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ImportanceThe presence of diabetic macular ischemia (DMI) on optical coherence tomography angiography (OCTA) images predicts diabetic retinal disease progression and visual acuity (VA) deterioration, suggesting an OCTA-based DMI evaluation can further enhance diabetic retinopathy (DR) management.ObjectiveTo investigate whether an automated binary DMI algorithm using OCTA images provides prognostic value on DR progression, diabetic macular edema (DME) development, and VA deterioration in a cohort of patients with diabetes.Design, Setting, and ParticipantsIn this cohort study, DMI assessment of superficial capillary plexus and deep capillary plexus OCTA images was performed by a previously developed deep learning algorithm. The presence of DMI was defined as images exhibiting disruption of fovea avascular zone with or without additional areas of capillary loss, while absence of DMI was defined as images presented with intact fovea avascular zone outline and normal distribution of vasculature. Patients with diabetes were recruited starting in July 2015 and were followed up for at least 4 years. Cox proportional hazards models were used to evaluate the association of the presence of DMI with DR progression, DME development, and VA deterioration. Analysis took place between June and December 2022.Main Outcomes and MeasuresDR progression, DME development, and VA deterioration.ResultsA total of 321 eyes from 178 patients were included for analysis (85 [47.75%] female; mean [SD] age, 63.39 [11.04] years). Over a median (IQR) follow-up of 50.41 (48.16-56.48) months, 105 eyes (32.71%) had DR progression, 33 eyes (10.28%) developed DME, and 68 eyes (21.18%) had VA deterioration. Presence of superficial capillary plexus–DMI (hazard ratio [HR], 2.69; 95% CI, 1.64-4.43; P P P = .003) and VA deterioration (HR, 2.12; 95% CI, 1.01-5.22; P = .04) after adjusting for age, duration of diabetes, fasting glucose, glycated hemoglobin, mean arterial blood pressure, DR severity, ganglion cell–inner plexiform layer thickness, axial length, and smoking at baseline.Conclusions and RelevanceIn this study, the presence of DMI on OCTA images demonstrates prognostic value for DR progression, DME development, and VA deterioration.

Objectives : We aim to study the viral kinetics and host inflammatory response of RSV infection in older adults, and their correlation with disease severity. Methods : We performed a prospective observational study in adults with RSV infection. We serially collected nasal-throat swabs for quantification of RSV-A and RSV-B viral load, and peripheral blood samples for measurement of cytokine/chemokine concentrations. The study endpoints were (i) requiring supplemental oxygen therapy, and (ii) non-invasive ventilation, intensive care, or died within 30 days of admission. We performed multivariable logistic regression models to identify independent variables for severe disease. Results : We enrolled 71 hospitalized patients and 10 outpatients treated for RSV infection (median age 75 years, 51% male, and 74% with comorbidities). Among hospitalized patients, 61% required supplemental oxygen therapy, and 18% had severe disease requiring non-invasive ventilation or intensive care, or died within 30 days. Inflammatory cytokine/chemokines IL-6, CXCL8/IL-8, CXCL9/MIG and CXCL10/IP-10 increased significantly during the acute phase of illness. IL-6 concentration was independently associated with severe disease after adjusting for confounding factors. RSV viral load was not associated with disease severity throughout the course of illness. Conclusion : Host inflammatory response is a major marker of severe disease in older adults with RSV infection.

Summary Objective To evaluate the prevalence of self-perceived voice problems and voice-related quality of life in a nontreatment seeking older population in Hong Kong. Study Design Prospective, cross-sectional survey. Methods One hundred and one older individuals aged 65 years or above were recruited from senior citizen community centers in Hong Kong. Each participant received a face-to-face interview with the researcher. The participants were asked to report the presence of voice problems and the voice symptoms that they experienced. They were also asked to complete the Cantonese version of the Voice Handicap Index to ascertain their voice-related quality of life. Results Over one-fourth (27.7%) of participants reported having current voice problems. Perceived voice problems were found to pose significant negative impacts on the older individuals’ voice-related quality of life. The prevalence of voice problems and extent of impacts of voice-related quality of life were similar across the young-old, old-old, and the oldest-old groups of participants. Conclusion The results suggest that voice problems are common in the older population and should not be underestimated. The study urges the need to allocate more resources to provide voice-related services from the young-old group for promoting positive aging.

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI). Viral genome sequencing revealed two key mutations had occurred following infection in the haemagglutinin (HA 226 L>Q) and nucleoprotein (NP 373 A>T) proteins. We further investigated the impact of the NP mutation and demonstrated that only chickens bearing a single nucleotide polymorphism (SNP) in their IFITM1 gene were susceptible to the H7N9 virus. Susceptible chickens demonstrated a distinct loss of CD8+ T cells from the periphery as well as a dysregulation of IFNγ that was not observed for resistant chickens, suggesting a role for the NP mutation in altered T cell activation. Alternatively, it is possible that this mutation led to altered polymerase activity, as the mutation occurs in the NP 360-373 loop which has been previously show to be important in RNA binding. These data have broad ramifications for our understanding of the pathobiology of AI in chickens and humans and provide an excellent model for investigating the role of antiviral genes in a natural host species.

