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We use single-forcing historical simulations with a coupled atmosphere–ocean global climate model to compare the effects of anthropogenic aerosols (AAs) and increasing long-lived greenhouse gases (LLGHGs) on simulated winter circulation in the Southern Hemisphere (SH). Our primary focus is on the subtropical jet, which is an important source of baroclinic instability, especially in the Australasian region, where the speed of the jet is largest. For the period 1950 to 2005, our simulations suggest that AAs weaken the jet, whereas increasing LLGHGs strengthen the jet. The different responses are explained in terms of thermal wind balance: increasing LLGHGs preferentially warm the tropical mid-troposphere and upper troposphere, whereas AAs have a similar effect of opposite sign. In the mid-troposphere, the warming (cooling) effect of LLGHGs (AAs) is maximal between 20S and 30S; this coincides with the descending branch of the Hadley circulation, which may advect temperature changes from the tropical upper troposphere to the subtropics of the SH. It follows that LLGHGs (AAs) increase (decrease) the mid-tropospheric temperature gradient between low latitudes and the SH mid-latitudes. The strongest effects are seen at longitudes where the southward branches of the Hadley cell in the upper troposphere are strongest, notably at those that correspond to Asia and the western Pacific warm pool.

Abstract The emerging fluid antenna technology enables a high‐density position‐switchable antenna in a small space to obtain enormous performance gains for wireless communications. To understand the theoretical performance of fluid antenna systems, it is important to account for the strong spatial correlation over the different positions (referred to as ‘ports'). Previous works used a classical, generalised correlation model to characterise the channel correlation among the ports but were limited by the lack of degree of freedom of the model to imitate the correlation structures in an actual antenna. In this letter, it is proposed to use a common correlation parameter and to choose it by setting the correlation coefficient of any two ports to be the same as the average correlation coefficient of an actual fluid antenna taking up a linear space. A closed‐form expression for the spatial correlation parameter is first derived assuming that the number of ports is large, and it is illustrated that the correlation parameter depends only on the size of the fluid antenna but not the port density. Simpler expressions are then obtained for small and large sizes of fluid antenna. The resulting model is finally used to study the performance of fluid antenna systems. Simulation results based on the proposed model are provided to confirm the promising performance of fluid antenna in single and multiuser environments.

Continuous monitoring of coastal water qualities is critical for water resource management and marine ecosystem sustainability. While remote sensing data such as Sentinel-2 satellite imagery routinely provide high-resolution observations for time-series analysis, the cloud-based Google Earth Engine (GEE) platform supports simple image retrieval and large-scale processing. Using coastal waters of Hong Kong as the study area, this study utilized GEE to (i) query and pre-process all Sentinel-2 observations that coincided with in situ measurements; (ii) extract the spectra to develop empirical models for water quality parameters using artificial neural networks; and (iii) visualize the results using spatial distribution maps, time-series charts and an online application. The modeling workflow was applied to 22 water quality parameters and the results suggested the potential to predict the levels of several nutrients and inorganic constituents. In-depth analyses were conducted for chlorophyll-a, suspended solids and turbidity which produced high correlations between the predicted and observed values when validated with an independent dataset. The selected input variables followed spectral characteristics of the optical constituents. The results were considered more robust compared to previous works in the same region due to the automatic extraction of all available images and larger number of observations from different years and months. Besides visualizing long-term spatial and temporal variabilities through distribution maps and time-series charts, potential anomalies in the monitoring period including algal bloom could also be captured using the models developed from historical data. An online application was created to allow novice users to explore and analyze water quality trends with a simple web interface. The integrated use of remotely-sensed images, in situ measurements and cloud computing can offer new opportunities for implementing effective monitoring programs and understanding water quality dynamics. Although the obtained levels of accuracies were below the desired standard, the end-to-end cloud computing workflow demonstrated in this study should be further investigated considering the cost and computational efficiency for timely information delivery.

Abstract Pulmonary hypertension (PH) is characterized by progressive dyspnea, fatigue, and reduced exercise capacity. Despite medical treatment, outcomes remain poor. While exercise training is well established in patients with heart failure, it is less established in patients with PH. This single‐blind, randomized controlled pilot study examined the feasibility and effect of 12‐week outpatient exercise (multidisciplinary rehabilitation or home walking program) on hemodynamics using cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH), a subset of PH. Sixteen participants were randomized to either multidisciplinary outpatient rehabilitation or a home walking program for 12 weeks. Primary outcome measures were changes in right ventricular ejection fraction and stroke volume index on cMRI. Secondary outcome measures included hemodynamics on RHC, quality of life (QOL), muscle strength (handgrip and vital capacity) and 6‐min walk test. This preliminary, pilot study suggests that outpatient exercise interventions may be associated with improved hemodynamic function (mean pulmonary artery wedge pressure, stroke volume, and stroke volume index), QOL (PH symptoms, depression, and anxiety), and muscular strength (vital capacity and handgrip strength) for people with PAH, but was not adequately powered to make any formal conclusions. However, our outpatient programs were feasible, safe, and acceptable to participants. Future studies are required to further explore the potential hemodynamic benefits of exercise in PAH.

