Heterogeneous integration of a GaN-based photonic integrated circuit with an Si-based transimpedance amplifier.

The heterogeneous integration of a GaN-based photonic integrated circuit (PIC) and an Si-based transimpedance amplifier (TIA) is demonstrated in this work. The monolithic GaN PIC, fabricated from a GaN-on-Si light-emitting diode (LED) wafer, comprises LEDs whose optical outputs are coupled to photodetectors (PD) through suspended waveguides. The PIC chip is mounted onto a printed circuit board together with a TIA chip and two filter chip capacitors, occupying a compact footprint. The components are interconnected directly using wire-bonds to minimize signal delays and attenuation. The integrated system achieves rise and fall times of 2.21 and 2.10 ns, respectively, a transmission delay of 3.54 ns, and a bandwidth exceeding 390 MHz. Transmission of a pseudorandom binary sequence-3 (PRBS-3) signal across the integrated system is also demonstrated at the data transmission rate of 280 Mbit/s with a clearly resolved open eye diagram.

Packaging of InGaN stripe-shaped light-emitting diodes.

We demonstrate the fabrication of InGaN/GaN stripe-shaped light-emitting diodes (LEDs) in flip-chip packaging (FC-LED) and vertically mounted packaging (VM-LED). Compared to conventionally packaged LEDs, these packaging schemes enhance light output and emission divergence in ways favorable for general lighting applications. The FC-LED can sustain efficiency at high current operations due to effective heat sinking, while the VM-LED excels at light extraction efficiency due to the exposure of two large emission surfaces. Together with the properties of low luminous exitance and emission uniformity, the stripe-shaped LEDs are ideal for the assembly of luminaires. An LED light tube comprising a continuous linear array of 10 stripe-shaped LED chips has been assembled. The optical performance of the light tube is compared to another light tube assembled with conventional square-shaped LED chips (with and without external diffuser) by confocal microscopy. It is found that emission uniformity of the stripe-shaped LED tube is significantly improved, with a threefold increase in illumination area, without efficiency loss associated with diffusers.

Flexible Free-Standing III-Nitride Thin Films for Emitters and Displays.

The majority of a GaN light-emitting diode (LED) is released from its sapphire substrate through selective-area laser lift-off to form a freely suspended light emitter. By virtue of being suspended in air without supporting substrates, the ultrathin crystalline and crack-free film possesses flexibility and bendability. The free-standing LEDs benefit from significant relaxation of strain, evident from red-shifting of the E2(high) phonon frequencies as measured by Raman spectroscopy toward those of strain-free free-standing GaN substrates. The phonon frequencies remain invariant upon bending of the film; this indicates that the properties of the flexible device will not be dependent on the bending curvatures. The observation of pronounced spectral blue-shifts from the photoluminescence (PL) spectrum from the flexible regions further confirms the occurrence of strain relaxation in the quantum wells. Being free-standing and thus lacking a direct heat-sinking pathway, emissions from the different regions of the suspended film can be affected by thermal effects to different extents, which are investigated by long-wave infrared thermometry. Heat accumulation is determined to be most severe at the far end of the flexible stripe at higher currents, leading to reduced efficiencies and electroluminescence (EL) spectral red-shifts. Based on this architecture, a monolithic 3 × 4 dot-matrix microdisplay prototype is demonstrated, comprising three adjacent flexible stripe emitters with four individually addressable pixels on each stripe. This proof-of-concept demonstration opens up new opportunities for GaN optoelectronics for a wide range of flexible display and visual applications.

Whispering gallery mode lasing in optically isolated III-nitride nanorings.

III-nitride nanorings fabricated from a combination of hybrid-nanosphere-lithography and laser lift-off processes is demonstrated. Being formed on an interfacial metallic layer optically coupling between the optical ring and its substrate is eliminated, maximizing optical confinement of whispering gallery resonant mode within the ring cavity. The tapered cross-sectional profile also promotes coupling of emitted light into resonant modes. Optically pumped lasing with a dominant peak at 421.5 nm is observed at room temperature, with threshold energy density of ∼6.5 mJ/cm2. Etch-induced sidewall roughness causes scattering of light at the interface to diminish confinement, and is also responsible for the mode-splitting effect according to finite-difference time-domain simulations.

