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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 Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW).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.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
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.
This study aimed to evaluate various associated risks between internet addiction (IA) and Attention deficit/Hyperactivity disorder (ADHD) children and adolescents by comparing ADHD group with and without IA problem.
Method
78 ADHD children and their parents were performed designed general demographic questionnaire and standardized measurement including Chen IA Scale (CIAS), Swanson, Nolan, and Pelham, Version IV ADHD questionnaire (SNAP-IV), Child Behavior Checklist (CBCL), Adult ADHD self Rating Scale (ASRS), Symptom Check List (SCL-90) and were then divided into ADHD with IA or without IA group according to IA cutting point. Various associated risks included the BMI value, general demographic data, subtype, comorbidity, childhood common behavior problem, parental ADHD diagnosis, parental symptom, nail biting, and media exposure problem.
Results
ADHD youth with IA problem was highly associated with overweight and playing computer game more than one hour. Stepwise logistic regression revealed that father of these ADHD children in this group were significantly younger, and children self having withdrawn tendency.
Conclusion
Father's younger age, overweight and withdrawal tendency on ADHD youth is risks associated with internet addiction problem and the presence of playing computer game more than one hour on ADHD child is at greater risk for developing internet addiction.
Types of sugar-sweetened beverages (SSB) can differ greatly between countries, with greater consumption of sweetened tea in Asia. This study aimed to understand changes in SSB consumption by adolescents in Taiwan over 18 years and their association with demographic characteristics and clinical outcome. This study used survey data from the 1993–1996 and 2010–2011 Nutrition and Health Surveys in Taiwan. Participants were high school students aged 13 to 18 years. Data were weighted and analysed using SUDAAN 11.0 and SAS 9.4. Participants were asked about intake frequencies of SSB and were grouped into four different SSB intake groups based on the combination of high or low frequency (including moderate frequency) of intake of sweetened tea and soda/sports/energy drinks. Results indicated over 99 % of teens reported having at least one SSB in the past week. Smoking status was significantly associated with SSB intake types with high tea intake (high tea and low soda (HL) group, OR 7·56, P < 0·001; high tea and high soda (HH) group, OR 9·96, P < 0·001). After adjustment for potential confounders, adolescents in the low tea and high soda (LH) group (β = 0·05, P = 0·034) had significantly higher mean serum uric acid values. In conclusion, sugary tea remains the SSB of choice for Taiwanese adolescents. Those with a frequent intake of soda/sports/energy drinks had a higher chance of being hyperuricaemic.
Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5–98) ml at 18 months of age and 111 (interquartile range 57–198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.
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.
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.
There has recently been an increased interest in mental health indicators for the monitoring of population wellbeing, which is among the targets of Sustainable Development Goals adopted by the United Nations. Levels of subjective wellbeing and suicide rates have been proposed as indicators of population mental health, but prior research is limited.
Methods.
Data on individual happiness and life satisfaction were sourced from a population-based survey in Hong Kong (2011). Suicide data were extracted from Coroner's Court files (2005–2013). Area characteristic variables included local poverty rate and four factors derived from a factor analysis of 21 variables extracted from the 2011 census. The associations between mean happiness and life satisfaction scores and suicide rates were assessed using Pearson correlation coefficient at two area levels: 18 districts and 30 quantiles of large street blocks (LSBs; n = 1620). LSB is a small area unit with a higher level of within-unit homogeneity compared with districts. Partial correlations were used to control for area characteristics.
Results.
Happiness and life satisfaction demonstrated weak inverse associations with suicide rate at the district level (r = −0.32 and −0.36, respectively) but very strong associations at the LSB quantile level (r = −0.83 and −0.84, respectively). There were generally very weak or weak negative correlations across sex/age groups at the district level but generally moderate to strong correlations at the LSB quantile level. The associations were markedly attenuated or became null after controlling for area characteristics.
Conclusions.
Subjective wellbeing is strongly associated with suicide at a small area level; socioeconomic factors can largely explain this association. Socioeconomic factors could play an important role in determining the wellbeing of the population, and this could inform policies aimed at enhancing population wellbeing.
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.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
Greenhouse studies indicated that 3,6-dichloro-o-anisic acid (dicamba) or its metabolic derivative was strongly accumulated in meristematic tissues of Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) and wild mustard (Sinapis arvensis L.) following both foliar and root uptake. In barley (Hordeum vulgare L.) and wheat (Triticum vulgare L.), it was distributed throughout the plants. Detoxification of dicamba occurred in all four species though not at equal rates, and a common major metabolite was identified chromatographically as 5-hydroxy-3,6-dichloro-o-anisic acid. A minor metabolite, 3,6-dichlorosalicylic acid, was found in barley and wheat but not in Tartary buckwheat or wild mustard. The four species tolerated dicamba treatment in the order of wheat, barley, wild mustard, and Tartary buckwheat. This ranking corresponds with the ability of the plants to detoxify dicamba and is inversely related to the extent of dicamba absorption and translocation in them.
Growth room and field studies indicated that coating the seeds of oats (Avena sativa L.) with NA (1,8-naphthalic anhydride) at rates of 0.5 to 1% by seed weight significantly reduced the phytotoxicity of barban (4-chloro-2-butynyl m-chlorocarbanilate) applied to the foliage at rates up to 1.2 kg/ha. Complete protection was obtained when barban was applied at 0.4 kg/ha, the highest rate recommended for the control of wild oats (Avena fatua L.) in cereal crops. Treatment of oat seeds with this antidote did not reduce the herbicidal effect of barban on wild oats grown in the same soil. Thus, coating oat seeds with the antidote may allow the use of barban for the selective control of wild oats in oat crops. NA seed treatment also slightly reduced oat injury from diallate [S-(2,3-dichloroallyl)diisopropylthiocarbamate] and triallate [S-(2,3,3-trichloroallyl)diisopropylthiocarbamate].