Abstract Background Severe spinal pain is an unusual presentation of gout. Due to its rarity and the difficulty of obtaining joint fluid or tissue for crystal analysis, dual energy computed tomography (DECT) may be a useful imaging modality in the management of axial gout. Case presentation Two patients independently presented to a major teaching hospital with severe spinal pain subsequently shown to be due to gout. The first patient presented with back pain and fevers and was initially thought to have lumbar facet joint septic arthritis. The second case presented with severe back pain. In both cases, DECT suggested monosodium urate deposition in spinal tissues as the cause of their presentation. Conclusions Axial gout should be considered in the differential diagnosis of severe spinal pain. A DECT study may be a useful diagnostic tool in the management of spinal gout.

Abstract Background Prognostic scoring systems are used to estimate the risk of mortality from metastatic renal cell carcinoma (mRCC). Outcomes from different therapies may vary within each risk group. These survival algorithms have been applied to assess outcomes in patients receiving T-cell checkpoint inhibitory immunotherapy and tyrosine kinase inhibitor therapy, but have not been applied extensively to patients receiving high dose interleukin-2 (HD IL-2) immunotherapy. Methods Survival of 810 mRCC patients treated from 2006 to 2017 with high dose IL-2 (aldesleukin) and enrolled in the PROCLAIMSM registry data base was assessed utilizing the International Metastatic RCC Database Consortium (IMDC) risk criteria. Median follow-up is 23.4 months (mo.) (range 0.2–124 mo.). Subgroup evaluations were performed by separating patients by prior or no prior therapy, IL-2 alone, or therapy subsequent to IL-2. Some patients were in two groups. We will focus on the 356 patients who received IL-2 alone, and evaluate outcome by risk factor categories. Results Among the 810 patients, 721 were treatment-naïve (89%) and 59% were intermediate risk. Overall, of the 249 patients with favorable risk, the median overall survival (OS) is 63.3 mo. and the 2-year OS is 77.6%. Of 480 patients with intermediate risk, median OS is 42.4 mo., 2-year OS 68.2%, and of 81 patients with poor risk, median OS 14 mo., 2-year OS 40.4%. Among those who received IL-2 alone (356 patients), median OS is 64.5, 57.6, and 14 months for favorable, intermediate and poor risk categories respectively. Two year survival among those treated only with HD IL-2 is 73.4, 63.7 and 39.8%, for favorable, intermediate and poor risk categories respectively. Conclusions Among mRCC patients treated with HD IL-2, all risk groups have median and 2-year survival consistent with recent reports of checkpoint or targeted therapies for mRCC. Favorable and intermediate risk (by IMDC) patients treated with HD IL-2 have longer OS compared with poor risk patients, with most durable OS observed in favorable risk patients. Favorable risk patients treated with HD IL-2 alone have a 2-year OS of 74%. These data continue to support a recommendation for HD IL-2 for patients with mRCC who meet eligibility criteria. Trial registration PROCLAIM, NCT01415167 was registered with ClinicalTrials.gov on August 11, 2011, and initiated for retrospective data collection until 2006, and prospective data collection ongoing since 2011.

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

Patients with pulmonary hypertension are more sedentary than the general population, but attitudes and experiences that may influence their exercise behaviour remain poorly understood. This study identified patterns of behaviour, attitudes towards exercise, barriers and enablers of exercise for people living with pulmonary hypertension. Accessibility of rehabilitation services from a patient perspective was also explored. A voluntary, international survey of people living with pulmonary hypertension was conducted, with mixed quantitative and qualitative data collection. Data from 187 participants in 19 countries were included in the analyses. In total, 52% (95/183) of people with pulmonary hypertension reported that they attempted to engage in regular physical activity. This was less than the proportion who did so prior to diagnosis (61%, 112/184, p = 0.006) and was accompanied by uncertainty and anxiety about exercise. In total, 63% (113/180) of the cohort reported experiencing previous adverse events while exercising, which was associated with a greater likelihood of ongoing exercise concerns and anxiety. Fear, frustration and uncertainty about exercise were noted as common barriers to engaging in exercise with pulmonary hypertension. Other barriers to exercise included intrinsic factors such as debilitating breathlessness and fatigue, and external factors such as cost and access to appropriate services. Most respondents (76%, 128/169) did not have access to a multi-disciplinary rehabilitation service, although an overwhelming majority (92%, 159/172) reported that this would be helpful. Respondents rated education; a supervised, structured exercise programme; and psychology input as the most important components of a multi-disciplinary rehabilitation service for pulmonary hypertension. Health professionals must work together with consumers to co-design rehabilitation services that will facilitate exercise and increased activity for people living with pulmonary hypertension.

