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Hoi Man Yuen,1 Andy CY Lai,1 Eric KH Liu,2 Ming Chung Lee,2 Winnie CW Chu,2 Joey WY Chan,3 Ngan Yin Chan,3 Yun Kwok Wing,3 Albert M Li,1,4,5 Kate C Chan,1,4,5 Chun Ting Au1,4,5 1Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 2Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 4Laboratory for Pediatric Respiratory Research, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5Hong Kong Hub of Pediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Kate C Chan; Chun Ting Au, Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China, Tel +852 35053515 ; +852 35052917, Fax +852 26360020, Email katechan@cuhk.edu.hk; junau@cuhk.edu.hkBackground: Lateral parapharyngeal wall (LPW) thickness is a potentially useful anatomical marker of childhood obstructive sleep apnea (OSA). Measuring LPW thickness by ultrasonography (USG) is technically feasible but its use in children has not been validated. Therefore, this study aimed to assess the intra- and inter-operator reliability of the sonographic measurements of LPW thickness in children and to assess its validity against magnetic resonance imaging (MRI) measurements.Methods: Prepubertal children aged 6– 11 years suspected to suffer from OSA were recruited. Repeated measurements of LPW thickness by USG were conducted to evaluate the intra- and inter-operator reliability, examined by intraclass correlation coefficient (ICC). LPW thickness was measured as the distance between the internal carotid artery and the echogenic surface of the pharynx in an oblique coronal plane by USG. LPW thickness was measured by MRI at the retropalatal level. The agreement between the LPW thickness measured by USG and MRI was assessed by ICC and Bland-Altman plot.Results: Thirty-four children (mean age: 8.66 ± 1.61, 26 male) were recruited. The intra- and inter-operator reliability of the LPW thickness by USG was good (ICC = 0.84 and 0.82, respectively). The agreement between the USG-measured and MRI-measured LPW thickness was moderate (ICC = 0.72). he Bland-Altman plot demonstrated a mean difference of 0.061 cm and a 95% limit of agreement from 0.91 to 1.12 cm.Conclusion: In this study, we demonstrated that ultrasonography is a valid and reliable method to assess LPW thickness in children. This study was supported by the Direct Grant for Research from the Research Committee of the Chinese University of Hong Kong (Project no. 2020.073).Keywords: pediatric, ultrasound, MRI, obstructive sleep apnea

Kate C Chan,1 Chun T Au,1 Michelle W Yu,1 Yun K Wing,2 Albert M Li1 1Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; 2Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, ChinaCorrespondence: Albert M Li; Chun T AuDepartment of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, 6/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, N.T., Hong Kong Special Administrative RegionTel +852-35052982; +852-35052917Fax +852-26360020Email albertmli@cuhk.edu.hk; junau@cuhk.edu.hkPurpose: Most respiratory events in childhood obstructive sleep apnea (OSA) take place during rapid-eye-movement (REM) sleep. This study aimed to describe the characteristics and natural history of childhood REM-OSA and to evaluate the associations between OSA subtypes and blood pressure (BP) outcomes.Participants and Methods: This was a prospective 10-year follow-up study of a cohort established for a childhood OSA epidemiologic study. All subjects from the original cohort were invited to undergo a polysomnography (PSG) and 24-hour ambulatory blood pressure (ABP) monitoring. REM-OSA was defined with a ratio of obstructive apnea hypopnea index (OAHI) during REM sleep (OAHIREM) to OAHI during non-REM sleep (OAHINREM) ≥ 2. Natural history was observed and linear mixed models were used to assess the associations between OSA subtypes and BP outcomes.Results: A total of 610 participants from baseline were included to study the epidemiology of REM-OSA in childhood. Among children with OSA, 65% had REM-OSA. At 10-year follow-up, 234 were included in the analysis. REM-OSA was more common at both baseline (58/92, 63%) and 10-year follow-up (34/58, 59%). For those with REM-OSA at baseline and persistent OSA at follow-up, the majority (72%) remained to have REM-OSA. Compared to those without OSA, subjects with REM-OSA had significantly higher nocturnal SBP (mean difference 2.19 mmHg, 95% confidence interval (CI): 0.12, 4.26; p = 0.039) and DBP (mean difference 1.58 mmHg, 95% confidence interval (CI): 0.11, 3.04; p = 0.035), and less nocturnal SBP dipping (mean difference − 1.84%, 95% CI: − 3.25, − 0.43; p = 0.011), after adjusting for potential confounders. This significant association between REM-OSA and nocturnal SBP dipping was observed at baseline visit only.Conclusion: REM-OSA was found to be a stable phenotype through childhood to young adulthood, and REM-OSA was associated with higher nocturnal BP and a lesser degree of nocturnal SBP dipping in children.Keywords: obstructive sleep apnea, children, epidemiology, stage-dependent OSA, rapid eye movement, phenotype, blood pressure

