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Leptomeningeal disease is rare in pancreatic cancer and prognosis remains poor. Mutation profiles are now directing therapy to improve survival. We describe a case of leptomeningeal and brain metastasis in BRCA1 interacting protein 1, or BRIP1-mutated pancreatic adenocarcinoma with progression through several lines of chemotherapy and immunotherapy. A woman in her late 50s presented with metastatic pancreatic adenocarcinoma on liver biopsy. She achieved complete response after modified FOLFIRINOX and started a poly (ADP-ribose) polymerase (PARP) inhibitor for a BRIP1 mutation. She had recurrence at 9 months and started pembrolizumab (programmed cell death protein 1, or PD-1receptor antibody) for tumour mutational burden of 10 muts/Mb. At 10 months, she presented with lower extremity weakness and back pain. MRI revealed leptomeningeal metastases from T11 to cauda equina roots and right occipital metastasis. Cerebrospinal fluid studies revealed elevated pressure (290 mm H2O) and protein (73 mg/dL) with negative cytology. Leptomeningeal carcinomatosis was diagnosed. She began palliative radiation but died at 11 months from initial diagnosis.

Background: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. Methods: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0–2], poor [modified Rankin Scale score 4–6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. Results: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P P P 0.8), except in predicting good outcome for cerebellum. Conclusions: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.

Background: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension. Methods: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years). Results: The hypertensive group was associated with GM alterations; however, significant differences in β-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus , Clostridium bolteae , and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men. Conclusions: GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.

Background: Viral bronchiolitis is a common condition and a leading cause of hospitali-zation in young children. Objective: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. Methods: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR “respiratory syncytial virus infection”. The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observation-al studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. Results: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young chil-dren. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagno-sis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effec-tive. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramus-cularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. Conclusions: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

Background: The author and his wife report their unique experience of international travels during the COVID-19 pandemic, and discuss issues encountered in various countries. Methods: Narrated discussion of issues encountered during the COVID-19 pandemic. Discussion: “Zero-COVID” versus “Living with COVID-19” strategies are compared. Children have unique issues with COVID-19 pandemic. Evaluation of efficacy of the approaches in pandem-ic with time should consider the main types of interventions (e.g., border management/quarantine; physical distancing; mask use; case isolation, testing and contact tracing; vaccination). The key met-rics that can be used to compare the impacts of different strategies between the cities (e.g., cumula-tive case rate, cumulative mortality rate, case fatality risk, stringency index, economic performance) should be identified. Research in these approaches can help manage future pandemics in corona-viruses and emerging infections. The UK started with very loose mitigation ('herd immunity') and then switched to a suppression approach in 2021, followed by "living with the virus" approach. Whereas HK has been targeting towards elimination throughout. In between, countries like Singa-pore, Australia and New Zealand have shifted from zero-COVID strategy to living with the virus. It is easier to have effective social control measures in Hong Kong because it has clear borders and an authoritarian government, but it did not have a clear exit policy when Omicron spread.

Purpose Glenoid component loosening is a potential complication of reverse total shoulder arthroplasty (rTSA), occurring in part due to lack of adequate screw purchase in quality scapular bone stock. This study was to determine the efficacy of a surgeon-designed, 3D-printed patient-specific instrumentation (PSI) compared to conventional instrumentation (CI) in achieving longer superior and inferior screw lengths for glenoid component fixation. Methods A multi-centre retrospective analysis of patients who underwent rTSA between 2015 and 2020. Lengths of the superior and inferior locking screws inserted for fixation of the glenoid baseplate component were recorded and compared according to whether patients received PSI or CI. Secondary outcomes included operative duration and incidence of complications requiring revision surgery. Results Seventy-three patients (31 PSI vs. 42 CI) were analysed. Average glenoid diameter was 24.5 mm (SD: 3.1) and 81% of patients had smaller glenoid dimensions compared to the baseplate itself. PSI produced significantly longer superior (44.7 vs. 30.7 mm; P P P = 0.229). No patients had radiographic loosening of the glenoid component with an average of 2-year follow-up. Conclusion PSI facilitates longer superior and inferior screw placement in the fixation of the glenoid component for rTSA. With sufficient training, PSI can be designed and implemented by surgeons themselves.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January–July 2022. We estimated that Omicron infected 45% (41–48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34–64%) and 69% (46–98%) for three and four doses of BNT162b2, respectively; VE of 30% (1–66%) and 56% (6–97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7–41%) and 35% (10–71%) for three and four doses of BNT162b2, and to 6% (0–29%) and 11% (0–54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.

