Observation of a Strongly Isospin-Mixed Doublet in

ß decay of proton-rich nuclei plays an important role in exploring isospin mixing. The ß decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through ß-delayed two-proton emission (ß2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P ß decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in ß-decay experiments.

Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects.

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

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.

Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study.

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

Identification of the Lowest T=2, J

Masses of ^{52g,52m}Co were measured for the first time with an accuracy of ∼10 keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous ß-γ measurements of ^{52}Ni, the T=2, J^{π}=0^{+} isobaric analog state (IAS) in ^{52}Co was newly assigned, questioning the conventional identification of IASs from the ß-delayed proton emissions. Using our energy of the IAS in ^{52}Co, the masses of the T=2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in ^{52}Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

Mad honey poisoning mimicking acute myocardial infarction.

We report a case of acute poisoning in a 48-year-old man who presented with chest pain, abdominal pain, dizziness, sweatiness, blurred vision, and severe hypotension after ingestion of honey. His electrocardiogram showed sinus bradycardia and transient ST elevation. He made a good recovery after treatment with atropine and close monitoring. Grayanotoxin was detected in his urine and the honey he ingested, which confirmed a diagnosis of mad honey poisoning. This is a condition prevalent in the Black Sea region around Turkey but rarely seen locally. Although mad honey poisoning is life-threatening, early use of atropine is life-saving. Such poisoning may present with ST elevation in the electrocardiogram and symptoms mimicking acute myocardial infarction. It is therefore essential for clinicians to recognise this unusual form of poisoning and avoid the disastrous use of thrombolytic therapy.

The use of the Digit Span Test in screening for cognitive impairment in acute medical inpatients.

BACKGROUND: There is no valid instrument currently in use at acute-care hospitals in Hong Kong to aid the detection of cognitive impairment. The objectives of this study were to (1) validate the Digit Span Test (DST) in the identification and differentiation of dementia and delirium; and (2) determine the prevalence of major cognitive impairment in elderly people in an acute medical unit. METHODS: During the study period from January to February 2010, 144 patients aged 75 years or more who had had unplanned medical admissions were assessed by nurses, using the Digit Span Forwards (DSF) and the Digit Span Backwards (DSB) tests. The DST scores were compared with the psychiatrists' DSM-IV-based diagnoses. Receiver Operating Characteristics curve (ROC) was used in conjunction with sensitivity and specificity measures to assess the performance of DST. RESULTS: The prevalence rates of dementia alone, delirium alone and delirium superimposed on dementia were 21.5%, 9% and 9% respectively. The prior case-note documentation rate was 13.2% for dementia and 2.8% for delirium. Regarding the detection of major cognitive impairment, the ROC curve of DSB showed a sensitivity of 0.77 and specificity of 0.78 at the optimal cutoff of <3. A significant association between scores on the DST and the Cantonese version of the Mini-Mental State Examination (CMMSE) was found in this study (p < 0.05 for DSF, p = 0.00 for DSB). CONCLUSIONS: Dementia and delirium were prevalent, yet under-recognized, in acute medical geriatric inpatients. The DSB is an effective tool in identifying patients with major cognitive impairment.

Ultrasonographic prediction of homozygous alpha0-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination?

OBJECTIVE: To compare the predictive values of three ultrasonographic parameters: placental thickness (PT), fetal cardiothoracic ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV), alone or in combination, in pregnancies affected by homozygous alpha(0)-thalassemia at 12-20 weeks' gestation. METHODS: Pregnant women at risk of carrying a fetus affected by homozygous alpha(0)-thalassemia were studied from 1995 to 2006 using serial ultrasonography at 12-15 weeks, 16-20 weeks and 30 weeks' gestation. We measured CTR and PT from 1995, and MCA-PSV as well from 1997. An invasive prenatal test was offered if cardiomegaly with or without placentomegaly was detected but the MCA-PSV results were used only retrospectively for analysis. RESULTS: Of a total of 777 at-risk fetuses studied, 138 (17.8%) were affected by homozygous alpha(0)-thalassemia. At 12-15 weeks' gestation, 598 ultrasound examinations were performed. CTR was better than both PT and MCA-PSV in the prediction of affected pregnancies. The highest sensitivity (98.3%) was achieved by the combination of CTR and/or MCA-PSV at a false-positive rate of 15.8%. At 16-20 weeks' gestation, 410 ultrasound examinations were performed, 121 of which were at the patient's first visit and 289 of which were at a follow-up visit. Both CTR and MCA-PSV predicted the affected pregnancies equally well. The sensitivity of CTR was 100.0%, but the false-positive rate was 5.2%. In contrast, the false-positive rate of MCA-PSV alone was 1.4% and that of the combination of CTR and MCA-PSV was 0%, although their sensitivities were less than 65%. CONCLUSIONS: The data suggest that adding MCA-PSV to CTR in the prediction of homozygous alpha(0)-thalassemia can increase the sensitivity at 12-15 weeks and decrease the false-positive rate at 16-20 weeks' gestation.

Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin Portland in fetuses affected by homozygous α0-thalassemia from 12 to 40 weeks' gestation.

OBJECTIVES: To determine haematological parameters in fetuses affected by homozygous α(0)-thalassemia. METHODS: This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α(0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. RESULTS: There were significant differences in the haematological parameters between homozygous α(0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous α(0)-thalassemia (alpha thalassemia trait) or normal. In homozygous α(0)-thalassemia, the median Hb level, proportion of Hb Bart's (γ(4)) and Hb Portland 1(ζ(2)γ(2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. CONCLUSION: Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ(2)γ(2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia.

Peri-operative blood transfusion increases length of hospital stay and number of postoperative complications in non-cardiac surgical patients.

OBJECTIVES: To test the hypothesis that blood transfusion alone was a significant risk factor for in-hospital morbidity in non-cardiac patients. DESIGN: Propensity analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive non-cardiac patients seen in our department from 2006 to early 2009 who underwent a major procedure under general or spinal anaesthesia were included. Propensity analysis was performed to neutralise the confounding effects of preoperative variables and identify the true effects of transfusions on surgical outcomes. MAIN OUTCOME MEASURES: Receipt of intra-operative and postoperative blood transfusion was established and the difference in proportions between patients who did and did not receive donor blood tested for mortality, overall morbidity, individual complications, and number of adverse events. RESULTS: Transfused patients were significantly older and sicker, more likely to be male, to have lower haemoglobin values and undergo longer and more emergency surgical procedures than those not receiving a transfusion. Blood transfusion was predictive of length of postoperative hospital stay and number of complications before discharge. The amount of transfused blood was predictive of in-hospital mortality, with an odds ratio of 1.4 for each unit of blood received. The risk of a surgical wound infection was almost doubled when the patient had received a blood transfusion. CONCLUSION: After controlling for the factors associated with an increased likelihood for receiving a blood transfusion, the actual transfusion was predictive of a slower and more eventful postoperative recovery with associated costs to both the patient and health services.

Outbreak of hypoglycaemia: sexual enhancement products containing oral hypoglycaemic agent.

OBJECTIVES: To describe a cluster of Hong Kong subjects with hypoglycaemia, after they had taken various non-prescription sildenafil products containing glibenclamide. DESIGN: Retrospective study. SETTING: A tertiary referral centre for clinical toxicology analysis in Hong Kong. PATIENTS: All men referred to the laboratory for investigation of suspected drug-induced hypoglycaemia from December 2007 to September 2008. MAIN OUTCOME MEASURES: The characteristics of these patients, including their clinical presentations, outcomes, drug history, urine toxicology analysis results, and in some instances, analysis results of unused products. RESULTS: A total of 144 male patients were referred for suspected drug-induced hypoglycaemia. Sildenafil and glibenclamide, or their metabolites, were detected in the urine specimens of 68 (47%) patients, none of whom had been prescribed either drug by a registered medical practitioner. Among these subjects, 24 (35%) denied any use of sexual enhancement products despite repeated questioning. Eight patients had repeated exposure resulting in re-admission. The sources of these sexual enhancement products included pharmacies in Mainland China, friends, local pharmacies, peddlers, or were unknown. Three patients died, one remains in a vegetative state and one suffered cognitive impairment; the remaining 63 recovered fully. Twenty-five unused sexual enhancement products of seven different kinds were recovered for analysis. The median (range) of sildenafil and glibenclamide per unit dose was 64 (0.05-198) mg and 70 (0-158) mg, respectively. CONCLUSION: These illegal products pose a severe and continued threat to society and therefore deserve widespread vigilance, so that such products can be eradicated at their source.

Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism.

Vpu from HIV-1 is an 81 amino acid type I integral membrane protein which consists of a cytoplasmic and a transmembrane (TM) domain. The TM domain is known to alter membrane permeability for ions and substrates when inserted into artificial membranes. Peptides corresponding to the TM domain of Vpu (Vpu(1-32)) and mutant peptides (Vpu(1-32)-W23L, Vpu(1-32)-R31V, Vpu(1-32)-S24L) have been synthesized and reconstituted into artificial lipid bilayers. All peptides show channel activity with a main conductance level of around 20 pS. Vpu(1-32)-W23L has a considerable flickering pattern in the recordings and longer open times than Vpu(1-32). Whilst recordings for Vpu(1-32)-R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu(1-32)-S24L do not exhibit any noticeable channel activity. Recordings of WT peptide and Vpu(1-32)-W23L indicate Michaelis-Menten behavior when the salt concentration is increased. Both peptide channels follow the Eisenman series I, indicative for a weak ion channel with almost pore like characteristics.

Towards a mechanism of function of the viral ion channel Vpu from HIV-1.

Vpu, an integral membrane protein encoded in HIV-1, is implicated in the release of new virus particles from infected cells, presumably mediated by ion channel activity of homo-oligomeric Vpu bundles. Reconstitution of both full length Vpu(1-81) and a short, the transmembrane (TM) domain comprising peptide Vpu(1-32) into bilayers under a constant electric field results in an asymmetric orientation of those channels. For both cases, channel activity with similar kinetics is observed. Channels can open and remain open within a broad series of conductance states even if a small or no electric potential is applied. The mean open time for Vpu peptide channels is voltage-independent. The rate of channel opening shows a biphasic voltage activation, implicating that the gating is influenced by the interaction of the dipole moments of the TM helices with an electric field.

Analogues of erectile dysfunction drugs: an under-recognised threat.

OBJECTIVES: To investigate the problem of drug analogue adulteration in male erectile dysfunction health products. DESIGN: Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong. SETTING: Tertiary referral centre for clinical toxicology analysis in Hong Kong. MAIN OUTCOME MEASURES: The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. RESULTS: Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product. CONCLUSIONS: The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.

Drug-induced hypoglycaemia--new insight into an old problem.

OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced hypoglycaemia without a known history of exposure to hypoglycaemic agents, referred to the Hospital Authority Toxicology Reference Laboratory from June 2005 to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases, laboratory findings, possible causes, age distribution, and final outcomes. RESULTS: A total of 51 such patients were referred, in whom the presence of oral hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23 patients, oral hypoglycaemic agents could only be detected by target analysis, not through broad-spectrum screening. Gliclazide and glibenclamide were detected in 14 and eight patients respectively, whereas glimepiride, nateglinide and rosiglitazone were detected in the remaining patient. Possible sources of oral hypoglycaemic agents included drug administration errors in residential care homes for the elderly (n=9), mistakenly taking medication of a family member or employer (n=6), taking stock medication by mistake (n=2), taking Chinese proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral hypoglycaemic agents is a recognised problem, particularly in cases where family members living in the same household are taking similar medications. Possible drug administration errors in residential care homes for the elderly should be investigated, and procedures rectified if confirmed. Health care providers should be vigilant to such potential errors, especially in cases of unexplained hypoglycaemia.