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The supermatrix approach to systematics.

Recent reviews of the construction of large phylogenies have focused on supertree methods that involve separate analyses of data sets and subsequent integration of the resulting trees. Here, we consider the alternative method of analyzing all character data simultaneously. Such 'supermatrix' analyses use information from each character directly and enable straightforward incorporation of diverse kinds of data, including characters from fossils. The approach has been extended by the development of new methods, including model-based techniques for analyzing heterogeneous data and hierarchical methods for constructing extremely large trees. Recent work also suggests that the problem of missing data in supermatrix analyses has been overstated. Although the supermatrix approach is not suited for all cases, we suggest that its inherent strengths will ensure that it will continue to have a central role in inferring large phylogenetic trees from diverse data.

Animals↗

Cryoablation of small peripheral renal masses: a retrospective analysis.

Renal cryoablation is a minimally invasive, nephron-sparing option that has shown promise in the treatment of patients with solitary small renal lesions suspicious for malignancy. Few large clinical studies have used this promising technology, although intermediate-term data are encouraging. We present a retrospective review and report the outcomes of a large cohort of patients who underwent renal cryotherapy. Patients who were candidates for partial nephrectomy with peripheral lesions < or = 5.0 cm in maximum diameter and no history of bleeding disorders were offered cryoablation as definitive therapy. Two freeze-thaw cycles were used for all lesions, and all were characterized by intraoperative ultrasound immediately before freezing. Data were collected as part of standard care, and chart review was performed only in cases of missing data. From February 2001 to March 2005, 85 consecutive patients with an average age of 67 years and a mean tumor size of 2.6 cm (range, 1.2-4.7 cm; median, 2.5 cm), underwent renal cryoablation; 70 procedures were performed laparoscopically. Mean estimated blood loss was 58 mL, with 2 patients requiring transfusion. Mean hospital stay was 3.0 days (range, 0-14 days; median, 2 days) for the entire cohort and 2.2 days (range, 0-7 days; median, 2 days) for the laparoscopic group. A total of 7 laparoscopic cases were converted to an open approach early in the experience, 2 of which were considered technical failures. Mean follow-up was 10 months (range, 3-36 months). Abnormal postoperative enhancement occurred in 2 patients at 3 months and 12 months. Radical nephrectomy in the first revealed no viable tumor; needle biopsy in the second revealed renal cell carcinoma, which prompted nephrectomy. Intraoperative needle biopsy yielded a 59% malignancy rate. We conclude that renal cryotherapy is a viable option for nephron-sparing surgery in small, peripheral renal lesions. The procedure is well tolerated, may be considered in patients who are not good candidates for open surgical approaches, results in minimal morbidity, and has shown encouraging treatment results. Close posttreatment surveillance is essential. Longer-term follow-up data will be necessary if the long-term durability of renal cryotherapy is to be established.

Adult↗

A Bayesian model for spatial wildlife disease prevalence data.

The analysis of the geographical distribution of disease on the scale of geographic areas such as administrative boundaries plays an important role in veterinary epidemiology. Prevalence estimates of wildlife population surveys are often based on regional count data generated by sampling animals shot by hunters. The observed disease rate per spatial unit is not an useful estimate of the underlying disease prevalence due to different sample sizes and spatial dependencies between neighbouring areas. Therefore, it is necessary to account for extra-sample variation and spatial correlations in the data to produce more accurate maps of disease incidence. The detection of spatial patterns is complicated by missing data in many of the geographical areas as the complete coverage of all areas is nearly impossible in wildlife surveys. For this purpose a hierarchical Bayesian model in which structured and unstructured over dispersion is modelled explicitly in terms of spatial and non-spatial components was implemented by Markov chain Monte Carlo methods. The model was empirically compared with the results of a non-spatial beta-binomial model using surveillance data of pseudorabies virus infections of European wild boars (Sus scrofa scrofa L.) in the Federal State of Brandenburg, Germany.

Animal Diseases↗

Effect of antipsychotic withdrawal on extrapyramidal symptoms: statistical methods for analyzing single-sample repeated-measures data.

