Liver X receptor alpha ensures blood-brain barrier function by suppressing SNAI2.

In Alzheimer's disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRß, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study, we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid-beta deposition and angiopoietin-like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients.

Population pharmacokinetics of alcohol on Chinese subjects using breath measures.

WHAT IS KNOWN AND OBJECTIVE: Alcohol is a widely used drug. Our objective was to examine alcohol pharmacokinetics in Chinese subjects through the breath measurement of blood alcohol concentration (BAC) to identify any measurable covariates that may help explain variability between subjects. METHODS: Breath-alcohol measurements of 184 healthy Chinese subjects were collected. Compartmental models including one- and two-compartment process were examined. First-order kinetics was applied to model alcohol absorption and elimination phases. For the sake of simplicity, only the subject's body weight, sex and stomach condition were investigated as covariates in our random effects modelling. RESULTS AND DISCUSSION: The body as a whole behaves as a single compartment, with the suggested one-compartment model being good enough to characterize the biological process. In line with other studies, food ingestion before/with the dose slowed down alcohol absorption into the central compartment. Female subjects exhibited a significantly higher BAC elimination rate than that of males. Body weight also contributed to the observed inter-subject variability in alcohol clearance. WHAT IS NEW AND CONCLUSION: We present a model for estimating blood-alcohol levels from breath-alcohol measurements. The results of our study are useful particularly in relation to drink-driving prosecutions because of the routine use of breath-alcohol measurements as evidence in such cases through the world.

A simple method for detection of imprinting effects based on case-parents trios.

Using data from families in which marker genotypes are known for the father, the mother and the affected offspring, a simple statistic for testing for imprinting effects is developed. The statistic considers whether the expected number of families in which the father carries more copies of a particular marker allele than the mother is equal to the expected number of families in which the mother carries more copies of the allele than the father. The proposed parent-of-origin effects test statistic (POET) is shown to be normally distributed and can be employed to test for imprinting in situations where the marker locus need not be a disease susceptibility locus and where the female and male recombination fractions are sex-specific. A simulation study is conducted to characterize the power of the POET and other properties, and its results show that it is appropriate to employ the POET.

Alcohol metabolism of local Chinese in Hong Kong: a statistical determination on the effects of various physiological factors.

A study was designed to examine the elimination rate of alcohol from the body of the local Chinese after consumption of different types of alcoholic drinks. The breath alcohol of 184 healthy volunteers was determined and converted into blood alcohol levels after they finished drinking. Information on the type and volume of alcoholic drinks consumed, age group, sex, drinking habit, and drinking on empty stomach or with/after meal was recorded for each participant. The results show that the elimination rate of an individual can be explained in terms of physiological variables including sex and drinking habit. The determined elimination rates allow forensic toxicologists to back calculate the blood alcohol concentration (BAC) of the drivers at the time of accident in drunk driving cases. The elimination rates of blood alcohol at 95% prediction intervals for male and female are in the range of 9.5-23.8 mg/100 ml/h and 11.1-37.1 mg/100 ml/h, respectively.

Influence curves for factor loadings.

Influence curves for the initial and rotated loadings are derived for the maximum likelihood factor analysis (MLFA) model. Cook's distances based on the empirical influence curves of factor loadings are proposed for the identification of influential observations. The distances are shown to be invariant under scale transformation and factor rotation. We find that an observation with a very large Cook's distance based on the sample influence curve may not necessarily exert an excessive influence on the factor loadings pattern but may change the ordering of the factors. The issue of the switching of factors is also studied by means of the empirical influence curve and factor scores.

Population data for the Identifier 15 STR loci in Hong Kong Chinese.

Allele frequencies for 15 STR loci, namely D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA, which are tested for by PE Applied Biosystem's Identifier kit, were obtained from a sample of 325 unrelated Chinese in Hong Kong.

Widmark factors for local Chinese in Hong Kong. A statistical determination on the effects of various physiological factors.

