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Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.
Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.
Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.
TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.
Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear.
Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified.
The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10–1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07–2.01) during the follow-up compared with the controls.
The unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.
Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.
Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.
FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.
Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.
Dilated Cardiomyopathy is a serious heart disorder that may induce sudden cardiac death and heart failure. Significant progress has been made in understanding the molecular basis of dilated cardiomyopathy. In previous studies, mutations in more than fifty genes have been identified in dilated cardiomyopathy patients. The purpose of this study was to detect the genetic lesion in a family from the central south of China affected by severe dilated cardiomyopathy.
Whole-exome sequencing combined with cardiomyopathy-related genes list were used to analyse the mutations of the proband. Co-segregation analysis was performed by Sanger sequencing.
Results and conclusions
Two novel heterozygous mutations – Myosin Binding Protein C: p.L1014RfsX6 and Titin: p.R9793X – were identified in the proband. The deletion mutation c.3041delT/p.L1014RfsX6 caused a premature stop codon at position 1020 in exon 28 of the Myosin Binding Protein C. The nonsense mutation, c.29377 C>T/ p. R9793X, of Titin was located in the highly evolutionarily conserved domain, resulting in truncation of the Titin protein as well. Co-segregation analysis further revealed that the Myosin Binding Protein C mutation came from his mother and the Titin mutation came from his father. Both mutations are reported in dilated cardiomyopathy patients for the first time. Our study not only provides a unique example of the genes and molecular mechanisms involved in dilated cardiomyopathy but also expands the spectrum of Myosin Binding Protein C and Titin mutations and contributes to the genetic diagnosis and counselling of dilated cardiomyopathy patients.
Attention-deficit hyperactivity disorder (ADHD) increases the risk of suicidal behaviours through psychiatric comorbidities; however, a significant direct association has not been observed between ADHD and suicide attempts.
To evaluate the risk of suicide attempt in adolescents and young adults with ADHD.
Using a nationwide, population-based insurance claims database, this longitudinal cohort study enrolled 20 574 adolescents and young adults with ADHD and 61 722 age- and gender-matched controls between 2001 and 2009. Any suicide attempt was identified from enrolment to 31 December 2011. The association between ADHD medications and the likelihood of suicide attempt was assessed.
ADHD was an independent risk factor for any suicide attempt (hazard ratio = 3.84, 95% CI = 3.19–4.62) and repeated suicide attempts (hazard ratio = 6.52, 95% CI = 4.46–9.53). Subgroup analyses of men, women, adolescents and young adults demonstrated the same trend. Methylphenidate or atomoxetine treatment did not increase the risk of suicide attempt or repeated suicide attempts. Long-term methylphenidate treatment was associated with a significantly decreased risk of repeated suicide attempts in men (hazard ratio = 0.46, 95% CI = 0.22–0.97).
ADHD was a risk factor for suicide attempt and a stronger predictor of repeated suicide attempts, independent of comorbidities. Further investigation is warranted to explore the mechanism underlying the association between ADHD and suicidal behaviours.
Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.
This paper presents a parameterized gait generator based on linear inverted
pendulum model (LIPM) theory, which allows users to generate a natural gait
pattern with desired step sizes. Five types of zero moment point (ZMP)
components are proposed for formulating a natural ZMP reference, where ZMP moves
continuously during single support phases instead of staying at a fixed point in
the sagittal and lateral plane. The corresponding center of mass (CoM)
trajectories for these components are derived by LIPM theory. To generate a
parameterized gait pattern with user-defined parameters, a gait planning
algorithm is proposed, which determines related coefficients and boundary
conditions of the CoM trajectory for each step. The proposed parameterized gait
generator also provides a concept for users to generate gait patterns with
self-defined ZMP references by using different components. Finally, the
feasibility of the proposed method is validated by the experimental results with
a teen-sized humanoid robot, David, which won first place in the sprint event at
the 20th Federation of International Robot-soccer Association (FIRA) RoboWorld
Obstacle avoidance is an important issue in robotics. In this paper, the particle
swarm optimization (PSO) algorithm, which is inspired by the collective
behaviors of birds, has been designed for solving the obstacle avoidance
problem. Some animals that travel to the different places at a specific time of
the year are called migrants. The migrants also represent the particles of PSO
for defining the walking paths in this work. Migrants consider not only the
collective behaviors, but also geomagnetic fields during their migration in
nature. Therefore, in order to improve the performance and the convergence speed
of the PSO algorithm, concepts from the migrant navigation method have been
adopted for use in the proposed hybrid particle swarm optimization (H-PSO)
algorithm. Moreover, the potential field navigation method and the designed
fuzzy logic controller have been combined in H-PSO, which provided a good
performance in the simulation and the experimental results. Finally, the
Federation of International Robot-soccer Association (FIRA) HuroCup Obstacle Run
Event has been chosen for validating the feasibility and the practicability of
the proposed method in real time. The designed adult-sized humanoid robot also
performed well in the 2015 FIRA HuroCup Obstacle Run Event through utilizing the
Multi-wavelength flares have routinely been observed from the supermassive black hole, Sagittarius A⋆ (Sgr A⋆), at our Galactic center. The nature of these flares remains largely unclear, despite many theoretical models. We study the statistical properties of the Sgr A⋆ X-ray flares and find that they are consistent with the theoretical prediction of the self-organized criticality system with the spatial dimension S = 3. We suggest that the X-ray flares represent plasmoid ejections driven by magnetic reconnection (similar to solar flares) in the accretion flow onto the black hole. Motivated by the statistical results, we further develop a time-dependent magnetohydrodynamic (MHD) model for the multi-band flares from Sgr A⋆ by analogy with models of solar flares/coronal mass ejections (CMEs). We calculate the X-ray, infrared flare light curves, and the spectra, and find that our model can explain the main features of the flares.
X-ray powder diffraction data, unit-cell parameters, and space group for thiamphenicol, C12H15Cl2NO5S, are reported [a = 17.346(3), b = 15.341(0), c = 5.790 (2) Å, α = β = γ = 90°, unit-cell volume V = 1540.8(3) Å3, Z = 4, and space group P212121]. All measured lines were indexed and are consistent with the P212121 space group. No detectable impurities were observed.
X-ray powder diffraction data for 1-(4-aminophenyl)-5,6-dihydro-3-(4-morpholinyl)-2(1H)-pyridinone, C15H19N3O2, are reported [a = 14.877(4) Å, b = 5.893(6) Å, c = 18.984(3) Å, α = 90°, β = 122.298(3)°, γ = 90°, unit-cell volume V = 1406.86 Å3, Z = 4, and space group P21/c]. All measured lines were indexed and are consistent with the P21/c space group. No detectable impurities were observed.
A 36-year-old woman, who had a history of myomectomy, presented with lightheadedness after changing position from sitting to standing and effort-related shortness of breath. Echocardiography demonstrated a hyperechoic elongated mobile mass extending from the inferior caval vein to the right atrium. The mass was surgically removed, and histological examination established the diagnosis of intravenous leiomyomatosis. This case caught the attention of our cardiology group to consider the diagnosis when an inferior caval vein or right atrium mass is found in a patient with a history of uterine leiomyomatosis.
Previous evidence has shown positive associations between post-traumatic
stress disorder (PTSD) and hypertension, dyslipidaemia and diabetes
mellitus, which are all risk factors for stroke, but the role of PTSD in
the subsequent development of stroke is still unknown.
To investigate the temporal association between PTSD and the development
Identified from the Taiwan National Health Insurance Research Database,
5217 individuals aged 18 years, with PTSD but with no history of stroke,
and 20 868 age- and gender-matched controls were enrolled between 2002
and 2009, and followed up until the end of 2011 to identify the
development of stroke.
Individuals with PTSD had an increased risk of developing any stroke
(hazard ratio (HR) 3.37, 95% CI 2.44–4.67) and ischaemic stroke (HR =
3.47, 95% CI 2.23–5.39) after adjusting for demographic data and medical
comorbidities. Sensitivity tests showed consistent findings (any stroke
HR = 3.02, 95% CI 2.13–4.28; ischaemic stroke HR = 2.89, 95% CI
1.79–4.66) after excluding the first year of observation.
Individuals with PTSD have an increased risk of developing any stroke and
ischaemic stroke. Further studies are required to investigate the
In order to obtain the dynamic variation rule of the sulfur content of liquid steel in
the LF refining process, a complete mathematical model including a desulfurization kinetic
model and temperature model in the deep desulfurization process is presented, based on the
practical production and reaction mechanism of ultra-low-sulfur steel in a LF. The results
show that the calculated values of the sulfur content in liquid steel using the model fit
the experimental values well, and the relative error is less than 8%. The effects of
refining slag on the desulfurization process are analyzed in this paper, which shows that
slag basicity is most important at the early and middle stages of the process, while slag
weight is most important at the middle and late stages. The effect of the above factors on
the final sulfur content of liquid steel is further analyzed quantitatively. The simulated
results provide a theoretical basis to segment control the refining process in order to
achieve the maximum effect, improving efficiency, saving energy and reducing
The authors investigated the effects of annealing in Ar atmosphere at different temperatures (350–1100 °C) on the densification and leakage current characteristics of thermally oxidized SiO2 films on n-type 4H-SiC. A strong correlation between densification improvement and leakage current reduction was observed. Densification of the SiO2 films, which were characterized by spectroscopic ellipsometry, Fouriertransform infrared spectroscopy and atomic force microscopy, can be significantly improved after annealing at moderate temperature (600 °C). The leakage current is decreased by two orders of magnitude of the SiO2 thin film after annealing at 600 °C. Based on the studies, SiO2 film of the highest quality can be obtained after annealing at 600 °C. Improvements in the quality of the SiO2 thin films after annealing at 600 °C may be explained by the consumption and formation of carbon-related and oxygen-related defects during annealing.
The optical properties of graphene-based nanomaterials have attracted much recent attention. This article provides an overview of recent advances in the study of linear and nonlinear optical transitions associated mostly with tailored energy bandgaps. In particular, the optical absorption characteristics and photoluminescence emissions due to various induced bandgaps and, in some cases, the formation of graphene quantum dots are highlighted. Nonlinear optical properties of these materials are reviewed with an emphasis on optical limiting through both nonlinear absorption and scattering mechanisms.
People with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder.
We aimed to compare the rates of a change in diagnosis to bipolar disorder among people with major depressive disorder with stratified responses to antidepressants during an 8-year follow-up period.
Information on individuals with major depressive disorder identified during 2000 (cohort 2000, n = 1485) and 2003 (cohort 2003, n = 2459) were collected from a nationally representative cohort of 1 000 000 health service users in Taiwan. Participants responding well to antidepressants were compared with those showing poor responses to adequate trials of antidepressants.
In 7.6–12.1% of those with a diagnosis of unipolar major depressive disorder this diagnosis was subsequently changed to bipolar disorder, with a mean time to change of 1.89–2.98 years. Difficult-to-treat participants presented higher rates of change to a bipolar diagnosis (25.6% in cohort 2000; 26.6% in cohort 2003) than easy-to-treat participants (8.8–8.9% in cohort 2000; 6.8–8.6% in cohort 2003; P<0.0001). Regression analysis showed that the variable most strongly associated with the change in diagnosis was antidepressant use history. The difficult-to-treat participants were associated most with diagnostic changing (cohort 2000: odds ratio (OR) = 1.88 (95% CI 1.12–3.16); cohort 2003: OR = 4.94 (95% CI 2.81–8.68)).
This is the first large-scale study to report an association between antidepressant response history and subsequent change in diagnosis from major depressive disorder to bipolar disorder. Our findings support the view that a history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar diathesis.
Chemical bath deposition (CBD) techniques for the growth of CdS polycrystalline thin films are now well developed. However, there usually appear different structures, grain sizes and energy gaps in CdS polycrystalline films by CBD, which implies that the influence of growth process on the structures and properties of CBD CdS thin films must be considered. In this paper, the optical, compositional and structural properties of CBD CdS thin films in the reaction process have been studied by XRD, AFM, XPS and optical transmission spectra measurements. The results can be explained using atomic mechanism and lattice transition in the CdS thin films.
A single choice test was performed to examine developmental strategies in the uniparental endoparasitoid Meteorus pulchricornis and its host, the cotton bollworm Helicoverpa armigera. The results support the dome-shaped model in which the fitness functions are ‘dome-shaped’ relative to size (and age) of host at parasitism. Older and, hence, larger host larvae were simply not better hosts for the developing parasitoids. Although parasitoid size (measured as cocoon weight and adult hind tibia length) was positively correlated with host instars at parasitism, parasitoids developing in larger hosts (L5 and L6) suffered much higher mortality than conspecifics developing in smaller hosts (L2–L4). Furthermore, egg-to-adult development time in M. pulchricornis was significantly longer in older host larvae (L4–L6) than in the younger. Performance of M. pulchricornis, as indicated by fitness-related traits, strongly suggests that the L3 host is the most suitable for survival, growth and development of the parasitoid, followed by both L2 and L4 hosts; whereas, L1, L5 and L6 are the least favourable hosts. The oviposition tendency of M. pulchricornis, represented by parasitism level, was not perfectly consistent with the performance of the offspring; L2–L4 hosts, although with the same parasitism level, had offspring parasitoids with differences in fitness-related performance. Larval development in Helicoverpa armigera was usually suspended, but occasionally advanced, in the final instar.