Effectiveness of Vaccines and Antiviral Drugs in Preventing Severe and Fatal COVID-19, Hong Kong.

We compared the effectiveness and interactions of molnupiravir and nirmatrelvir/ritonavir and 2 vaccines, CoronaVac and Comirnaty, in a large population of inpatients with COVID-19 in Hong Kong. Both the oral antiviral drugs and vaccines were associated with lower risks for all-cause mortality and progression to serious/critical/fatal conditions (study outcomes). No significant interaction effects were observed between the antiviral drugs and vaccinations; their joint effects were additive. If antiviral drugs were prescribed within 5 days of confirmed COVID-19 diagnosis, usage was associated with lower risks for the target outcomes for patients >60, but not <60, years of age; no significant clinical benefit was found if prescribed beyond 5 days. Among patients >80 years of age, 3-4 doses of Comirnaty vaccine were associated with significantly lower risks for target outcomes. Policies should encourage COVID-19 vaccination, and oral antivirals should be made accessible to infected persons within 5 days of confirmed diagnosis.

Optimizing Interplanar Spacing, Oxygen Vacancies and Micromorphology via Lithium-Ion Pre-Insertion into Ammonium Vanadate Nanosheets for Advanced Cathodes in Aqueous Zinc-Ion Batteries.

Ammonium vanadates, featuring an N─H···O hydrogen bond network structure between NH4 + and V─O layers, have become popular cathode materials for aqueous zinc-ion batteries (AZIBs). Their appeal lies in their multi-electron transfer, high specific capacity, and facile synthesis. However, a major drawback arises as Zn2+ ions tend to form bonds with electronegative oxygen atoms between V─O layers during cycling, leading to irreversible structural collapse. Herein, Li+ pre-insertion into the intermediate layer of NH4V4O10 is proposed to enhance the electrochemical activity of ammonium vanadate cathodes for AZIBs, which extends the interlayer distance of NH4V4O10 to 9.8 Å and offers large interlaminar channels for Zn2+ (de)intercalation. Moreover, Li+ intercalation weakens the crystallinity, transforms the micromorphology from non-nanostructured strips to ultrathin nanosheets, and increases the level of oxygen defects, thus exposing more active sites for ion and electron transport, facilitating electrolyte penetration, and improving electrochemical kinetics of electrode. In addition, the introduction of Li+ significantly reduces the bandgap by 0.18 eV, enhancing electron transfer in redox reactions. Leveraging these unique advantages, the Li+ pre-intercalated NH4V4O10 cathode exhibits a high reversible capacity of 486.1 mAh g-1 at 0.5 A g-1 and an impressive capacity retention rate of 72% after 5,000 cycles at 5 A g-1.

Probing the structure and function of the protease domain of botulinum neurotoxins using single-domain antibodies.

Botulinum neurotoxins (BoNTs) are among the deadliest of bacterial toxins. BoNT serotype A and B in particular pose the most serious threat to humans because of their high potency and persistence. To date, there is no effective treatment for late post-exposure therapy of botulism patients. Here, we aim to develop single-domain variable heavy-chain (VHH) antibodies targeting the protease domains (also known as the light chain, LC) of BoNT/A and BoNT/B as antidotes for post-intoxication treatments. Using a combination of X-ray crystallography and biochemical assays, we investigated the structures and inhibition mechanisms of a dozen unique VHHs that recognize four and three non-overlapping epitopes on the LC of BoNT/A and BoNT/B, respectively. We show that the VHHs that inhibit the LC activity occupy the extended substrate-recognition exosites or the cleavage pocket of LC/A or LC/B and thus block substrate binding. Notably, we identified several VHHs that recognize highly conserved epitopes across BoNT/A or BoNT/B subtypes, suggesting that these VHHs exhibit broad subtype efficacy. Further, we identify two novel conformations of the full-length LC/A, that could aid future development of inhibitors against BoNT/A. Our studies lay the foundation for structure-based engineering of protein- or peptide-based BoNT inhibitors with enhanced potencies and cross-subtypes properties.

High-Energy-Density Cathode Achieved via the Activation of a Three-Electron Reaction in Sodium Manganese Vanadium Phosphate for Sodium-Ion Batteries.

Sodium superionic conductor (NASICON)-type Na3 V2 (PO4 )3 has attracted considerable interest owing to its stable three-dimensional framework and high operating voltage; however, it suffers from a low-energy density due to the poor intrinsic electronic conductivity and limited redox couples. Herein, the partial substitution of Mn3+ for V3+ in Na3 V2 (PO4 )3 is proposed to activate V4+ /V5+ redox couple for boosting energy density of the cathodes (Na3 V2- x Mnx (PO4 )3 ). With the introduction of Mn3+ into Na3 V2 (PO4 )3 , the band gap is significantly reduced by 1.406 eV and thus the electronic conductivity is greatly enhanced. The successive conversions of four stable oxidation states (V2+ /V3+ , V3+ /V4+ , and V4+ /V5+ ) are also successfully achieved in the voltage window of 1.4-4.0 V, corresponding to three electrons involved in the reversible reaction. Consequently, the cathode with x = 0.5 exhibits a high reversible discharge capacity of 170.9 mAh g-1 at 0.5 C with an ultrahigh energy density of 577 Wh kg-1 . Ex-situ x-ray diffraction (XRD) analysis reveals that the sodium-storage mechanism for Mn-doped Na3 V2 (PO4 )3 consists of single-phase and bi-phase reactions. This work deepens the understanding of the activation of reversible three-electron reaction in NASICON-structured polyanionic phosphates and provides a feasible strategy to develop high-energy-density cathodes for sodium-ion batteries.

Efficient Suppression of Dendrites and Side Reactions by Strong Electrostatic Shielding Effect via the Additive of Rb2 SO4 for Anodes in Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) have attracted considerable attention due to their low cost and environmental friendliness. However, the rampant dendrite growth and severe side reactions during plating/stripping on the surface of zinc (Zn) anode hinder the practicability of AZIBs. Herein, an effective and non-toxic cationic electrolyte additive of Rb2 SO4 is proposed to address the issues. The large cation of Rb+ is preferentially adsorbed on the surface of Zn metal to induce a strong shielding effect for realizing the lateral deposition of Zn2+ ions along the Zn surface and isolating water from Zn metal to effectively inhibit side reactions. Consequently, the Zn||Zn symmetric cell with the addition of 1.5 mm Rb2 SO4 can cycle more than 6000 h at 0.5 mA cm-2 /0.25 mAh cm-2 , which is 20 times longer than that without Rb2 SO4 . Besides, the Zn||Cu asymmetric cell with Rb2 SO4 achieves a very high average Coulombic efficiency of 99.16% up to 500 cycles. Moreover, the electrolyte with Rb2 SO4 well matches with the VO2 cathode, achieving high initial capacity of 412.7 mAh g-1 at 5 A g-1 and excellent cycling stability with a capacity retention of 71.6% at 5 A g-1 after 500 cycles for the Zn//VO2 full cell.

A semiparametric joint model for cluster size and subunit-specific interval-censored outcomes.

Clustered data frequently arise in biomedical studies, where observations, or subunits, measured within a cluster are associated. The cluster size is said to be informative, if the outcome variable is associated with the number of subunits in a cluster. In most existing work, the informative cluster size issue is handled by marginal approaches based on within-cluster resampling, or cluster-weighted generalized estimating equations. Although these approaches yield consistent estimation of the marginal models, they do not allow estimation of within-cluster associations and are generally inefficient. In this paper, we propose a semiparametric joint model for clustered interval-censored event time data with informative cluster size. We use a random effect to account for the association among event times of the same cluster as well as the association between event times and the cluster size. For estimation, we propose a sieve maximum likelihood approach and devise a computationally-efficient expectation-maximization algorithm for implementation. The estimators are shown to be strongly consistent, with the Euclidean components being asymptotically normal and achieving semiparametric efficiency. Extensive simulation studies are conducted to evaluate the finite-sample performance, efficiency and robustness of the proposed method. We also illustrate our method via application to a motivating periodontal disease dataset.

Massively parallel de novo protein design for targeted therapeutics.

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study.

BACKGROUND: The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics. METHODS: To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples. RESULTS: Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seasonal H1N1 influenza A virus (sH1N1)-specific CD4 and CD8 T cells was associated with 28% (95% CI 11%, 41%) and 22% (95% CI 8%, 33%) lower pH1N1 infection odds, respectively. We observed the same associations for individuals with pre-epidemic hemagglutination inhibition (HAI) titers < 40. There was no correlation between pre-existing influenza virus-specific CD4 and CD8 T cell response and HAI titer. CONCLUSIONS: We demonstrated homosubtypic and cross-strain protection against influenza infections was associated with T cell response, especially CD4 T cell response. These protections were independent of the protection associated with HAI titer. Therefore, T cell response could be an assessment of individual and population immunity for future epidemics and pandemics, in addition to using HAI titer.

Ratio estimators of intervention effects on event rates in cluster randomized trials.

We consider five asymptotically unbiased estimators of intervention effects on event rates in non-matched and matched-pair cluster randomized trials, including ratio of mean counts r1 , ratio of mean cluster-level event rates r2 , ratio of event rates r3 , double ratio of counts r4 , and double ratio of event rates r5 . In the absence of an indirect effect, they all estimate the direct effect of the intervention. Otherwise, r1 , r2, and r3 estimate the total effect, which comprises the direct and indirect effects, whereas r4 and r5 estimate the direct effect only. We derive the conditions under which each estimator is more precise or powerful than its alternatives. To control bias in studies with a small number of clusters, we propose a set of approximately unbiased estimators. We evaluate their properties by simulation and apply the methods to a trial of seasonal malaria chemoprevention. The approximately unbiased estimators are practically unbiased and their confidence intervals usually have coverage probability close to the nominal level; the asymptotically unbiased estimators perform well when the number of clusters is approximately 32 or more per trial arm. Despite its simplicity, r1 performs comparably with r2 and r3 in trials with a large but realistic number of clusters. When the variability of baseline event rate is large and there is no indirect effect, r4 and r5 tend to offer higher power than r1 , r2, and r3 . We discuss the implications of these findings to the planning and analysis of cluster randomized trials.

The Use of Close Friends on Instagram, Help-Seeking Willingness, and Suicidality Among Hong Kong Youth: Exploratory Sequential Mixed Methods Study.

BACKGROUND: Social networking sites (SNSs) have gained popularity in recent years for help seeking and self-distress expression among adolescents. Although online suicidal expression is believed to have major benefits, various concerns have also been raised, particularly around privacy issues. Understanding youths' help-seeking behavior on SNSs is critical for effective suicide prevention; however, most research neglects the impacts of the private SNS context. OBJECTIVE: This study aims to examine youths' private SNS use via the new Instagram feature, Close Friends, and its association with both online and offline help-seeking willingness as well as youths' suicidality. METHODS: This study employed an exploratory sequential mixed methods approach with a combination of explorative qualitative interviews and a systematic quantitative survey, targeting youth aged 15-19 years in Hong Kong. The motivations for utilizing Close Friends and concerns regarding online expression were addressed in the focus group and individual interviews (n=40). A cross-sectional survey (n=1676) was conducted subsequently with eligible secondary school students to examine the prevalence of Close Friends usage, their online and offline help-seeking willingness, and suicide-related experiences. RESULTS: A total of 3 primary motives for using Close Friends were identified during interviews, including (1) interaction and help seeking, (2) release of negative emotions, and (3) ventilation and self-expression. Most participants also highlighted the privacy concerns associated with public online communication and the importance of contacting close friends for emotional support. Survey results showed that use of Close Friends was quite prevalent among adolescents (1163/1646, 70.66%), with around 46% (754/1646, 45.81%) of respondents being frequent users. Differences by gender and school academic banding were also revealed. Regarding help-seeking intentions, youths were generally positive about seeking help from peers and friends offline (1010/1266, 79.78%) yet negative about seeking assistance from online friends or professionals with whom they had not yet developed a real-world connection (173/1266, 13.67%). Most notably, frequencies of Close Friends usage were differentially associated with online and offline help-seeking willingness and youths' suicidality. Compared with nonusers, those who had ever used the feature were more likely to seek offline support (adjusted odds ratios [AORs] 1.82-2.36), whereas heavy use of Close Friends was associated with increased odds of online help-seeking willingness (AOR 1.76, 95% CI 1.06-2.93) and a higher risk of suicidality (AOR 1.53, 95% CI 1.01-2.31). CONCLUSIONS: The popularity of Close Friends reflects the increasing need for private online expression among youth. This study demonstrates the importance of Close Friends for self-expression and private conversation and inadequacy of peer support for suicidal adolescents. Further research is needed to identify the causal relationship between Close Friends usage and help-seeking willingness to guide the advancement of suicide prevention strategies. Researchers and social media platforms may cooperate to co-design a risk monitoring system tailored to the private SNS context, assisting professionals in identifying youth at risk of suicide.

Robotic Natural Orifice Transluminal Endoscopic Surgery Hysterectomy and Salpingo-Oophorectomy in a Porcine Model.

Purpose. The emergence of robotic-assisted surgical techniques has gained significant indications in terms of reduced trauma, shortened recovery, and higher patients' satisfaction. However, limitations by present surgical robotic systems used in natural orifice transluminal endoscopic surgery (NOTES) gynecology still exists, such as arm collisions, countertraction, instrument dexterity, and, in particular, space confinement due to the narrow pelvic anatomy. The current study evaluated the use of a miniaturized single-site surgical robotic system and its feasibility in performing robotic NOTES gynecological procedures using a live porcine animal model. Methods. Using a transrectal approach, the fully internalized robotic arms were deployed in a reverse configuration to access the lower pelvic cavity of the animals to perform NOTES gynecological procedures. Results. Robotic-assisted transrectal gynecological procedures were successfully performed using the new robotic system. A hemi-hysterectomy with unilateral salpingo-oophorectomy was completed in the first animal and a total hysterectomy with bilateral salpingo-oophorectomy in the second animal with an average docking time of 22.5 minutes and console time of 63 minutes and 58 minutes, respectively. The overall blood loss for each procedure was estimated to be <20 mL per animal with no intraoperative complications. Conclusions. The reverse configuration of the miniaturized surgical robotic system has demonstrated its capability to provide a potential solution to maintain clear visualization of the surgical field, optimal triangulation, and dexterity robotic NOTES gynecological procedures within the deep confined space of the pelvic cavity.

Estimation and statistical inferences of variance components in the analysis of single-case experimental design using multilevel modeling.

Multilevel models (MLMs) can be used to examine treatment heterogeneity in single-case experimental designs (SCEDs). With small sample sizes, common issues for estimating between-case variance components in MLMs include nonpositive definite matrix, biased estimates, misspecification of covariance structures, and invalid Wald tests for variance components with bounded distributions. To address these issues, unconstrained optimization, model selection procedure based on parametric bootstrap, and restricted likelihood ratio test (RLRT)-based procedure are introduced. Using simulation studies, we compared the performance of two types of optimization methods (constrained vs. unconstrained) when the covariance structures are correctly specified or misspecified. We also examined the performance of a model selection procedure to obtain the optimal covariance structure. The results showed that the unconstrained optimization can avoid nonpositive definite issues to a great extent without a compromise in model convergence. The misspecification of covariance structures would cause biased estimates, especially with small between case variance components. However, the model selection procedure was found to attenuate the magnitude of bias. A practical guideline was generated for empirical researchers in SCEDs, providing conditions under which trustworthy point and interval estimates can be obtained for between-case variance components in MLMs, as well as the conditions under which the RLRT-based procedure can produce acceptable empirical type I error rate and power.