The Widmark formula has been widely adopted in forensic applications to drink driving cases for the last 70 years. It is known that the amount of alcohol consumed and the body weight of the drinkers are important information for the estimation of blood alcohol concentration (BAC). However, the direct application of the Widmark factors derived from Caucasian to the calculation of BAC for the Chinese population often encounters serious challenges. Owing to this inherent weakness, a thorough analysis to determine the theoretical Widmark factors for the Chinese population, r(0) at the start of drinking and the practical factors, r(peak), at peak BAC was conducted. In the present study, other factors such as gender, stomach condition and other physiological conditions are taken into account. The determined theoretical Widmark factors, r(0,) for local Chinese male and female are 0.68 and 0.59 (with BAC in the units of weight/volume), respectively, demonstrating the applicability of the Widmark formula to the Chinese population. The practical factors at peak BAC, r(peak), were also determined to serve the forensic purpose of refuting the "hip-flask" defence in drink driving cases. Findings show that gender and stomach condition are the key factors that could statistically explain the variability of both r(0) and r(peak).

The evaluation of mixed stains from different ethnic origins: general result and common cases.

In some situations, it can be inferred from the crime circumstances that the mixed stain donors are of different ethnic groups. The evaluation of DNA mixtures with contributors coming from more than one ethnic group is considered under the assumption of independence of alleles within and between ethnic groups. A general formula is derived for the assessment of the weight of evidence in mixed stain problems. This formula is equivalent to that of Fukshansky and Bär, but we give a different derivation. For the convenience of practitioners, the explicit expressions of the likelihood ratios for 14 common cases are presented. The effect of different ethnic groups to the assessment of the evidence is shown in the well-known Simpson case.

Allele frequencies for nine STR loci in Beijing Chinese.

Allele frequencies for nine STR loci namely, D3S1358, HUMvWA, HUMFIBRA/FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 were obtained from a sample of 198 unrelated Chinese in Beijing, China.

Porphyria cutanea tarda and melioidosis.

Porphyria cutanea tarda is a metabolic disorder in the haem biosynthetic pathway. It includes a heterogeneous group of conditions, which may be inherited or, more commonly, acquired. Although porphyria cutanea tarda presents with cutaneous lesions only, it is often associated with systemic disease. A 64-year-old Chinese patient, who developed sporadic porphyria cutanea tarda 1 year after the diagnosis of pulmonary melioidosis, is discussed. The patient presented with a history of recurrent photosensitive vesicles, blisters, and skin fragility on the sun-exposed areas of both forearms and hands, 6 months after commencing doxycycline and amoxycillin. Both the histological and biochemical findings were characteristic of porphyria cutanea tarda. All the lesions subsided after cessation of these antibiotics. The patient was free of further lesions at follow-up 6 months later. The association seen in this case between porphyria cutanea tarda and melioidosis is unlikely to be coincidental, because these two diseases are both very rare in Hong Kong. In addition, the temporal relationship between the antibiotic therapy and the clinical course of skin lesions in this patient suggests that the drugs were a trigger factor, precipitating their appearance.

Syntheses, photophysics, and photochemistry of trinuclear copper(I) thiolate and hexanuclear copper(I) selenolate complexes: X-ray crystal structures of [Cu(6)(mu-dppm)4(mu(3)-SePh)4](BF(4))2 and [Cu(6)(mu-(Ph(2)P)(2)NH(4))(mu(3)-SePh)4](BF(4)2.

A series of trinuclear copper(I) thiolate complexes, [Cu(3)(mu-dppm)(3)(mu(3)-SR)(2)]BF(4) (R = C(6)H(4)Cl-4, C(6)H(4)CH(3)-4, C(6)H(4)OCH(3)-4, C(6)H(4)(OCH(3))(2)-3,4, C(6)H(4)-benzo-15-crown-5, or (t)()Bu), [Cu(3)(mu-dppm)(3)(mu(3)-S(t)()Bu)](BF(4))(2), and [Cu(3)(mu-dppm)(3)(mu(3)-SR)(mu(3)-Cl)]BF(4) (R = C(6)H(4)CH(3)-4, C(6)H(4)(t)()Bu-4, or C(6)H(4)(CH(3))(3)-2,4,6) and two hexanuclear copper(I) selenolate complexes, [Cu(6)(mu-P(wedge)P)(4)(mu(3)-SePh)(4)](BF(4))(2) (P(wedge)P = dppm, (Ph(2)P)(2)NH), have been synthesized, and their photophysical properties have been studied. The X-ray crystal structures of both copper(I) selenolate complexes have been determined. These complexes have been shown to exhibit long-lived low-energy emission in solution, attributed to an excited state of predominantly ligand-to-metal charge-transfer [chalcogenolate to copper(I)] origin.

