Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.     

Simple, effective countermeasures to P300-based tests of detection of concealed information

We found countermeasures to protocols using P300 in concealed information tests. One, the "six-probe" protocol, in Experiment 1, uses six different crime details in one run. The countermeasure: generate covert responses to irrelevant stimuli for each probe category. Hit rates were 82% in the guilty group; 18% in the countermeasure group. The average reaction time (RT) distinguished these two groups, but with overlap in RT distributions. The "one-probe" protocol, in the second experiment, uses one crime detail as a probe. Here, one group was run in 3 weeks as a guilty group, a countermeasure group, and again as in Week 1. COUNTERMEASURE: Covert responses to irrelevant stimuli. In Week 1, hit rate was 92%. In Week 2, it was 50%. In Week 3, 58%. There was no overlap in the irrelevant RT distribution in Week 2: Countermeasure use was detectable. However, in Week 3, the RT distributions resembled those of Week 1; test-beaters could not be caught. These studies have shown that tests of deception detection based on P300 amplitude as a recognition index may be readily defeated with simple countermeasures that can be easily learned.     

Automatic time perception in the human brain for intervals ranging from milliseconds to seconds

Time perception in everyday life deals with various intervals. Here we investigated whether an automatic duration-discrimination mechanism in audition operates even for intervals of an order of seconds, by using the mismatch negativity (MMN), an index of automatic change detection in audition. In Experiment 1, occasional decrements of the duration of a repetitive "standard" tone elicited an MMN in subjects ignoring auditory stimulation, even with the standard-stimulus durations over a second. Nevertheless, the MMN amplitude was significantly diminished with standard-stimulus durations of 800 ms and above, despite the fact that a constant deviant versus standard duration ratio was used. Complementary experiments varying the interstimulus interval (Experiment 2) and the magnitude of duration change (Experiment 3) yielded corroborating results. The present results suggest that automatic duration discrimination in audition operates even for durations of the order of seconds; yet its optimum time scale might be of the order of milliseconds.     

Alert threshold algorithms and malaria epidemic detection

We describe a method for comparing the ability of different alert threshold algorithms to detect malaria epidemics and use it with a dataset consisting of weekly malaria cases collected from health facilities in 10 districts of Ethiopia from 1990 to 2000. Four types of alert threshold algorithms are compared: weekly percentile, weekly mean with standard deviation (simple, moving average, and log-transformed case numbers), slide positivity proportion, and slope of weekly cases on log scale. To compare dissimilar alert types on a single scale, a curve was plotted for each type of alert, which showed potentially prevented cases versus number of alerts triggered over 10 years. Simple weekly percentile cutoffs appear to be as good as more complex algorithms for detecting malaria epidemics in Ethiopia. The comparative method developed here may be useful for testing other proposed alert thresholds and for application in other populations.     

Participation in annual skin cancer screening among women seeking routine mammography

BACKGROUND: Early detection of skin cancer is associated with improved prognosis. The American Cancer Society's current skin cancer screening (SCS) recommendation states that adults over the age of 40 should receive an annual skin examination conducted by a health professional. However, little is known about the psychosocial factors related to participation in annual SCS, which remains relatively low among the general public. METHODS: Data were collected from women, aged 50 and older, seeking routine mammography at a large, urban, breast diagnostic facility. RESULTS: A total of 253 eligible women completed the survey. Overall, 20.2% of women reported receiving annual clinical SCS. Physician recommendation, self-efficacy, perceived susceptibility, and age were significantly associated with participation in annual skin screening. CONCLUSIONS: Similar to previously reported findings in the literature, our rates of participation in annual clinical skin screening were lower than reported rates for other types of cancer screening. Among older women, multiple covariates for participation in annual skin cancer screening were determined and may serve to guide future health education interventions to promote screening. Our findings suggest that participation could improve through increasing physician recommendation, screening self-efficacy, and individuals' sense of perceived susceptibility to skin cancer.     

