Mapping Disease-Susceptibility Genes in Admixed Populations Using Interval Principal Component Tests

Family-based association approach for mapping disease-susceptibility genes of complex human diseases is a topical issue in genetic epidemiology. It is well known that admixture between genetically differentiated populations can result in high levels of linkage disequilibrium at loci separated far apart. This property has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. The authors describe a new approach for admixture mapping--the "interval principal component test" (IPCT). The genome is divided into a multitude of non-overlapping "intervals" (with interval length of 10-20 cM) and the information of the markers in the same interval is integrated using the principal component analysis. Monte-Carlo simulation shows that an interval-by-interval scan using IPCT has much better performances than a conventional marker-by-marker scan using the transmission/disequilibrium test (TDT).     

Bone-mineral density deficits from childhood cancer and its therapy

The growing population of childhood cancer survivors—currently estimated at 1 in 900 young adults aged 15–45 years—underscores the importance of studying long-term complications of oncotherapy. While these patients are returning to the mainstream of life, they carry with them toxicities from prior therapy that may compound or potentiate changes typically seen with the normal aging process. Skeletal toxicities such as scoliosis, craniofacial dysplasia, and limb-length discrepancy are readily apparent. However, others such as osteoporosis and osteonecrosis are silent until they reach advanced stages when attempts at amelioration may be unsuccessful. This review addresses bone-mineral density deficits that may predispose childhood cancer survivors to earlier onset and more severe osteopenia and osteoporosis than the normal population.This study was supported in part by grants P30 CA-21765 and P01 CA-20180 from the National Cancer Institute, a Center of Excellence grant from the state of Tennessee from the National Institutes of Health and by the American Lebanese Syrian Associated Charities (ALSAC)     

Cryopreservation of human spermatozoa: comparison of two cryopreservation methods and three cryoprotectants

OBJECTIVE: To evaluate the ability of two cryopreservation methods and three cryoprotectants to preserve sperm quality. DESIGN: A prospective clinical study. SETTING: Male infertility clinic at a tertiary healthcare center. PATIENT(S): Twenty infertile men and 10 healthy donors. INTERVENTION(S): In the first experiment, semen was cryopreserved by either the Irvine Scientific method (IS) or the Cleveland Clinic Foundation (CCF) method. In the second experiment, semen was cryopreserved by the IS method and one of three cryoprotectants: TES and Tris yolk buffer, Sperm Freezing Medium, or Enhance Sperm Freeze. MAIN OUTCOME MEASURE(S): Postthaw sperm motility, cryosurvival, and kinematics. RESULT(S): Percentages of postthaw sperm motility and cryosurvival were higher in the IS cryopreservation method compared with in the CCF method (15.94 +/- 9.19 vs. 12.07 +/- 7.31 and 47.42 +/- 17.44 vs. 35.76 +/- 17.56). However, the CCF method resulted in significantly better sperm kinematics. Postthaw motility in the donors and patients was highest in the samples frozen in TES and Tris yolk buffer medium. CONCLUSION(S): The IS method was associated with more flash freezing compared with the CCF method and resulted in better preservation of sperm motility and a higher cryosurvival rate. TES and Tris yolk buffer was most effective at protecting sperm from the negative effects of the cryopreservation process. This may be due to the presence of egg yolk along with glycerol.     

Comprehensive decision analytical modelling in economic evaluation: a Bayesian approach

Decision analytical models are widely used in economic evaluation of health care interventions with the objective of generating valuable information to assist health policy decision-makers to allocate scarce health care resources efficiently. The whole decision modelling process can be summarised in four stages: (i) a systematic review of the relevant data (including meta-analyses), (ii) estimation of all inputs into the model (including effectiveness, transition probabilities and costs), (iii) sensitivity analysis for data and model specifications, and (iv) evaluation of the model. The aim of this paper is to demonstrate how the individual components of decision modelling, outlined above, may be addressed simultaneously in one coherent Bayesian model (sometimes known as a comprehensive decision analytical model) and evaluated using Markov Chain Monte Carlo simulation implemented in the specialist software WinBUGS. To illustrate the method described, it is applied to two illustrative examples: (1) The prophylactic use of neurominidase inhibitors for the prevention of influenza. (2) The use of taxanes for the second-line treatment of advanced breast cancer.The advantages of integrating the four stages outlined into one comprehensive decision analytical model, compared to the conventional 'two-stage' approach, are discussed.     

Responses to standard gambles: are preferences ‘well constructed’?

Standard gamble (SG) is commonly used to elicit preferences in order to assess health related quality of life. There has been little qualitative research exploring how respondents answer such questions. An SG study was designed to elicit values for the health states associated with anti-hypertensive medication, stroke and cardiovascular disease. This paper describes a qualitative study that was carried out alongside the SG exercise in order to document the thought processes respondents bring to bear in formulating their responses. Data were generated using 'think aloud' techniques and semi-structured interviews. Values were generally well-constructed: responses were thoroughly considered, and respondents made complex trade-offs and arrived at a point of indifference. However, some respondents incorporated inappropriate information into their choices, redefining the hypothetical 'Option B' resulting in problems interpreting the probabilistic information. Consideration of non-health factors was commonplace, in particular the impact of choices on others. We discuss these findings in terms of the use of qualitative methods in health economics and the wider discourse surrounding the theoretical underpinnings of health state valuation.     

Simulation of a Hirschman-Herfindahl index without complete market share information

This paper utilizes maximum likelihood methods to simulate a Hirschman-Herfindahl index (HHI) for markets in which complete market share information is unavailable or delayed. Many jurisdictions either may be unable to administratively collect data or experience delays in collection that make data regarding turbulent markets of limited use. With the development of this method, regulatory authorities monitoring health-care competition or health-care firms can now use market surveys--in which reliable recall is often limited to the largest three or four firms--to produce an on-the-spot measure of market concentration.     

Framing the doctor-patient relationship in chronic illness: a comparative study of general practitioners' accounts

How family doctors conceptualise chronic illness in the consultation has important implications for both the delivery of medical care, and its experience by patients. In this paper, we present the results of a re-analysis of qualitative data collected in a series of studies of British family doctors between 1995 and 2001, to explore the ways in which the legitimacy and authority of medical knowledge and practice are organised and worked out in relation to three kinds of chronic illness (menorrhagia; depression; and chronic low back pain/medically unexplained symptoms). We present a comparative analysis of (a). the moral evaluation of the patient (and judgements about the legitimacy of symptom presentation); (b). the possibilities of disposal; and (c). doctors' empathic responses to the patient, in each of these clinical cases. Our analysis defines some of the fundamental conditions through which general practitioners frame their relationships with patients presenting complex but sometimes diffuse combinations of 'social', 'psychological' and 'medical' symptoms. These are fundamental to, yet barely touched by, the increasingly voluminous literature on how doctors should interact with patients. Moving beyond the individual studies from which our data are drawn, we have outlined some of the highly complex and demanding features of what is often seen as routine and unrewarding medical work, and some of the key requirements for the local negotiation of patients' problems and their meanings (for both patients and doctors) in everyday general practice.     

Maternal Dietary Risk Factors in Childhood Acute Lymphoblastic Leukemia (United States)

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and the second most common cause of mortality in children aged 1-14 years. Recent research has established that the disease can originate in utero, and thus maternal diet may be an important risk factor for ALL. METHODS: The Northern California Childhood Leukemia Study is a population-based case-control study of risk factors for childhood leukemia, including maternal diet. Cases (n = 138) and controls (n = 138) were matched on sex, date of birth, mother's race, Hispanicity, and county of residence at birth. Maternal dietary intake in the 12 months prior to pregnancy was obtained by a 76-item food frequency questionnaire. RESULTS: Consumption of the vegetables (OR = 0.53; 95% CI, 0.33-0.85; p = 0.008), protein sources (OR = 0.40; 95% CI, 0.18-0.90, p = 0.03), and fruits (OR = 0.71; 95% CI, 0.49-1.04; p = 0.08) food groups were inversely associated with ALL. Among nutrients, consumption of provitamin A carotenoids (OR = 0.65, 95% CI, 0.42-1.01; p = 0.05), and the antioxidant glutathione (OR = 0.42; 95% CI, 0.16-1.10; p = 0.08) were inversely associated with ALL. CONCLUSION: Maternal dietary factors, specifically the consumption of vegetables, fruits, protein sources and related nutrients, may play a role in the etiology of ALL. Dietary carotenoids and glutathione appear to be important contributors to this effect.     

Dementia Care Mapping reconsidered: exploring the reliability and validity of the observational tool

BACKGROUND: Dementia Care Mapping (DCM) is a widely used observational method for evaluating the service quality provided to people with dementia. However, there is little evidence concerning its reliability and validity when used by routine care staff for whom it was designed. METHOD: The study evaluated levels of inter-observer agreement; The ability of the five-minute time frame to reflect the 'actual passing of time'; And the nature of the relationship between individual Well/Ill-Being values (WIB) and dependency levels.Data collected using DCM and continuous time sampling (CTS) were compared. The methods were used in parallel where the CTS coder and the DCM mapper(s) observed the same participants.Observations were carried out with 64 people with dementia within a day hospital and a continuing care ward. Inter-observer agreement was calculated across 20 participants.Dependency levels were measured using the Clifton Assessment Procedure for the Elderly (CAPE) (Pattie and Gilleard, 1979). RESULTS: Low levels of inter-observer agreement were found where 11 of the 25 Behaviour Category codes and all six Well/Ill-being Codes produced unacceptable kappas (<0.6).The Behaviour coding frame provided a meaningful picture of activities participants engaged in, but significantly underestimated participant levels of inactivity.A strong relationship was demonstrated between participants' WIB score and levels of dependency, thus DCM was unable to measure well-/ill-being as a separate construct from participants' levels of dependency. CONCLUSIONS: Questions were raised regarding the reliability and validity of DCM as used by routine care staff. Possible reasons for this, and suggestions for amendments are made.