The recent advances in G-quadruplex-selective ligands in the fields of live cell imaging, chemical biology and therapeutic prospects against bacterial infections.

Wang Chun Kwok,1,* Sze Him Isaac Leung,2,* Terence Chi Chun Tam,1 James Chung Man Ho,1 David Chi-Leung Lam,1 Mary Sau Man Ip,1 Pak Leung Ho3 1Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People’s Republic of China; 2Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China; 3Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pak Leung Ho, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong Special Administrative Region, People’s Republic of China, Tel +852 2255 2584, Fax +852 2855 1241, Email plho@hku.hkBackground: While different COVID-19 vaccines have been developed, there has been lack of data on the efficacy comparison between mRNA and inactivated whole virus vaccine among patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis.Methods: This was a retrospective case control study on the efficacy of BNT162b2 (mRNA vaccine) and CoronaVac (inactivated whole virus vaccine) against COVID-19 in patients with chronic respiratory diseases. A total of 327 patients were included, with 109 patients infected with COVID-19 matched with 218 patients without COVID-19. The co-primary outcomes were vaccine effectiveness against symptomatic COVID-19, COVID-19-related hospitalization and COVID-19-related respiratory failure. Vaccine effectiveness was calculated using the formula (1-adjusted odds ratio) x 100.Results: Patients who received at least 2 doses of CoronaVac had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination, with adjusted odds ratio (OR) of 0.189 (95% CI = 0.050– 0.714, p = 0.014) and 0.128 (95% CI = 0.026– 0.638, p = 0.012) respectively. Patients who received at least 2 doses of BNT162b2 had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination with adjusted OR of 0.207 (95% CI = 0.043– 0.962, p = 0.050) and 0.093 (95% CI = 0.011– 0.827, p = 0.033) respectively. There was no statistically significant difference in the risks of being hospitalized for COVID-19 and developing respiratory failure between patients who received at least 2 doses of CoronaVac or BNT162b2.Conclusion: BNT162b2 and CoronaVac vaccines are effective in preventing hospitalization for COVID-19 and respiratory failure complicating COVID-19 among patients with chronic respiratory diseases. Patients with chronic respiratory diseases should be encouraged to have COVID-19 vaccination.Keywords: COVID-19, COPD, asthma, bronchiectasis, vaccine

Background: Video feedback is a technique used in cognitive therapy for social anxiety disorder (CT-SAD) to update patients' negative self-perceptions of how they appear to others. Clients are supported to watch video of themselves engaging in social interactions. While typically undertaken in session with a therapist, this study aimed to investigate the effectiveness of remotely delivered video feedback embedded within an Internet-based cognitive therapy program (iCT-SAD). Methods: We examined patients' self-perceptions and social anxiety symptoms before and after video feedback in two randomised controlled trials. Study 1 compared 49 iCT-SAD participants with 47 from face-to-face CT-SAD. Study 2 was a replication using data from 38 iCT-SAD participants from Hong Kong. Results: In Study 1, ratings of self-perceptions and social anxiety showed significant reductions following video feedback, in both treatment formats. 92 % of participants in iCT-SAD, and 96 % in CT-SAD thought they looked less anxious compared to their predictions after viewing the videos. The change in self-perception ratings was larger in CT-SAD compared to iCT-SAD, but there was no evidence that the impact of video feedback on social anxiety symptoms around a week later differed between the two treatments. Study 2 replicated the iCT-SAD findings of Study 1. Limitations: The level of therapist support in iCT-SAD videofeedback varied with clinical need and was not measured. <>Conclusions: The findings indicate that video feedback can be delivered effectively online, and that its impact on social anxiety is not significantly different from in-person treatment delivery.