Using symptom severity ratings of extrapyramidal side effects (EPS) during a 4-week antipsychotic washout period, we illustrate particular problems associated with repeated measures of symptom severity and demonstrate four analysis methods. The often suggested analysis of variance and multivariate analysis of variance found no mean change in weekly Simpson Angus scores over the 4-week washout despite the fact that 43% had clinically significant EPS prior to drug discontinuation. On the other hand, the Friedman Analysis of Ranks and Cochran-Mantel-Haenszel (CMH) statistics found significant change over the washout period. These two less well-known techniques place fewer restrictions on the data, can be more sensitive to patterns of change, and may be more appropriate for psychiatric data. The CMH method is particularly attractive since it does not require complete data on all subjects as do many other techniques. This minimizes the number of cases lost to missing data and increases the generality of the results.

Adult↗

Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review.

Published studies of the prognostic value of the early response to induction treatment in childhood acute lymphoblastic leukaemia (ALL) were analysed. Three criteria were used to judge the early treatment response: persistence of peripheral blasts (PPB) or of bone marrow blasts (PBMB) during induction therapy and minimal residual disease (MRD) after completion of induction therapy. Studies with more than 50 patients, published between 1980 and 2000, were reviewed. Among 13 659 distinct articles published on ALL, we identified only 43 applicable studies. Within- and between-laboratory variations were evaluated in only one study. Treatment modalities differed among, and sometimes within, studies. The cut-off points used in the statistical analyses were never discussed, and in many studies appeared to be selected after multiple tests. The proportion of missing data was > 30% in almost all studies of MRD, as a result of technical difficulties and not missing samples. PPB and PBMB were associated with shorter survival in, respectively, 13 out of 14 and 15 out of 16 studies. Detection of MRD was associated with poor outcome in 12 of the 13 studies. Because none of the parameters used to measure the early response to induction therapy for childhood ALL have been properly assessed as prognostic factors, we conclude that they should be considered only as candidate prognostic indicators pending more thorough studies.

Bone Marrow↗

Pathology of canine cataract surgery complications.

AIM: To compare pathological complications arising from 2 methods of canine cataract surgery, manual extracapsular cataract extraction (MECCE) and the more automated phacoemulsification and aspiration (PA). METHODS: Case material presented to the Comparative Ophthalmic Pathology Laboratory, University of North Carolina over the previous 20 years (1979-1999) was searched for cases with a history of prior cataract surgery. Data were obtained from the pathology accession forms, and submitting veterinarians were contacted to verify and complete missing data where possible. The slides were re-examined, histological features of surgical complications were noted and secondary changes recorded. RESULTS: Fourteen canine post-cataract-surgery cases were reviewed, the average age of the group being 7.7 years. Of the 14 eyes, 7 had surgery performed using MECCE, and 7 using PA. Of the 7 eyes that underwent MECCE surgery, 5 were enucleated and diagnosed on both clinical and pathological grounds with glaucoma. Of the 7 eyes that underwent PA, 4 were diagnosed with infectious endophthalmitis. CONCLUSIONS: Complications observed were related to the surgical technique performed. Failures of manual extracapsular surgical procedures were more commonly associated with postoperative synechia and glaucoma, compared with failures of phacoemulsification, which were more commonly associated with infection and rhegmatogenous retinal detachments. CLINICAL RELEVANCE: To minimise post surgical complications, MECCE should be accompanied by rigorous efforts to reduce surgically induced inflammation, while PA should be performed using excellent aseptic technique. It is important with both techniques to totally remove cortical material while maintaining the integrity of the posterior capsule.

Journal Article↗

Urban air pollution monitoring and correlation properties between fixed-site stations.