In this manuscript, we developed a two-fold symmetric linchpin (TSL) that converts readily available phage-displayed peptides libraries made of 20 common amino acids to genetically-encoded libraries of bicyclic peptides displayed on phage. TSL combines an aldehyde-reactive group and two thiol-reactive groups; it bridges two side chains of cysteine [C] with an N-terminal aldehyde group derived from the N-terminal serine [S], yielding a novel bicyclic topology that lacks a free N-terminus. Phage display libraries of SX1CX2X3X4X5X6X7C sequences, where X is any amino acid but Cys, were converted to a library of bicyclic TSL-[S]X1[C]X2X3X4X5X6X7[C] peptides in 45 ± 15% yield. Using this library and protein morphogen NODAL as a target, we discovered bicyclic macrocycles that specifically antagonize NODAL-induced signaling in cancer cells. At a 10 μM concentration, two discovered bicyclic peptides completely suppressed NODAL-induced phosphorylation of SMAD2 in P19 embryonic carcinoma cells. The TSL-[S]Y[C]KRAHKN[C] bicycle inhibited NODAL-induced proliferation of NODAL-TYK-nu ovarian carcinoma cells with apparent IC50 of 1 μM. The same bicycle at 10 μM concentration did not affect the growth of the control TYK-nu cells. TSL-bicycles remained stable over the course of the 72 hour-long assays in a serum-rich cell-culture medium. We further observed general stability in mouse serum and in a mixture of proteases (Pronase™) for 21 diverse bicyclic macrocycles of different ring sizes, amino acid sequences, and cross-linker geometries. TSL-constrained peptides to expand the previously reported repertoire of phage-displayed bicyclic architectures formed by cross-linking Cys side chains. We anticipate that it will aid the discovery of proteolytically stable bicyclic inhibitors for a variety of protein targets., A two-fold symmetric linchpin (TSL) converts readily available phage-displayed disulfide peptide libraries to proteolytically stable bicyclic peptides. The bicyclic phage library was screened to discover an antagonist of NODAL morphogen.

Significant global efforts have been directed towards understanding the epidemiology of highly pathogenic avian influenza (HPAI) across poultry production systems and in wild-bird reservoirs, yet understanding of disease dynamics in the village poultry setting remains limited. This article provides a detailed account of the first laboratory-confirmed outbreak of HPAI in the south-eastern provinces of Lao PDR, which occurred in a village in Sekong Province in October 2018. Perspectives from an anthropologist conducting fieldwork at the time of the outbreak, clinical and epidemiological observations by an Australian veterinarian are combined with laboratory characterization and sequencing of the virus to provide insights about disease dynamics, biosecurity, outbreak response and impediments to disease surveillance. Market-purchased chickens were considered the likely source of the outbreak. Observations highlighted the significance of a-lack-of pathognomonic clinical signs and commonness of high-mortality poultry disease with consequent importance of laboratory diagnosis. Sample submission and testing was found to be efficient, despite the village being far from the national veterinary diagnostic laboratory. Extensively raised poultry play key roles in ritual, livelihoods and nutrition of rural Lao PDR people. Unfortunately, mass mortality of chickens due to diseases such as HPAI and Newcastle disease (ND) imposes a significant burden on smallholders in Lao PDR, as in most other SE Asian countries. We observed that high mortality of chickens is perceived by locals as a new 'normal' in raising poultry; this sense of it being 'normal' is a disincentive to reporting of mortality events. Establishing effective people-centred disease-surveillance approaches with local benefit, improving market-biosecurity and veterinary-service support to control vaccine-preventable poultry diseases could all reduce mass-mortality event frequency, improve veterinary-producer relationships and increase the likelihood that mortality events are reported. Priority in each of these aspects should be on working with smallholders and local traders, appreciating and respecting their perspectives and local knowledge.

Aim To review international guidelines and to share our infection control experience during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary eye centre in Hong Kong. Methods Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed. The measures at our hospital were drawn up as per international and local health authorities' guidelines and implemented with the collaboration of doctors, nurses and administrative staff. Results The aims of our infection control measures are to 1) minimize cross-infection within the hospital; 2) protect and support hospital staff; 3) ensure environmental control. To minimize the risk of cross-infection, outpatient attendance and elective surgery have been reduced by 40%, and general anesthesia procedures were reduced by 90%. Patients entering the hospital are screened for fever, travel history, contact and cluster history, and COVID-19 related symptoms. To protect and support hospital staff, we ensure provision of adequate personal protective equipment (PPE) and provide clear guidelines on the level of PPE needed, depending on the clinical situation. Other protective measures include provision of work uniforms, easy access to alcohol-based hand rub, opening new lunch areas, implementation of self-monitoring and self-reporting systems, and communication via online education and updates. Finally, environmental control is achieved by ensuring regular disinfection of the hospital premise, enhancing ventilation, and usage of disposable ophthalmic instruments. Conclusion Our multi-pronged approach to infection control is, so far, successful in minimizing infection risks, while allowing the maintenance of essential ophthalmic services.

Background An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients’ diverse clinical trajectories and low event rates. Methods A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts’ datasets (2015/2016−2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. Results Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ± SD, 4.3 ± 0.6 vs 3.5 ± 0.6, P Conclusions The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development.

OBJECTIVES Multiple studies have suggested that women have worse outcomes than men following mitral valve (MV) surgery—most of those studies reported on conventional sternotomy (CS) MV surgery. Therefore, we aimed to explore whether or not the minimally invasive mitral valve surgery (MIMVS) approach might mitigate a worse survival in women following MV surgery. METHODS We identified patients with isolated primary MV operations with or without tricuspid valve repair performed between 2007 and 2019. Patients were propensity score-matched across the MIMVS and CS surgical approaches. Sex was excluded from the matching process to discern whether female patients had a different likelihood of receiving minimally invasive surgery than males. A Cox proportional hazards model was fitted in the matched cohort and adjusted for the imbalance in baseline characteristics using the propensity score. RESULTS Of 956 patients (417 MIMVS, 539 CS; 424 females), the matched set comprised 342 pairs (684 patients; 296 females) of patients who were well balanced across MIMVS and CS groups with regard to preoperative clinical characteristics. We observed a 47/53% female/male ratio in the CS group and a 39/61% in the MIMVS group, P = 0.054. In both matched groups, women were older than males. A Cox model adjusted for propensity scores showed no survival difference with sex, surgical type or interaction. CONCLUSIONS Women present to the surgical team at an older age. They appear less likely to be considered for a MIMVS approach than men. Neither sex nor surgical approach was associated with worse survival in a matched sample.

Most of our understanding of the ecology and evolution of avian influenza A virus (AIV) in wild birds is derived from studies conducted in the northern hemisphere on waterfowl, with a substantial bias towards dabbling ducks. However, relevant environmental conditions and patterns of avian migration and reproduction are substantially different in the southern hemisphere. Through the sequencing and analysis of 333 unique AIV genomes collected from wild birds collected over 15 years we show that Australia is a global sink for AIV diversity and not integrally linked with the Eurasian gene pool. Rather, AIV are infrequently introduced to Australia, followed by decades of isolated circulation and eventual extinction. The number of co-circulating viral lineages varies per subtype. AIV haemagglutinin (HA) subtypes that are rarely identified at duck-centric study sites (H8-12) had more detected introductions and contemporary co-circulating lineages in Australia. Combined with a lack of duck migration beyond the Australian-Papuan region, these findings suggest introductions by long-distance migratory shorebirds. In addition, we found no evidence of directional or consistent patterns in virus movement across the Australian continent. This feature corresponds to patterns of bird movement, whereby waterfowl have nomadic and erratic rainfall-dependant distributions rather than consistent intra-continental migratory routes. Finally, we detected high levels of virus gene segment reassortment, with a high diversity of AIV genome constellations across years and locations. These data, in addition to those from other studies in Africa and South America, clearly show that patterns of AIV dynamics in the Southern Hemisphere are distinct from those in the temperate north.Author SummaryA result of the ever-growing poultry industry is a dramatic global increase in the incidence of high pathogenicity avian influenza virus outbreaks. In contrast, wild birds are believed to be the main reservoir for low pathogenic avian influenza A virus. Due to intensive research and surveillance of AIV in waterfowl in the Northern Hemisphere, we have a better understanding of AIV ecology and evolution in that region compared to the Southern Hemisphere, which are characterised by different patterns of avian migration and ecological conditions. We analysed 333 unique AIV genomes collected from wild birds in Australia to understand how Australia fits into global AIV dynamics and how viruses are maintained and dispersed within the continent of Australia. We show that the Southern Hemisphere experiences differing evolutionary dynamics to those seen in Northern Hemisphere with Australia representing a global sink for AIV.

Objectives To establish a normative profile of health-related quality of life (HRQoL) for Hong Kong (HK) Chinese residents aged 18 years and above and to examine the relationship between socioeconomic characteristics and health conditions and the preference-based health index. Methods We recruited 1014 representative Cantonese-speaking residents across 18 geographical districts. The normative profiles of HRQoL were derived using established HK value sets. Mean values were computed by sex, age group, and educational attainment to obtain the EQ-5D HK normative profile for the general HK population. To explore the relationships among potential covariates (socioeconomic characteristics and health conditions) and the HK health index, a multivariable homoscedastic Tobit regression model was employed for the analysis. Results The mean index value was 0.919 using the EQ-5D-5L HK value set. Younger ages reported greater problems with anxiety or depression than did older ages, whereas older ages reported greater problems with pain or discomfort than did younger ages. Persons with higher educational attainment and those who reported higher life satisfaction reported significantly higher health index scores (P < .05). On the contrary, receiving government allowance and having experienced a serious illness were significantly associated (P < .05) with a lower health index. Conclusions The norm values fully represent the societal preferences of the HK population, and knowledge of societal preferences can enable policy makers to allocate resources and prioritize service planning. The study was conducted with the EuroQol International EQ-5D-5L Valuation Protocol and therefore enabled us to compare the EQ-5D-5L values with other countries to facilitate understanding of societal preferences in different jurisdictions.

Financial markets are noisy learning environments. We propose an approach that regularizes the Temporal Convolutional Network using a supervised autoencoder, which we term the Supervised Temporal Autoencoder (STAE). We show that the addition of the auxiliary reconstruction task is beneficial to the primary supervised learning task in the context of stock return time-series forecasting. We also show that STAE is able to learn features directly from transformed price series, alleviating the need for handcrafted features. The autoencoder also improves interpretability as users can observe output of the decoder and inspect features retained by the network.

In this manuscript, we developed a Two-fold Symmetric Linchpin (TSL) that converts readily available phage display peptides libraries made of 20 common amino acids to genetically-encoded libraries of bicyclic peptides displayed on phage. TSL combines an aldehyde-reactive group and two thiol-reactive groups; it bridges two side chains of cysteine [C] with an N-terminal aldehyde group derived from the N-terminal serine [S], yielding a novel bicyclic topology that lacks a free N-terminus. Phage display libraries of SX1CX2X3X4X5X6X7C sequences, where Xi is any amino acids but Cys, were converted to a library of bicyclic TSL-[S]X1[C]X2X3X4X5X6X7[C] peptides in 45 ± 15% yield. Using this library and protein morphogen NODAL as a target, we discovered bicyclic macrocycles that specifically antagonize NODAL-induced signaling in cancer cells. At a 10 µM concentration, two discovered bicyclic peptides completely suppressed NODAL-induced phosphorylation of SMAD2 in P19 embryonic carcinoma. The TSL-[S]Y[C]KRAHKN[C] bicycle inhibited NODAL-induced proliferation of NODAL-Tky-nu ovarian carcinoma cells with apparent IC50 1 µM. The same bicycle at 10 µM concentration did not affect the growth of the control Tky-nu cells. TSL-bicycles remained stable over the course of the 72 hour-long assays in a serum-rich cell-culture medium. We further observed general stability in mouse serum and in a mixture of proteases (PronaseTM) for 33 diverse bicyclic macrocycles of different ring sizes, amino acid sequences, and cross-linker geometries. TSL-constrained peptides expand the previously reported repertoire of phage display bicyclic architectures formed by cross-linking Cys side chains. We anticipate that it will aid the discovery of proteolytically stable bicyclic inhibitors for a variety of protein targets.