Marginal analysis of current status data with informative cluster size using a class of semiparametric transformation cure models.

This research is motivated by a periodontal disease dataset that possesses certain special features. The dataset consists of clustered current status time-to-event observations with large and varying cluster sizes, where the cluster size is associated with the disease outcome. Also, heavy censoring is present in the data even with long follow-up time, suggesting the presence of a cured subpopulation. In this paper, we propose a computationally efficient marginal approach, namely the cluster-weighted generalized estimating equation approach, to analyze the data based on a class of semiparametric transformation cure models. The parametric and nonparametric components of the model are estimated using a Bernstein-polynomial based sieve maximum pseudo-likelihood approach. The asymptotic properties of the proposed estimators are studied. Simulation studies are conducted to evaluate the performance of the proposed estimators in scenarios with different degree of informative clustering and within-cluster dependence. The proposed method is applied to the motivating periodontal disease data for illustration.

Antibiotic prescriptions by medical interns in Hong Kong: influence of the hospital settings and prescription culture.

BACKGROUND: Inappropriate antibiotic prescribing practices predispose to resistance emergence. Despite the inclusion of the topic in medical school curricula worldwide, it is uncertain whether newly graduated medical interns have confidence in proper antibiotic prescription. OBJECTIVES: This study aimed to explore the antibiotic prescribing behaviours of the medical interns in Hong Kong and their barriers to appropriate antibiotic prescription. METHODS: Two focus groups were conducted among medical interns with training experiences in different public hospitals. Their prescribing behaviours and barriers were further examined with a questionnaire survey just before completion of internship. RESULTS: Focus group interviews identified a variety of hospital workplace cultures, including inappropriate empirical prescriptions and dosages, interns' passive roles in prescribing antibiotics and varied guidelines between different departments. Defensive medicine and lack of clinical experience were other barriers encountered. The interns believed that the incorrect practice learnt would perpetuate in their minds and affect their future practice. The top barriers reported by the survey respondents were adaptation to prescription culture of different hospitals (93.5%), lack of experience in antibiotic prescription (88.3%), inadequate knowledge in the choice of antibiotics (85.7%) and compliance with the seniors' instructions (80.6%). However, some focus group participants perceived weaker barriers in paediatric departments which provided close monitoring of antibiotic use. CONCLUSIONS: Inadequate knowledge and low confidence in antibiotic prescription led to the passive role of medical interns in antibiotic prescription, predisposing to future inappropriate practice. Inconsistent guidelines and prescription cultures between different hospitals and departments might further exacerbate their barriers.

An Improved Vulnerability Exploitation Prediction Model with Novel Cost Function and Custom Trained Word Vector Embedding.

Successful cyber-attacks are caused by the exploitation of some vulnerabilities in the software and/or hardware that exist in systems deployed in premises or the cloud. Although hundreds of vulnerabilities are discovered every year, only a small fraction of them actually become exploited, thereby there exists a severe class imbalance between the number of exploited and non-exploited vulnerabilities. The open source national vulnerability database, the largest repository to index and maintain all known vulnerabilities, assigns a unique identifier to each vulnerability. Each registered vulnerability also gets a severity score based on the impact it might inflict upon if compromised. Recent research works showed that the cvss score is not the only factor to select a vulnerability for exploitation, and other attributes in the national vulnerability database can be effectively utilized as predictive feature to predict the most exploitable vulnerabilities. Since cybersecurity management is highly resource savvy, organizations such as cloud systems will benefit when the most likely exploitable vulnerabilities that exist in their system software or hardware can be predicted with as much accuracy and reliability as possible, to best utilize the available resources to fix those first. Various existing research works have developed vulnerability exploitation prediction models by addressing the existing class imbalance based on algorithmic and artificial data resampling techniques but still suffer greatly from the overfitting problem to the major class rendering them practically unreliable. In this research, we have designed a novel cost function feature to address the existing class imbalance. We also have utilized the available large text corpus in the extracted dataset to develop a custom-trained word vector that can better capture the context of the local text data for utilization as an embedded layer in neural networks. Our developed vulnerability exploitation prediction models powered by a novel cost function and custom-trained word vector have achieved very high overall performance metrics for accuracy, precision, recall, F1-Score and AUC score with values of 0.92, 0.89, 0.98, 0.94 and 0.97, respectively, thereby outperforming any existing models while successfully overcoming the existing overfitting problem for class imbalance.