Exercise training was not traditionally recommended for patients with pulmonary hypertension. However, recent work has demonstrated that exercise improves endurance and quality-of-life in patients with pulmonary hypertension. Unfortunately, patients with pulmonary hypertension are often sedentary. While some studies have examined patient attitudes to exercise, none have investigated physician perspectives on exercise in patients with pulmonary hypertension. This multinational survey of physicians involved in treating patients with pulmonary hypertension sought to ascertain physician attitudes to exercise and physician-identified barriers and enablers of exercise in this patient population. We collected cross-sectional survey data from a cohort of 280 physicians, including rehabilitation physicians, cardiologists, respiratory physicians and rheumatologists. We found that overall, 86% physicians recommended exercise, in line with current guidelines, although there were differences in the rationale for prescribing exercise and in the type of exercise prescription. Barriers to exercise included patient-related factors, such as patient ill health preventing exercise; poor patient motivation and lack of understanding regarding the benefits of exercise. Systemic barriers included cost/funding issues and limited availability of appropriate services. Perceived enablers of exercise included access to appropriate programmes, provision of education and supportive treating clinicians. Further research is required to identify and implement interventions to promote physical activity in patients with pulmonary hypertension.

The effects of epigenetic regulators on different tumor cell populations can affect their potential as anticancer targets. In this study, the authors demonstrate that the histone methyltransferase G9a is a suppressor of lung tumor-propagating cells and tumor progression, acting through chromatin modification with MMP10 as one of its targets for metastasis regulation.

Identification and mapping of various habitats with sufficient spatial details are essential to support environmental planning and management. Considering the complexity of diverse habitat types in a heterogeneous landscape, a context-dependent mapping framework is expected to be superior to traditional classification techniques. With the aim to produce a territory-wide habitat map in Hong Kong, a three-stage mapping procedure was developed to identify 21 habitats by combining very-high-resolution satellite images, geographic information system (GIS) layers and knowledge-based modification rules. In stage 1, several classification methods were tested to produce initial results with 11 classes from a WorldView-2/3 image mosaic using a combination of spectral, textural, topographic and geometric variables. In stage 2, modification rules were applied to refine the classification results based on contextual properties and ancillary data layers. Evaluation of the classified maps showed that the highest overall accuracy was obtained from pixel-based random forest classification (84.0%) and the implementation of modification rules led to an average 8.8% increase in the accuracy. In stage 3, the classification scheme was expanded to all 21 habitats through the adoption of additional rules. The resulting habitat map achieved >80% accuracy for most of the evaluated classes and >70% accuracy for the mixed habitats when validated using field-collected points. The proposed mapping framework was able to utilize different information sources in a systematic and controllable workflow. While transitional mixed habitats were mapped using class membership probabilities and a soft classification method, the identification of other habitats benefited from the hybrid use of remote-sensing classification and ancillary data. Adaptive implementation of classification procedures, development of appropriate rules and combination with spatial data are recommended when producing an integrated and accurate map.

Abstract Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the PROCLAIMSM registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all PROCLAIMSM patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p

Lightweight unmanned aerial vehicle (UAV) loaded with novel sensors offers a low cost and minimum risk solution for data acquisition in complex environment. This study assessed the performance of UAV-based hyperspectral image and digital surface model (DSM) derived from photogrammetric point clouds for 13 species classification in wetland area of Hong Kong. Multiple feature reduction methods and different classifiers were compared. The best result was obtained when transformed components from minimum noise fraction (MNF) and DSM were combined in support vector machine (SVM) classifier. Wavelength regions at chlorophyll absorption green peak, red, red edge and Oxygen absorption at near infrared were identified for better species discrimination. In addition, input of DSM data reduces overestimation of low plant species and misclassification due to the shadow effect and inter-species morphological variation. This study establishes a framework for quick survey and update on wetland environment using UAV system. The findings indicate that the utility of UAV-borne hyperspectral and derived tree height information provides a solid foundation for further researches such as biological invasion monitoring and bio-parameters modelling in wetland.