Highlights • Many SARS-CoV-2 diagnostic tests are available for patient use with incomplete evidence as to their diagnostic accuracy. • Current publications on SARS-CoV-2 diagnostic accuracy have imperfect study design, heterogeneous methods, and a high risk for bias., Summary Objectives To assess the methodologies used in the estimation of diagnostic accuracy of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and other nucleic acid amplification tests (NAATs) and to evaluate the quality and reliability of the studies employing those methods. Methods We conducted a systematic search of English-language articles published December 31, 2019-June 19, 2020. Studies of any design that performed tests on ≥10 patients and reported or inferred correlative statistics were included. Studies were evaluated using elements of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Results We conducted a narrative and tabular synthesis of studies organized by their reference standard strategy or comparative agreement method, resulting in six categorizations. Critical study details were frequently unreported, including the mechanism for patient/sample selection and researcher blinding to results, which lead to concern for bias. Conclusions Current studies estimating test performance characteristics have imperfect study design and statistical methods for the estimation of test performance characteristics of SARS-CoV-2 tests. The included studies employ heterogeneous methods and overall have an increased risk of bias. Employing standardized guidelines for study designs and statistical methods will improve the process for developing and validating rRT-PCR and NAAT for the diagnosis of COVID-19.

Background: Deep throat saliva (DTS) and pooled nasopharyngeal swab and throat swab (NPSTS) are utilized for viral detection. DTS is challenging for children. Swabbing the respiratory mucosa requires trained personnel and may trigger sneezing and coughing, which generate droplets. A reliable, simple and safe sampling method applicable to a wide age range is required for community-based surveillance. Methods: We introduced nasal strip as an easy and low-risk collection method. Asymptomatic and symptomatic SARS-CoV-2 infected patients (n = 38) were recruited. Nasal epithelial lining fluid (NELF) (n = 43) strip paired with nasal swab (n = 13) were collected by a healthcare worker to compare with NPSTS (n = 21) or DTS (n =22) collected within 24 hours as reference. All samples were subjected to viral RNA quantitation by real-time PCR targeting the nucleoprotein gene. Results: Comparable Ct values were observed between paired nasal strip and nasal swab samples. The agreement between nasal strip samples and NPSTS was 94.44% and 100% for NPSTS positive and negative samples. Higher viral RNA concentration was detected in nasal strips than DTS samples. False-negative results were recorded in six DTS specimens, of which four were from children. Storage at room temperature up to 72 (n = 3) hours did not affect diagnostic yield of nasal strips. Conclusions: Nasal strip is a reliable and non-invasive sampling method for SARS-CoV-2 detection, and viral detection remains stable for at least 72 hours. It can be used as an alternative tool for community-based surveillance. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by the HMRF-commissioned grant (Ref: COVID190112 to RWYC, COVID190103 to MHTW and COVID190107 to PKSC) and Hong Kong Institute of Allergy Research Grant 2020 to RWYC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Joint Chinese University of Hong Kong, New Territories East Cluster Clinical Research Ethics Committee (CREC: 2020.076 and 2020.442) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Not applicable

This is the first work that revealed the neuro-protective effect of functionalized quantum dots against the cytotoxicity induced by beta-amyloid peptides. This study gives insight into the future treatment of Alzheimer's disease. It opens many avenues for the development of the next generation nanotechnology for biomedical and therapeutic applications.

The panzootic caused by A/goose/Guangdong/1/96-lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human-to-human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human-to-human transmissibility and impact on human health should such human-to-human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts.

We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility to oseltamivir and zanamivir. The NAs of four viruses were identified as extreme outliers to oseltamivir, based on statistical analysis by box plots, with IC50 values ranging from 46 to 62 nM. The NAs of two of these viruses from Sumatra and Aceh, had an N294S substitution, while one virus from Sulawesi had an S246N NA substitution. The NAs of all four viruses showed a specific loss of slow binding to oseltamivir in an IC50 kinetics assay. As observed in our previous surveillance, there was only a minimal effect on the sensitivity to zanamivir or peramivir for these mutants or any of the other isolates tested. The continued circulation of subtype H5N1 viruses in avian species poses an on-going zoonotic threat. The fact that we continue to identify avian isolates with naturally occurring mutations conferring reduced oseltamivir susceptibility remains a concern, given oseltamivir will be a key antiviral in the event of a new pandemic emerging.

