Ranking negative emissions technologies under uncertainty.

Existing mitigation strategies to reduce greenhouse gas (GHG) emissions are inadequate to reach the target emission reductions set in the Paris Agreement. Hence, the deployment of negative emission technologies (NETs) is imperative. Given that there are multiple available NETs that need to be evaluated based on multiple criteria, there is a need for a systematic method for ranking and prioritizing them. Furthermore, the uncertainty in estimating the techno-economic performance levels of NETs is a major challenge. In this work, an integrated model of fuzzy analytical hierarchy process (AHP) and interval-extended Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is proposed to address the multiple criteria, together with data uncertainties. The potential of NETs is assessed through the application of this hybrid decision model. Sensitivity analysis is also conducted to evaluate the robustness of the ranking generated. The result shows Bioenergy with Carbon Capture and Storage (BECCS) as the most optimal alternative for achieving negative emission goals since it performed robustly in the different criteria considered. Meanwhile, energy requirement emerged as the most preferred or critical criterion in the deployment of NETs based on the decision-maker. This paper renders a new research perspective for evaluating the viability of NETs and extends the domains of the fuzzy AHP and interval-extended TOPSIS hybrid model.

Induction approach via P-Graph to rank clean technologies.

Identification of appropriate clean technologies for industrial implementation requires systematic evaluation based on a set of criteria that normally reflect economic, technical, environmental and other aspects. Such multiple attribute decision-making (MADM) problems involve rating a finite set of alternatives with respect to multiple potentially conflicting criteria. Conventional MADM approaches often involve explicit trade-offs in between criteria based on the expert's or decision maker's priorities. In practice, many experts arrive at decisions based on their tacit knowledge. This paper presents a new induction approach, wherein the implicit preference rules that estimate the expert's thinking pathways can be induced. P-graph framework is applied to the induction approach as it adds the advantage of being able to determine both optimal and near-optimal solutions that best approximate the decision structure of an expert. The method elicits the knowledge of experts from their ranking of a small set of sample alternatives. Then, the information is processed to induce implicit rules which are subsequently used to rank new alternatives. Hence, the expert's preferences are approximated by the new rankings. The proposed induction approach is demonstrated in the case study on the ranking of Negative Emission Technologies (NETs) viability for industry implementation.

Poisoning by toxic plants in Hong Kong: a 15-year review.

INTRODUCTION: Hong Kong has a great diversity of plants, many of which are toxic to humans. The aim of this study was to identify the plant species most commonly involved in cases of plant poisoning in Hong Kong and to provide clinicians with a reference tool for the diagnosis and management of plant poisoning. METHODS: We retrospectively reviewed all plant poisoning cases referred to the Hospital Authority Toxicology Reference Laboratory from 1 January 2003 to 31 December 2017. Demographics, clinical presentation, laboratory findings, treatment and outcomes of patients, as well as morphological identification and analytical testing of the plant specimens, were investigated. RESULTS: A total of 62 cases involving 26 poisonous plant species were identified, among which Alocasia macrorrhizos (Giant Alocasia), Gelsemium elegans (Graceful Jessamine), and Rhododendron (Azalea) species were the three most commonly encountered. Gastrointestinal toxicity (n=30, 48%), neurological toxicity (n=22, 35%), and hepatotoxicity (n=6, 10%) were the three most common clinical problems. Forty-nine (79%) and eight (13%) patients had mild and moderate toxicity, respectively; they all recovered shortly with supportive treatment. The remaining five (8%) patients experienced severe toxicity requiring intensive care support. Most patients (n=61, 98%) used the plants intentionally: as a medicinal herb (n=31), as food (n=29), and for attempting suicide (n=1). Reasons for using the poisonous plants included misidentification (n=34, 55%), unawareness of the toxicity (n=20, 32%), and contamination (n=6, 10%). CONCLUSIONS: Although most plant exposure resulted in a self-limiting disease, severe poisonings were encountered. Epidemiology of plant poisonings is geographically specific. Clinicians should be aware of local poisonous plants and their toxicities.

Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine.

Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their ability to detect common drugs of abuse; however, the performance of such devices on simultaneous screening for ketamine has been scarcely investigated. The present study evaluated three ROFT devices (DrugWipe® 6S, Ora-Check® and SalivaScreen®) on the detection of ketamine, opiates, methamphetamine, cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry (LCMS) assay was firstly established and validated for confirmation analysis of the six types of drugs and/or their metabolites. In the field test, the three ROFT devices were tested on subjects recruited from substance abuse clinics/rehabilitation centre. Oral fluid was also collected using Quantisal® for confirmation analysis. A total of 549 samples were collected in the study. LCMS analysis on 491 samples revealed the following drugs: codeine (55%), morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and cocaine (2%). No MDMA-positive cases were observed. Results showed that the overall specificity and accuracy were satisfactory and met the DRUID standard of >80% for all 3 devices. Ora-Check® had poor sensitivities (ketamine 36%, methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe® 6S showed good sensitivities in the methamphetamine (83%) and opiates (93%) tests but performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%). SalivaScreen® also demonstrated good sensitivities in the methamphetamine (83%) and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The test completion rate (proportion of tests completed with quality control passed) were: 52% (Ora-Check®), 78% (SalivaScreen®) and 99% (DrugWipe® 6S).

Screening for impaired renal function in outpatients before iodinated contrast injection: Comparing the Choyke questionnaire with a rapid point-of-care-test.

RATIONALE AND PURPOSE: To determine the usefulness of the Choyke questionnaire with a creatinine point-of-care test (POCT) to detect impaired renal function amongst outpatients receiving intravenous iodinated contrast in a tertiary centre. MATERIALS AND METHODS: Between July and December 2012, 1361 outpatients had their serum creatinine determined by POCT and answered the Chokye questionnaire just before their examination. RESULTS: Four hundred and eighty (35.2%) patients had at least one 'Yes' response. Forty-four patients (3.2%) had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and 14 patients (1.0%) have eGFR <45 mL/min/1.73 m(2). Sensitivity, specificity, positive predictive value and negative predictive value of the Choyke criteria in detecting patients with eGFR <60 mL/min/1.73 m(2) are respectively: 65.9%, 65.8%, 6.0% and 98.3% and to detect eGFR <45 mL/min/1.73 m(2): 92.9%, 65.3%, 2.7% and 99.9%. Only 'Yes' responses to 'Have you ever been told you have renal problems?' and 'Do you have diabetes mellitus?' were statistically significant in predicting eGFR <45 mL/min/1.73 m(2), with odds ratio 98.7 and 4.4 respectively. CONCLUSION: The Choyke questionnaire has excellent sensitivity and moderate-to-good specificity in detecting patients with <45 mL/min/1.73 m(2), below this level it has been shown that risk of contrast induced nephropathy increases significantly, making it an effective screening tool. Also the use of POCT can potentially reduce waiting time.

Effects of a plasma heating procedure for inactivating Ebola virus on common chemical pathology tests.

