Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Nature of partial sigma bond.

This study investigates the formation of partial sigma (σ) covalent bonds in experimentally synthesizable biradicals formed from hydrogenated and fluorinated C8, C20, and C60 cage structures, by assessing their stability, geometry, and bonding character in singlet and triplet states using restricted B3LYP-D3/6-31+G(d,p) theory, natural bond orbital (NBO) analysis, and complete active space self-consistent field (CASSCF) method. The results show that these partial σCC bonds have Wiberg bond orders of 0.38 to 0.48 and bond lengths ranging from 2.62 Å to 5.93 Å. Cage size influences the characteristics of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), with electrons favoring more antibonding orbitals in smaller cages where electrons reside more on the exterior of the cage and favoring bonding orbitals in larger ones where electrons are more in the interior. Fluorination enhances electron density on bonding orbitals. The analysis further clarified that the differentiation between antibonding and bonding features of HOMOs and LUMOs extends beyond merely electron transfer from s- to p-atomic orbitals, also noting possible interactions of the same symmetry repel. The study also introduces hyperconjugation from α-position CH bonds as a factor in stabilizing partial σ-bond formation. The results also caution against the use of broken symmetry methodology in unrestricted SCF wavefunctions for biradicals, such as those in this study as it may cause large spin contamination and thus errors in the calculated electronic properties results.

COMPUTATIONAL DESIGN OF 3D LANTERN ORGANIC FRAMEWORK.

This study employed a computational approach, particularly Density Functional Theory at B3LYP-D3/6-31+G(d) level to design two new classes of three-dimensional (3D) Lantern Organic Frameworks (LOFs) materials based on trisilasumanene and porphyrin core building units. Particularly, we detail strategies for transitioning from 1DLOF nanowires to extended 3D structures: first by connecting planar-molecule base units of trisilasumanene or porphyrin using benzene-based linkers, and then connecting silicon anchoring atoms on the bases with other bases that are vertically stacked by sp3-hydrocarbon chains. The 3D-LOF structures are designed to have different pore sizes through the use of various bases, bridges, and linkers. Comparisons of electronic properties of these 3D structures lead to one designing rule. That is, the gap between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the 3D materials depends only on its base and is nearly independent of the stack size or the length of the sp3-hydrocarbon bridges. Additionally, connecting base units with linkers also extends π-electron conjugation system leading to a reduction in HOMO-LUMO gap. For instance, linking two trisilasumanene molecules significantly narrows HOMO-LUMO gap by 1.75 eV while stacking these bases vertically and connecting them by linear pentane-based bridges yield insignificant change to the gap.

Hologram classification of occluded and deformable objects with speckle noise contamination by deep learning.

Advancements in optical, computing, and electronic technologies have enabled holograms of physical three-dimensional (3D) objects to be captured. The hologram can be displayed with a spatial light modulator to reconstruct a visible image. Although holography is an ideal solution for recording 3D images, a hologram comprises high-frequency fringe patterns that are almost impossible to recognize with traditional computer vision methods. Recently, it has been shown that holograms can be classified with deep learning based on convolution neural networks. However, the method can only achieve a high success classification rate if the image represented in the hologram is without speckle noise and occlusion. Minor occlusion of the image generally leads to a substantial drop in the success rate. This paper proposes a method known as ensemble deep-learning invariant occluded hologram classification to overcome this problem. The proposed new method attains over 95% accuracy in the classification of holograms of partially occluded handwritten numbers contaminated with speckle noise. To achieve the performance, a new augmentation scheme and a new enhanced ensemble structure are necessary. The new augmentation process includes occluded objects and simulates the worst-case scenario of speckle noise.

The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program.

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

Perinatal mortality rate in multiple pregnancies: a 20-year retrospective study from a tertiary obstetric unit in Hong Kong.