Conventional Al-air battery has many disadvantages for miniwatt applications, such as the complex water management, bulky electrolyte storage and potential leakage hazard. Moreover, the self-corrosion of Al anode continues even when the electrolyte flow is stopped, leading to great Al waste. To tackle these issues, an innovative cotton-based aluminum-air battery is developed in this study. Instead of flowing alkaline solution, cotton substrate pre-deposited with solid alkaline is used, together with a small water reservoir to continuously wet the cotton and dissolve the alkaline in-situ. In this manner, the battery can be mechanically recharged by replacing the cotton substrate and refilling the water reservoir, while the thick aluminum anode can be reused for tens of times until complete consumption. The cotton substrate shows excellent ability for the storage and transportation of alkaline electrolyte, leading to a high peak power density of 73 mW cm−2 and a high specific energy of 930 mW h g−1. Moreover, the battery discharge capacity is found to be linear to the loading of pre-deposited alkaline, so that it can be precisely controlled according to the mission profile to avoid Al waste. Finally, a two-cell battery pack with common water reservoir is developed, which can provide a voltage of 2.7 V and a power output of 223.8 mW. With further scaling-up and stacking, this cotton-based Al-air battery system with low cost and high energy density is very promising for recharging miniwatt electronics in the outdoor environment.

International audience; Environmentally induced reductions in fitness components (survival, fecundity) are generally considered as passive, maladaptive responses to stress. However, there is also mounting evidence for active, programmed forms of environmentally induced cell death in unicellular organisms. While conceptual work has questioned how such programmed cell death (PCD) might be maintained by natural selection, few experimental studies have investigated how PCD influences genetic differences in longer-term fitness across environments. Here, we tracked the population dynamics of two closely related strains of the halotolerant microalga Dunaliella salina, following transfers across salinities. We showed that after a salinity rise, only one of these strains displayed a massive population decline (-69% in one hour), largely attenuated by exposure to a PCD inhibitor. However, this decline was followed by a rapid demographic rebound, characterized by faster growth than the non-declining strain, such that sharper decline was correlated with faster subsequent growth across experiments and conditions. Strikingly, the decline was more pronounced in conditions more favourable to growth (more light, more nutrients, less competition), further suggesting that it was not simply passive. We explored several hypotheses that could explain this decline-rebound pattern, which suggests that successive stresses could select for higher environmentally induced death in this system.

Despite the advancement of the knowledge of unsaturated soil behaviour developed over the past decades, the understandings remain largely at the macro or element scale. Existing testing systems allow simultaneous in situ loading and X-ray imaging to facilitate the studies at micro or pore scale, but the soils of concern are normally two-phase (i.e., dry or saturated). This paper develops a new suction-controlled miniature triaxial apparatus for studying the micro-hydro-mechanical behaviour of three-phase unsaturated soils via in situ quantification of the evolutions of soil microstructures, aided by micro-X-ray computer tomography imaging. The apparatus can independently control combinations of net mean stress and matric suction whilst permitting high-resolution full-field imaging of the entire samples through the image analysis via methods of pore network modelling and discrete digital image correction. Results reveal that at equilibrium, suction at the “transition zone” of the soil does not necessarily mean to have both the air and water phases continuous, as otherwise recognized at the element scale. This phenomenon leads to nonuniform distributions of local void ratio and degree of saturation. Post-peak strain localization and shear band development are explained by the movements of pore fluid and the associated influences on local soil void ratio change.