OBJECTIVES: The recent declaration of Ebola virus disease as epidemic by the World Health Organization indicates urgency for affected countries and their laboratories to evaluate and provide treatment to patients potentially infected by the Ebola virus. A heat inactivation procedure involving treating specimens at 60°C for 60 minutes has been suggested for inactivation of the Ebola virus. This study aimed at evaluating the effect of plasma heating on common biochemical tests. DESIGN: Comparative experimental study. SETTING: A regional chemical pathology laboratory in Hong Kong. METHODS: Forty consecutive plasma specimens for general chemistry analytes on Beckman Coulter AU5822 and another 40 plasma specimens for troponin I analysis on Access 2 Immunoassay System were obtained, anonymised, and divided into two aliquots. One aliquot was analysed directly and the other was analysed after heating at 60°C for 60 minutes. RESULTS: A total of 20 chemical pathology tests were evaluated. Nine tests (sodium, potassium, chloride, urea, creatinine, total calcium, phosphate, total protein, and glucose) were not significantly affected by the heat inactivation procedure and remained clinically interpretable. Results for magnesium (15% mean increase), albumin (41% mean increase), bilirubin (8% mean decrease), amylase (27% mean decrease), and troponin I (76% mean decrease) were still interpretable using regression estimation with proportional bias. However, all enzymes studied except amylase (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, and lactate dehydrogenase) were inactivated to a significant degree. Their Pearson r or Spearman rho values ranged from no significant correlation (P≥0.05) to 0.767, and most normality was rejected. CONCLUSION: Heat inactivation results in no significant change in electrolytes, glucose, and renal function tests, but causes a significant bias for many analytes. Recognition of the relationship between pre- and post-heat inactivation specimens allows clinical interpretation of affected values and contributes to patient care. For safety and diagnostic accuracy, we recommend use of a point-of-care device for blood gases, electrolytes, troponin, and liver and renal function tests within a class 2 or above biosafety cabinet with level 3 or above biosafety laboratory practice.

Risk factors for hospital and long-term mortality of critically ill elderly patients admitted to an intensive care unit.

BACKGROUND: Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. MATERIALS AND METHODS: Adult patients (n = 1563, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. RESULTS: 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. CONCLUSIONS: Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.

A puzzle over several decades: eye anomalies with FRAS1 and STRA6 mutations in the same family.

Fraser syndrome (FS) and microphthalmia syndromic 9 (MCOPS9) are autosomal recessive conditions with distinct, and some overlapping features affecting the ocular, respiratory and cardiac systems. Mutations in FRAS1 and FREM2 occur in FS, and mutations in STRA6 occur in MCOPS9. We report two sibships, in the same family, where four deceased offspring had ocular, respiratory and cardiac abnormalities. Two sibs with microphthalmia had syndactyly and laryngeal stenosis, suggesting a clinical diagnosis of FS. Our results indicate that they were compound heterozygotes for novel FRAS1 mutations, p.Cys729Phe and p.Leu3813Pro. The other two sibs, first cousins to the first sib pair, had anophthalmia, lung hypoplasia and cardiac anomalies, suggesting a retrospective diagnosis of MCOPS9. Our results indicate compound heterozygous STRA6 mutations, a novel frameshift leading to p.Tyr18* and a p.Thr644Met mutation. The one surviving individual from these sibships is heterozygous for the p.Tyr18*STRA6 mutation and has bilateral ocular colobomata and microphthalmia. This work emphasises the need for careful phenotypic characterisation to determine genes for assessment in ocular syndromic conditions. It also indicates that heterozygous STRA6 mutations may rarely contribute to microphthalmia and coloboma.

Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis.

Muscle weakness in patients with thyrotoxicosis during hypokalemic episodes (thyrotoxic periodic paralysis [TPP]) occurs sporadically and mostly in males. It is treated by infusion or oral supplementation with potassium and with resolution of the thyrotoxicosis state. The clinical features of TPP resemble familial hypokalemic periodic paralysis (hypoKPP), which has been linked to two mutations in the gene encoding the skeletal muscle calcium channel alpha-1 subunit (CACN1AS; Arg528His and Arg1239His) and to the sodium channel alpha-subunit (SCN4A; Arg672His). We screened for the mutations (CACN1AS by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]; SCN4A by single-strand conformation polymorphism analysis) described in hypoKPP in 20 unrelated patients with documented episodes of TPP (mean age, 40.0 +/- 12.3 years 19 males). Forty-eight patients with hyperthyroidism resulting from Graves' disease (48.5 +/- 12.3 years; 13 males), 1 patient with idiopathic hypoKPP (a 32-year-old male) and 32 healthy subjects (41.0 +/- 19.1 years; 16 males) were included. We found none of the TPP patients carry CACN1AS and SCN4A mutations. The hyperthyroid patients and control subjects were also negative for the mutations. The patient with idiopathic hypoKPP was genotyped to have the Arg528His mutation. These results suggest that despite close similarities between TPP and hypoKPP, a likely genetic basis for TPP does not involve the same gene mutations associated with hypoKPP.

Varicella screening and vaccination for healthcare workers at KK Women's and Children's Hospital.

INTRODUCTION: Varicella is a highly contagious disease with significant morbidity and mortality, especially in adults. It can lead to nosocomial transmission with dire consequences, especially in a healthcare facility where children and pregnant women form the majority of patients. At KK Women's and Children's Hospital, we embarked on a programme in 2 phases, between 1997 and 1999, to screen healthcare workers (HCWs) for varicella immunity and to offer varicella vaccination to those who tested negative for antibody. MATERIALS AND METHODS: HCWs were initially screened via a questionnaire; those with no previous history of chickenpox underwent a blood test for varicella zoster antibody. Varicella vaccine was offered to those who tested negative for antibody and they were monitored for adverse reactions. RESULTS: Of the HCWs surveyed, 14.7% and 26.9% in phases 1 and 2, respectively, had no previous history of chickenpox. Of these, 55.3% in phase 1 and 26.1% in phase 2 tested negative for antibodies. Thus, the overall seronegativity of all HCWs surveyed was between 6.5% and 7.6%. Among those who tested negative for antibodies, 42.9% in phase 1 and 74% in phase 2 were vaccinated. Hence, the overall vaccination rate in HCWs was 3.2% and 4.8% in phases 1 and 2, respectively. Adverse reactions were observed in 2 (22.2%) HCWs in phase 1 and in 9 (9.3%) in phase 2, consisting mostly of maculopapular rashes or vesicles around the injection site. CONCLUSIONS: Our study shows that 26% to 55% of HCWs with no history of chickenpox and who tested negative for antibody against varicella required vaccination. Hence, in healthcare facilities, varicella screening and vaccination should be offered to all HCWs.

Low prevalence of autoimmune diabetes markers in a mixed ethnic population of Singaporean diabetics.

BACKGROUND: Circulating antibodies to glutamic acid decarboxylase (GADab) and tyrosine phosphatase-like molecule IA-2 (IA-2ab) are major indicators for auto-immune destruction of pancreatic islet cells. They identify a majority of Caucasians with type 1 diabetes and approximately 50% of Asians, providing evidence of an idiopathic aetiology in the latter. The present study investigated these autoantibodies in a mixed ethnic group. METHODS: Hospital clinic patients with clinically defined type 1 (n = 93) and type 2 (n = 300) diabetes and representing Singapore's major ethnic groups--Chinese, Indians and Malays--were studied. GADab and IA-2ab frequencies, and association of autoimmunity status with clinical and biochemical profiles were analysed. RESULTS: Radio-immunoprecipitation assays detected either or both antibodies (seropositivity) in 41.9% of subjects with type 1 diabetes. GADab was detected in 36.6% and IA-2ab in 23.7% of type 1 diabetics. Prevalence of IA-2ab showed a reduction in frequency with disease duration (P = 0.026). In clinical type 2 diabetics, seropositivity was 10.0% with higher frequency in Malays (17.5%) than Chinese (9.7%) and Indians (4.5%). Multivariate analysis revealed that low fasting C-peptide was associated with seropositivity (odds ratio (OR) = 0.15; 95% confidence interval (CI) = 0.04-0.58). A significant relationship (OR = 13.5; 95% CI = 5.0-36.7) between insulin requirement and duration (>5 years) was also revealed. In patients with type 2 diabetes there was a trend of gradual progression to insulin dependency. However, there was considerable variation in body mass index between ethnic subgroups of type 2 diabetics, particularly for Chinese (mean (SD) = 26.0 (4.7)) and Malays (mean (SD) = 29.2 (5.9); P < 0.001). CONCLUSIONS: Presence of both antibodies in our mixed ethnic group of type 1 diabetes patients was much lower than in Caucasians. Significant numbers of patients were seronegative for antibodies. Influences due to ethnicity and adiposity would require further investigations.

Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases.

AIM: An epidemic of hand, foot and mouth disease (HFMD) occurred in Singapore between September and November 2000. During the epidemic, there were four HFMD-related deaths and after the epidemic, another three HFMD-related deaths. This study sought to determine the risk factors predictive of death from HFMD disease. METHODS: The risk factors for fatal HFMD were determined by comparing clinical and laboratory findings between fatal cases (n = 7) and non-fatal controls (n = 131) admitted between September 2000 and April 2001. Enterovirus 71 positive fatal cases (n = 4) and non-fatal controls (n = 63) were also compared. RESULTS: In total, 138 HFMD cases with a mean age of 32 mo were studied. The majority of fatal cases died from interstitial pneumonitis, of whom three also had brainstem encephalitis. Of the 131 non-fatal cases, 3 had concomitant infections (respiratory syncytial virus bronchiolitis, right-sided pneumonia, Haemophilus influenzae type b meningitis), 2 had aseptic meningitis, and 1 each had transient drowsiness, intravenous immunoglobulin-related complications and transverse myelitis. By multivariate logistic regression analysis, atypical physical findings (p = 0.0006), raised total white cell count (p = 0.0128), vomiting (p = 0.0116) and absence of mouth ulcers (p = 0.043) were predictive of a fatal course. Although previous epidemics have described neurogenic pulmonary oedema as the main cause of death, the fatal cases in this study died mainly from interstitial pneumonitis alone or with myocarditis or encephalitis. CONCLUSION: Although HFMD is generally a benign disease, risk factors such as vomiting, absence of mouth ulcers, atypical presentation and raised total white cell count should alert the physician of a fatal course of illness.

IgG1 subclass dominates autoimmune response to tyrosine phosphatase-like molecule IA-2 in Chinese type 1 diabetes patients.

BACKGROUND AND AIMS: Islet autoantibodies are known markers for type 1 diabetes with an immune-mediated basis; their isotype or subclass profiles may also provide clues to changes in immune response during disease or after intervention. For ICAs and GADab, the IgG1 subclass consistently dominates in recent-onset disease. The aims of our study were to determine the isotype patterns for IA-2ab in Asian Chinese patients with autoimmune diabetes. MATERIALS AND METHODS: From an initial screening of over 400 diabetes patients, 40 subjects (mean age 22.2 +/- 15.8 years) with IA-2ab were enrolled for this study. IA-2ab was detected by radioimmunoassay of [35S]-labelled recombinant human IA-2 ic(605 - 979). Of them, 31 (median age 15 years, range 2 - 57 years; 16 children) had clinical type 1 diabetes (that is, they required insulin at onset or within 1 year) with the majority having been recently diagnosed (< 1 year). The other 9 patients had clinical type 2 diabetes phenotype. RESULTS: IA-2ab IgG subclasses determined with monospecific secondary antibodies showed that both type 1 diabetic adults and children had similarly non-restricted isotype patterns with a strong presence of IgG1-IA-2ab. The rank order was IgG1 > 3 > 2 > 4; 15 subjects had detectable IgG4-IA-2ab. Clonality of immune response determined with kappa/lambda chain-specific antibodies also showed a non-restricted pattern. Patients aged 38.2 +/- 15.2 years with type 2 diabetes had broad patterns of isotypes - IgG1/3 was detected more frequently (n = 8) than IgG2/4 (n = 5). Of three patients on insulin treatment, one was also positive for GADab. The remaining 6 patients were on oral hypoglycaemic treatment. IA-2ab in type 2 diabetes showed a low titre compared to type 1 diabetes. CONCLUSIONS: Isotype responses to IA-2 had a strong IgG1 presence, similar to ICAs and GADab. With IgG3 subclass representation, a predominant Th1 milieu in the systemic environment is likely. There is no suggestion of differences in immune response to IA-2 between adults and children with type 1 diabetes.

Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus.

Type 1 diabetes in most Asian populations may not have a salient autoimmune basis when assessed with single determinations of the major markers, islet cell antibodies (ICAs) and glutamic acid decarboxylase antibodies (GAD65ab). With the inclusion of antibodies to tyrosine phosphatase-like protein IA-2 (IA-2ab) as an additional major marker, we re-examined autoimmune diabetes in a group of Chinese patients. We studied 272 subjects at various stages of disease with blood samples procured for biochemical analysis. ICAs were measured by immunofluorescence, GAD65ab and IA-2ab by radioimmunoassay. Sixty-seven patients fulfilled clinical diagnosis of type 1 diabetes and the remaining 205 patients were type 2. Prevalence of single autoantibody type in recent-onset type 1 diabetes ( < 1 year duration; n = 47) showed 10.6% with ICAs, 44.7% GAD65ab and 36.2% IA-2ab. GAD65ab account for more than two-thirds of the markers found in type 1 diabetes. Combined analysis further showed that 51.1% had at least one antibody type, 31.9% with two or more antibodies and 8.5% with all three antibodies. Islet autoimmunity presence in childhood-onset type 1 diabetes improved with the addition of IA-2ab, though less impact was seen in the adult-onset. Similarly, combined analysis for type 2 patients with recent diabetes showed a modest increase to 13% with islet autoimmunity compared to 8% when assessed by GAD65ab alone. Combining IA-2ab and GAD65ab assays results detected slightly more immune-mediated diabetes, compared to using a single GAD65ab determination. Non-autoimmune causes need to be considered in the pathogenesis of type 1 diabetes in Chinese, particularly in adults.

Prevention of human immunodeficiency virus (HIV) transmission from mother to child--a cohort study in Singapore.

INTRODUCTION: The landmark Paediatric AIDS Clinical Trials Group (PACTG) trial 076 showed in 1994 that antiretroviral therapy (ART) was effective in reducing maternal-child transmission of human immunodeficiency virus (HIV). This trial included antenatal oral zidovudine (ZDV), intrapartum intravenous ZDV, 6 weeks of oral ZDV to the babies and no breastfeeding. MATERIALS AND METHODS: This study is an on-going, prospective, open-label trial conducted from 1995 in which we enrolled HIV-infected pregnant women using the above strategy. Since 1997, the antenatal component of the regimen was modified to include lamivudine with ZDV. All babies had serial HIV polymerase chain reaction (PCR) and antibody tests including enzyme-linked immunosorbent assay (EIA), particle agglutination (PA) and Western blot (WB) at day 1, 1 week, 1, 2, 3, 6, 12 and 18 months. RESULTS: A total of 16 out of 19 eligible women were recruited from 1995 to 1999. The median age was 26 years (range 22 to 38 years), 38% were Singaporeans, median CD4 was 421 cells/mL (range 18 to 713 cells/mL) and median baseline gestational age was 23.5 weeks (range 8 to 32 weeks). None of the 16 children was infected as evidenced by 2 negative HIV PCRs including 1 done > 4 months old with a follow-up of 6 months to 2 years. There was a statistically significant difference between the 3 HIV antibody tests at 12 months of age (P = 0.003), there being more negative results with WB as compared to PA (P = 0.02). However, the difference between the 3 tests at 18 months was not statistically significant. No long-term side effects in these children were seen. CONCLUSION: Although the number of patients in this study is small, the absolute prevention of transmission (95% confidence intervals 0%-17%) in this cohort supports the recommendation of antenatal HIV screening and treatment of those infected.

Prevalence of ICA and GAD antibodies at initial presentation of type 1 diabetes mellitus in Singapore children.