Introduction. This study aimed to validate the Hong Kong version of the Knee Injury and Osteoarthritis Outcome Score (HK-KOOS) for patients with knee osteoarthritis. Methods. Content validity was assessed using the Item and Scale Content Validity Index (I-CVI and S-CVI). Test-retest reliability and internal consistency were assessed by the Intraclass Correlation Coefficient (ICC) and Cronbach’s alpha. Dimensionality was assessed by performing exploratory factor analysis (EFA). Convergent and Divergent Validity was performed by examining the correlation between the HK-KOOS and the Chinese version of the Short Form 12 (SF-12) Health Survey, the Chinese Modified Barthel Index (C-MBI), and the Visual Analogue Scale for Pain (VAS-Pain). Ceiling and floor effects were also examined. Results. A total of 125 participants were recruited in this study. In general, all instructions, items, and response options were considered as understandable, indicating a satisfactory cross-cultural adaptation. The I-CVI and S-CVI scores were 0.80-1 and 0.90-1, respectively, indicating excellent content validity in terms of relevance, representativeness, and understandability. The test-retest reliability of all HK-KOOS subscales was satisfactory with ICC exceeding 0.70 for all domains. Cronbach’s alpha exceeded 0.80 for all subscales, indicating satisfactory internal consistency. Medium to strong correlations were found between the HK-KOOS and the VAS-Pain, SF-12, and C-MBI. However, factor analysis indicated a seven-factor structure, rather than the original five-factor structure. Items on pain and activities of daily living were loaded in the same factors. A floor effect was present in the sports and recreation subscale. Discussion and Conclusions. Future studies should further examine the dimensionality of the KOOS. The HK-KOOS is a culturally adapted, reliable, and valid outcome measure instrument to be used in Hong Kong patients with primary knee osteoarthritis.

We use a coupled atmosphere-ocean global climate model (CSIRO-Mk3.6) to investigate the drivers of trends in summer rainfall and circulation in the vicinity of northern Australia. As part of the Coupled Model Intercomparison Project Phase 5 (CMIP5), we perform a 10-member 21st century ensemble driven by Representative Concentration Pathway 4.5 (RCP4.5). To investigate the roles of different forcing agents, we also perform multiple 10-member ensembles of historical climate change, which are analysed for the period 1951–2010. The historical runs include ensembles driven by "all forcings" (HIST), all forcings except anthropogenic aerosols (NO_AA) and forcing only from long-lived greenhouse gases (GHGAS). Anthropogenic aerosol-induced effects in a warming climate are calculated from the difference of HIST minus NO_AA. CSIRO-Mk3.6 simulates a strong summer rainfall decrease over north-western Australia (NWA) in RCP4.5, whereas simulated trends in HIST are weakly positive (but insignificant) during 1951–2010. The weak rainfall trends in HIST are due to compensating effects of different forcing agents: there is a significant decrease in GHGAS, offset by an aerosol-induced increase. Observations show a significant increase of summer rainfall over NWA during the last few decades. The large magnitude of the observed NWA rainfall trend is not captured by 440 unforced 60-yr trends calculated from a 500-yr pre-industrial control run, even though the model's decadal variability appears to be realistic. This suggests that the observed trend includes a forced component, despite the fact that the model does not simulate the magnitude of the observed rainfall increase in response to "all forcings" (HIST). We investigate the mechanism of simulated and observed NWA rainfall changes by exploring changes in circulation over the Indo-Pacific region. The key circulation feature associated with the rainfall increase in reanalyses is a lower-tropospheric cyclonic circulation trend off the coast of NWA, which enhances the monsoonal flow. The model shows an aerosol-induced cyclonic circulation trend off the coast of NWA in HIST minus NO_AA, whereas GHGAS shows an anticyclonic circulation trend. This explains why the aerosol-induced effect is an increase of rainfall over NWA, and the greenhouse gas-induced effect is of opposite sign. Possible explanations for the cyclonic (anticyclonic) circulation trend in HIST minus NO_AA (GHGAS) involve changes in the Walker circulation or the local Hadley circulation. In either case, a plausible atmospheric mechanism is that the circulation anomaly is a Rossby wave response to convective heating anomalies south of the Equator. We also discuss the possible role of air-sea interactions, e.g. an increase (decrease) of sea-surface temperatures off the coast of NWA in HIST minus NO_AA (GHGAS). Further research is needed to better understand the mechanisms and the extent to which these are model-dependent. In summary, our results suggest that anthropogenic aerosols may have "masked" greenhouse gas-induced changes in rainfall over NWA and in circulation over the wider Indo-Pacific region. Due to the opposing effects of greenhouse gases and anthropogenic aerosols, future trends may be very different from trends observed over the last few decades.

Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Qβ. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-γ production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages.