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Lower-crust-derived adakitic rocks in the Gangdese belt provide important constraints on the timing of Tibetan crustal thickening and on the relative contributions of magmatic and tectonic processes. Here we present geochronological and geochemical data for the Wangdui porphyritic monzogranites in the western Gangdese belt. Zircon U–Pb dating yields emplacement ages of 46–44 Ma. All samples have high Sr (321–599 ppm), low Yb (0.76–1.33 ppm) and Y (10.6–18.3 ppm) contents, with high La/Yb (51.1–72.3) and Sr/Y (21.0–51.4) ratios, indicating adakitic affinities. The low MgO (0.97–1.76 wt %), Cr (7.49–53.6 ppm) and Ni (4.75–29.1 ppm) contents, as well as high 87Sr/86Sr(i) (0.7143–0.7145), low ϵNd(t) (−10.4 to −9.8) and zircon ϵHf(t) (−17.7 to 0.4) values, suggest that the Wangdui pluton most likely originated from partial melting of the thickened ancient lower crust. In combination with previously published data, despite the east–west-trending heterogeneity of crustal composition in the Gangdese belt, the La/Yb ratios of magmatic rocks reveal that both western and eastern segments experienced remarkable crustal thickening in the Eocene. However, in contrast to the thickened juvenile lower crust in the eastern segment formed by the underplating of mantle-derived magmas, tectonic shortening plays a more crucial role in thickening of the ancient basement in western Gangdese. In fact, such Eocene-thickened ancient lower-crust-derived adakitic rocks are widely distributed in the central Himalayan–Tibetan orogen. This, together with the extensive development of fold–thrust belts, suggests that tectonic shortening might be the main mechanism accounting for the crustal thickening associated with the India–Asia collision.
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global health crisis that may cause mental health problems and heighten suicide risk. We investigated the impact of the COVID-19 pandemic on trends in suicide attempts and suicide deaths in New Taipei City, Taiwan.
Methods
The current study used the official daily data on suicide attempts and deaths in New Taipei City, Taiwan (4 million inhabitants) between 2015 and 2020 from the Taiwan National Suicide Prevention Reporting System. Interrupted time-series (ITS) analyses with parameters corrected by the estimated autocorrelations were applied on weekly aggregated data to examine whether the suicide trends during the early COVID-19 pandemic (late January to July 2020) deviated from previous trends (January 2015 to late January 2020). The impact due to the suicide prevention policy change was also examined (since August 2020).
Results
ITS analyses revealed no significant increases in both mean and trend on weekly suicide deaths during the COVID-19 pandemic and after the policy change. In contrast, there was a significant increasing trend in weekly suicide attempts since the COVID-19 outbreak at the rate of 1.54 attempts per week (95% confidence interval 0.49–2.60; p = 0.004). Sex difference analysis revealed that, however, this increasing trend was observed only in females not in males.
Conclusions
The COVID-19 pandemic has different impacts on suicides attempts and deaths during the early pandemic in New Taipei City, Taiwan. The COVID-19 outbreak drastically increased the trend of suicide attempts. In contrast, the number of suicide deaths had remained constant in the investigated periods.
A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups.
Methods
This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups.
Results
The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups.
Conclusions
Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.
Traditionally, the strata of the Luonie Valley, Dechang County, SW Sichuan, China, are considered to contain a suite of felsic volcanic rocks (the Huili Group) that erupted after c. 1050 Ma. However, we report here new age constraints, elemental and Lu–Hf isotope geochemistry for a different suite of older basaltic agglomerate lava, basaltic tuff lava and basalt from the same area, which we name the Luonie Formation. New dating results show that the basaltic volcanic suite of the upper part of the Luonie Formation formed at 1126.1 ± 9.9 Ma, significantly earlier than deposition of the Huili Group, but comparable in age to the 1142 ± 16 Ma Laowushan Formation in central Yunnan Province. Granite intrusion into the Luonie Formation dated 1050.7 ± 12.7 Ma provides crucial supporting evidence for this earlier depositional age. We also report a maximum sedimentary age of c. 1158 Ma for the underlying arkose, implying stratigraphic conformity with the basaltic volcanic rock suite.
