Qualitative Screening of Amphetamine- and Ketamine-Type Abuse Drugs in Urine Employing Dual Mode Extraction Column by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS).

This manuscript reported a fast and rapid qualitative screening method for abuse drugs in urine by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The scope of the abuse drugs under investigation included methamphetamine (MA), amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), paramethoxymethamphetamine (PMMA), ephedrine, pseudoephedrine, ketamine (KET), deschloroketamine (DCK), 2-fluorodeschloroketamine (2 F-DCK) and deschloro-N-ethylketamine (2-oxo-PCE). The method employed a dual mode extraction (DME) column as a novel clean-up method for the urine matrix. To an aliquot of 0.2 mL urine, internal standards (ISTDs) and 0.4 mL of acidified methanol were added. After vortex and centrifugation, the supernatant was passed through a DME column before LC-MS-MS analysis. Chromatographic separation was achieved with a C18 column by gradient elution. The limits of detection (LODs) for MA, AMP, MDMA, MDA and PMMA were 3 ng/mL, whereas those for ephedrine and pseudoephedrine were 10 ng/mL and those for KET, DCK, 2 F-DCK and 2-oxo-PCE were 1 ng/mL. The matrix effects ranged from -12% to 7% (%CV from 4% to 19%). This method is fit for the intended purpose for forensic toxicology, as well as for forensic analysis of drugs facilitating sexual assault and other criminal acts.

Health Behaviors of Chinese Childhood Cancer Survivors: A Comparison Study with Their Siblings.

Purpose: This study aimed to compare health behaviors between the childhood cancer survivors (CCS) and their sibling controls and to examine the pattern of health behaviors of the Hong Kong Chinese CCS and its associations with their health-related quality of life and psychological distress. Methods: A cross-sectional telephone survey was conducted. A total of 614 CCS and 208 sibling controls participated in this study. Patterns of health behaviors including lifestyle behaviors, cancer screening practices, and insurance coverage were compared. Multivariate regression analyses were performed for examining factors associated with health behaviors in CCS. Results: CCS had less alcohol consumption when compared with their sibling controls (adjusted odds ratio (AOR) = 0.65, p = 0.035). The sibling controls were more likely to have cancer screening practices (AOR = 0.38, p = 0.005) and health (AOR = 0.27, p < 0.001) and life insurance coverage (AOR = 0.38, p < 0.001). Among the CCS, those who were male, having a job or higher education, shorter time since diagnosis, and type of cancer suffered were significantly associated with alcohol consumption. Those CCS who were drinkers indicated poorer mental health (p = 0.004) and more psychological distress. Female CCS undertaking cancer screening were more likely to be employed, married/cohabiting, and have received intensive cancer treatment. Conclusion: This study reveals that Chinese childhood cancer survivors are less likely to engage in unhealthy lifestyle behaviors, insurance coverage and cancer screening, when compared with their siblings. Implications for Cancer Survivors: It is crucial for healthcare professionals to identify strategies or target interventions for raising CCS's awareness of their cancer risks and healthy lifestyle throughout their life.

Could Defects on a Rubber Stamp be Reproduced on a Duplicated Rubber Stamp?

The examination of stamp impressions has been an integral part of questioned document examination since its inception. Matching in design details and unique defects has proven to be essential factors for rubber stamps and stamp impression examination. In this study, several duplicate stamps were made from various rubber stamp manufacturers in Hong Kong, from the same original stamp impression(s). The objective was to examine the stamp impressions prepared from these duplicated stamp products and compared with each other and to determine whether they could be distinguished from the source stamp impression(s); by comparison of the size and defects deliberated introduced onto the latter. Further consideration of this study was an attempt to create a perfect duplicate stamp from an original stamp impression. The results of the analysis showed that the quality of source stamp impression(s) and scanner device of the stamp manufacturing process, and the knowledge of the stamp manufacturer were critical to the quality and outcome of the duplicated stamp products. It is concluded that although a perfect duplicate stamp could only be made under several essential control conditions, it was still possible to create a duplicate stamp that replicated the features of the original when a high-quality source stamp impression was available.

Competency for Chinese Handwriting and Signature Examination.

Chinese characters had their root some 4000 years ago and, with the growth in population, are used by over 1.3 billion people worldwide today; it is inevitable that document examiners would encounter cases involving the examination of Chinese handwriting regardless of their location. Although there are extensive studies on the examination of English handwriting in the literature, similar studies on Chinese handwriting are relatively limited. We are seeking to explore the obstacles and challenges for a document examiner who is unfamiliar with Chinese characters to apply the principles of identification and elimination of authorship described in the literature to examine Chinese handwriting, and how can these document examiners demonstrate their competency for conducting Chinese handwriting examination. This study provides a review of the literature, compares the methodology and key features in English and Chinese handwriting examination, and describes various workshops and proficiency testing programs organized to assist document examiners seeking development in Chinese handwriting and signature examination.

