Biological plausibility and stochasticity in scalable VO2 active memristor neurons.

Neuromorphic networks of artificial neurons and synapses can solve computationally hard problems with energy efficiencies unattainable for von Neumann architectures. For image processing, silicon neuromorphic processors outperform graphic processing units in energy efficiency by a large margin, but deliver much lower chip-scale throughput. The performance-efficiency dilemma for silicon processors may not be overcome by Moore's law scaling of silicon transistors. Scalable and biomimetic active memristor neurons and passive memristor synapses form a self-sufficient basis for a transistorless neural network. However, previous demonstrations of memristor neurons only showed simple integrate-and-fire behaviors and did not reveal the rich dynamics and computational complexity of biological neurons. Here we report that neurons built with nanoscale vanadium dioxide active memristors possess all three classes of excitability and most of the known biological neuronal dynamics, and are intrinsically stochastic. With the favorable size and power scaling, there is a path toward an all-memristor neuromorphic cortical computer.

Diamond FinFET without Hydrogen Termination.

In this letter we report the first diamond fin field-effect transistor (diamond FinFET) without a hydrogen-terminated channel. The device operates with hole accumulation by metal-oxide-semiconductor (MOS) structures built on fins to maintain effective control of the channel conduction. Devices with 100-nm-wide fins were designed and fabricated to ensure that the channel pinched off at zero gate bias. The transfer characteristic of FinFET showed a greater than 3000 on/off ratio, successfully demonstrating the transistor behavior. Devices were characterized at room temperature and at 150 °C, showing 30 mA/mm current density at 150 °C, 35 times more than current density at room temperature. The diamond FinFET, which leverages the fin concept from the silicon industry and the material advance of diamond, enables a new class of diamond transistors for applications from digital to power and radio frequency (RF) electronics.

Endobronchial Foreign Body Presenting as Exacerbation of Asthma.

Airway foreign bodies are a leading cause of death among children and require urgent recognition by medical personnel. While most cases are diagnosed readily from a clinical history of acute respiratory distress, some cases remain more indolent and present later. We report the case of a 7-year-old boy who aspirated a "LEGO" toy and presented with a week history of increasing respiratory distress compatible with known asthma. Despite a normal chest X-ray, a low-dose computed tomography showed the presence of a foreign body in the left main bronchus, which was subsequently removed by fiberoptic bronchoscopy. Our case serves to reemphasize the importance of considering airway foreign bodies as a cause of respiratory distress, especially in young children.

Efficacy of bevacizumab with cisplatin and gemcitabine in Asian patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy: a substudy of the Avastin in Lung trial.

AIM: The phase III AVAiL study evaluated the efficacy and safety of the anti-vascular epidermal growth factor agent bevacizumab combined with platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a preplanned analysis of Asian patients enrolled in AVAiL. METHODS: Patients with recurrent or advanced non-squamous NSCLC were randomized to receive bevacizumab 7.5 mg/kg, bevacizumab 15 mg/kg or placebo, plus cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles, followed by bevacizumab or placebo until disease progression. An exploratory analysis was undertaken to assess efficacy and safety in an Asian subgroup. RESULTS: Of the 1043 patients enrolled, 105 were Asian and were included in the subgroup analysis. Progression-free survival was 8.5 months (95% CI 7.3-10.8) in the bevacizumab 15-mg/kg group, 8.2 (95% CI 6.6-11.7) in the 7.5-mg/kg group and 6.1 (95% CI 5.1-8.0) in the placebo group. Median overall survival in the 7.5-mg/kg bevacizumab group was prolonged compared with placebo group (HR 0.46; 95% CI 0.22-0.97). Nausea was the most common adverse event, occurring at similar rates (ranging from 69-76%) in all study groups. Hypertension was the most common adverse event of special interest, seen in 29, 55 and 16% of patients in the 7.5-mg/kg and 15-mg/kg bevacizumab and placebo groups, respectively. CONCLUSION: Study results strongly suggest that bevacizumab at a dose of 7.5 mg/kg improves the duration of overall survival when combined with cisplatin-gemcitabine in Asian patients. Bevacizumab was well tolerated in this patient group.