INTRODUCTION: Multiple pregnancies have become more common, but their perinatal mortality rate remains higher than the rate among singleton pregnancies. This retrospective study investigated the prevalence and causes of perinatal mortality among multiple pregnancies in Hong Kong. METHODS: All multiple pregnancies in a university tertiary obstetric unit between 2000 and 2019 were reviewed, and the medical records of cases complicated by stillbirth and neonatal death were identified. The causes of perinatal mortality were determined based on clinical assessment and laboratory results, then compared between the first (2000-2009) and second (2010-2019) decades. RESULTS: The prevalence of multiple pregnancies increased from 1.41% in the first decade to 1.91% in the second decade (P<0.001). Compared with the first decade, the second decade had a lower stillbirth rate (14.72 vs 7.68 [both per 1000 births]; P=0.026), late neonatal death rate (4.78 vs 1.16 [both per 1000 livebirths]; P=0.030), and total mortality rate (25.32 vs 13.82 [both per 1000 births]; P=0.006). The decline in stillbirth rate was related to improvements in antenatal care and treatment. The decline in the late neonatal death rate was related to a reduction in preterm birth before 34 weeks (18.5% vs 15.2%; P=0.006), as well as an improvement in the mortality rate in the subgroup of 31-33 weeks (19.23 vs 0 [both per 1000 livebirths]; P=0.035). CONCLUSION: Although the prevalence of multiple pregnancies increased during the study period, the corresponding total perinatal mortality rate improved by 45.4%.

Neonatal mortality in singleton pregnancies: a 20-year retrospective study from a tertiary perinatal unit in Hong Kong.

INTRODUCTION: The global neonatal death (NND) rate has been declining in recent decades, but there are no comprehensive data concerning the characteristics of NNDs in Hong Kong. This study investigated the trends and aetiologies of NNDs among singleton pregnancies in Hong Kong. METHODS: This study included all cases of NND from singleton pregnancies in a tertiary hospital in Hong Kong between 2000 and 2019. The rates, clinical characteristics, and aetiologies of NND were compared between the first (2000-2009) and the second (2010-2019) decades. RESULTS: The NND rate decreased from 1.66/1000 livebirths (97 cases) in the first decade to 1.32/1000 livebirths (87 cases) in the second decade. Congenital or genetic abnormalities (82 cases) caused 44.6% of all NNDs. There was a significant reduction from 0.82/1000 livebirths in the first decade to 0.52/1000 livebirths in the second decade (P=0.037). Other causes of NND were prematurity (69 cases; 37.5%), sepsis (16 cases; 8.7%), hypoxic-ischaemic encephalopathy (15 cases; 8.2%), and sudden infant death syndrome (2 cases; 1.1%). Gestational age-specific neonatal mortality for moderately preterm neonates (31-33 weeks of gestation) significantly decreased from 34.73/1000 in 2000-2009 to 8.63/1000 in 2010-2019 (P=0.001), but there were no significant changes in neonatal mortality for other gestations. CONCLUSION: The NND rate in Hong Kong is among the lowest worldwide. Neonatal deaths in our centre declined over the past two decades, mainly because of improvements in the prenatal diagnosis and treatment of congenital or genetic abnormalities, as well as an improved survival rate among moderately preterm neonates.

Optimal sampled phase-only hologram (OSPOH).

A sampled phase-only hologram (SPOH) is the phase component of the hologram of an object image with pixels being sampled with a periodic grid-cross pattern. The reconstructed image of a SPOH is a sparse image with abundant empty voids and degradation in sharpness and contrast. In this paper we proposed a method based on a new sampling scheme, together with stochastic binary search (SBS), to obtain an optimal sampling lattice that can be applied to generate phase-only holograms with enhanced reconstructed image. Experimental results show that with our proposed method, the fidelity and quality of the reconstructed image are increased.

Scientific evidence on natural disasters and health emergency and disaster risk management in Asian rural-based area.

INTRODUCTION: Disaster epidemiological studies indicate that Asia has the highest frequency of natural disasters. Rural communities are heavily impacted by natural disasters and have different healthcare needs to urban ones. Referencing Asian countries, this paper's objective is to provide an overview of health impacts and the current evidence for designing programmes and policies related to rural health emergency and disaster risk management (health-EDRM). SOURCES OF DATA: This paper uses published English-only reports and papers retrieved from PubMed, Google Scholar, Embase, Medline and PsycINFO on rural disaster and emergency responses and relief, health impact and disease patterns in Asia (January 2000-January 2018). AREAS OF AGREEMENT: Earthquakes are the most studied natural disasters in rural communities. The medical burden and health needs of rural communities were most commonly reported among populations of extreme age. Most of the existing research evidence for rural interventions was reported in China. There lacks published peer-reviewed reports of programme impacts on personal and community preparedness. AREAS OF CONTROVERSY: There is a lack of evidence-based health-EDRM interventions to evaluate implementation effectiveness in rural areas despite vast volumes of health-related disaster literature. GROWING POINTS: Climate change-related disasters are increasing in frequency and severity. Evidence is needed for disaster risk reduction interventions to address the health risks specific to rural populations. AREAS TIMELY FOR DEVELOPING RESEARCH: To support global policy development, urgent evidence is needed on the intervention effectiveness, long-term health outcomes, local and cultural relevance as well as sustainability of health relief produced by Health-EDRM programmes in rural areas.