Population data for 12 STR loci in Hong Kong Chinese.

The allele distributions at the 12 short tandem repeat (STR) loci D3S1358, HUMvWA, HUMFIBRA/FGA, HUMTHO1, HUMTPOX, HUMCSF1P0, D5S818, D13S317, D7S820, D8S1179, D21S11 and D18S51 have been determined for 284 unrelated Chinese in Hong Kong. The combined probability of identity for the 12 STR loci was about 4.1 x 10(-14) and the overall probability of excluding paternity 0.999978. None of the 12 loci were found to deviate from Hardy-Weinberg expectations according to the results of the exact test. There was also little evidence for association of alleles between loci. The results demonstrate that the loci are useful for forensic human identification and parentage testing for the Chinese population in Hong Kong.

Genetic polymorphism at three STR loci--CSF1PO, HUMTHO1 and TPOX, and the AMP-FLP locus D1S80 for the Chinese population in Hong Kong.

Allele frequencies for three STR loci, namely, CSF1PO, HUMTHO1 and TPOX, and the AMP-FLP locus D1S80 were obtained from a sample of 351 unrelated Chinese in Hong Kong.

Prevalence of skin disease among school children and adolescents in a Student Health Service Center in Hong Kong.

We document the prevalence and the pattern of dermatologic diseases among primary and secondary school students visiting a Student Health Service Center in Hong Kong. In this study, the differences in prevalence of skin diseases between these two groups are pointed out. A total of 1006 students from both primary (n = 559) and secondary schools (n = 447) were seen in a regional, population-based screening center during the period from October 1996 to September 1997. Each student was asked to answer a simple questionnaire to identify any skin problems and to explore health-seeking behavior. Students were then examined for evidence of skin disease. A total of 314 students (31.3%) had one or more skin disorders, the most common of which were acne vulgaris (9.9%), eczema (6.8%), café au lait spots (4.4%), congenital melanocytic nevus (3.6%), superficial fungal infections (2.2%), keratosis pilaris (1.3%), and pityriasis alba (1.0%), which represented 93% of the skin disorders encountered. Acne vulgaris and tinea cruris were distinctly more common in secondary school students, while atopic eczema and congenital melanocytic nevi were more commonly found in primary school students. Among the 314 students with skin disease, 129 (41%) had symptoms while 185 (59%) did not. Ninety of the 129 students (70%) with symptomatic skin problems did not seek medical attention. The two predominant skin diseases, acne vulgaris and endogenous eczema, both chronic skin problems, incur not only morbidity in affected individuals and families, but also use considerable resources in the community. The lack of medical intervention reported by symptomatic students in this study was unexpectedly high. Therefore it is useful to monitor the epidemiology of skin problems in children so that relevant skin health education programs and preventive measures can be planned and implemented effectively.

An in vivo trial comparing the use of different types of 532 nm Nd:YAG lasers in the treatment of facial lentigines in Oriental patients.