In this paper, we present and validate the galaxy sample used for the analysis of the baryon acoustic oscillation (BAO) signal in the Dark Energy Survey (DES) Y3 data. The definition is based on a colour and redshift-dependent magnitude cut optimized to select galaxies at redshifts higher than 0.5, while ensuring a high-quality determination. The sample covers ~4100 deg2 to a depth of i = 22.3 (AB) at 10s. It contains 7031 993 galaxies in the redshift range from z = 0.6 to 1.1, with a mean effective redshift of 0.835. Redshifts are estimated with the machine learning algorithm DNF, and are validated using the VIPERS PDR2 sample. We find a mean redshift bias of zbias~0.01 and a mean uncertainty, in units of 1 + z, of σ68~0.03. We evaluate the galaxy population of the sample, showing it is mostly built upon Elliptical to Sbc types. Furthermore, we find a low level of stellar contamination of ≤ 4 per cent. We present the method used to mitigate the effect of spurious clustering coming from observing conditions and other large-scale systematics.We apply it to the BAO sample and calculate weights that are used to get a robust estimate of the galaxy clustering signal. This paper is one of a series dedicated to the analysis of the BAO signal in DES Y3. In the companion papers, we present the galaxy mock catalogues used to calibrate the analysis and the angular diameter distance constraints obtained through the fitting to the BAO scale.

Abstract Background It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. Method One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. Results There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. Conclusion The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

BackgroundFor people living with HIV (PLWH), alcohol use is harmful and may be influenced by unique challenges faced by PLWH living in rural areas. We describe patterns of alcohol use across rurality among PLWH.MethodsVeterans Aging Cohort Study electronic health record data were used to identify patients with HIV (ICD-9 codes for HIV or AIDS) who completed AUDIT-C alcohol screening between February 1, 2008, and September 30, 2014. Regression models estimated and compared 4 alcohol use outcomes (any use [AUDIT-C > 0] and alcohol use disorder [AUD; ICD-9 codes for abuse or dependence] diagnoses among all PLWH, and AUDIT-C risk categories: lower- [1-3 men/1-2 women], moderate- [4-5 men/3-5 women], higher- 6-7]), and severe-risk [8-12], and heavy episodic drinking (HED; ≥1 past-year occasion) among PLWH reporting use) across rurality (urban, large rural, small rural) and census-defined region.FindingsAmong 32,699 PLWH (29,540 urban, 1,301 large rural, and 1,828 small rural), both any alcohol use and AUD were highest in urban areas, although this varied across region. Predicted prevalence of any alcohol use was 54.1% (53.5%-54.7%) in urban, 49.6% (46.9%-52.3%) in large rural, and 50.6% (48.3%-52.9%) in small rural areas (P < .01). Predicted prevalence of AUD was 14.4% (14.0%-14.8%) in urban, 11.8% (10.0%-13.5%) in large rural, and 12.3% (10.8%-13.8%) in small rural areas (P < .01). Approximately 12% and 25% had higher- or severe-risk drinking and HED, respectively, but neither differed across rurality.ConclusionThough some variation across rurality and region was observed, alcohol-related interventions are needed for PLWH across all geographic locations.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Clinical studies have shown plasma Epstein-Barr virus (EBV) DNA level to be an independent prognostic biomarker for nasopharyngeal carcinoma (NPC). However, the proportion of NPC patients whose tumors are associated with EBV vary with geographic location, and there are a variety of assays for plasma EBV. To develop the level of evidence needed to demonstrate the clinical utility of plasma EBV DNA detection for NPC patients and encourage widespread adoption of this biomarker test in clinical laboratories, validated harmonized assays are needed. In 2015, the National Cancer Institute (NCI) convened a Workshop on Harmonization of EBV Testing for Nasopharyngeal Cancer, where experts in head and neck oncology and laboratory medicine addressed the limitations of currently available polymerase chain reaction-based EBV DNA quantitation assays and discussed strategies for advancing the development of harmonized EBV DNA assays and their appropriate clinical use. This article presents the key recommendations to direct future efforts in assay harmonization and validation.

© Sun et al.Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixe

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

BackgroundThe effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown.ObjectiveTo compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo.Study designSerial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (

: Introduction: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi‐annual pVL monitoring on treatment outcomes in Asian CLWH. Methods: Data on children with perinatally acquired HIV aged 1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi‐annual pVL monitoring (n = 4) respectively. Pre‐cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log[sub.10] copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine‐based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow‐up period, 258 (25%) CLWH with annual and 40 (23%) with semi‐annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient‐years of follow‐up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59). Conclusions: Annual compared to semi‐annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first‐line NNRTI‐based cART., Abbreviations Introduction In 2017, there were an estimated 1.8 million children younger than 15 years of age living with HIV (CLWH) worldwide, of whom 110,000 were in the Asia‐Pacific region. [...]