Large soil movements arising from the installation of jack-up spudcan foundations may induce detrimental effects on piles supporting adjacent permanent jacket platforms. Particularly, in a dense sand-over-clay profile, there is a risk of spudcan rapid penetration due to underlying clay bearing capacity failure, known as spudcan punch-through failure, which can cause further damage to piles in the proximity. This study investigates the foundation interaction between the spudcan and adjacent pile in a sand-overlying-clay soil profile by way of centrifuge modelling. Issues investigated include thickness of the upper sand layer with incidence of sand plug beneath the spudcan and spudcan–pile clearance. The experimental findings reveal that spudcan punch-through hazard and the magnitude of induced pile moments amplifies primarily due to the increase in the thickness of the upper sand. In addition, the magnitude of induced pile moment in a sand-over-clay profile is significantly higher than that in a single clay profile because of the post-peak bearing behaviour observed in stratified soil, yielding to a greater risk to pile integrity. Soil pressure profiles on the piles are also back-analysed. Two generalised induced soil pressure profiles are deduced, with the first profile representing the onset of spudcan punch-through and the second profile denoting the situation of post-punch-through failure.

A novel high-resolution regional reanalysis is used to investigate the mesoscale processes that preceded the formation of Tropical Cyclone (TC) Mora (2017). Both satellite observations and the regional reanalysis show early morning mesoscale convective systems (MCSs) persistently initiated and organized in the downshear quadrant of the preexisting tropical disturbance a few days prior to the genesis of TC Mora. The diurnal MCSs gradually enhanced the meso-α-scale vortex near the center of the preexisting tropical disturbance through vortex stretching, providing a vorticity-rich and moist environment for the following burst of deep convection and enhancement of the meso-β-scale vortex. The regional reanalysis shows that the gravity waves that radiated from afternoon convection over the northern coast of the Bay of Bengal might play an important role in modulating the diurnal cycle of pregenesis MCSs. The diurnal convectively forced gravity waves increased the tropospheric stability, reduced the column saturation fraction, and suppressed deep convection within the preexisting tropical disturbance from noon to evening. A similar quasi-diurnal cycle of organized deep convection prior to TC genesis has also been observed over other basins. However, modeling studies are needed to conclusively demonstrate the relationships between the gravity waves and pregenesis diurnal MCSs. Also, whether diurnal gravity waves play a similar role in modulating the pregenesis deep convection in other TCs is worth future investigations. Significance Statement Tropical cyclogenesis is a process by which a less organized weather system in the tropics develops into a tropical cyclone (TC). Observations indicate that thunderstorms occurring prior to the tropical cyclogenesis often show a distinct quasi-diurnal cycle, while the related physical mechanisms are still unclear. In this study, we used a novel high-resolution dataset to investigate the diurnal thunderstorms occurring prior to the genesis of TC Mora (2017). We find that the pregenesis diurnal thunderstorms played a crucial role in spinning up the circulation of the atmosphere and provided a favorable environment for the rapid formation of Mora. It is likely that gravity waves emitted by afternoon thunderstorms over the inland region were responsible for regulating the diurnal variation of pregenesis thunderstorms over the ocean.

Learning view-invariant representation is a key to improving feature discrimination power for skeleton-based action recognition. Existing approaches cannot effectively remove the impact of viewpoint due to the implicit view-dependent representations. In this work, we propose a self-supervised framework called Focalized Contrastive View-invariant Learning (FoCoViL), which significantly suppresses the view-specific information on the representation space where the viewpoints are coarsely aligned. By maximizing mutual information with an effective contrastive loss between multi-view sample pairs, FoCoViL associates actions with common view-invariant properties and simultaneously separates the dissimilar ones. We further propose an adaptive focalization method based on pairwise similarity to enhance contrastive learning for a clearer cluster boundary in the learned space. Different from many existing self-supervised representation learning work that rely heavily on supervised classifiers, FoCoViL performs well on both unsupervised and supervised classifiers with superior recognition performance. Extensive experiments also show that the proposed contrastive-based focalization generates a more discriminative latent representation.