InGaN light-emitting diode stripes with reduced luminous exitance.

InGaN light-emitting diodes of stripe geometries have been demonstrated. The elongated geometry facilitates light spreading in the longitudinal direction. The chips are further shaped by laser-micromachining to have partially-inclined sidewalls. The light extraction efficiencies of such 3D chip geometries are enhanced by ~12% (~8% according to ray-trace simulations), leading to a reduction of junction temperatures. The effective emission area is also increased four times compared to a cubic chip. The stripe LEDs are thus more efficient emitters with reduced luminous exitance, making them more suitable for a wide range of lighting applications.

The benefit of prothrombin complex concentrate in decreasing neurological deterioration in patients with warfarin-associated intracerebral haemorrhage.

OBJECTIVE: To compare the outcomes of patients with warfarin-associated intracerebral haemorrhage given different treatments to reverse the effect of anticoagulation. DESIGN: Historical cohort study. SETTING: A regional hospital in Hong Kong. PATIENTS: Patients on warfarin who developed intracerebral haemorrhage. INTERVENTIONS: Prothrombin complex concentrate versus fresh frozen plasma treatment. MAIN OUTCOME MEASURES: The primary outcome measures included the international normalised ratio before and after prothrombin complex concentrate treatment and the neurological deterioration in patients with Glasgow Coma Scale score of more than 8/not intubated/not planned for immediate surgery (target group). Secondary outcome measures were haematoma expansion, 7-day and 30-day mortality rates, and 3-month functional outcome. Safety outcome was the occurrence of a thrombotic event after prothrombin complex concentrate treatment within the index admission. RESULTS: Among 33 patients with clearly documented time of infusion of prothrombin complex concentrate, and whose international normalised ratio was checked before and after prothrombin complex concentrate treatment, the mean international normalised ratio was reduced from 2.81 to 1.21 within 24 hours. Within the target group of patients, there was a significantly lower rate of neurological deterioration in the prothrombin complex concentrate group (17.4% of 23 patients) versus fresh frozen plasma group (45.5% of 33 patients) [P=0.027]. In terms of the 7-day mortality, 30-day mortality, and 3-month functional outcome, prothrombin complex concentrate-treated group showed a favourable trend although the difference did not reach a statistical significance. No patient developed thrombotic complications after prothrombin complex concentrate treatment. CONCLUSIONS: Prothrombin complex concentrates can reverse the warfarin effect of prolonged international normalised ratio in a timely manner. It might better improve the outcome of warfarin-associated intracerebral haemorrhage compared with fresh frozen plasma treatment by reduction in neurological deterioration.

Chronic health problems and health-related quality of life in Chinese children and adolescents: a population-based study in Hong Kong.

OBJECTIVE: We examined the association of different chronic physical and mental conditions, individually or comorbidly on health-related quality of life (QoL) in Chinese children aged ≤14 years in Hong Kong. DESIGN: Population-based cross-sectional survey. PARTICIPANTS: Approximately 7500 Chinese children aged <14 years in Hong Kong. INTERVENTIONS: Nil. PRIMARY AND SECONDARY OUTCOME MEASURES: Various health concepts of validated Chinese version of Child Health Questionnaire (CHQ), a health-related QoL questionnaire in children. RESULT: There was significant association of physical and mental health conditions, either individually or comorbidly, on the various concepts of CHQ. Children with mental health problems were apparently more affected than those with physical health problems. Chronic renal disease and congenital malformation were the physical health conditions associated with the lowest scores in CHQ concepts in children aged 5-10 years and aged 10-14 years, respectively. Behavioural problem was the mental health condition associated with the lowest score in CHQ concepts in both age groups. CONCLUSIONS: Our study shows important information concerning the prevalence of different health conditions and its association, either individually or comorbidly on the QoL in a representative sample of Chinese children in HK.

A rare neurological complication due to lithium poisoning.