OBJECTIVE: To determine the prevalence of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD) in Asian children with diabetes mellitus (DM) at the time of diagnosis. PATIENTS AND METHODS: 41 children were studied at their initial presentation from 1993 to 2000. RESULTS: Mean age of onset (+/- SD) of DM was 7.6 (+/- 4.2) years. One or both of the two autoantibodies, ICA and anti-GAD, were present in 17 of the 41 children (41.5%) at the time of diagnosis. Comparing the group of children with autoantibodies and the group without detectable autoantibodies, there were no significant differences in body mass index (15.4 vs. 16.3 kg/m2), age of onset (7.4 vs. 7.8 years), random C-peptide levels (203 vs. 311 pmol/l), HbA1c levels (13.2 vs. 12.7%), and frequency of diabetic ketoacidosis at presentation (53.3 vs. 55%). CONCLUSION: Prevalence of antibodies at presentation of DM in Singapore (41.5%) is lower than in Caucasian populations (60-90%). Other autoantibodies yet to be identified may be contributory. Alternatively, non-immune mediated mechanisms may be responsible for a significant proportion of type 1 DM in Singapore children.

Evaluation of a rapid screening test for microalbuminuria with a spot measurement of urine albumin-creatinine ratio.

INTRODUCTION: Microalbuminuria has been established as a marker of incipient diabetic nephropathy, and a regular screening programme has been advocated in patients with diabetes mellitus. We investigated if urine albumin levels normalised by creatinine give results comparable to the urinary albumin excretion rate (UAER) with a timed 24-h urine for detecting microalbuminuria. MATERIALS AND METHODS: Morning urine specimens and 24-h collections were obtained from 65 diabetic patients. Albumin and creatinine levels in the spot urine specimens were measured in a single rapid (7 min) assay format using the Bayer DCA2000+ desktop system. Results of albumin/creatinine ratio and urine albumin concentration were then compared to the reference laboratory method of measuring UAER with the timed 24-h urine sample. RESULTS: The determination of the albumin/creatinine ratio gave good performance characteristics for diagnosis of microalbuminuria (defined as > 30 mg/g creatinine) with sensitivity of 71.4% and specificity of 98.0%. With urine albumin concentration alone, sensitivity was 64.3% and specificity was 96.1%. Receiver operating characteristic (ROC) curves, however, suggest similar diagnostic usefulness for screening microalbuminuria with albumin levels expressed in concentration units or as a ratio of creatinine compared to the reference method. Analysis also indicated that lowering the established cut-off values in general, improves diagnostic performance. CONCLUSIONS: Measurement of microalbuminuria with a spot morning specimen using the DCA2000+ desktop system that simultaneously measures albumin and creatinine levels, provides a rapid and reliable method for incipient diabetic nephropathy in clinical practice.

Systemic levels of cytokines and GAD-specific autoantibodies isotypes in Chinese IDDM patients.

It is not clear if a Th1/Th2 imbalance in Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) would lead to a particular antigen-specific IgG subclass dominant as had been shown in the mouse model. In new-onset Type 1 diabetics, an autoantibody response to glutamate decarboxylase (GADab) is frequently observed but the GADab subclass repertoire is not well-established. We determined the systemic levels of representative Th1 and Th2 cytokines and the GADab IgG subclass distribution in 41 Chinese IDDM patients of whom 26 were recently diagnosed (< or = 1 year) and 32 had GADab, to ascertain a likely association of antigen-specific antibody isotype and the Th1/Th2 dichotomy. With high-sensitivity ELISA systems that measure sub-picogram cytokine concentrations, 26 of the 41 patients (63.4%) had at least one of the pro-inflammatory Th1 cytokines (TNF-alpha, IFN-gamma and IL-12) detected. Fewer patients (4/41) had the anti-inflammatory Th2 cytokine IL-4 detected. For IL-10, all subjects had measurable quantities but only three diabetics had levels above the upper limit for healthy subjects (n = 20). Grouped according to the profile of detectable cytokines, there were 24 Th1, 2 Th2 and 2 Th0 patterns. GAD-specific IgG1 antibody was more frequently expressed; 22 of 32 GADab[+] patients. The rank order for the GADab subclasses was IgG1 > 4 > 3 > 2; IgG2 was found in 11 GADab[+] patients. Recent-onset diabetics have a similar ranking of the GAD-specific IgG subclasses. In human Type 1 diabetes, a predominance of GAD-specific IgG1 antibody response is observed together with a dominant Th1 cytokine pattern.