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Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.
Coupling of clearance joint and harsh aerodynamic heating environment is an inevitable nonlinear factor in folding mechanism of the fin of high-speed aircrafts that remarkably modifies natural frequencies and modes of vibration from the initial design state. However, accurately predicting dynamic properties of deployable fin with full consideration of these effects is not common industry practice. A practical semi-analytical model based on Hertz contact theory and ESDU-78035 model is proposed in this study to investigate high-temperature connection stiffness of local hinged–locked mechanisms. Material property degradation and clearance variation caused by thermal expansion are comprehensively considered and quantified in this model. Vibration characteristics of the assembled deployable fin are then solved using finite element method (FEM). The real-time evolutionary process of thermal mode of the fin is discussed. And natural frequencies of fixed-value and time-varying connection stiffness are compared. The simulation results of this study demonstrate that the relative error of structure temperature between the sequential approach and fully coupled simulations is less than 6.98%. The connection stiffness (slope of the load-displacement curve) of the folding mechanism under high temperature conditions decreases by 3.52%, and the variation is mainly caused by the degradation of the elastic modulus of the material, while the clearance change due to the thermal expansion has no significant effect on the slope. The natural frequency of the deployable fin exhibits an inverse correlation with the temperature change trend, and the first three frequencies decrease by 1.67, 7.75, and 16.28 Hz compared to the initial value, respectively.
Young people are most vulnerable to suicidal behaviours but least likely to seek help. A more elaborate study of the intrinsic and extrinsic correlates of suicidal ideation and behaviours particularly amid ongoing population-level stressors and the identification of less stigmatising markers in representative youth populations is essential.
Methods
Participants (n = 2540, aged 15–25) were consecutively recruited from an ongoing large-scale household-based epidemiological youth mental health study in Hong Kong between September 2019 and 2021. Lifetime and 12-month prevalence of suicidal ideation, plan, and attempt were assessed, alongside suicide-related rumination, hopelessness and neuroticism, personal and population-level stressors, family functioning, cognitive ability, lifetime non-suicidal self-harm, 12-month major depressive disorder (MDD), and alcohol use.
Results
The 12-month prevalence of suicidal ideation, ideation-only (no plan or attempt), plan, and attempt was 20.0, 15.4, 4.6, and 1.3%, respectively. Importantly, multivariable logistic regression findings revealed that suicide-related rumination was the only factor associated with all four suicidal outcomes (all p < 0.01). Among those with suicidal ideation (two-stage approach), intrinsic factors, including suicide-related rumination, poorer cognitive ability, and 12-month MDE, were specifically associated with suicide plan, while extrinsic factors, including coronavirus disease 2019 (COVID-19) stressors, poorer family functioning, and personal life stressors, as well as non-suicidal self-harm, were specifically associated with suicide attempt.
Conclusions
Suicide-related rumination, population-level COVID-19 stressors, and poorer family functioning may be important less-stigmatising markers for youth suicidal risks. The respective roles played by not only intrinsic but also extrinsic factors in suicide plan and attempt using a two-stage approach should be considered in future preventative intervention work.
Brief measurements of the subjective experience of stress with good predictive capability are important in a range of community mental health and research settings. The potential for large-scale implementation of such a measure for screening may facilitate early risk detection and intervention opportunities. Few such measures however have been developed and validated in epidemiological and longitudinal community samples. We designed a new single-item measure of the subjective level of stress (SLS-1) and tested its validity and ability to predict long-term mental health outcomes of up to 12 months through two separate studies.
Methods
We first examined the content and face validity of the SLS-1 with a panel consisting of mental health experts and laypersons. Two studies were conducted to examine its validity and predictive utility. In study 1, we tested the convergent and divergent validity as well as incremental validity of the SLS-1 in a large epidemiological sample of young people in Hong Kong (n = 1445). In study 2, in a consecutively recruited longitudinal community sample of young people (n = 258), we first performed the same procedures as in study 1 to ensure replicability of the findings. We then examined in this longitudinal sample the utility of the SLS-1 in predicting long-term depressive, anxiety and stress outcomes assessed at 3 months and 6 months (n = 182) and at 12 months (n = 84).
Results
The SLS-1 demonstrated good content and face validity. Findings from the two studies showed that SLS-1 was moderately to strongly correlated with a range of mental health outcomes, including depressive, anxiety, stress and distress symptoms. We also demonstrated its ability to explain the variance explained in symptoms beyond other known personal and psychological factors. Using the longitudinal sample in study 2, we further showed the significant predictive capability of the SLS-1 for long-term symptom outcomes for up to 12 months even when accounting for demographic characteristics.
Conclusions
The findings altogether support the validity and predictive utility of the SLS-1 as a brief measure of stress with strong indications of both concurrent and long-term mental health outcomes. Given the value of brief measures of mental health risks at a population level, the SLS-1 may have potential for use as an early screening tool to inform early preventative intervention work.
Bipolar disorder is associated with premature mortality, but evidence is mostly derived from Western countries. There has been no research evaluating shortened lifespan in bipolar disorder using life-years lost (LYLs), which is a recently developed mortality metric taking into account illness onset for life expectancy estimation. The current study aimed to examine the extent of premature mortality in bipolar disorder patients relative to the general population in Hong Kong (HK) in terms of standardised mortality ratio (SMR) and excess LYLs, and changes of mortality rate over time.
Methods
This population-based cohort study investigated excess mortality in 12 556 bipolar disorder patients between 2008 and 2018, by estimating all-cause and cause-specific SMRs, and LYLs. Trends in annual SMRs over the 11-year study period were assessed. Study data were retrieved from a territory-wide medical-record database of HK public healthcare services.