The rate of chronic opioid use after cardiac surgery is high compared with other surgical specialties; however evidence regarding optimal prescribing is limited. The purpose of this study was to evaluate patterns of opioid consumption after cardiac surgery to guide prescribing practices.Consecutive patients undergoing sternotomy-based cardiac operations were considered for enrollment. Patients with opioid use within 3 months of surgery and those discharged to a nonhome facility were excluded. A patient diary and researcher-directed pill count was used to track pain and opioid use for 10 days after discharge.One hundred four patients were included in the final analysis. Of the 63 patients discharged with an opioid, 22 (34.9%) used none and 12 (19.0%) used fewer than half of the pills prescribed. Overall, pain and opioid consumption decreased significantly throughout the discharge period (P.001). In those who used opioids after discharge, median total consumption was 64 morphine milligram equivalents (interquartile range, 38-128), or the equivalent of 9 oxycodone 5-mg tablets. Patients who used opioids were younger (60.9 vs 70.0, P.001), but there were no differences based on sex, history of substance use, smoking, or procedure. After risk adjustment the mean pain score ≥ 3 on the day of discharge was predictive of opioid use (odds ratio, 2.9; 95% confidence interval, 1.8-4.8; P.001). Most patients (88.5%) were satisfied or very satisfied with pain management.Fewer than half of all patients used opioids after discharge in this study. These data support the need for the development of prescription recommendations after cardiac surgery.

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab. Methods: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan–Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy. Results: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis. Conclusion: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients.

This paper describes the new open-source framework PyFLEXTRKR (Python FLEXible object TRacKeR), a flexible atmospheric feature tracking software package with specific capabilities to track convective clouds from a variety of observations and model simulations. This software can track any atmospheric 2D objects and handle merging and splitting explicitly. The package has a collection of multi-object identification algorithms, scalable parallelization options, and has been optimized for large datasets including global high-resolution data. We demonstrate applications of PyFLEXTRKR on tracking individual deep convective cells and mesoscale convective systems from observations and model simulations ranging from large-eddy resolving (∼100s m) to mesoscale (∼10s km) resolutions. Visualization, post-processing, and statistical analysis tools are included in the package. New Lagrangian analyses of convective clouds produced by PyFLEXTRKR applicable to a wide range of datasets and scales facilitate advanced model evaluation and development efforts as well as scientific discovery.

The challenges brought by a growing number of large-scale land development projects (e.g., Northern Metropolis, Lantau Tomorrow, and related infrastructures) in Hong Kong must be met by innovative land acquisition planning and processes. A recent quick win solution to land supply for Works projects has been in trial commissioning the provisional draft land resumption plan preparations and related survey works from the government to consultants, specifically the Authorized Land Surveyor (ALS) in the private sector. The industry therefore must consider the necessary and diverse sources of expertise available, and the existing land surveying technical resources that will render support to such new initiatives. Collaboration is called for between the spheres of public sector, education, and works industry to successfully move the use of cadastral survey for land management forwards, bridging the gap between lands and works practices for efficient processing of Works projects, and smart city development of Hong Kong.This paper will examine the new approach of professional surveying that private practicing ALSs bring, and why the overall number of ALS and engineering surveyors in the construction industry is growing so slowly. It will additionally compare Hong Kong's practice with that of the mainland China, Singapore, and the UK to grasp global learning points. The paper recommends the establishment of a Cadastral Survey Lab (CSL) firstly to explore the policy implementation of a sound cadastral system. The processing of lot boundary determination by ALS is reviewed. The regulatory roles of the Land Survey Authority (LSA) are requested in approving new land boundary plans; this both replaces the Demarcation District (DD) Sheet boundary and improves land boundary records. Secondly, the CSL can serve as a coordinating body in curating various kinds of land records from diverse sources, and aids the research and knowledge management of cadastral survey, land law, land tenure, land registration systems, land boundary record keeping, problematic lot boundary determination, etc. These topics can be considered in the refining geomatics education curriculum, and furthermore developed into guidance notes for geomatics survey practitioners.The evolution of the traditional land surveying profession into the geomatics services has become a recent international trend that is growing in popularity in the survey profession. Combining geo-spatial data from the planning and design stages, alongside the use of standardised survey data processing in project implementation and asset management, would encourage data sharing, avoid duplicate efforts, and facilitate the formation of a digital city. The spectrums of geomatics education in universities should be widened with a refined curriculum on combining geomatics with cadastral survey that has evolved from the traditional lot boundary survey to multi-purpose cadastre, city information modelling, urban informatics, smart city administration, and a full-blown Spatial Data Infrastructure (SDI).

