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Biomedical subjects

Alan Lee

Publications and source records attributed to Alan Lee.

8 recordsLinked to original sources
PubMed2006

Estimating sensitivity and bias in a yes/no task.

The estimation of sensitivity and bias from data collected in a yes/no detection-theoretic experiment is complicated by the possibility of proportions of 0 or 1 appearing in the resulting contingency table. Inverse normal transforms of these probabilities result in mathematically intractable infinities. Typically, some transformation of the data must be applied prior to parameter estimation. Several transformations have been reviewed in the literature, in terms of both the bias and the variance of the estimates they produce. We propose three generalized transformations, which contain the two most reported transformations as special cases, and consider their performance in terms of the mean square error of the estimates they produce. Results indicate that the '1/N ' and the adaptive log-linear transformations outperform the others. Guidelines for the application of these transformations are presented.

Analysis of Variance↗
PubMed2004

The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC protein pickpocket1.

BACKGROUND: Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 (FMR1) gene. How FMR1 affects the function of the central and peripheral nervous systems is still unclear. FMR1 is an RNA binding protein that associates with a small percentage of total mRNAs in vivo. It remains largely unknown what proteins encoded by mRNAs in the FMR1-messenger ribonuclear protein (mRNP) complex are most relevant to the affected physiological processes. RESULTS: Loss-of-function mutations in the Drosophila fragile X-related (dfmr1) gene, which is highly homologous to the human fmr1 gene, decrease the duration and percentage of time that crawling larvae spend on linear locomotion. Overexpression of DFMR1 in multiple dendritic (MD) sensory neurons increases the time percentage and duration of linear locomotion; this phenotype is similar to that caused by reduced expression of the MD neuron subtype-specific degenerin/epithelial sodium channel (DEG/ENaC) family protein Pickpocket1 (PPK1). Genetic analyses indicate that PPK1 is a key component downstream of DFMR1 in controlling the crawling behavior of Drosophila larvae. DFMR1 and ppk1 mRNA are present in the same mRNP complex in vivo and can directly bind to each other in vitro. DFMR1 downregulates the level of ppk1 mRNA in vivo, and this regulatory process also involves Argonaute2 (Ago2), a key component in the RNA interference pathway. CONCLUSIONS: These studies identify ppk1 mRNA as a physiologically relevant in vivo target of DFMR1. Our finding that the level of ppk1 mRNA is regulated by DFMR1 and Ago2 reveals a genetic pathway that controls sensory input-modulated locomotion behavior.

Animals↗
PubMed2003

Counseling versus antidepressant therapy for the treatment of mild to moderate depression in primary care: economic analysis.

OBJECTIVE: To compare the cost-effectiveness of generic psychological therapy (counseling) with routinely prescribed antidepressant drugs in a naturalistic general practice setting for a follow-up period of 12 months. METHODS: Economic analysis alongside a randomized clinical trial with patient preference arm. Comparison of depression-related health service costs at 12 months. Cost-effectiveness analysis of bootstrapped trial data using net monetary benefits and acceptability curves. RESULTS: No significant difference between the mean observed costs of patients randomized to antidepressants or to counseling (342 pounds sterling vs 302 pounds sterling , p = .56 [t test]). If decision makers are not willing to pay more for additional benefits (value placed on extra patient with good outcome, denoted by K, is zero), then we find little difference between the treatment modalities in terms of cost-effectiveness. If decision makers do place value on additional benefit (K > 0 pounds sterling), then the antidepressant group becomes more likely to be cost-effective. This likelihood is in excess of 90% where decision makers are prepared to pay an additional 2,000 pounds sterling or more per additional patient with a good global outcome. The mean values for incremental net monetary benefits (INMB) from antidepressants are substantial for higher values of K (INMB = 406 pounds sterling when K = 2,500 pounds sterling). CONCLUSION: For a small proportion of patients, the counseling intervention (as specified in this trial) is a dominant cost-effective strategy. For a larger proportion of patients, the antidepressant intervention (as specified in this trial) is the dominant cost-effective strategy. For the remaining group of patients, cost-effectiveness depends on the value of K. Since we cannot observe K, acceptability curves are a useful way to inform decision makers.

Antidepressive Agents↗
PubMed2003

Theories of general personality and mental disorder.

BACKGROUND: A major shortcoming of current research into personality is its failure to explore the relationship between theories of general personality and mental disorder. AIMS: To provide preliminary data to address this deficit. METHOD: In the first of two studies, we examined the relationship between the Neuroticism, Extraversion and Other - Five-Factor Inventory (NEO-FFI) and DSM personality disorders in a consecutive series of mentally disordered offenders. In the second, we sought to separate the personality dimension neuroticism from symptoms of depressive disorder in a sample of subjects with current depression. RESULTS: Factors from the NEO-FFI were associated with different personality disorders in a predictable manner (first study). It was possible to identify a component of neuroticism (i.e. 'worry') that could be separated from depressive symptoms (second study). CONCLUSIONS: Theories of general personality theory can enlighten and refine descriptions of abnormal mental states by informing both their aetiology and their prognosis.

Adult↗
PubMed2003

Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1.

Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1 loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.

Animals↗
PubMed2002

Effect of list errors on the estimation of population size.

In many situations, it is possible to estimate the size of a closed population if some members of the population are recorded on one or more administrative lists. An important example is estimating the prevalence of a disease, where some members of the disease population may be recorded on lists such as disease registries, hospital admission records, and general practitioner records. An incomplete contingency table is formed by matching the lists and the missing cell count estimated by prediction based on a fitted model, which assumes that the matching is done without error. In practice, matching errors do occur, and in this article, we examine the effect of these errors on the estimation process and show how the standard models may be modified to allow for matching errors.

Diabetes Mellitus↗
PubMed2002

Resiliency in the victim-offender cycle in male sexual abuse.

The prevalence of childhood sexual abuse in child molesters is considerably higher than that in the general population. This finding had led to the "victim-offender cycle" being popularized as an explanation for sexual offending. However, not all child molesters were victimized as children, so it is of interest to examine the factors that contribute to the victim-offender cycle or, conversely, resiliency. This study examined the "moderating factors" that may prevent a male victim of sexual abuse from entering the victim-offender cycle. Two groups were interviewed as part of the study: a "resilient group" (n = 47) and a victim-offender group (n = 41). After correction for age and education level, the resilient group were less likely to have fantasized and masturbated about the abuse, less likely to report deriving pleasure from the abuse, more likely to have had frequent social contact with adolescent peers and to have had more family and nonfamily support during childhood. The findings support the need for multifactorial models of resiliency, the victim-offender cycle, and sexual offending. Recommendations about the prevention of the victim-offender cycle are made, including the need for a thorough systemic assessment of all male victims of sexual abuse and the involvement of their family system in counseling.

Adult↗