The rich regional air-monitoring network of the Emilia-Romagna region of Italy has been used to quantify the spatial variability of the main pollutants within urban environments and to analyze the correlations between stations. The spatial variability of the concentrations of the majority of pollutants within the city was very high, making it difficult to differentiate and characterize the urban environments and to apply legal limits with uniform criteria. On the other hand, the correlations between the fixed-site monitoring stations were high enough for their data to be retained generally very appropriately for controlling temporal trends. Starting from the high correlation level, a procedure was proposed and tested to derive pollution levels, using short-term measurements, such as passive samplers and mobile-station data. The importance of long-term statistics in urban air pollution mapping was emphasized. Treatment of missing data in time series and quality assurance were indicated as possible fields for applications for the correlation properties.

Air Pollutants↗

Forecasting influent flow rate and composition with occasional data for supervisory management system by time series model.

The information on the incoming load to wastewater treatment plants is not often available to apply modelling for evaluating the effect of control actions on a full-scale plant. In this paper, a time series model was developed to forecast flow rate, COD, NH4(+)-N and PO4(3-)-P in influent by using 250 days data of field plant operation data. The data for 150 days and 100 days were used for model development and model validation, respectively. The missing data were interpolated by the spline method and the time series model. Three different methods were proposed for model development: one model and one-step to seven-step ahead forecasting (Method 1); seven models and one-step-ahead forecasting (Method 2); and one model and one-step-ahead forecasting (Method 3). Method 3 featured only one-step-ahead forecasting that could avoid the accumulated error and give simple estimation of coefficients. Therefore, Method 3 was the reliable approach to developing the time series model for the purpose of this research.

Forecasting↗

Forecasting the need for physicians in the United States: the Health Resources and Services Administration's physician requirements model.

OBJECTIVE: The Health Resources and Services Administration's Bureau of Health Professions developed a demographic utilization-based model of physician specialty requirements to explore the consequences of a broad range of scenarios pertaining to the nation's health care delivery system on need for physicians. DATA SOURCE/STUDY SETTING: The model uses selected data primarily from the National Center for Health Statistics, the American Medical Association, and the U.S. Bureau of Census. Forecasts are national estimates. STUDY DESIGN: Current (1989) utilization rates for ambulatory and inpatient medical specialty services were obtained for the population according to age, gender, race/ethnicity, and insurance status. These rates are used to estimate specialty-specific total service utilization expressed in patient care minutes for future populations and converted to physician requirements by applying per-physician productivity estimates. DATA COLLECTION/EXTRACTION METHODS: Secondary data were analyzed and put into matrixes for use in the mainframe computer-based model. Several missing data points, e.g., for HMO-enrolled populations, were extrapolated from available data by the project's contractor. PRINCIPAL FINDINGS: The authors contend that the Bureau's demographic utilization model represents improvements over other data-driven methodologies that rely on staffing ratios and similar supply-determined bases for estimating requirements. The model's distinct utility rests in offering national-level physician specialty requirements forecasts.

Adolescent↗

Inadequacies of death certification in Beirut: who is responsible?

OBJECTIVE: To assess the completeness of data on death certificates over the past 25 years in Beirut, Lebanon, and to examine factors associated with the absence of certifiers' signatures and the non-reporting of the underlying cause of death. METHODS: A systematic 20% sample comprising 2607 death certificates covering the 1974, 1984, 1994, 1997 and 1998 registration periods was retrospectively reviewed for certification practices and missing data. FINDINGS: The information on the death certificates was almost complete in respect of all demographic characteristics of the deceased persons except for occupation and month of birth. Data relating to these variables were missing on approximately 95% and 78% of the certificates, respectively. Around half of the certificates did not carry a certifier's signature. Of those bearing such a signature, 21.6% lacked documentation of the underlying cause of death. The certifier's signature was more likely to be absent on: certificates corresponding to the younger and older age groups than on those of persons aged 15-44 years; those of females than on those of males; those of persons who had been living remotely from the registration governorate than on those of other deceased persons; and those for which there had been delays in registration exceeding six months than on certificates for which registration had been quicker. For certificates that carried the certifier's signature there was no evidence that any of the demographic characteristics of the deceased person was associated with decreased likelihood of reporting an underlying cause of death. CONCLUSION: The responsibility for failure to report causes of death in Beirut lies with families who lack an incentive to call for a physician and with certifying physicians who do not carry out this duty. The deficiencies in death certification are rectifiable. However, any changes should be sensitive to the constraints of the organizational and legal infrastructure governing death registration practices and the medical educational systems in the country.