Ensemble convolutional neural network for classifying holograms of deformable objects.

Recently, a method known as "ensemble deep learning invariant hologram classification" (EDL-IHC) for classifying of holograms of deformable objects with deep learning network (DLN) has been demonstrated. However DL-IHC requires substantial computational resources to attain near perfect success rate (≥99%). In practice, it is always desirable to have higher success rate with a low complexity DLN. In this paper we propose a low complexity DLN known as "ensemble deep learning invariant hologram classification" (EDL-IHC). In comparison with DL-IHC, our proposed hologram classifier has promoted the success rate by 2.86% in the classification of holograms of handwritten numerals.

Factors influencing the acceptance of referrals for clinical pharmacist managed disease states in primary care.

OBJECTIVE: Clinical pharmacists use population health methods to generate chronic disease management referrals for patients with uncontrolled chronic conditions. The purpose of this study was to compare primary care providers' (PCPs) referral responses for 4 pharmacist-managed indications and to identify provider and patient characteristics that are predictive of PCP response. DESIGN: Retrospective cohort study. SETTING: This study occurred in an academic internal medicine clinic. PARTICIPANTS: Clinical pharmacy referrals generated through a population health approach between 2012 and 2016 for hypertension, chronic pain, depression, and benzodiazepine management were included. MAIN OUTCOME MEASURES: Proportion of referrals accepted, left pending, or rejected and influencing provider and patient characteristics. RESULTS: Of 1769 referrals generated, PCPs accepted 869 (49%), left pending 300 (17%), and rejected 600 (34%). Compared with referrals for hypertension, benzodiazepine management, and depression, chronic pain referrals had the lowest likelihood of rejection (odds ratio [OR] 0.31; 95% CI 0.19-0.49). Depression referrals had an equal likelihood of being accepted or rejected (OR 1.04; 95% CI 0.66-1.64). Provider characteristics were not significantly associated with referral response, but residents were more likely to accept referrals. Patient characteristics associated with lower referral rejection included black race (OR 0.39; 95% CI 0.18-0.87), higher systolic blood pressure (OR 0.98; 95% CI 0.97-0.99), and missed visits (OR 0.24; 95% CI 0.07-0.81). CONCLUSION: The majority of referrals for clinical pharmacists in primary care settings were responded to, varying mostly between acceptance and rejection. There was variability in referral acceptance across indications, and some patient characteristics were associated with increased referral acceptance.

Activation of the NLRP3 and AIM2 inflammasomes in a mouse model of Schistosoma mansoni infection.

Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.

Generation of 1 kHz, 2.3 mJ, 88 fs, 2.5 µm pulses from a Cr2+:ZnSe chirped pulse amplifier.

We demonstrate the generation of 2.3 mJ, 88 fs, 2.5 µm laser pulses at 1 kHz repetition rate from a three-stage chirped pulse amplifier employing Cr2+:ZnSe crystals as the active gain media. 5 µJ seed of the amplifier is obtained via intrapulse difference frequency generation in a bismuth triborate (BIBO) crystal from spectrally broadened Ti:Sapphire amplifier output. A multi-pass amplifier followed by two single-pass amplifiers pumped by Q-switched Ho:YAG lasers boost the pulse energy to 6.5 mJ, yielding 2.3 mJ, 88 fs pulses upon pulse compression. Our results show the highest peak power at 2.5 µm with 1 kHz repetition rate. Such a laser will be a powerful source for studying strong-field physics and extending high-harmonic generation towards the keV region.

Mortality and morbidity of extremely low birth weight infants in Hong Kong, 2010-2017: a single-centre review.