Organizing a Proficiency Testing Program on Stamp Impressions Examination in Accordance with ISO/IEC 17043 Requirements.

Stamps and stamp impressions examinations are based on matching defects and design details on the questioned and control samples. These examinations are routinely carried out by document examiners around the world. International proficiency tests for questioned documents examination have been available for decades while similar programs specifically focusing on stamp impressions examination are rare. This study reported a recent proficiency testing program on stamp impressions examination organized by an accredited provider in accordance with ISO/IEC 17043 requirements. Twenty-four forensic laboratories registered for the program. Apart from giving details on the design and operation of the program, this study also aimed to provide the limitations and difficulties encountered in sample preparations, homogeneity, and stability tests of the testing materials. Various comments and feedbacks received from the participants, particularly in respect of examination approaches, challenges faced by the participants in forming conclusions and their suggestions for further improvement would be evaluated.

A Prototype of Mathematical Treatment of Pen Pressure Data for Signature Verification.

A prototype using simple mathematical treatment of the pen pressure data recorded by a digital pen movement recording device was derived. In this study, a total of 48 sets of signature and initial specimens were collected. Pearson's correlation coefficient was used to compare the data of the pen pressure patterns. From the 820 pair comparisons of the 48 sets of genuine signatures, a high degree of matching was found in which 95.4% (782 pairs) and 80% (656 pairs) had rPA > 0.7 and rPA > 0.8, respectively. In the comparison of the 23 forged signatures with their corresponding control signatures, 20 of them (89.2% of pairs) had rPA values < 0.6, showing a lower degree of matching when compared with the results of the genuine signatures. The prototype could be used as a complementary technique to improve the objectivity of signature examination and also has a good potential to be developed as a tool for automated signature identification.

Health-related quality-of-life and psychological distress of young adult survivors of childhood cancer in Hong Kong.

BACKGROUND AND PURPOSE: Previous literatures on young adult survivors of childhood cancer show inconsistent findings with regards to their psychological distress and health-related quality of life (HRQOL). Much of the available data focus on negative patient outcomes following cancer treatments prescribed from 1970 to 1990. In the present study, HRQOL and psychological distress of young adult survivors in Hong Kong was examined. It focused on subjects who had received cancer treatments prescribed in the last two decades. METHODS: A structured telephone survey was conducted with 614 eligible survivors and 208 sibling controls in Hong Kong. RESULTS: The survivors reported significantly lower mean scores in physical role and functioning, whereas their mental, social, and psychological well-being was similar to that of their sibling controls. Being female, older age, longer survival time, and specific cancer diagnoses were the factors associated with poorer physical and mental adaptation. HRQOL was negatively correlated with psychological distress. CONCLUSIONS: Findings of the study suggest that most survivors adjusted fairly well in mental, psychological, and social aspects. Survivors with a higher risk of poor HRQOL could benefit from appropriate screening and counseling at an early stage to mitigate their survivorship difficulties. Prospective follow-up studies on childhood cancer survivors are recommended to detect changes over longer survival periods.

A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression.

Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese ß-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.

Survival of homozygous alpha-thalassemia with aplasia/hypoplasia of phalanges and jejunal atresia.

We report a case of survival of homozygous alpha-thalassemia with aplasia/hypoplasia of phalanges and jejunal atresia. The occurrence of these malformations is consistent with the postulation that intra-uterine hypoxia due to the presence of hemoglobin Bart's (Hb Bart's) is the causative factor for the development of these malformations. There were two pitfalls in diagnosis: normal spun hematocrit level despite a low hemoglobin level and absence of hydropic features. Our case illustrated that nitric oxide and high frequency ventilation were ineffective in ameliorating persistent pulmonary hypertension of newborn until exchange transfusion was done replacing Hb Bart's with normal hemoglobin.

Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong.

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.

Significance of sequence of strokes in Chinese handwriting examination.