Adolescent↗

Clinically relevant breast cancer reporting: using process measures to improve anatomic pathology reporting.

OBJECTIVE: Breast cancer reports form an important part of the basis of clinical decision making for patients. Our objectives were to improve breast cancer reporting in the Urban Central Region in Utah of Intermountain Health Care in a clinically relevant manner and to show that the method chosen actually improved information transfer among physicians of breast cancer patients and led to durable changes in pathologist behavior. METHODS/INTERVENTION: Pathologists designed a synoptic report based on interviews with oncologists about what data were meaningful. The report format was piloted with one hospital pathology group, modified, and implemented in three hospitals. A report evaluation of missing information was done before, immediately after, and 2 years after the intervention. Oncologists were surveyed after 2 years to evaluate satisfaction with report format. RESULTS: Changing breast cancer reporting to a synoptic format significantly decreased information missing from pathology reports. Prior to implementation, 32 of 365 reports lacked some item(s) of pathology information desirable to clinicians; after the intervention, 8 of 250 reports contained missing information. After 2 years, 1 in 190 reports contained missing data elements. Synoptic breast cancer reports continued to be used by pathologists throughout the reporting period. Oncologists responding to a survey reported uniform satisfaction with the new reporting format. SUMMARY: Pathologists are important members of the clinical oncology team. They provide patient-specific information crucial to patient care. Activities designed to improve the quality of reporting processes should use clinically relevant indicators of process improvement, such as measurement of missing information and satisfaction of clinical colleagues with format/quality of information.

Breast Neoplasms↗

Speech and language therapy for aphasia following stroke.

BACKGROUND: Aphasia describes language impairment associated with a brain lesion. OBJECTIVES: The objective of this review was to assess the effects of formal speech and language therapy and non-professional types of support from untrained providers for people with aphasia after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched: March 1999), and reference lists of relevant articles to December 1998. We also contacted academic institutions and other researchers to identify further published and unpublished trials. We searched The International Journal of Disorders of Communication by hand (known by other names in the past), from 1969 to 1998. Date of most recent searches: January 1999. SELECTION CRITERIA: Randomised controlled trials comparing: 1. Any type of formal speech and language therapy in any setting administered by trained speech and language therapists versus no treatment. 2. Any type of formal speech and language therapy in any setting administered by trained speech and language therapists versus any type of informal support for aphasia, given by speech and language therapists or volunteers, whether these were trained or untrained. 3. One type of speech and language therapy versus another type. Outcome measures included measures of any type of communication, other measures of functioning, numbers of drop-outs, and other non-clinical outcomes. DATA COLLECTION AND ANALYSIS: The principal reviewer collected the data, and assessed the quality of the trials with independent data checking and methodological advice. If we could not perform a statistical combination of different studies, we sought missing data. Failing that we provided a description. MAIN RESULTS: We considered sixty studies in detail, from which we identified twelve trials suitable for the review. Most of these trials were relatively old with poor or unassessable methodological quality. None of the trials was detailed enough for us to complete description and analysis. We could not determine whether formal speech and language therapy is more effective than informal support. REVIEWER'S CONCLUSIONS: The main conclusion of this review is that speech and language therapy treatment for people with aphasia after a stroke has not been shown either to be clearly effective or clearly ineffective within a RCT. Decisions about the management of patients must therefore be based on other forms of evidence. Further research is required to find out if effectiveness of speech and language therapy for aphasic patients is effective. If researchers choose to do a trial, this must be large enough to have adequate statistical power, and be clearly reported.

Aphasia↗

Continuous versus intermittent beta-agonists in the treatment of acute asthma.