BACKGROUND: Versapulse is a system that consists of four laser modalities and was developed with the aim of increasing cost-effectiveness. However, as these lasers share a common power supply, for the Q-switched (QS) Nd:YAG 532 nm laser a large spot diameter is necessary to lower the fluence to a suitable level. This can increase the risk of hyperpigmentation when used for the treatment of lentigines in dark-skinned patients. OBJECTIVE: The aim of our study was to access the clinical efficacy and the complication rate of the Versapulse QS Nd:YAG 532 nm laser, the Versapulse long-pulsed Nd:YAG 532 nm laser (without the chill tip), and a conventional QS Nd:YAG 532 nm laser in the treatment of lentigines in Chinese patients. METHODS: Thirty-four Chinese patients with lentigines were randomized to receive laser surgery, with one side of the face treated by one laser and the other side treated by a different system. Patients were monitored for 6 weeks to assess the degree of clearing, hyperpigmentation, hypopigmentation, and erythema. Assessments involved patients interviewed using a visual analog questionnaire and two blinded observers who evaluated the pre- and posttreatment clinical photographs. RESULTS: The Versapulse QS Nd:YAG 532 nm laser was associated with a statistically higher risk of complications. The Versapulse long-pulsed Nd:YAG 532 nm laser was compatible with the conventional QS Nd:YAG 532 nm laser in terms of clinical efficacy and complication rates. CONCLUSION: The Versapulse long-pulsed 532 nm laser is more effective and should be used instead of the Versapulse QS Nd:YAG 532 nm laser for the treatment of lentigines in dark-skinned patients.

The statistical variability of blood alcohol concentration measurements in drink-driving cases.

Like many other places in the world, Hong Kong has drink-driving legislation which prohibits a driver from having in his blood alcohol exceeding a prescribed limit while in control of a motor vehicle. The accuracy of measuring this alcohol concentration is obviously of prime concern as an erroneous result can avert the administration of justice. The common practice is to deduct all errors from the measured value and compare the deducted value with the prescribed limit, so that the benefit of all errors of the measurement is given to the driver. It is therefore important for any laboratory responsible for measuring blood alcohol concentrations to identify and quantify all errors associated with the measurement. The present study examined 900 blood alcohol determinations carried out by the Hong Kong Government Laboratory (HKGL) on cases of suspected drink driving. The determinations were performed by 5 different analysts with two different sets of instruments during 1995-1997. Statistical analysis indicated that the instruments had no bearing on the random error or variability and that even though analyst was a significant factor on variability, the deviation from the mean so caused was only 0.3% and of no practical significance. When the systematic error introduced by the tolerance limits of the certified alcohol standards (purchased from the Laboratory of Government Chemists, UK) was taken into account, the total uncertainty (random plus systematic errors) of an alcohol determination at 99.5% confidence level was found to be 4%. It is recommended that laboratories engaged in blood alcohol determination should adopt similar statistical treatment of their analytical results to find out the error and to ensure that the results are independent of analyst and instrument used.

Method of medians for lifetime data with Weibull models.

The Weibull family of distributions is frequently used in failure time models. The maximum likelihood estimator is very sensitive to occurrence of upper and lower outliers, especially when the hazard function is increasing. We consider the method of medians estimator for the two-parameter Weibull model. As an M-estimator, it has a bounded influence function and is highly robust against outliers. It is easy to compute as it requires solving only one equation instead of a pair of equations as for most other M-estimators. Furthermore, no assumptions or adjustments are needed for the estimator when there are some possibly censored observations at either end of the sample. About 16 per cent of the largest observations and 34 per cent of the smallest observations may be censored without affecting the calculations. We also present a simple criterion to choose between the maximum likelihood estimator and the method of medians estimator to improve on the finite-sample efficiency of the Weibull model. Robust inference on the shape parameter is also considered. The usefulness with contaminated or censored samples is illustrated by examples on three lifetime data sets. A simulation study was carried out to assess the performance of the proposed estimator and the confidence intervals of a variety of contaminated Weibull models.

The identification of credit card encoders by hierarchical cluster analysis of the jitters of magnetic stripes.

The relative bit density variation graphs of 207 specimen credit cards processed by 12 encoding machines were examined first visually, and then classified by means of hierarchical cluster analysis. Twenty-nine credit cards being treated as 'questioned' samples were tested by way of cluster analysis against 'controls' derived from known encoders. It was found that hierarchical cluster analysis provided a high accuracy of identification with all 29 'questioned' samples classified correctly. On the other hand, although visual comparison of jitter graphs was less discriminating, it was nevertheless capable of giving a reasonably accurate result.