Background EQ-5D-5L valuation studies previously reported many inconsistent responses in time trade-off (TTO) data. A number of possible elements, including ordering effects of the valuation tasks, mistakes at the sorting question, and interviewers' (learning) effects, may contribute to their inconsistency. Objectives This study aimed to evaluate the effect of two modifications on consistency of TTO data in The Netherlands (NL) and Hong Kong (HK): (1) separating the valuation of the Better than Dead (BTD) and Worse than Dead (WTD) states; and (2) Implementation of feedback (FB) module by offering an opportunity to review TTO responses. Methods A crossover design with two study arms was used to test the effect of the modifications. In each jurisdiction, six interviewers were involved where half the interviewers started using the standard version, and the other half started with the split version. Each version was switched after every 25 (NL) or 30 (HK) interviews until 400 interviews were completed. Results In the NL and HK, 404 and 403 respondents participated, respectively. With the use of the FB module, the proportion of respondents with inconsistent responses was lowered from 17.8% to 10.6% ( P P = 0.003) in HK. The result of separating the valuation of BTD and WTD states was not straightforward because it reduced the inconsistency rate in NL but not in HK. Conclusions The results support implementation of the FB module to promote the consistency of the data. The separation of the BTD and WTD task is not supported.

Background The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. Setting A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. Methods Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. Results Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. Conclusions Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

Highly pathogenic avian influenza (HPAI) H5Nx viruses of the goose/Guangdong/96 lineage continue to cause outbreaks in poultry and wild birds globally. Shorebirds, known reservoirs of avian influenza viruses, migrate from Siberia to Australia along the East-Asian-Australasian Flyway. We examined whether migrating shorebirds spending nonbreeding seasons in Australia were exposed to HPAI H5 viruses. We compared those findings with those for a resident duck species. We screened >1,500 blood samples for nucleoprotein antibodies and tested positive samples for specific antibodies against 7 HPAI H5 virus antigens and 2 low pathogenicity avian influenza H5 virus antigens. We demonstrated the presence of hemagglutinin inhibitory antibodies against HPAI H5 virus clade 2.3.4.4 in the red-necked stint (Calidris ruficolis). We did not find hemagglutinin inhibitory antibodies in resident Pacific black ducks (Anas superciliosa). Our study highlights the potential role of long-distance migratory shorebirds in intercontinental spread of HPAI H5 viruses.

Background Chronic hepatitis B virus (HBV) infection increases the risk of liver injury in patients who undergo antituberculosis treatment. It is uncertain whether antiviral treatment for HBV at the time of tuberculosis diagnosis would reduce the risk of liver injury. Methods We performed a population-level, retrospective, cohort study that involved all patients with tuberculosis-HBV coinfection treated in public hospitals in Hong Kong over a 16-year period. Patients who received antiviral treatment at the time of tuberculosis diagnosis were considered "patients on antiviral therapy." A multivariable Cox proportional hazards model was used to determine the adjusted hazard ratio of hospitalization due to drug-induced liver injury within 1 year in patients on antiviral therapy, adjusting for the propensity score. Results Of 3698 patients with tuberculosis-HBV coinfection, 488 (13.2%) were patients on antiviral therapy. Of the remaining 3210 patients, 446 (13.9%) started antiviral therapy within 1 year of tuberculosis diagnosis. Adjusting for the propensity score, patients on antiviral therapy had a lower risk of hospitalization due to drug-induced liver injury compared with those not on treatment (adjusted hazard ratio, 0.44; 95% confidence interval .26-.72). Compared with patients who started antiviral therapy within 1 year of tuberculosis diagnosis, patients on antiviral therapy also had a lower risk of hospitalization due to drug-induced liver injury and a lower risk of liver-related mortality. Conclusions We show that antiviral treatment for HBV given at the time of tuberculosis diagnosis reduced the risk of liver injury in tuberculosis-HBV coinfected patients.

Significant mortalities of racing pigeons occurred in Australia in late 2011 associated with a pigeon paramyxovirus serotype 1 (PPMV-1) infection. The causative agent, designated APMV-1/pigeon/Australia/3/2011 (P/Aus/3/11), was isolated from diagnostic specimens in specific pathogen free (SPF) embryonated eggs and was identified by a Newcastle Disease virus (NDV)-specific RT-PCR and haemagglutination inhibition (HI) test using reference polyclonal antiserum specific for NDV. The P/Aus/3/11 strain was further classified as PPMV-1 using the HI test and monoclonal antibody 617/161 by HI and phylogenetic analysis of the fusion gene sequence. The isolate P/Aus/3/11 had a slow haemagglutin-elution rate and was inactivated within 45 min at 56 °C. Cross HI tests generated an R value of 0.25, indicating a significant antigenic difference between P/Aus/3/11 and NDV V4 isolates. The mean death time (MDT) of SPF eggs infected with the P/Aus/3/11 isolate was 89.2 hr, characteristic of a mesogenic pathotype, consistent with other PPMV-1 strains. The plaque size of the P/Aus/3/11 isolate on chicken embryo fibroblast (CEF) cells was smaller than those of mesogenic and velogenic NDV reference strains, indicating a lower virulence phenotype in vitro and challenge of six-week-old SPF chickens did not induce clinical signs. However, sequence analysis of the fusion protein cleavage site demonstrated an 112RRQKRF117 motif, which is typical of a velogenic NDV pathotype. Phylogenetic analysis indicated that the P/Aus/3/11 isolate belongs to a distinct subgenotype within class II genotype VI of avian paramyxovirus type 1. This is the first time this genotype has been detected in Australia causing disease in domestic pigeons and is the first time since 2002 that an NDV with potential for virulence has been detected in Australia.