BACKGROUND: Patients with acute asthma treated in the emergency department are frequently treated with intermittent inhaled beta-agonists delivered by nebulisation. The use of continuous beta-agonist (CBA) via nebulisation in the emergency setting may offer additional benefits in acute asthma. OBJECTIVES: To determine the efficacy (e.g., reductions in admission, improvement in pulmonary functions) and risks (e.g., adverse events, effects on vital signs) of continuous versus intermittent inhaled beta-agonists for the treatment of patients with acute asthma managed in the emergency department. SEARCH STRATEGY: Randomised controlled trials were identified from the Cochrane Airways Review Group "Asthma and WHEEZ*" Register which is a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. The search is considered updated to June 2003. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with either continuous or intermittent inhaled beta-agonists early in the ED treatment. "Continuous" nebulisation was defined as truly continuous aerosol delivery of beta-agonist medication (e.g., using a commercially available large-volume nebuliser, or a small-volume nebuliser with infusion pump) or sufficiently frequent nebulisations that medication delivery was effectively continuous (i.e., 1 nebulisation every 15 minutes or > 4 nebulisations per hour). Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and two additional reviewers independently selected articles for inclusion. Methodological quality was independently assessed by two reviewers. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager (Version 4.1). Relative risks (RR), weighted mean differences (WMD) and standardized mean differences (SMD) are reported with corresponding 95% confidence intervals (CI); both peak expiratory flow rates (PEFR) and forced expiratory volume in one second (FEV-1) data are reported. MAIN RESULTS: 165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEV-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD: -2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI: -0.2 to 0.2). REVIEWER'S CONCLUSIONS: Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it.

Acute Disease↗

Humidified air inhalation for treating croup.

BACKGROUND: Croup (laryngotracheobronchitis) is a common cause of upper airway obstruction in children with a peak incidence of 60 per 1000 child years in those aged between one and two years. It is characterised by hoarseness, a barking cough, and inspiratory stridor. These symptoms are thought to occur as a result of oedema of the larynx and trachea, which have been triggered by a recent viral infection. Para influenza virus type 1 is the agent most commonly identified in cases of croup. Severe cases are admitted to hospital and steroid treatment is established to reduce disease severity. Treatment with humidified air was previously widely used and is still commonly recommended as home treatment. OBJECTIVES: To assess the efficacy of humidified air in the treatment of croup. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to January 2006) and EMBASE (1990 to January 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving children suffering from croup treated with humidified air. DATA COLLECTION AND ANALYSIS: Two authors independently identified potentially relevant abstracts identified from the search and then assessed the full papers for inclusion and methodological quality. Outcome measures included mortality, ventilation, admission to hospital, re-contact with medical services, number of days off school and relief of symptoms; these were separately analysed for the week following treatment. Data extraction was performed by the two authors then entered by one and checked by the second author. Missing data were obtained from trails authors where possible. Data were analysed using Review Manager version 4.2. Sensitivity and sub-group analysis were not possible due to the paucity of trials. MAIN RESULTS: Three studies in emergency settings provided data on 135 patients with moderate croup for the main outcome (croup score). The combined results from 20 to 60 minutes in the three studies marginally favoured the treatment group with a weighted standardised mean difference of -0.14 (95% confidence interval (CI) -0.75 to 0.47). No other outcomes were significantly different between the groups. AUTHORS' CONCLUSIONS: The croup score of children managed in an emergency setting with mild to moderate croup probably does not improve greatly with inhalation of humidified air. Further research is needed in primary care settings, using a wider range of more sensitive outcome measures.

Air↗

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported in 2001. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: We identified additional RCTs from the Cochrane Airways Group Specialised Register. Searches were current as of July 2004. SELECTION CRITERIA: We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least four weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We calculated weighted mean differences (WMD) using a random-effects model. We requested missing data from the authors of the primary study. MAIN RESULTS: We included the 23 randomized controlled trials (RCTs) in the 2001 Cochrane review. Eight additional RCTs (for a total of 31) met the inclusion criteria. We found statistically significant improvements for all the outcomes. In four important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units (for example: Dyspnoea score: WMD 1.0 units; 95% confidence interval: 0.8 to 1.3 units; n = 12 trials). Statistically significant improvements were noted in two of the three domains of the St. Georges Respiratory Questionnaire. For FEC and MEC, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 meters; 95% CI: 32 to 65; n = 16 trials). AUTHORS' CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Dyspnea↗

Data mining techniques applied to medical information.