BACKGROUND: Extremely low birth weight (ELBW) infants exhibit high rates of mortality and morbidity. We retrospectively assessed factors associated with mortality and morbidity among ELBW infants. METHODS: Perinatal demographic data were reviewed for all ELBW infants born between 2010 and 2017 at a tertiary neonatal unit. RESULTS: For non-survivors (21% of ELBW infants) and survivors, the median gestational ages were 24.1 and 26.2 weeks, respectively, and median birth weights were 650 g and 780 g, respectively (all P<0.001). Regression analyses showed that non-survival was positively associated with lower gestational age (adjusted odds ratio [aOR]=6.71 for every 1-week decrease; 95% confidence interval [CI]=1.73-26.00; P=0.006) and grade 3 or 4 intraventricular haemorrhage (aOR=29.23; 95% CI=1.39-613.84; P=0.030); non-survival was negatively associated with the presence of bronchopulmonary dysplasia (aOR=0.01; 95% CI= <0.001-0.23; P=0.005); length of neonatal intensive care unit stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=89.60; 95% CI=43.86-135.34; P<0.001); and length of hospital stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=2.08; 95% CI=0.43-3.73; P=0.015) and a low Apgar score at 1 minute (B-coefficient=-0.63; 95% CI=-1.04 to -0.22; P=0.003). CONCLUSION: Extremely low birth weight infants exhibited significant mortality and morbidity; there was no survival prior to 23.6 weeks' gestation or below 550 g birth weight. The presence of grade 3 or 4 intraventricular haemorrhage was independently associated with non-survival. Survivors were significantly more likely to exhibit bronchopulmonary dysplasia; survivors with necrotising enterocolitis were more likely to require longer stays in the neonatal intensive care unit and in hospital.

Duration of puberty in preterm girls.

OBJECTIVES: Preterm birth is associated with altered pubertal timing, but the effect on pubertal duration has rarely been assessed. Here, we tested the hypothesis that preterm birth is associated with shorter duration of puberty among girls in Hong Kong where preterm birth has little social patterning. METHODS: In the population-representative Chinese birth cohort "Children of 1997", we used multivariable linear regression to assess the association of preterm status (≤36 completed gestational weeks, n = 170; term birth 37-42 gestational weeks, n = 3476) with duration of puberty, adjusted for parent's highest education, mother's place of birth, maternal smoking during pregnancy, gestational diabetes, preeclampsia, and mother's age of menarche. RESULTS: The mean duration from thelarche to menarche was 2.53 years. Preterm girls had a shorter duration from thelarche to menarche by 2.6 months, 95% confidence interval 0.5-4.7 months. Age of menarche did not differ by preterm status but preterm girls had later thelarche. Preterm birth was not associated with a shorter duration from pubarche to menarche. CONCLUSIONS: Preterm births may be associated with shorter duration of puberty from thelarche to menarche, possibly through effects of in utero estrogen exposure, the drivers of thelarche, or the drivers of pubertal duration/progression, with potential implications for subsequent risk of cardiovascular disease and hormonal cancers.

Chaperones and intimate physical examinations: what do male and female patients want?

INTRODUCTION: Many studies of patients' perception of a medical chaperone have focused on female patients; that of male patients are less well studied. Moreover, previous studies were largely based on patient populations in English-speaking countries. Therefore, this study was conducted to investigate the perception and attitude of male and female Chinese patients to the presence of a chaperone during an intimate physical examination. METHODS: A cross-sectional guided questionnaire survey was conducted on a convenient sample of 150 patients at a public teaching hospital in Hong Kong. RESULTS: Over 90% of the participants considered the presence of a chaperone appropriate during intimate physical examination, and 84% felt that doctors, irrespective of gender, should always request the presence of a chaperone. The most commonly cited reasons included the availability of an objective account should any legal issue arise, protection against sexual harassment, and to provide psychological support. This contrasted with the experience of those who had previously undergone an intimate physical examination of whom only 72.6% of women and 35.7% of men had reportedly been chaperoned. Among female participants, 75.0% preferred to be chaperoned during an intimate physical examination by a male doctor, and 28.6% would still prefer to be chaperoned when being examined by a female doctor. Among male participants, over 50% indicated no specific preference but a substantial minority reported a preference for chaperoned examination (21.2% for male doctor and 25.8% for female doctor). CONCLUSIONS: Patients in Hong Kong have a high degree of acceptance and expectations about the role of a medical chaperone. Both female and male patients prefer such practice regardless of physician gender. Doctors are strongly encouraged to discuss the issue openly with their patients before they conduct any intimate physical examination.