Microalgae have been used as energy resources in recent decades to mitigate the global energy crisis. As the demand for pure microalgae strains for commercial use increases, designing an effective photobioreactor (PBR) for mass cultivation is important. Chlorella vulgaris, a local freshwater microalga, was used to study the algal biomass cultivation and lipid production using various PBR configurations (bubbling, air-lift, porous air-lift). The results show that a bubbling column design is a better choice for the cultivation of Chlorella vulgaris than an air-lift one. The highest biomass concentration in the bubbling PBR was 0.78 g/L while the air-lift PBR had a value of 0.09 g/L. Key operating parameters, including draft-tube length and bubbling flowrate, were then optimized based on biomass production and lipid yield. The highest lipid content was in the porous air-lift PBR and the air-lift PBR with shorter draft tube (35 cm) was also better than a longer one (50 cm) for algal cultivation, but the microalgae attachment on the inner tube of PBR always occurred. The highest biomass concentration could be produced under the highest gas flowrate of 2.7 L/min, whereas the lowest dry cell mass was under the lowest gas flowrate of 0.2 L/min.

Scenedesmus quadricauda, a local freshwater microalga, was used to treat primary settled and filtrate wastewater and to produce algal lipid. For the primary settled wastewater, the maximum biomass concentrations of acclimated and unacclimated microalgae were 0.995 g/L and 0.940 g/L, respectively. Over 90% orthophosphate and 95% ammonia nitrogen in the acclimated and unacclimated cultures, respectively, were removed after five days. The lipid contents of the microalgae were higher than 13% in all cultures. The highest growth rate occurred in the 25% filtrate culture. Over 80% phosphate was removed under the 25% and 50% filtrate cultures within six days, while over 90% ammonia nitrogen was removed within five days under both conditions. The lipid content was the highest (18.1%) under the 50% filtrate condition. C16:0, C18:2n6, and C18:3n3 were dominant fatty acids. In conclusion, S. quadricauda is a viable candidate for wastewater treatment and lipid production.

A prospective study among adults hospitalized for polymerase chain reaction–confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1–2, 7.29 ± 1.47; day 3–4, 7.28 ± 1.41; day 5–8, 6.66 ± 1.87 log10 copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log10 copies/mL increase, 95% confidence interval, 1.03–1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population.

In March 2014, avian influenza in poultry in Laos was caused by an emergent influenza A(H5N6) virus. Genetic analysis indicated that the virus had originated from reassortment of influenza A(H5N1) clade 2.3.2.1b, variant clade 2.3.4, and influenza A(H6N6) viruses that circulate broadly in duck populations in southern and eastern China.

The concept of a double burden of care, in this case, refers to the burden of caring for the older generation (parents) as well as the younger (children) simultaneously. While previous studies have focused on the impact of these two types of care separately, this chapter examines the burden of those responsible for both types of care. Based on survey data collected in Hong Kong from late 2013 to early 2014, the chapter offers an account of the level of stress and the concerns of those providing care. It was found that their stress levels were not particularly alarming, largely due to the good health of the caregivers and care receivers. However, there were concerns about the adequacy of and hence expectations regarding public services.

Neural Network has been widely used to model the dynamics of chlorophyll-a concentration for over a decade. Previous studies were always based on shallow network structures (i.e. 3–5 layers) and used time-lagged data from the localized region as model inputs. Recent ecological studies have shown that the coastal ocean current circulation is one of the key factors for the formation of algae bloom (red tide), hence the level of chlorophyll-a concentration increases. This suggests that the data from nearby regions should be included in the modeling process along with the localized data. This study investigates the classification performance among models with and without the use of data from nearby regions under deep neural network learning models. Networks with 3 to 12 layers are employed in two distinct structures respectively for conducting the empirical analysis on 1990–2016 monthly marine water quality data obtained from the Hong Kong Environmental Protection Department. The deep networks are shown to be able to extract useful information from 108 input attributes consolidated from 5 nearby coastal regions in Deep Bay water control zone. The 5-fold cross valuation results indicated that the use of additional layers tends to improve the classification performance and the optimal result is achieved by using 11 layers under the two proposed network structures.

The mortality rate in patients with haemodynamically unstable pelvic fractures is as high as 40–60%. Despite the new advances in trauma care which are in phase in trauma centres in Hong Kong, the management of haemodynamically unstable pelvic fracture is still heterogeneous. The aim of this study is to review the results of management of haemodynamically unstable pelvic fracture patients in Hong Kong over a five year period. This is a retrospective multi-centred cohort study of patients with haemodynamic and mechanically unstable pelvic fractures from 1 January 2010 to 31 December 2014. The primary outcome investigated is mortality of patients (including overall, 30-day, 7-day and 24-hour mortalities). Implementation of three-in-one pelvic damage control protocol was identified to be a significant independent predictive factor for overall, 30-day, seven-day and 24-hour mortalities. The overall in-hospital and 30-day mortality rates for patients managed with three-in-one protocol was 12.5%, while it was 11% for seven day mortality and 6% for 24 hour mortality. There were no significant differences in demographic characteristics, physiological measurements, types of pelvic fracture, severity and mechanism of injury between patients managed with or without three-in-one protocol. Implementation of the multidisciplinary three-in-one pelvic damage control protocol reduces mortality and therefore should be highly recommended. The results are convincing as it has eliminated the limitations of our previous single-centred trial.