Knowledge discovery from the dramatically increased data of an auto-stored medical information system is still in its infancy. The purpose of this study is to use widely available and easily operated techniques that can satisfy general users in extracting specific knowledge to make the medical information system more functional. Data mining techniques, including data visualisation, correlation analysis, discriminant analysis, and neural networks supervised classification, were applied to heart disease databases. These techniques can help to identify high risk patients, define the most important factors (variables) in heart disease, and build a multivariate relationship model to show the relationship between any two variables in a way that such relationships are easy to view. Simple visualization techniques were utilised to construct this model, which corresponds with current medical knowledge. Two nonparametric (distribution assumption free) classification tools were employed to identify high risk heart disease patients. Both the neural networks supervised classification methods and the discriminant analysis method produced reliable classification rates for heart disease patients. However, neural networks yielded a higher percentage of correct classifications (averaging 89%) than discriminant analysis (79%). Data visualisation and correlation analysis resulted in similar conclusions regarding the most important factors in heart disease. These data mining tools provide simple and effective methods of extracting knowledge from general medical information. The treatment of missing data is also discussed.

Computer Graphics↗

The value of molecular haplotypes in a family-based linkage study.

Novel methods that could improve the power of conventional methods of gene discovery for complex diseases should be investigated. In a simulation study, we aimed to investigate the value of molecular haplotypes in the context of a family-based linkage study. The term "haplotype" (or "haploid genotype") refers to syntenic alleles inherited on a single chromosome, and we use the term "molecular haplotype" to refer to haplotypes that have been determined directly by use of a molecular technique such as long-range allele-specific polymerase chain reaction. In our study, we simulated genotype and phenotype data and then compared the powers of analyzing these data under the assumptions that various levels of information from molecular haplotypes were available. (This information was available because of the simulation procedure.) Several conclusions can be drawn. First, as expected, when genetic homogeneity is expected or when marker data are complete, it is not efficient to generate molecular haplotyping information. However, with levels of heterogeneity and missing data patterns typical of complex diseases, we observed a 23%-77% relative increase in the power to detect linkage in the presence of heterogeneity with heterogeneity LOD scores >3.0 when all individuals are molecularly haplotyped (compared with the power when only standard genotypes are used). Furthermore, our simulations indicate that most of the increase in power can be achieved by molecularly haplotyping a single individual in each family, thereby making molecular haplotyping a valuable strategy for increasing the power of gene mapping studies of complex diseases. Maximization of power, given an existing family set, can be particularly important for late-onset, often-fatal diseases such as cancer, for which informative families are difficult to collect.

Computer Simulation↗

What follow-up studies say about postschool life for young men and women with learning disabilities: a critical look at the literature.

Follow-up studies examining the outcomes for children and youth with learning disabilities who attended special education have appeared in the literature for decades. As American society becomes more technologically advanced and competitive, postsecondary school opportunities and subsequent employment choices that are meaningful and provide a livable wage teeter out of the reach of young people with learning disabilities. Follow-up study investigators seek to understand how to better prepare youth to meet these challenges by studying their long-term outcomes. The authors review data from 13 frequently referenced follow-up studies regarding postschool outcomes, postsecondary education, and employment, with attention to gender differences, for youth with learning disabilities who were served by and graduated from special education programs nationwide. They take a critical look at contradictions in the findings and discuss five methodological issues that seem to influence the conduct and interpretation of follow-up studies: aggregating data across disability categories; combining data on graduates who have been out of school for unequal periods of time; ignoring the issues of missing data, participant attrition, and incomplete data sets; combining data from different informants; and using nonequivalent databases to make comparisons to a population with no disabilities. The authors provide recommendations for conducting follow-up research on the long-term quality of life of children and youth with disabilities and their families.

Adult↗