This paper reports a statistical study on the sequence of strokes of 61 commonly encountered Chinese radicals and characters written by 372 invited subjects. The distribution of different writing sequence of these Chinese radicals and characters was examined. Comparison of the sequence of strokes executed by the subjects with the standard rule of writing these Chinese radicals and characters revealed that around 60% of the subjects wrote in the correct sequence. Pair comparison of sequences of strokes in Chinese handwriting among the 372 subjects was also performed. The results demonstrated that no two individuals wrote all the 61 radicals and characters with the same sequence of strokes. The findings indicate that, despite some basic rules governing the writing sequence of Chinese characters, writers tend to develop their own habits. The findings also support the hypothesis that the handwriting of experienced writers is individual.

Individuality of handwritten Arabic numerals in local population.

This paper reports the statistical study of writing habits for Arabic Numerals of 187 subjects in Hong Kong. A classification system of writing habits for Arabic numerals based on assigned codes of characteristic features such as slant, writing direction, relative position of strokes, angularity of turnings, shape of initial and ending strokes, etc. was developed. A set of characteristic codes representing the profile of writing habits pertaining to Arabic numerals was assigned to each writer. Apart from the distribution of characteristic features, statistical analysis of the assigned codes demonstrated homogeneity of individual hand-writing patterns. It has been shown that irrespective of the structural simplicity of Arabic numerals, no two individuals exhibited the same set of characteristic codes. The findings support the hypothesis of individuality in handwriting.

Is the timing of exposure to infection a major determinant of acute lymphoblastic leukaemia in Hong Kong?

The hypothesis that protection of infants from exposure to infectious agents with delayed first exposure to one or more specific agents together contribute to the aetiology of childhood leukaemia, especially common acute lymphoblastic leukaemia (cALL), has substantial indirect support from descriptive epidemiology and case-control studies in developed Western countries. A case-control study of childhood leukaemia diagnosed at ages 2-14 years has now been conducted in Hong Kong. Cases (n=98) formed a consecutive series of Chinese children diagnosed with acute leukaemia; controls (n=228) were identified following a survey using random digit dialling and required to attend for medical examination by a paediatrician. Interviews with mothers were conducted in hospital by one trained interviewer using a structured questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) are reported for exposure variables capable of serving as proxies for exposure to infection in two critical time periods: first year of life, year before reference date (diagnosis for cases, corresponding date for controls). Analyses used logistic regression with adjustment for appropriate confounders. Change of area of residence reduced risk if during the first time period (OR = 0.47 [95% CI 0.23, 0.98]) and increased risk if during the second (OR=3.92, [95% CI 1.47, 10.46]). Reported roseola and/or fever and rash in the first year of life reduced risk (OR=0.33 [95% CI 0.16, 0.68]) whereas tonsillitis in the period 3-12 months before reference date increased risk (OR=2.56 [95% CI 1.22, 5.38]). Some other proxies for exposure to infection at the critical times were associated with predicted patterns of risk but day-care attendance failed to show predicted associations. These results provide support for the delayed exposure hypothesis in an affluent geographical setting in which population exposure to infectious agents is quite distinct from the settings of previous case-control studies.

DNA-based diagnosis of isolated sulfite oxidase deficiency by denaturing high-performance liquid chromatography.

Isolated sulfite oxidase deficiency is a rare autosomal recessive disease, characterized by severe neurological abnormalities, seizures, mental retardation, and dislocation of the ocular lenses, that often leads to death in infancy. There is a special demand for prenatal diagnosis, since no effective treatment is available for isolated sulfite oxidase deficiency. Until now, the cDNA sequence of the sulfite oxidase (SUOX) gene has been available, but the genomic sequence of the SUOX gene has not been published. In this study, we have performed a DNA-based diagnosis of isolated sulfite oxidase deficiency in a Chinese patient. To do so, we designed oligonucleotide primers for amplification of the predicted exons and intron-exon boundaries of the SUOX gene obtained from the completed draft version of the human genome. Using overlapping PCR products, we confirmed the flanking intronic sequences of the coding exons and that the entire 466-residue mature peptide is encoded by the last exon of the gene. We then performed mutation detection using denaturing high-performance liquid chromatography (DHPLC). The DHPLC chromatogram of exon 2b showed the presence of heteroduplex peaks only after mixing of the mutant DNA with the wild-type DNA, indicating the presence of a homozygous mutation. Direct DNA sequencing showed a homozygous base substitution at codon 160, changing the codon from CGG to CAG, which changes the amino acid from arginine to glutamine, i.e., R160Q. The DNA-based diagnosis of isolated sulfite oxidase deficiency will enable us to make an accurate determination of carrier status and to perform prenatal diagnosis of this disease. The availability of the genomic sequences of human genes from the completed draft human genome sequence will simplify the development of molecular genetic diagnoses of human diseases from peripheral blood DNA.