Results
Patients had higher all-cause [SMR: 2.60 (95% CI: 2.45–2.76)], natural-cause [SMR: 1.90 (95% CI: 1.76–2.05)] and unnatural-cause [SMR: 8.63 (95% CI: 7.34–10.03)] mortality rates than the general population. Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Men and women with bipolar disorder had 6.78 (95% CI: 6.00–7.84) years and 7.35 (95% CI: 6.75–8.06) years of excess LYLs, respectively. The overall mortality gap remained similar over time, albeit slightly improved in men with bipolar disorder.
Conclusions
Bipolar disorder is associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to natural causes. Persistent mortality gap underscores an urgent need for targeted interventions to improve physical health of patients with bipolar disorder.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.
The influence of combined corrosion and vibration to the anti-loosening performance of a precision locknut used in a machine tool is investigated. Firstly, the locknut was submerged in 5% NaCl solution according to ASTM B895 standard for corrosion testing. The locknuts, after submerged in 1-hr, 2-hr and 4-hr periods, respectively, were then installed on the rotating spindle in a vertical dynamic impact tester for performing anti-loosening test. The initial installed pretension was 9800 N and the spindle was rotating in a constant speed of 1000 rpm. Turmogrease Li 802 EP lubricant was used on the contact surface between spindle thread and locknut. The set screws on the locknut were tightened sequentially and evenly in three-stage of torque: 1.96 N-m, 3.92 N-m and 5.88 N-m. Its real-time pretension variation with the periodic transverse impact and its final loosening torque were measured. Accordingly, the axial force ratio and anti-loosening torque ratio were calculated and discussed. It was found that corrosion treatment had similar influence on both the axial force ratio and the anti-loosening torque ratio. More corrosion on the locknut with longer submersion in NaCl solution deteriorated its anti-loosening characteristics. The result could serve as the reference for evaluating the fastening performance of precision locknut and guide the design and manufacturing for the application improvement.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Method
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Results
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
Conclusion
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
Method
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Results
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Conclusion
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
The second Singapore Mental Health Study (SMHS) – a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010.
Methods
Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
Results
The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010.
Conclusions
The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.
Plant nitrogen (N) links with many physiological progresses of crop growth and yield formation. Accurate simulation is key to predict crop growth and yield correctly. The aim of the current study was to improve the estimation of N uptake and translocation processes in the whole rice plant as well as within plant organs in the RiceGrow model by using plant and organ maximum, critical and minimum N dilution curves. The maximum and critical N (Nc) demand (obtained from the maximum and critical curves) of shoot and root and Nc demand of organs (leaf, stem and panicle) are calculated by N concentration and biomass. Nitrogen distribution among organs is computed differently pre- and post-anthesis. Pre-anthesis distribution is determined by maximum N demand with no priority among organs. In post-anthesis distribution, panicle demands are met first and then the remaining N is allocated to other organs without priority. The amount of plant N uptake depends on plant N demand and N supplied by the soil. Calibration and validation of the established model were performed on field experiments conducted in China and the Philippines with varied N rates and N split applications; results showed that this improved model can simulate the processes of N uptake and translocation well.
Nasal irrigation is commonly performed in patients with chronic rhinosinusitis after functional endoscopic sinus surgery. This study systematically assessed the clinical efficacy of nasal irrigation from the medical literature.
Methods
The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched using a comprehensive strategy, limited to English-language articles, published from October 1971 to March 2017, and comprising human subjects.
Results
A total of 824 trials were identified, 5 of which, involving 331 participants, were included in this systematic review. After selection, only three trials were eligible for inclusion in a meta-analysis. Nasal irrigation using normal saline and various solutions was found to be effective in reducing symptom scores and endoscopic scores for chronic rhinosinusitis patients after functional endoscopic sinus surgery. Comparison of outcome measures, such as eosinophil count reduction, revealed that various solutions are more effective than normal saline alone; however, no statistical significance was found in terms of reduced symptom or endoscopic scores.
Conclusion
Based on the current limited evidence, nasal irrigation is an effective therapy for chronic rhinosinusitis patients after functional endoscopic sinus surgery. However, when comparing various solutions with normal saline, no significant difference was found in symptom scores or endoscopic scores.
Phase relations in the system PbS-PbSe-PbTe were investigated in the temperature range between 1150 and 300°C. There is a complete solid solution series along the join PbS-PbSe, whereas miscibility gaps exist below ∼ 350°C and 805°C along joins PbSe-PbTe and PbS-PbTe, respectively. Both gaps extend into the ternary system, and the range of the gap between PbS and PbTe reduces in size with temperature as well as Se-content.
By using the subregular model of mixing (Ganguly and Saxena, 1987), mixing energetics and activity composition relations of PbX were derived. The temperature-dependence of the interaction parameters was calculated to be 5057.6 − 1.7T, 9605.2 − 4.4T, 3933.2 − 3.1T (T < 500°C), 6410.3 − 6.35T (T < 500°C) 1649 − 0.26T, 1594.6 − 0.2T, and 12906.3 − 17.3T for WWSte, WTeS, WSeTe, WTeSe, WSSe, WSeS, and WSSeTe, respectively. A critical temperature along the join PbS-PbSe at ∼ 100°C was obtained from interaction parameter calculation, which suggests the separation of the PbS-PbSe series.
Correlation of solid-solution ranges established in this study with natural occurrences was made.
Equilibrium relations of lead-tin sulphides in the system SnS-PbSnS2 were studied using a sealed silica-tube technique. A complete series of solid solutions forms in the system, and lattice parameters were found to vary lineally with composition. The melting temperature of the solid solution decreases with increasing amount of PbS from herzenbergite at 880 °C to teallite at 725 °C.
Evidences were found to indicate the existence of this series of solid solution in ore deposits.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.