An indirect comparison of bevacizumab plus cisplatin-gemcitabine and cisplatin plus pemetrexed treatment for patients with advanced first-line non-squamous non-small cell lung cancer in East Asia.

AIMS: To compare the relative efficacy of bevacizumab plus cisplatin-gemcitabine chemotherapy (BevCG) with cisplatin plus pemetrexed (CP) in the first-line treatment of advanced or recurrent non-small cell lung cancer (NSCLC) in East Asian patients. In the absence of evidence from head-to-head trials, an adjusted indirect treatment comparison (ITC) approach was selected to compare these treatments. METHODS: BevCG and CP treatments have been compared in their relative effects versus their common comparator, the CG treatment. Outcomes from the ITC were used in a statistical model to estimate progression-free survival (PFS) and overall survival (OS) of the two treatments. The non-proportional hazards log-logistic, accelerated failure time model was selected as it provided the best fit. The ITC hazard ratio (HR) was conservatively adjusted to match what was observed between the cumulative hazard functions until the end of the Avastin in Lung trial follow-up period. RESULTS: The ITC analysis suggests that patients treated with Bev-based treatment can expect more favorable outcomes in terms of both PFS and OS (PFS HR=0.71 and OS HR=0.41). Probabilistic sensitivity analyses of PFS and OS HR showed that HR values below 1 are likely to occur in 82% of patients for PFS HR and in 94% of patients for OS HR. CONCLUSION: BevCG can be considered a more effective therapy than CP for NSCLC patients in East Asia.

Clinical challenges in managing bronchiectasis.

Bronchiectasis is a common disease in the Asia-Pacific and affected patients suffer from chronic sputum production and recurrent exacerbations. Bronchiectasis is largely idiopathic although there is diverse aetiology. The pathogenesis of bronchiectasis comprises infective, inflammatory and emzymetic elements. These interact to perpetuate continued airway damage in bronchiectasis leading to progressive airway and lung damages. Treatment of bronchiectasis is unsatisfactory and there are only very few trials. Existing data suggest some efficacy of inhaled corticosteroid therapy, which has been shown recently to clinical and anti-inflammatory properties in bronchiectasis. Immunomodulating agent such as low-dose macrolides have also been shown to have some efficacy although more data are needed to advocate their long-term usage. Antibiotic therapy is complex in bronchiectasis and includes short-term empirical treatment for acute exacerbation, and consideration of long-term maintenance of oral, nebulized and i.v. therapy. This long-neglected illness should receive more research attention in order that we can have better understanding of its aetiology, pathogenesis and treatment.

The burden of lung disease in Hong Kong: a report from the Hong Kong Thoracic Society.

BACKGROUND AND OBJECTIVE: The burden of lung disease in Hong Kong is not known. This study determined the mortality and hospitalization rates of respiratory diseases in Hong Kong in 2005, their trend in the past decade and their incidence/prevalence. METHODS: Mortality data were obtained from the Department of Health and hospitalization data from the Hospital Authority, Hong Kong. Incidence/prevalence data were obtained from local registries or local studies. Trends of mortality and hospitalization rates of various respiratory diseases from 1997 and 2005 were calculated after age standardization and were tested for significance using negative binomial regression analysis. Age standardized mortality rates in Hong Kong were compared with those of the UK and globally. RESULTS: Respiratory disease was the most common cause of mortality and hospitalization in Hong Kong in 2005. Globally and in the UK, cardiovascular disease ranked first in mortality. Respiratory infections ranked first in respiratory mortality, followed by respiratory tract cancer and chronic obstructive lung disease. Respiratory infections also ranked first followed by chronic obstructive lung disease in the utilization of respiratory inpatient bed-days. While mortality rates from all respiratory diseases decreased in the past decade, hospitalization rates remained unchanged. Unlike other respiratory diseases, mortality from respiratory infections have increased since 2001. Smoking is the most important risk factor in non-communicable respiratory diseases. CONCLUSIONS: Respiratory disease is responsible for the highest health-care burden locally. Increased efforts in improving management and prevention of these diseases, including tobacco control, improving air quality and vaccination against influenza and pneumococci, are necessary.

Respiratory infections unique to Asia.

Asia is a highly heterogeneous region with vastly different cultures, social constitutions and populations affected by a wide spectrum of respiratory diseases caused by tropical pathogens. Asian patients with community-acquired pneumonia differ from their Western counterparts in microbiological aetiology, in particular the prominence of Gram-negative organisms, Mycobacterium tuberculosis, Burkholderia pseudomallei and Staphylococcus aureus. In addition, the differences in socioeconomic and health-care infrastructures limit the usefulness of Western management guidelines for pneumonia in Asia. The importance of emerging infectious diseases such as severe acute respiratory syndrome and avian influenza infection remain as close concerns for practising respirologists in Asia. Specific infections such as melioidosis, dengue haemorrhagic fever, scrub typhus, leptospirosis, salmonellosis, penicilliosis marneffei, malaria, amoebiasis, paragonimiasis, strongyloidiasis, gnathostomiasis, trinchinellosis, schistosomiasis and echinococcosis occur commonly in Asia and manifest with a prominent respiratory component. Pulmonary eosinophilia, endemic in parts of Asia, could occur with a wide range of tropical infections. Tropical eosinophilia is believed to be a hyper-sensitivity reaction to degenerating microfilariae trapped in the lungs. This article attempts to address the key respiratory issues in these respiratory infections unique to Asia and highlight the important diagnostic and management issues faced by practising respirologists.

A novel approach using tendon vibration of the human flexor carpi radialis muscle to study spinal reflexes.

Although most muscle spindle investigations have used the cat model and invasive measurement techniques, several investigators have used microneurography to record from the Ia and II fibres in humans during tendon vibration. In these studies the muscle spindle primary endings are stimulated using transverse vibration of the tendon at reflex sub-threshold amplitudes. Others have used low amplitude vibration and the stretch evoked M-wave response to determine reflex properties during both agonist and antagonist voluntary contractions. In the past we have developed a PC based instrument that uses Labview and a linear servomotor to study tendon reflex properties by recording stretch evoked M-wave responses from single tendon taps or electrical stimuli to the afferent nerve. In this paper we describe a further development of this system to provide precise vibrations of the tendon up to 65 Hz with amplitudes up to 4 mm. The resultant M-wave train is extracted from background noise via phase coherent subtractive filtering. Test results from vibrating the human distal flexor carpi radialis tendon at 10 and 30 Hz, for relaxed, slight flexion and slight extension, are also presented.

Antimicrobial resistance in Escherichia coli outpatient urinary isolates from women: emerging multidrug resistance phenotypes.

This study evaluated the antimicrobial resistance profile of outpatient urinary Escherichia coli isolated from women obtained throughout Hong Kong during 2004-2005. Of 1067 single patient isolates analyzed, 60.1% were resistant to ampicillin, 34% were resistant to co-trimoxazole, and 22.1% were resistant to ciprofloxacin. Thirty-four (6.6%) of 519 isolates in 2004 and 55 (10%) of 548 isolates in 2005 were extended-spectrum beta-lactamase (ESBL) producers with a CTX-M phenotype. Rates of non-beta-lactam resistance and ESBL production were strongly influenced by patient age. The age-stratified rates for dual co-trimoxazole and ciprofloxacin resistance and for ESBL production were 10.9% and 7.6% in women aged 18-35 years, 13% and 6.9% in women aged 36-50 years, 20.4% and 8.8% in women aged 51-64 years, and 23.7% and 11.8% in women aged > or =65 years, respectively. Nitrofurantoin and fosfomycin remain active against >90% of the isolates, irrespective of the resistance phenotypes for other drugs. Our results documented the emergence of problematic resistance phenotypes among community urinary E. coli and highlight the need to explore strategies for their containment.

Stress and psychological distress among SARS survivors 1 year after the outbreak.

OBJECTIVE: Our study examined the stress level and psychological distress of severe acute respiratory syndrome (SARS) survivors 1 year after the outbreak. METHOD: During the SARS outbreak in 2003, we used the 10-item Perceived Stress Scale (PSS-10) to assess SARS survivors treated in 2 major hospitals (non-health care workers, n = 49; health care workers, n = 30). We invited SARS survivors from the same hospitals (non-health care workers, n = 63; health care workers, n = 33) to complete the PSS-10 again in 2004. At that time, they were also asked to complete the General Health Questionnaire (GHQ-12) and measures of depression, anxiety, and posttraumatic symptoms. PSS-10 scores were also obtained from matched community control subjects during the outbreak (n = 145) and again in 2004 (n = 112). RESULTS: SARS survivors had higher stress levels during the outbreak, compared with control subjects (PSS-10 scores = 19.8 and 17.9, respectively; P < 0.01), and this persisted 1 year later (PSS-10 scores = 19.9 and 17.3, respectively; P < 0.01) without signs of decrease. In 2004, SARS survivors also showed worrying levels of depression, anxiety, and posttraumatic symptoms. An alarming proportion (64%) scored above the GHQ-12 cut-off that suggests psychiatric morbidity. During the outbreak, health care worker SARS survivors had stress levels similar to those of non-health care workers, but health care workers showed significantly higher stress levels in 2004 (PSS-10 score = 22.8, compared with PSS-10 score = 18.4; P < 0.05) and had higher depression, anxiety, posttraumatic symptoms, and GHQ-12 scores. CONCLUSIONS: One year after the outbreak, SARS survivors still had elevated stress levels and worrying levels of psychological distress. The situation of health care worker SARS survivors is particularly worrying. The long-term psychological implications of infectious diseases should not be ignored. Mental health services could play an important role in rehabilitation.

Immediate and sustained psychological impact of an emerging infectious disease outbreak on health care workers.

OBJECTIVE: To assess the immediate and sustained psychological health of health care workers who were at high risk of exposure during the severe acute respiratory syndrome (SARS) outbreak. METHODS: At the peak of the 2003 SARS outbreak, we assessed health care workers in 2 acute care Hong Kong general hospitals with the Perceived Stress Scale (PSS-10). One year later, we reassessed these health care workers with the PSS-10, the 21-Item Depression and Anxiety Scale (DASS-21), and the Impact of Events Scale-Revised (IES-R). We recruited high-risk health care workers who practised respiratory medicine and compared them with nonrespiratory medicine workers, who formed the low-risk health care worker control group. RESULTS: In 2003, high-risk health care workers had elevated stress levels (PSS-10 score = 17.0) that were not significantly different from levels in low-risk health care worker control subjects (PSS-10 score = 15.9). More high-risk health care workers reported fatigue, poor sleep, worry about health, and fear of social contact, despite their confidence in infection-control measures. By 2004, however, stress levels in the high-risk group were not only higher (PSS-10 score = 18.6) but also significantly higher than scores among low-risk health care worker control subjects (PSS-10 score = 14.8, P < 0.05). In 2004, the perceived stress levels in the high-risk group were associated with higher depression, anxiety, and posttraumatic stress scores (P < 0.001). Posttraumatic stress scores were a partial mediator of the relation between the high risk of exposure to SARS and higher perceived stress. CONCLUSIONS: Health care workers who were at high risk of contracting SARS appear not only to have chronic stress but also higher levels of depression and anxiety. Front-line staff could benefit from stress management as part of preparation for future outbreaks.

Community emergence of CTX-M type extended-spectrum beta-lactamases among urinary Escherichia coli from women.