The ϵHf(t) values of the basaltic volcanic rocks are mainly positive, indicating that the rocks are mainly derived from the depleted mantle and slightly stained by crustal materials. The characteristics of P*, Nb* and Zr* anomalies also support this view. The distribution patterns of trace and rare earth elements indicate that the basaltic volcanic rocks formed in an extensional setting. The Zr/4–Y–2Nb and Th–Nb/16–Zr/117 discrimination diagrams also provide evidence for this understanding. Lithofacies analysis shows that basaltic volcanic wrocks with the characteristics of both continental and marine facies should be formed in a littoral–neritic environment. We propose here that the evidence is consistent with a phase of continental extension that preceded the convergence of the SW Yangtze Block to form part of Rodinia.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
Aims
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
Method
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
Results
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
Conclusions
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
During the first postnatal week in rodents, cholinergic retinal waves initiate in starburst amacrine cells (SACs), propagating to retinal ganglion cells (RGCs) and visual centers, essential for visual circuit refinement. By modulating exocytosis in SACs, dynamic changes in the protein kinase A (PKA) activity can regulate the spatiotemporal patterns of cholinergic waves. Previously, cysteine string protein-α (CSPα) is found to interact with the core exocytotic machinery by PKA-mediated phosphorylation at serine 10 (S10). However, whether PKA-mediated CSPα phosphorylation may regulate cholinergic waves via SACs remains unknown. Here, we examined how CSPα phosphorylation in SACs regulates cholinergic waves. First, we identified that CSPα1 is the major isoform in developing rat SACs and the inner plexiform layer during the first postnatal week. Using SAC-specific expression, we found that the CSPα1-PKA-phosphodeficient mutant (CSP-S10A) decreased wave frequency, but did not alter the wave spatial correlation compared to control, wild-type CSPα1 (CSP-WT), or two PKA-phosphomimetic mutants (CSP-S10D and CSP-S10E). These suggest that CSPα-S10 phosphodeficiency in SACs dampens the frequency of cholinergic waves. Moreover, the level of phospho-PKA substrates was significantly reduced in SACs overexpressing CSP-S10A compared to control or CSP-WT, suggesting that the dampened wave frequency is correlated with the decreased PKA activity. Further, compared to control or CSP-WT, CSP-S10A in SACs reduced the periodicity of wave-associated postsynaptic currents (PSCs) in neighboring RGCs, suggesting that these RGCs received the weakened synaptic inputs from SACs overexpressing CSP-S10A. Finally, CSP-S10A in SACs decreased the PSC amplitude and the slope to peak PSC compared to control or CSP-WT, suggesting that CSPα-S10 phosphodeficiency may dampen the speed of the SAC-RGC transmission. Thus, via PKA-mediated phosphorylation, CSPα in SACs may facilitate the SAC-RGC transmission, contributing to the robust frequency of cholinergic waves.
Direct numerical simulation of spanwise-rotation-driven flow transitions in viscoelastic plane Couette flow from a drag-reduced inertial to a drag-enhanced elasto-inertial turbulent flow state followed by full relaminarization is reported for the first time. Specifically, this novel flow transition begins with a drag-reduced inertial turbulent flow state at a low rotation number $0\leqslant Ro \leqslant 0.1$, and then transitions to a rotation/polymer-additive-driven drag-enhanced inertial turbulent regime, $0.1\leqslant Ro \leqslant 0.3$. In turn, the flow transitions to a drag-enhanced elasto-inertial turbulent state, $0.3\leqslant Ro \leqslant 0.9$, and eventually relaminarizes at $Ro=1$. In addition, two novel rotation-dependent drag enhancement mechanisms are proposed and substantiated. (1) The formation of large-scale roll cells results in enhanced convective momentum transport along with significant polymer elongation and stress generated in the extensionally dominated flow between adjacent roll cells at $Ro\leqslant 0.2$. (2) Coriolis-force-generated turbulent vortices cause strong incoherent transport and homogenization of significant polymer stress in the bulk via their vortical circulations at $Ro=0.5 - 0.9$.
The flow physics of inertio-elastic turbulent Taylor–Couette flow for a radius ratio of $0.5$ in the Reynolds number ($Re$) range of $500$ to $8000$ is investigated via direct numerical simulation. It is shown that as $Re$ is increased the turbulence dynamics can be subdivided into two distinct regimes: (i) a low $Re \leqslant 1000$ regime where the flow physics is essentially dominated by nonlinear elastic forces and the main contribution to transport and mixing of momentum, stress and energy comes from large-scale flow structures in the bulk region and (ii) a high $Re \geqslant 5000$ regime where inertial forces govern the flow physics and the flow dynamics is mainly governed by small-scale flow structures in the near-wall region. Flow–microstructure coupling analysis reveals that the elastic Görtler instability in the near-wall region is triggered via significant polymer extension and commensurately high hoop stresses. This instability gives rise to small-scale elastic vortical structures identified as elastic Görtler vortices which are present at all $Re$ considered. In fact, these vortices develop herringbone streaks near the inner wall that have a longer average life span than their Newtonian counterparts due to their elastic origin. Examination of the budgets of mean streamwise enstrophy, mean kinetic energy, turbulent kinetic energy and Reynolds shear stress demonstrates that increasing fluid inertia hinders the generation of elastic stresses, leading to a monotonic reduction of the elastic-related effects on the flow physics.
Although democratic governance imposes temporal constraints, the timing of government policy making activities such as bill initiation is still poorly understood. This holds especially under coalition governments, in which government bills need to find approval by a partner party in parliament. We propose a dynamic temporal perspective in which ministers do not know whether they face a cooperative or competitive partner at the beginning of a term, but they learn this over time and use their agenda control to time further bill initiation in response. A circular regression analysis using data on more than 25,000 government bills from 11 parliamentary democracies over 30 years supports this temporal perspective, showing that ministers initiate bills later in the term when their previous bills have experienced greater scrutiny. Ministers further delay bill initiation when coalition parties’ incentives to deviate from compromise increase and when they have less power to constrain their bills’ scrutiny.
The results of epidemiological studies involving n-3 PUFA and polycystic ovary syndrome (PCOS) are scarce. This matched case–control study assessed the associations between n-3 PUFA and PCOS prevalence in 325 pairs of PCOS cases and healthy controls. Dietary information was assessed using a 102-item FFQ. Fatty acids in serum phospholipids were measured with a GC method. We found that n-3 PUFA in serum phospholipids were inversely associated with PCOS prevalence, including total, long-chain and individual PUFA (e.g. docosapentaenoic acid (DPA), EPA and DHA). Compared with the lowest tertile (T1), the adjusted OR and their 95% CI for the highest tertile (T3) were 0·63 (0·40, 0·93) for total n-3 PUFA, 0·60 (0·38, 0·92) for long-chain n-3 PUFA, 0·68 (0·45, 1·01) for DHA, 0·70 (0·45, 1·05) for EPA and 0·72 (0·45, 1·08) for DPA. For dietary intake of n-3 PUFA, significant inverse associations were found only for long-chain n-3 PUFA (Ptrend = 0·001), EPA (Ptrend = 0·047) and DHA (Ptrend = 0·030). Both dietary and serum n-3 PUFA, mainly EPA and DPA, were negatively correlated with PCOS-related parameters, such as BMI, fasting insulin, total testosterone and high-sensitivity C-reactive protein, but positively correlated with follicle-stimulating hormone and sex hormone-binding globulin. These results indicated inverse associations between n-3 PUFA, especially long-chain n-3 PUFA, and PCOS prevalence. Higher intakes of n-3 PUFA might be considered a protective factor for PCOS among Chinese females.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
Embryogenic callus induction and regeneration are useful in many aspects of plant biotechnology, especially in the functional characterization of economically important genes. However, in sugarcane, callus induction and regeneration vary across genotypes. Saccharum spontaneum is an important wild germplasm that confers disease resistance and stress tolerance to modern sugarcane cultivars, and its genome has been completely sequenced. The aim of this study was to investigate the effect of genetic variations on embryogenic callus induction and regeneration in S. spontaneum and to screen genotypes having high tissue culture susceptibility. The study was performed using nine genotypes of S. spontaneum and the following five parameters were assessed to determine the response of genotypes to embryogenic callus induction and regeneration: callus induction, embryogenic callus ratio, embryogenic callus induction, embryonic callus regeneration and regeneration capacity. All the genotypes varied significantly (P < 0.01) in all the parameters, except for embryonic callus regeneration, which was high (>80%) for all the genotypes. High broad-sense heritability (86.1–96.8%) indicated that genetic differences are the major source of genotypic variations. Callus induction was found to be strongly positively correlated with embryogenic callus induction (r = 0.890, P < 0.01) and regeneration capacity (r = 0.881, P < 0.01). Among the nine tested genotypes, VN2 was found to be the most responsive to tissue culture and could therefore be used to characterize functional genes in S. spontaneum. We also suggested an approach with potential applications in facilitating the rapid identification of sugarcane genotypes susceptible to tissue culture.
Direct numerical simulations (DNS) of oscillatory flow around a cylinder show that the Stokes–Wang (S–W) solution agrees exceptionally well with DNS results over a much larger parameter space than the constraints of $\beta K^2\ll 1$ and $\beta \gg 1$ specified by the S–W solution, where $K$ is the Keulegan–Carpenter number and $\beta$ is the Stokes number. The ratio of drag coefficients predicted by DNS and the S–W solution, $\varLambda _K$, mapped out in the $K\text {--}\beta$ space, shows that $\varLambda _K < 1.05$ for $K\leq {\sim }0.8$ and $1 \leq \beta \leq 10^6$, which contradicts its counterpart based on experimental results. The large $\varLambda _K$ values are primarily induced by the flow separation on the cylinder surface, rather than the development of three-dimensional (Honji) instabilities. The difference between two-dimensional and three-dimensional DNS results is less than 2 % for $K$ smaller than the corresponding $K$ values on the iso-line of $\varLambda _K = 1.1$ with $\beta = 200\text {--}20\,950$. The flow separation actually occurs over the parameter space where $\varLambda _K\approx 1.0$. It is the spatio-temporal extent of flow separation rather than separation itself that causes large $\varLambda _K$ values. The proposed measure for the spatio-temporal extent, which is more sensitive to $K$ than $\beta$, correlates extremely well with $\varLambda _K$. The conventional Morison equation with a quadratic drag component is fundamentally incorrect at small $K$ where the drag component is linearly proportional to the incoming velocity with a phase difference of ${\rm \pi} /4$. A general form of the Morison equation is proposed by considering both viscous and form drag components and demonstrated to be superior to the conventional equation for $K < {\sim }2.0$.
Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China.
Methods
Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions.
Results
The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty.
Conclusions
This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.
The coronavirus disease 2019 (COVID-19) pandemic is a major threat to the public. However, the comprehensive profile of suicidal ideation among the general population has not been systematically investigated in a large sample in the age of COVID-19.
Methods
A national online cross-sectional survey was conducted between February 28, 2020 and March 11, 2020 in a representative sample of Chinese adults aged 18 years and older. Suicidal ideation was assessed using item 9 of the Patient Health Questionnaire-9. The prevalence of suicidal ideation and its risk factors was evaluated.
Results
A total of 56,679 participants (27,149 males and 29,530 females) were included. The overall prevalence of suicidal ideation was 16.4%, including 10.9% seldom, 4.1% often, and 1.4% always suicidal ideation. The prevalence of suicidal ideation was higher in males (19.1%) and individuals aged 18–24 years (24.7%) than in females (14.0%) and those aged 45 years and older (11.9%). Suicidal ideation was more prevalent in individuals with suspected or confirmed infection (63.0%), frontline workers (19.2%), and people with pre-existing mental disorders (41.6%). Experience of quarantine, unemployed, and increased psychological stress during the pandemic were associated with an increased risk of suicidal ideation and its severity. However, paying more attention to and gaining a better understanding of COVID-19-related knowledge, especially information about psychological interventions, could reduce the risk.
Conclusions
The estimated prevalence of suicidal ideation among the general population in China during COVID-19 was significant. The findings will be important for improving suicide prevention strategies during COVID-19.
High fibre intake is associated with reduced mortality risk in both general and chronic kidney disease populations. However, in dialysis patients, such data are limited. Therefore, the association between dietary fibre intake (DFI) and the risk of all-cause and CVD mortality was examined in this study. A total of 1044 maintenance haemodialysis (MHD) patients from eight outpatient dialysis centres in China were included in this study. Data on DFI were collected using 24-h dietary recalls for 3 d in a week and were normalised to actual dry weight. The study outcomes included all-cause and CVD mortality. Over a median of 46 months of follow-up, 354 deaths were recorded, of which 210 (59 %) were due to CVD. On assessing DFI as tertiles, the CVD mortality risk was significantly lower in patients in tertiles 2–3 (≥0·13 g/kg per d; hazard ratio (HR) 0·71; 95 % CI 0·51, 0·97) compared with those in tertile 1 (<0·13 g/kg per d). A similar but non-significant trend was found for the association between DFI (tertiles 2–3 v. tertile 1; HR 0·83; 95 % CI 0·64, 1·07) and all-cause mortality. In summary, higher DFI was associated with lower CVD mortality risk among Chinese MHD patients. This study emphasises the significance of DFI in MHD patients and provides information that is critical for the improvement of dietary guidelines for dialysis patients.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.
Little is known about methylphenidate (MPH) use and mortality outcomes.
Aims
To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis.
Method
This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4–17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan.
Results
The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67–0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01–1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70–0.98).
Conclusions
MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.