by a multidisciplinary team. RESULTS: One hundred and seventy-seven children in the Barwon region were identified as having ASD (82% response rate). The prevalence of ASD was one per 255 children aged two to 17 years. The prevalence increased 10 fold over a 16-year period and this increase was relatively even across all levels of child intellectual functioning. Forty-two percent of children were intellectually disabled (IQ < 70) and performance IQ was significantly higher than verbal IQ but typical block design-comprehension subtest patterns were not common. Nine sibling pair families were identified, 24% were labelled as having attention deficit hyperactivity disorder (ADHD), 6% had epilepsy, and 18.3% were macrocephalic where data were available. Family difficulty was associated with the degree of obsessions/rituals, frequency and intensity of anger/aggression, and ADHD but overall was not associated with the child's intellectual status. CONCLUSIONS: The relatively rapid increase in prevalence is consistent with overseas studies and suggests significant changes in diagnostic criteria, increasing community awareness and the need for support at all levels of intellectual functioning. Increased occurrence in siblings and relatives gives further evidence for a genetic cause.

Adolescent↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine.

OBJECTIVES: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication. METHODS: Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off. RESULTS: Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p<0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p<0.05). Total daily apomorphine dose was reduced by 68.9% (p<0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination. CONCLUSIONS: In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.

Aged↗
PubMed2001

Local transgenic expression of granulocyte macrophage-colony stimulating factor initiates autoimmunity.

Mechanisms leading to breakdown of immunological tolerance and initiation of autoimmunity are poorly understood. Experimental autoimmune gastritis is a paradigm of organ-specific autoimmunity arising from a pathogenic autoimmune response to gastric H/K ATPase. The gastritis is accompanied by autoantibodies to the gastric H/K ATPase. The best characterized model of experimental autoimmune gastritis requires neonatal thymectomy. This procedure disrupts the immune repertoire, limiting its usefulness in understanding how autoimmunity arises in animals with intact immune systems. Here we tested whether local production of GM-CSF, a pro-inflammatory cytokine, is sufficient to break tolerance and initiate autoimmunity. We generated transgenic mice expressing GM-CSF in the stomach. These transgenic mice spontaneously developed gastritis with an incidence of about 80% after six backcrosses to gastritis-susceptible BALBc/CrSlc mice. The gastritis is accompanied by mucosal hypertrophy, enlargement of draining lymph nodes and autoantibodies to gastric H/K ATPase. An infiltrate of dendritic cells and macrophages preceded CD4 T cells into the gastric mucosa. T cells from draining lymph nodes specifically proliferated to the gastric H/K ATPase. CD4 but not CD8 T cells transferred gastritis to nude mouse recipients. CD4(+) CD25(+) T cells from the spleen retained anergic suppressive properties that were reversed by IL-2. We conclude that local expression of GM-CSF is sufficient to break tolerance and initiate autoimmunity mediated by CD4 T cells. This new mouse model should be useful for studies of organ-specific autoimmunity.

Adoptive Transfer↗
PubMed2001

Investigation of spatial clustering from individually matched case-control studies.

The paper demonstrates how existing theory to assess spatial clustering based on second-moment properties of a labelled point process can be adapted to matched case-control studies. The null hypothesis that cases are a random sample from the superposition of cases and controls is replaced by the hypothesis that each case is a random sample from the set consisting of itself and its k matched controls. We compare the proposed test with other tests of spatial clustering, and describe an application to data on childhood diabetes in Yorkshire, England.

Journal Article↗
PubMed2001

Emotional change processes in music-assisted reframing.

Affective processes are critical to understanding and promoting lasting therapeutic change. Using a sample of 40 anxious adults, the researchers examined the use of music to increase affective modification and emotional restructuring in a cognitive reframing intervention. Subjects were assigned to either a typical reframing intervention or a music-assisted reframing intervention. Using the State-Trait Anxiety Inventory, Subjective Units of Distress Scale, Depression Adjective Checklist, and a Think-Aloud measure, the groups were compared on basis of anxiety-reduction, affective modification, and imagery vividness. Results indicate that the music-assisted reframing intervention was more efficacious than the typical reframing intervention in reducing anxiety, modifying affect, and promoting imagery-vividness.

Adult↗
PubMed2001

The effects of assisted reproduction on the trends and zygosity of multiple births in England and Wales 1974-99.

Assisted reproductive techniques have led to an increase in the proportion of maternities that are multiple. Though predominantly dizygotic, they are at greater risk of monozygotic division than those spontaneously conceived. England and Wales data 1974-99 on stillbirths and livebirths were analysed for 4 periods: 1974-80 (pre-assisted reproduction; 1982-8; 1989-91 (pre-redefinition of stillbirth); 1993-9 (post-redefinition of stillbirth). For twin data, Weinberg's rule was applied to estimate the proportions that were mono- (MZ) and dizygotic (DZ). Compared with the period before assisted reproduction, the most recent period shows an increase in twin maternities of 3.81 per 1,000 comprised of 3.22 (95% CI 3.10 to 3.33; p < 0.0001) DZ and 0.60 (95% CI 0.51 to 0.68; p < 0.0001) MZ twins. It is estimated that 15.7% of assisted reproduction twins are MZ. Higher order multiple births showed an increase of 3.06 (95% CI 2.85 to 3.29; p < 0.0001) per 10,000 maternities. Stillbirth rates in MZ twins are of the same order of magnitude as those in higher order multiple births but higher than those in DZ twins. The improvement in stillbirth rates over the 26 year study period is of the same order magnitude in singletons, DZ and MZ twins and higher order multiples. Assisted reproduction has led to a significant increase in the proportion of MZ twins. These are at high risk of fetal death and this needs to be considered when local stillbirth and perinatal mortality rates are used in auditing obstetric services.

England↗
PubMed2001

Convulsive syncope in young adults: think of a cardiac cause.

Convulsive syncope is often misdiagnosed as epilepsy because of its similarity in clinical presentation. We present the case of a patient who had several such episodes before a definitive diagnosis was made. The diagnosis of prolonged sinus arrest was finally made with the valuable assistance of cardiac monitoring during a witnessed episode of convulsive syncope. Appropriate therapy was promptly introduced, i.e. temporary then permanent cardiac pacing. It is possible that any further delay in reaching the correct diagnosis and delivering appropriate treatment might have carried a significant risk of morbidity and mortality. Continuous electrocardiographic monitoring performed at an early stage is therefore crucial in the initial assessment of a young adult presenting with convulsive syncope, as a significant proportion may have a cardiovascular aetiology, particularly arrhythmias, for their syncopal episodes.

Adult↗