Lithium salts have been used in treatment of depression and bipolar disorder for more than 50 years. Neurotoxic side-effects such as nystagmus, ataxia, tremor, fasciculation, clonus, seizure and even coma have been well described in the literature. We present a case of generalised peripheral neuropathy following lithium intoxication. It is a rare presentation with delayed onset and characterised by a rapid downhill course. Diagnosis was confirmed by nerve conduction tests, which showed axonal neuropathy. Despite the profound neurological effects of this toxicity, it is readily reversible with supportive care and the prognosis is good.

A validation study of the Chinese wearing off questionnaire 9-symptom for Parkinson's disease.

OBJECTIVE: Development of wearing off (WO) often goes unnoticed for both patients with Parkinson's disease (PD) and physicians due to the complexity of this phenomenon. A brief 9-symptom WO questionnaire (WOQ-9) was recently found to be highly sensitive in its detection. We aimed to validate a Chinese version WOQ-9 (CWOQ-9) among Chinese patients with PD. METHODS: We recruited 101 literate Chinese PD patients among 4 different neurology or movement disorders clinics in Hong Kong to participate in this study by completing the CWOQ-9. Clinical judgment by the specialists was considered the gold standard for diagnosing WO. RESULTS: The mean age (±SD) of the patients was 61 (±9) years and 35 (34.7%) of them were female. The disease duration was 7.4 (±5.4) years and 69 (68.3%) of them were diagnosed clinically to have WO by the specialists. The positive and negative predictive values, sensitivity and specificity of CWOQ-9 were 86%, 71%, 87%, and 69% respectively. The area under curve (AUC) was 0.78 (p<0.001). CONCLUSION: This simple patient questionnaire is a valid tool for the detection of WO among Chinese PD patients.

Systolic-diastolic coupling of myocardial deformation of the left ventricle in children with left ventricular noncompaction.

Disruption of the myocardial architecture in left ventricular noncompaction (LVNC) may alter myocardial deformation. We evaluated LV myocardial deformation and tested the hypothesis that tight systolic-diastolic coupling occurs in LVNC. Longitudinal and circumferential strain and strain rates (SRs) as determined by speckle tracking echocardiography in nine children aged 5.6 ± 5.5 years was compared with those in nine controls. Left ventricular systolic myocardial deformation parameters were correlated with ejection fraction and indices of diastolic deformation. Compared with controls, patients had lower global LV systolic longitudinal strain (P = 0.008), systolic SR (P = 0.05) and early diastolic SR (P < 0.001). Similarly, LV systolic circumferential strain (base, P = 0.04; papillary muscle level, P = 0.01; apex, P = 0.04), systolic SR (base, P = 0.04) and early diastolic SR (papillary muscle level, P = 0.004, apex, P = 0.02) were lower in patients than in controls. Among patients, the LV ejection fraction correlated with global longitudinal systolic strain and SR and circumferential systolic strain and SR at all levels (all P < 0.05). Positive correlations existed between early diastolic and systolic SRs in corresponding dimensions (longitudinal r = 0.80, P = 0.01; circumferential at base, r = 0.91, P = 0.001; papillary muscle level, r = 0.96, P < 0.001; apex r = 0.98, P = <0.001). In conclusion, LV myocardial deformation is reduced in the longitudinal and circumferential dimensions and manifests tight systolic-diastolic coupling in children with LVNC.

Pulmonary valve replacement after surgical repair of tetralogy of Fallot.

OBJECTIVE: To evaluate the results of pulmonary valve replacement in patients with severe pulmonary regurgitation after tetralogy of Fallot repair in Hong Kong. DESIGN: Retrospective review. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive patients undergoing pulmonary valve replacement after repair of tetralogy of Fallot between August 2002 and December 2008. MAIN OUTCOME MEASURES: Magnetic resonance imaging of right ventricular volume and cardiopulmonary exercise test data before and after the operation were documented and compared. RESULTS: Over a 6-year period, 16 patients underwent pulmonary valve replacement for severe pulmonary regurgitation after prior complete repair for tetralogy of Fallot. There was no in-hospital mortality. The mean time interval between the initial repair and pulmonary valve replacement was 19 (standard deviation, 9) years. In three patients, the indication for pulmonary valve replacement was symptomatic severe pulmonary regurgitation, and asymptomatic progressive right ventricular dilatation in the remaining 13 patients. After pulmonary valve replacement, there was a significant decrease in the mean indexed right ventricular end-diastolic volume from 173 (standard deviation, 44) mL/m(2) to 103 (19) mL/m(2) (P=0.043). After the operation, there was also a tendency for improvement of the right ventricular ejection fraction and the maximum oxygen consumption: from 42% (standard deviation, 9%) to 47% (6%) [P=0.173], and 27 (4) mL/kg/min to 29 (4) mL/kg/min (P=0.208), respectively. CONCLUSION: Pulmonary valve replacement for severe pulmonary regurgitation after tetralogy of Fallot repair is a safe procedure. However, the indications for such an operation in asymptomatic patients remain controversial. Further studies are required to better delineate the timing of pulmonary valve replacement in this patient group.

Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis.

BACKGROUND AND PURPOSE: Apremilast is an orally administered phosphodiesterase-4 inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic inflammatory diseases. The inhibitory effects of apremilast on pro-inflammatory responses of human primary peripheral blood mononuclear cells (PBMC), polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes were explored in vitro, and in a preclinical model of psoriasis. EXPERIMENTAL APPROACH: Apremilast was tested in vitro against endotoxin- and superantigen-stimulated PBMC, bacterial peptide and zymosan-stimulated polymorphonuclear cells, immunonoglobulin and cytokine-stimulated NK cells, and ultraviolet B light-activated keratinocytes. Apremilast was orally administered to beige-severe combined immunodeficient mice, xenotransplanted with normal human skin and triggered with human psoriatic NK cells. Epidermal skin thickness, proliferation index and inflammation markers were analysed. KEY RESULTS: Apremilast inhibited PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon-gamma and tumour necrosis factor (TNF)-alpha, and interleukins (IL)-2, IL-12 and IL-23. Production of TNF-alpha by NK cells and keratinocytes was also inhibited. In vivo, apremilast significantly reduced epidermal thickness and proliferation, decreased the general histopathological appearance of psoriasiform features and reduced expression of TNF-alpha, human leukocyte antigen-DR and intercellular adhesion molecule-1 in the lesioned skin. CONCLUSIONS AND IMPLICATIONS: Apremilast displayed a broad pattern of anti-inflammatory activity in a variety of cell types and decreased the incidence and severity of a psoriasiform response in vivo. Inhibition of TNF-alpha, IL-12 and IL-23 production, as well as NK and keratinocyte responses by this phosphodiesterase-4 inhibitor suggests a novel approach to the treatment of psoriasis.

Effect of deferasirox (ICL670) on arterial function in patients with beta-thalassaemia major.

Deferasirox (ICL670) has been shown to have rapid accessibility to intracellular labile iron. We tested the hypothesis that oral deferasirox improves arterial dysfunction in patients with beta-thalassaemia major. Nineteen thalassaemia patients, aged 23 +/- 7 years, with normal left ventricular (LV) function were treated with deferasirox at 25-35 mg/kg/d for 12 months. LV function, brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, and serum ferritin levels were determined at baseline prior to initiation, after 6 months and after 12 months of therapy. The baseline cardiovascular indices were compared with those of 17 age-matched controls. Longitudinal changes in patients during the treatment period were also determined. Compared with controls, patients had similar echocardiographic indices of LV function (all P > 0.05), while their baseline brachial FMD was reduced (P < 0.001) and carotid stiffness increased (P = 0.019). An increase in FMD (P < 0.001) and a decrease in carotid stiffness (P = 0.007) were found at 6 and 12 months follow-up. The stiffness index correlated inversely with FMD (r = -0.42, P = 0.001). Although there was an increase in ferritin level at 12 months (3303 +/- 1185 ng/ml vs. 2714 +/- 780 ng/ml at baseline, P = 0.006), no significant correlation existed between ferritin level and FMD or carotid stiffness. In conclusion, deferasirox therapy in thalassaemia patients is associated with improved arterial function.

New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function.

OBJECTIVES: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. DESIGN: Cross-sectional study. SETTING: Tertiary paediatric cardiac centre. METHODS: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. RESULTS: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s(2) vs 1.56 (0.53) m/s(2), p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = -0.65, p<0.001 and r = -0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). CONCLUSIONS: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.