Biomedical subjects

Patrick Miller

Publications and source records attributed to Patrick Miller.

6 recordsLinked to original sources

PubMed2025

In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene.

Homology-directed repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested Repair Drive, a platform technology for selectively expanding HDR-corrected hepatocytes in adult mice in vivo. Repair Drive involves transient conditioning of the liver by knocking down an essential gene, fumarylacetoacetate hydrolase (Fah), and delivering an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive increased the percentage of correctly targeted hepatocytes in healthy wild-type mice up to 25%, which resulted in a fivefold increased expression of a therapeutic transgene, human factor IX (FIX). Repair Drive was well tolerated and did not induce toxicity or tumorigenesis during a 1-year follow-up. This approach may broaden the range of liver diseases that can be treated with somatic genome editing.

Animals↗

PubMed2002

Heavy cannabis use among UK teenagers: an exploration.

Findings are presented from a survey of a sample of 2641 UK school students aged 15--16 years. This exercise was part of the 30 country European School Survey Project on Alcohol and other Drugs (ESPAD). The 201 students who reported using cannabis (marihuana) 40 times or more were examined using cluster analysis. They were also compared to other students. Three clusters of heavy cannabis users emerged. The smallest was largely distinguished by antisocial behaviour. Another cluster were clearly unhappy, with little support from parents and friends, high levels of depressed mood and low levels of self-esteem. The largest cluster were 'ordinary' and had little to distinguish them apart from a belief that their environment was stable and predictable and that society's rules should be obeyed. Although clear relationships emerged between heavy cannabis use and heavy use of other substances, the 'ordinary' cluster of heavy cannabis users were less likely than the others to have used other illicit drugs. It is therefore concluded that teenage heavy cannabis users have varied motivations and contexts for their usage. They should not be seen as a homogeneous group and many do not appear to use other illicit drugs.

Adolescent↗

PubMed2002

Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms.

BACKGROUND: Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. These are thought to be neurodevelopmental in origin, but when they become evident is unknown. AIMS: To determine if temporal lobe volumes reduce during the development of symptoms of schizophrenia in initially well people at high risk of this disorder. METHOD: A group of 66 people who had at least two first- or second-degree relatives with schizophrenia and a control group of 20 healthy people had a structural MRI scan of the whole brain which was repeated after approximately 2 years. Regions of interest, specifically the amygdala-hippocampus complex and the temporal lobes, were traced semi-automatically by three masked raters with good inter-and intrarater reliability. RESULTS: Regional brain volume changes over 2 years did not differ between high-risk and healthy participants. Within the high-risk group, the 19 people with psychotic symptoms (12 at first assessment) had a mean reduction of 2163 mm(3) in the right temporal lobe compared with 97 mm(3) in the 47 without symptoms (P=0.02). CONCLUSIONS: Our findings suggest that people at high risk of schizophrenia with psychotic symptoms show reductions in temporal lobe volumes.

Adult↗

PubMed2002

Schizotypal components in people at high risk of developing schizophrenia: early findings from the Edinburgh High-Risk Study.

BACKGROUND: The study of high-risk groups and the development of schizophrenia. AIMS: To investigate further schizotypy, measured by the Structured Interview for Schizotypy (SIS), and to examine relationships between schizotypal components, psychotic symptoms on the Present State Examination (PSE) and subsequent schizophrenia. METHOD: The SIS and PSE were administered on entry. Schizophrenia onsets were recorded during follow-up. RESULTS: The SIS yielded four principal components labelled social withdrawal, psychotic symptoms, socio-emotional dysfunction and odd behaviour. On entry, these differentiated between controls, subjects at risk for schizophrenia with and without symptoms and patients with schizophrenia. Seven of 78 subjects at risk developed schizophrenia within 39 months. This was best predicted by combining the four SIS components. CONCLUSIONS: Schizotypy is heterogeneous and may become psychosis, particularly if several of its components are present. As psychosis develops, odd behaviour gives way to psychotic symptoms and social function deteriorates.

Adolescent↗

PubMed1997

Struggle.

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Advance Care Planning↗

PubMedDate not supplied

Family structure, parent-child relationships, and alcohol and other drug use among teenagers in France and the United Kingdom.

This paper compares samples of 15-16-year-olds from the UK and France on their usage of alcohol, tobacco and illicit drugs and also seeks to describe the associations between alcohol and other drug use with "family variables" within the two countries. Compared to UK adolescents, French adolescents showed a slightly higher rate of cigarette smoking, were almost identical on cannabis use, rather lower on the use of other illicit drugs and very considerably lower on alcohol use. Family variables were related to substance use. In the two countries, children from non-intact families, those who were not satisfied with their relationships with their father or mother and those who were less closely monitored, were more likely to be heavy substance users than other students. Logistic regressions showed that parental knowledge of the whereabouts of their offspring on Saturday evenings was the strongest factor, in both countries, that family structure is frequently still significant in the UK, and that paternal relationships are highly significant among French students. Differences in national drinking culture, urbanization and parental practices are discussed in an attempt to interpret some of these findings.

Adolescent↗