Background It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. Methods To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. Results Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mean = 90.7%); by society: 3.2% for DSM-oriented somatic problems to 8.0% for DSM-oriented anxiety problems (mean = 6.3%); and by culture cluster: 0.0% for DSM-oriented avoidant personality to 11.6% for DSM-oriented anxiety problems (mean = 3.0%). For strengths, individual differences accounted for 80.8% of variance, societal differences 10.5%, and cultural differences 8.7%. Age and gender had very small effects. Conclusions Overall, adults' self-ratings of mental health problems and strengths were associated much more with individual differences than societal/cultural differences, although this varied across scales. These findings support cross-cultural use of standardized measures to assess mental health problems, but urge caution in assessment of personal strengths.

In this study, the relationship between AO and winter synoptic temperature variability (STV) over the Northern Hemisphere is examined in 34 CMIP5/CMIP6 model outputs. With significant model bias around the North Pacific and North Atlantic, most models fail to capture the correct AO–STV pattern in historical simulations compared to observations. To investigate the bias of AO–STV relationship simulations, AO-related processes for the connection between AO and winter STV are examined in high pattern score (HPS) models and low pattern score (LPS) models, respectively. Furthermore, the bias of AO impact can be traced back to AO pattern simulations. On the one hand, compared to observations, HPS models can overall capture the intensity in the North Pacific and North Atlantic center of AO. On the other hand, LPS models tend to overestimate the North Pacific center and underestimate the North Atlantic center. In addition, similar to historical simulations, a robust AO–STV relationship can still be found over the Northern Hemisphere in future projections based on HPS models. Meanwhile, the uncertainty of the projected AO–STV relationship in the multimodel ensemble is confined mainly to the North Pacific, consistent with the large diversity of intensity over the North Pacific center of AO, which is related to the uncertainty of the relationship between AO and regional mode variability.

Hematopoietic cell transplantation (HCT) is the only readily available cure for many life-threatening pediatric nonmalignant diseases (NMD), but most patients lack a matched related donor and are at higher risk for graft-versus-host disease (GVHD). Use of abatacept (Aba) to target donor T-cell activation has been safe and effective in preventing GVHD after unrelated donor (URD) HCT for malignant diseases (Aba2 trial). Our primary objective was to evaluate the tolerability of Aba added to standard GVHD prophylaxis (cyclosporine and mycophenolate mofetil) in pediatric patients with NMD undergoing URD HCT. In this single-arm, single-center phase 1 trial, 10 patients receiving reduced intensity or nonmyeloablative conditioning underwent URD HCT. Immune reconstitution was assessed longitudinally via flow cytometry and compared to pediatric patients on Aba2. Nine patients successfully engrafted, with 1 primary graft rejection in the setting of inadequate cell dose; secondary graft rejection occurred in 1 patient with concurrent cytomegalovirus viremia. Two deaths occurred, both unrelated to Aba. One patient developed probable posttransplant lymphoproliferative disease, responsive to rituximab and immune suppression withdrawal. No patients developed severe acute or chronic GVHD, and 8 patients were off systemic immunosuppression at 1 year. Immune reconstitution did not appear to be impacted by Aba, and preservation of naïve relative to effector memory CD4+ T cells was seen akin to Aba2. Thus, 4 doses of Aba were deemed tolerable in pediatric patients with NMD following URD HCT, with encouraging preliminary efficacy and supportive immune correlatives in this NMD cohort.