Background An international valuation protocol exists for obtaining societal values for each of the 3125 health states of the five-level EuroQol-five dimensions (EQ-5D-5L) questionnaire. A feedback module (FM) that can be related to theoretical models used in behavioral economics was recently included in this protocol. Objectives Our objective was to assess the impact of using an FM to estimate an EQ-5D-5L value set in Hong Kong. Methods EQ-5D-5L health states were elicited using a composite time trade-off (C-TTO) and a discrete-choice (DC) experiment. Use of the FM according to participant characteristics and the impact of the FM on the number of inconsistent C-TTO responses were assessed. We employed a main-effects hybrid model that combined data from both elicitation techniques. Results In total, 1014 individuals completed the survey. The sample was representative of the general Chinese Hong Kong population in terms of sex, educational attainment, marital status, and most age groups but not for employment status. The use of the FM reduced the number of C-TTO inconsistencies. Participant characteristics differed significantly between those who used and did not use the FM. The model without a constant resulted in logical consistent coefficients and was therefore selected as the model to produce the value set. The predicted EQ-5D-5L values ranged from −0.864 to 1. Conclusions The use of an FM to allow participants to exclude C-TTO responses reduced the number of inconsistent responses and improved the quality of the data when estimating an EQ-5D-5L value set in Hong Kong. Electronic supplementary material The online version of this article (doi:10.1007/s40271-017-0278-0) contains supplementary material, which is available to authorized users.

The dependence of stochastic resonance in the feed-forward-loop neuronal network motifs on the noise and time delay are studied in this paper. By computational modeling, Izhikevich neuron model with the chemical coupling is used to build the triple-neuron feed-forward-loop motifs with all possible motif types. Numerical results show that the correlation between the periodic subthreshold signal’s frequency and the dynamical response of the network motifs is resonantly dependent on the intensity of additive spatiotemporal noise. Interestingly, the excitatory intermediate neuron could induce intermittent stochastic resonance, whereas the inhibitory one weakens its influence on the intermittent mode. More importantly, it is found that the increasing delays can induce the intermittent appearance of regions of stochastic resonance. Based on the effects of the time delay on the stochastic resonance, the reasons and conditions of such intermittent resonance phenomenon are analyzed.

The outbreak of highly pathogenic H5N1 avian influenza, with its international spread, confirmed that emerging infectious disease control must be underpinned by effective laboratory services. Laboratory results are the essential data underpinning effective surveillance, case diagnosis, or monitoring of responses. Importantly, laboratories are best managed within national and international networks of technological support rather than in isolation. A well planned laboratory network can deliver both a geographical spread of testing capacity and also a cost effective hierarchy of capability. Hence in the international context regional networks can be particularly effective. Laboratories are an integral part of a country's veterinary services and their role and function should be clearly defined in the national animal health strategy and supporting government policies. Not every laboratory should be expected to deliver every possible service, and integration into regional and broader international networks should be a part of the overall strategy. The outputs required of each laboratory should be defined and then ensured through accredited quality assurance. The political and scientific environment in which laboratories operate changes continuously, not only through evolving national and regional animal health priorities but also through new test technologies and enhancements to existing technologies. Active networks help individual laboratories to monitor, evaluate, and respond to such challenges and opportunities. The end result is enhanced emerging infectious disease preparedness across the region.

Introduction Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. Methods Study design: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3months (1month per drug). Primary endpoints: P1CP, QTc Results 11 stroke survivors (5 female), aged 71+4, BP 139/81mmHg+20/11mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone–Placebo=−24 ug/L, 95% CI=−40 to −6.9; Amiloride–Placebo=−28 ug/L, 95% CI=−44 to −11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=−18ms 1/2 , 95% CI=−36 to −0.55; Amiloride vs Placebo=−25ms 1/2 , 95% CI=−42 to −7.5]. Conclusions Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

Background It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. Methods A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. Results Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. Conclusions We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. Clinical trials registration ClinicalTrials.gov, NCT01052961.

Background. Better understanding of complications and outcomes of adults hospitalized with respiratory syn-cytial virus (RSV) infection is necessary.Methods. A retrospective cohort study was conducted on all adults (≥18 years) admitted to 3 acute care generalhospitals in Hong Kong with virologically confirmed RSV infection during 2009–2011 (N=607). Adults hospital-ized forseasonal influenza during the period wereused forcomparison (n=547). Both infections were prospectivelydiagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists.Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalizationduration. Cox proportional hazards models were used foranalyses.Results. Themeanage ofRSV patients was75 (SD,16) years; 87% hadunderlyingconditions. Lower respiratoryand cardiovascularcomplications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic ob-structive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterialsuperinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively.Crude all-cause mortality was 9.1% and 11.9% within 30days and 60 days, respectively; mean length ofstayof survi-vors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superin-fection, and elevated urea level and white blood cell count were independently associated with poorer survival.Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall out-comes of survival and length of stay were not significantly different from those in influenza.Conclusions. RSV can cause severe lower respiratory complications in older adults, resulting in respiratoryfailure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem toimprove outcomes. The unmet need forantiviral therapy and vaccination against RSV in adults should be promptlyaddressed.Keywords. RSV; hospitalization; respiratory failure; lower respiratory tract infection; adults.Respiratory syncytial virus (RSV) is known to be animportant cause of lower respiratory tract infection ininfants and young children, leading to hospitalizationsand deaths [1]. Its impact in adults, however, has onlybeen appreciated in recent years. It has been estimatedthat RSV infects 3%–10% of adults annually; althoughmost infections are mild, increasing evidence suggeststhat severe lower respiratory tract infections can occur,especially among older adults and those with underlyingconditions [2–4].RSV may have accounted for 5%–15%of community-acquired pneumonia, 9%–10% of hospi-tal admissions for acute cardiorespiratory diseases, andexcessive deaths duringseasonalpeaks [3,4].Thedisease

To determine the pathobiology of Indonesian H5N1 highly pathogenic avian influenza, two viruses representing clades 2.1.1 and 2.1.3 were inoculated into broiler chickens and Pekin ducks via the eyes, nostrils and oropharynx. In chickens, both viruses produced fulminant disease; tissue tropism was broad but predominantly endothelial and viral loads in tissues were high. Except for one case of meningoencephalitis, the infection in ducks was sub-clinical, leading only to seroconversion. In these ducks, virus and viral antigen occurred in lower amounts, mainly in the respiratory tract (airsac and sinuses), prior to day 7 after inoculation. During clinical disease, chickens shed high virus titres orally and cloacally. Ducks intermittently shed low virus titres from the oral route for up to 8 days post-inoculation. We discuss the significance of the data for understanding the pathogenesis and pathobiology of Indonesian H5N1 in chickens and ducks.

In this research, nonengagement is conceived as a manifestation of spiritual emptiness characterized by alienation and despair. Three scales with satisfactory reliabilities, alienation, despair and hope, were developed and used as predictors of health, coping, and social and family nonengagement among 428 nonengaged youths (309 males and 119 females) aged 15–24 years in Hong Kong. The results show that alienation and despair are associated with (a) poorer health, (b) more frequent use of negative coping, especially by hiding oneself and, to a lesser extent, (c) nonengagement. Hope is associated with better health and more frequent use of positive coping. These results support the contention that nonengagement is a loss of hope, meaning and purpose in life.

Introduction − Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking. Method − A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0–10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data. Results − Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: β −0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline −83.4% vs −59.5%), CXCL8/IL-8 (β −0.018, 95%CI-0.037,0.000, P = 0.056; −80.5% vs −58.0%), IL-17 (β −0.064, 95%CI-0.117,-0.012, P = 0.015; −74.0% vs −34.3%), CXCL9/MIG (β −0.010, 95%CI-0.020,0.000, P = 0.043; −71.3% vs −56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (β −0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin. Conclusion − We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study. [ClinicalTrials.gov NCT01779570]

Identifying the cellular binding targets of drugs and other bioactive small molecules is a crucial step for understanding their molecular mechanisms of action as well as potential off-target effects. The field of chemical proteomics is an emerging discipline in chemical biology using synthetic chemistry and high-throughput detection techniques to study small molecule-protein interactions. In this chapter, we describe a quantitative chemical proteomics protocol combining bioorthogonal click chemistry and quantitation by isobaric tags for relative and absolute quantification (iTRAQ) to identify the specific binding targets of drugs and bioactive small molecules such as natural products. A modified drug probe with a click chemistry-enabling addition is synthesized and used in live cell treatments where it undergoes covalent interactions with its cognate cellular targets. The probes are then ligated to biotin through click chemistry and enriched with avidin beads, followed by iTRAQ labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for protein identification and relative quantitation discriminating specific targets from nonspecific binding proteins. The presented protocol has been used to successfully profile prominent drugs and natural products including andrographolide, aspirin, curcumin, etc., and can be a powerful tool to study the molecular mechanisms of bioactive small molecules.

BackgroundTo describe direct medical costs of influenza in hospitalized elderly, with and without intensive care unit (ICU) admission, during the 2014–2015 season in Hong Kong.MethodsA retrospective study was conducted in 110 inpatients aged ≥65 years with laboratory-confirmed influenza treated by antiviral therapy during season 2014–2015 in a tertiary hospital. Resource utilization of influenza-related diagnostic and laboratory tests, medications for influenza treatment, usage of general medical ward and ICU during the influenza-related length of hospital stay (IR-LOS) were collected.ResultsThere were 18 (16.4%) and 92 (83.4%) cases with and without ICU admission, respectively. The difference in influenza-related mortality rates between patients with (11.1%) and without ICU admission (2.2%) was not statistically significant ( P=0.064). Patients with ICU admission reported longer IR-LOS (12.7 ±6.0 days versus 5.5 ±2.7 days; PConclusionsHospitalization cost in elderly for seasonal influenza was substantial in Hong Kong. The cost in patients with ICU admission was significantly higher than those without ICU care. Respiratory complications and male gender predicted ICU admission. Influenza B infection predicted high-cost hospitalization in non-ICU survivors.

Summary Background Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. Aim To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. Methods Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy (1H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). Results All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4–13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1–6.2) kPa vs. 4.2 (IQR 3.6–5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29–12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. Conclusions HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

This article explores the potential of using an electro-coagulation-flotation (ECF) harvester to allow flotation of microalgae cells for surface harvesting. A response surface methodology (RSM) model was used to optimize ECF harvesting by adjusting electrode plate material, electrode plate number, charge of the electrodes, electrolyte concentration, and pH value of the culture solution. The result revealed that three aluminum electrode plates (one anode and two cathodes), brine solution (8 g/L), and acidity (pH = 4) of culture solution (optimized ECF harvester) The highest flocculant concentration was measured at 2966 mg/L after 60 min and showed a 79.8 % increase of flocculation concentration. Such results can provide a basis for designing a large-scale microalgae harvester for commercial use in the future.

In an observational cohort study, we found that adults hospitalized for oseltamivir-resistant (H275Y) seasonal H1N1 influenza (n = 46) were older than those infected with oseltamivir-susceptible strains (n = 31) [74(IQR 59–83) versus 64(IQR 48–76) years; P = 0·045], and most had major comorbidities (78% versus 65%). Disease severity and clinical outcomes were comparable between the two groups: radiographic pneumonia 40–42%, supplemental oxygen use 47–48%, critical illness 11–13%, median duration of hospitalization 5–6 days, death rate 6–9%. Failure to receive effective antiviral therapy was associated with progression to critical illness (23% versus 0%, P = 0·016) and death (20% versus 0%, P = 0·033) in hospitalized patients with seasonal H1N1 influenza.