Added surfactant and high relative humidity enhanced penetration of 4-amino-3,5,6-trichloropicolinic acid (picloram) into leaves of Canada thistle (Cirsium arvense (L.) Scop.). Leaves and roots of Canada thistle readily absorbed picloram after which it was translocated in both phloem and xylem. Picloram tended to accumulate in young, growing leaves following both foliar and root uptake. In field-grown plants, injury symptoms appeared in young shoots as far as 1 m from treated shoots. The results are in harmony with a “source-to-sink” pattern of picloram translocation in the phloem. Leaves, but not roots, retained a substantial portion of the picloram absorbed. Following foliar application, small amounts of picloram were exuded by the roots into surrounding soil.
The herbicide 3,6-dichloro-o-anisic acid (dicamba) is very mobile in Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.), a susceptible weedy species. After foliar or root application, the compound was translocated rapidly to meristematic tissues at the shoot apex and in leaf axils. Redistribution of dicamba in the shoot, to young tissues, continued for at least 20 days. Metabolism of dicamba occurred very slowly, both in intact plants and in detached leaves, and the only metabolite detected was conjugated with sugars. The nonphytotoxic metabolite was identified by paper and thin-layer chromatography as 5-hydroxy-3,6-dichloro-o-anisic acid. Decarboxylation of dicamba also occurred in the plants but extremely slowly. The rapid entry and translocation of dicamba, its continued mobility in treated plants, and its very low rate of detoxification are major contributing factors to the effectiveness of dicamba for controlling Tartary buckwheat.
The foliage and roots of Canada thistle (Cirsium arvense (L.) Scop.) readily absorbed 2-methoxy-3,6-dichlorobenzoic acid (dicamba) after which it was translocated by both phloem and xylem. The results are in harmony with a source-to-sink system of dicamba translocation in the phloem. Following foliar application, small amounts of dicamba were exuded by the roots into surrounding soil. Dicamba tended to accumulate in young, growing leaves following both foliar or root uptake. Leaves, but not roots, retained a substantial portion of the dicamba taken up. After 54 days, 63.1% of the recovered radioactivity in the treated leaf was still in the form of unaltered dicamba. The remaining 36.9% was in the form of an unidentified product. In other plant parts, much less change occurred. During a 54-day period, one-fifth of the dicamba applied was recovered as radioactive CO2.
In growth room studies, N,N-diallyl-2,2-dichloroacetamide (hereafter referred to as R-25788) was the most effective of three antidotes for the reduction of EPTC (S-ethyl dipropylthiocarbamate) injury to corn (Zea mays L. ‘United Hybrid 106’). R-25788 reduced EPTC injury to corn as a seed treatment, as an incorporated soil spray, or in nutrient solution in quartz sand nutrient culture. CDAA (N,N-diallyl-2-chloroacetamide) was also an EPTC antidote for corn when applied to the soil or in nutrient solution but was itself toxic to corn when applied as a seed treatment. The antidote 1,8-naphthalic anhydride (hereafter referred to as naphthalic anhydride) was less effective than R-25788 as a seed treatment and was ineffective when applied to the soil. Naphthalic anhydride was the only one of the three antidotes which also reduced EPTC toxicity to green foxtail [Setaria viridis (L.) Beauv.].
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.
Method
The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.
Results
We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.
Conclusions
Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Three-dimensional integrated circuit packages with through-silicon vias (TSVs) provide a good solution to the integration of different chips and help achieve high performance. The signals are transmitted to different layers directly through the vias, thereby enabling the high performance of the chips. Plasma-enhanced chemical vapor-deposited SiO2, polyimide, and benzo-cyclo-butene are commonly used as the passivation layer for three-dimensional packages. In the 3D stacked chips, mismatch of the coefficient of thermal expansion between the passivation material and silicon will generate thermal/mechanical stress in the metal trace and the stress affects the behavior of electromigration. However, few studies have examined the relationship among the external mechanical stress and critical product of electromigration. In the present study, external stress is applied to the aluminum thin film by a four-point bending equipment. In order to apply higher external stress in the aluminum thin film, the fracture strength of the silicon substrate should be improved. Reduces the edge chipping of the test sample is a key factor for improving the fracture strength of the silicon substrate and a special cutting approach is employed to obtain higher silicon strength. A two-step cutting method is applied to reduce front side chipping and also a dicing before grinding approachis adopted to reduce backside chipping, the above-mentioned technology can enable more than 275MPa of external stress on the aluminum thin film and can make the critical length effect more visible. The residual stress of the aluminum thin film is at stress-free state after annealing at 300°C for 10h. The critical product is found to be reduced from 1,294A/cm to 1,281A/cm when 120MPa of mechanical tensile stress is applied. It increased to 1,315A/cm under 120MPa of mechanical compressive stress. Clearly, electromigration behavior is enhanced by tensile stress and decreased by compressive stress. In the current research, a modified equation for Blech condition is proposed with a stress-dependent effective charge number, the effective charge number increased when tensile stress was applied and decreased when compressive stress was applied.