OBJECTIVES: To conduct a territory-wide study of extended-spectrum beta-lactamases (ESBLs) among community isolates of urinary Escherichia coli from women in Hong Kong. METHODS: Up to 50 consecutive single-patient E. coli isolates, collected from 13 laboratories in 2004, were studied. The ESBLs were characterized by PCR sequencing using specific primers. The epidemiological relationship of the isolates was studied by PFGE and phylogenetic group PCRs. RESULTS: Forty-two ESBL producers were found among 600 consecutive isolates tested. The ESBL prevalence was 7.3% (15/205) for women aged 18-35 years, 5% (11/219) for women aged 36-50 years, 6.3% (4/63) for women aged 51-64 years and 10.6% (12/113) for women aged >or=65 years (P=0.3). The ESBL-producing isolates were often multidrug-resistant and CTX-M-14 was found in 37 isolates, CTX-M-15 in 3 isolates and CTX-M-3 in 2 isolates. PFGE revealed no significant clusters among the ESBL producers. Overall, CTX-M-14 producers were significantly more likely to belong to group D than non-ESBL producers [18/37 (48.6%) versus 13/57 (22.8%), P=0.009]. However, 7 of 13 (53.8%) CTX-M-14 producers from women aged 18-35 years represented phylogenetic group B2, compared with 7 of 24 (29.2%) for women of all other ages (P=0.1). CONCLUSIONS: The study documented the community emergence of CTX-M as the predominant ESBL type among urinary isolates from women. The spread of CTX-M enzymes among isolates from young women is concerning and deserves close monitoring.

Perception of benefits and costs during SARS outbreak: An 18-month prospective study.

In this study, the authors examined perceived benefits and costs of the outbreak of severe acute respiratory syndrome (SARS). Mixed accounts of benefits and costs, rather than exclusive accounts of only benefits or costs, were proposed to be characterized by nondefensiveness and enduring changes in psychosocial resources. Participants were 70 SARS recoverers, 59 family members of SARS recoverers, and 172 healthy adults residing in Hong Kong--a SARS-affected region. Results show that participants giving an exclusive account of benefits had higher levels of defensiveness than those giving a mixed account and those giving an exclusive account of costs. Only the perceived impact of benefits given in mixed accounts were related to future accruements in personal and social resources over an 18-month period.

Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells.

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels, and lung cancer risk in Chinese in Hong Kong.

INTRODUCTION: Antioxidants play an important role in counteracting the effects of potential carcinogens. We investigated the risk of lung cancer development with respect to manganese superoxide dismutase (MnSOD) and catalase genetic polymorphisms and their association with erythrocyte antioxidant activities. PATIENTS AND METHODS: This was a case-control study involving patients with confirmed lung cancer and age-matched healthy controls. Genotyping of MnSOD and catalase in DNA extracted from peripheral white cells was performed by polymerase chain reaction-based restriction fragment length polymorphism. Erythrocyte superoxide dismutase and catalase activities were measured spectrophotometrically using chemical kinetic reactions. RESULTS: We recruited 240 patients with lung cancer (63% male, aged 55.6 +/- 11.9 years, 58% adenocarcinoma, 85% clinical stage III or IV) and 240 age-matched healthy controls. The frequencies of the Val allele of MnSOD gene and the C allele of catalase gene were common (>86% and 90%, respectively), with similar distribution, in both patients with lung cancer and controls. The homozygous variant genotypes of MnSOD and catalase were not associated with increased lung cancer risk. The erythrocyte SOD and catalase activity was significantly lower among all patients with lung cancer as a whole compared with controls, irrespective of genotypes. However, patients with adenocarcinoma and non-adenocarcinoma showed differences in SOD and catalase activity among different genotypes in comparison with controls. CONCLUSION: The common Val16Ala MnSOD polymorphism and C-T substitution in the promoter region of the catalase gene do not confer increased or reduced risk of lung cancer in Chinese in Hong Kong.

Elevated levels of transforming growth factor-beta(1) in serum of patients with stable bronchiectasis.

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.