Testing for change-point in the covariate effects based on the Cox regression model.

Models with change-point in covariates have wide applications in cancer research with the response being the time to a certain event. A Cox model with change-point in covariate is considered at which the pattern of the change-point effects can be flexibly specified. To test for the existence of the change-point effects, three statistical tests, namely, the maximal score, maximal normalized score, and maximal Wald tests are proposed. The asymptotic properties of the test statistics are established. Monte Carlo approaches to simulate the critical values are suggested. A large-scale simulation study is carried out to study the finite sample performance of the proposed test statistics under the null hypothesis of no change-points and various alternative hypothesis settings. Each of the proposed methods provides a natural estimate for the location of the change-point, but it is found that the performance of the maximal score test can be sensitive to the true location of the change-point in some cases, while the performance of the maximal Wald test is very satisfactory in general even in cases with moderate sample size. For illustration, the proposed methods are applied to two medical datasets concerning patients with primary biliary cirrhosis and breast cancer, respectively.

Factors that facilitate recognition and management of domestic violence by primary care physicians in a Chinese context - a mixed methods study in Hong Kong.

BACKGROUND: Domestic violence is common in the community. Many of its victims present to primary care physicians (PCPs) but are not being recognized and managed. The barriers, with specific reference to a Chinese cultural context, were investigated earlier. This paper explored the factors which facilitated the process of recognizing and managing suspected cases of domestic violence by PCPs in Hong Kong. METHODS: Four focus group interviews were conducted to explore in-depth the experiences of PCPs in recognition, management and referral of domestic violence cases from which facilitators were identified. The relevant themes were then investigated in a questionnaire survey with 504 PCPs working in public and private sectors. RESULTS: The focus group participants emphasized mood symptoms as useful indicators for probable abuse and continuity of care was important to unmask issues of domestic violence. The top facilitators perceived by the respondents of the survey included: a trusting doctor-patient relationship (99.8%), good communication skills (99.0%), patients' unexplained bruises (96.3%), medical history (94.6%), and mood symptoms (94.4%). Further, the survey found that PCPs with longer years of practice, a medical degree obtained from Western countries, and postgraduate training in family counselling or psychological medicine perceived more facilitators in managing domestic violence. CONCLUSIONS: Without a local screening policy and training protocol to manage domestic violence, PCPs regarded their skills in mental healthcare and good relationships with patients as the key facilitators. While training in mental health care helps PCPs manage domestic violence, a specific protocol emphasizing medical-social collaboration is anticipated to facilitate them to take a more proactive and effective stance from screening to management.

Associations between demographic factors and psychological distress among Chinese residents in Hong Kong: beyond socioeconomic classes.

Most studies highlighted the association between psychological distress and socioeconomic status (SES). There were weaker explanations for distress found in the middle classes, especially in Asian countries. We conducted a questionnaire survey with 1626 adult Chinese primary-care attenders from 13 private and 6 public clinics in different districts of Hong Kong. Their demographic background and distress level measured by GHQ-12 were analysed. We found that respondents with younger age, better education, and lower income were more likely to be distressed. In a multiple logistic regression model, age and income, but not education, were significant predictors for distress. Highest rates of distress were found among the unemployed (45.5%) and the students (37.1%), followed by service workers and shop sales workers (33.0%), associate professionals (32.0%), and clerks (29.2%). Craftworkers (9.1%), plant and machine operators (11.5%), and retired people (12.8%) were least likely to be distressed, followed by professionals (21.0%). Apart from SES, the findings suggest that young age, academic and job stressors, and low self-esteem are significant factors for distress. These factors may be intensified in a Chinese context by peer comparison resulting in a state of relative deprivation.

Stereotactic Radiosurgery for Brain Arteriovenous Malformations: Evaluation of Obliteration and Review of Associated Predictors.

BACKGROUND: High arteriovenous malformation (AVM) obliteration rates have been reported with stereotactic radiosurgery (SRS), and multiple factors have been found to be associated with AVM obliteration. These predictors have been inconsistent throughout studies. We aimed to analyze our experience with linear accelerator (LINAC)-based SRS for brain AVMs, evaluate outcomes, assess factors associated with AVM obliteration and review the various reported predictors of AVM obliteration. METHODS: Electronic medical records were retrospectively reviewed to identify consecutive patients with brain AVMs treated with SRS over a 27-year period with at least 2 years of follow-up. Logistic regression analysis was performed to identify factors associated with AVM obliteration. RESULTS: One hundred twenty-eight patients with 142 brain AVMs treated with SRS were included. Mean age was 34.4 years. Fifty-two percent of AVMs were associated with a hemorrhage before SRS, and 14.8% were previously embolized. Mean clinical and angiographic follow-up times were 67.8 months and 58.6 months, respectively. The median Spetzler-Martin grade was 3. Mean maximal AVM diameter was 2.8 cm and mean AVM target volume was 7.4 cm3 with a median radiation dose of 16 Gy. Complete AVM obliteration was achieved in 80.3%. Radiation-related signs and symptoms were encountered in 32.4%, only 4.9% of which consisted of a permanent deficit. Post-SRS AVM-related hemorrhage occurred in 6.3% of cases. In multivariate analysis, factors associated with AVM obliteration included younger patient age (P = .019), male gender (P = .008), smaller AVM diameter (P = .04), smaller AVM target volume (P = .009), smaller isodose surface volume (P = .005), a higher delivered radiation dose (P = .013), and having only one major draining vein (P = .04). CONCLUSIONS: AVM obliteration with LINAC-based radiosurgery was safe and effective and achieved complete AVM obliteration in about 80% of cases. The most prominent predictors of AVM success included AVM size, AVM volume, radiation dose, number of draining veins and patient age.

Crystal structure of the FliF-FliG complex from Helicobacter pylori yields insight into the assembly of the motor MS-C ring in the bacterial flagellum.

The bacterial flagellar motor is a self-assembling supramolecular nanodevice. Its spontaneous biosynthesis is initiated by the insertion of the MS ring protein FliF into the inner membrane, followed by attachment of the switch protein FliG. Assembly of this multiprotein complex is tightly regulated to avoid nonspecific aggregation, but the molecular mechanisms governing flagellar assembly are unclear. Here, we present the crystal structure of the cytoplasmic domain of FliF complexed with the N-terminal domain of FliG (FliF C -FliG N ) from the bacterium Helicobacter pylori Within this complex, FliF C interacted with FliG N through extensive hydrophobic contacts similar to those observed in the FliF C -FliG N structure from the thermophile Thermotoga maritima, indicating conservation of the FliF C -FliG N interaction across bacterial species. Analysis of the crystal lattice revealed that the heterodimeric complex packs as a linear superhelix via stacking of the armadillo repeat-like motifs (ARM) of FliG N Notably, this linear helix was similar to that observed for the assembly of the FliG middle domain. We validated the in vivo relevance of the FliG N stacking by complementation studies in Escherichia coli Furthermore, structural comparison with apo FliG from the thermophile Aquifex aeolicus indicated that FliF regulates the conformational transition of FliG and exposes the complementary ARM-like motifs of FliG N , containing conserved hydrophobic residues. FliF apparently both provides a template for FliG polymerization and spatiotemporally controls subunit interactions within FliG. Our findings reveal that a small protein fold can serve as a versatile building block to assemble into a multiprotein machinery of distinct shapes for specific functions.