A Comparison of Diabetes Care in Rural and Urban Medical Clinics in Alabama

This study sought to determine the differences in the level of diabetes care of patients in a rural family practice clinic and an urban internal medicine clinic in Alabama. Medical records of patients with diabetes were reviewed and management practices were compared to current American Diabetes Association (ADA) standards of care. The rural practice had fewer patients at goal A1c, goal LDL, and goal blood pressure. Rural patients were also less likely to receive screening and preventative services such as lipid profiles, eye examinations, microalbumin screening, aspirin therapy, and vaccinations than urban patients. Although, adherence to the ADA standards of care was lower with rural patients, the results suggest that there exists significant opportunity to improve the delivery of diabetes care services to both patient populations.     

黄连(味连)"有限成分组合质量标准"的研究

目的：制定黄连(味连)“有限成分组合质量标准”;探索建立评价中药材质量的方法学体系及其在中成药质量评价中的应用可行性。方法：分析味连各主产地样品成分,比较各样品在成分组成和药效上的差异,确定质量评价指标,并测定其在以黄连为主药的中成药中的含量。结果：制定了以小檗碱、黄连碱、药根碱、巴马汀及总生物碱含量上下限为指标的味连“有限成分组合质量标准”;提出了制定中药材质量标准的方法及操作规程;该方法可间接应用于中成药的质量标准制定。     

Experience with the Platelia Candida ELISA for the diagnostics of invasive candidosis in neutropenic patients

Invasive Candida infections (IC) belong to the most important opportunistic fungal infections in immunocompromised patients. IC is difficult to diagnose, because clinical symptoms are nonspecific and cultural methods lack sensitivity or specificity. We evaluated the Platelia Candida enzyme immunoassay (Candida EIA) for the diagnosis of IC in patients with haematological malignancies. A total of 62 neutropenic patients with 469 serum samples were included in the study. Candida colonization was monitored by weekly cultures of mouth washings, urine, and stool samples. Yeasts were grown from samples of 42 patients (68%), mainly Candida albicans (50%), followed by Candida glabrata (23%) and Candida krusei (20%). According to the criteria of the EORTC/NIH, the patients were categorized: (1) 3 patients with proven IC; (2) 6 patients with probable IC; (3) 34 patients colonized with Candida; (4) 19 patients without Candida colonization and without IC. In the patient categories (1) to (4), 3/3 (100%), 3/6 (50%), 20/34 (59%), and 7/19 (37%) patients were Candida EIA positive (>0.5 ng/ml) in at least one serum sample. The sensitivity of the assay for the detection of proven IC was 100%, for proven and probable IC 67%, the specificity was 49% for both groups. An increase of the cut-off value to 2.0 ng/ml raised the specificity to 61%, but lowered the sensitivity to 56%. In conclusion, the Platelia Candida EIA does not discriminate between Candida colonization and probable invasive infection in haematological patients.     

Methodological Issues in Group-Matching Designs: α Levels for Control Variable Comparisons and Measurement Characteristics of Control and Target Variables

Group-matching designs are commonly used to identify the diagnosis-specific characteristics of children with developmental disabilities. In this paper, we address three issues central to the use of this design. The first concerns the alpha level to be used for considering groups to be matched on the control variable(s). The second involves the measurement characteristics of the control and target variables. We discuss the properties of standard scores, raw scores, and age equivalents and argue against the use of age equivalents. In addition, we consider the appropriateness of the commonly made prediction that groups that are matched for a control variable such as language ability or nonverbal reasoning ability but are not matched for chronological age should perform at equivalent levels on the target variable. Finally, we discuss issues related to the interpretation of significant between-group differences on the target variable, assuming groups are well-matched on the control variables, and describe the benefits of a method that focuses on characterizing a disorder on a case-by-case basis and then aggregating the cases, using the measures of sensitivity and specificity from signal detection theory.