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In order to reveal the quantitative relationship between fatigue crack deflection path and cross-sectional grain boundary (GB) arrangement of metallic nanolayered composites (NLCs), a stochastic model was established based on the interface-dominant fatigue damage for the ultrafine-scale NLCs. The model indicates that the crack deflection length decreases with decreasing GB arrangement deviation and grain size of constituent layers. The observation and quantitative analysis of fatigue cracking behavior of the Cu/W multilayers with a layer thickness of 5 and 20 nm was conducted to verify the model.
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.
Fatigue properties of Mo/W multilayers with individual layer thickness (λ) of 5, 20, 50 and 100 nm on flexible polyimide substrates were investigated. The experimental results show that the fatigue resistance increases with decreasing λ from 100 nm to 20 nm, and reaches the maximum at λ=20 nm, and then decreases when further decreasing λ. Fatigue cracks of Mo/W multilayers with different λ were found to propagate along columnar grain boundary in the out-of-plane direction and along the boundary of cluster structures. The enhanced fatigue resistance is attributed to the larger cluster inclination angles and the more tortuous in-plane cracking paths.
Fatigue performance of metallic nanolayered composites (NLCs) has been gaining more and more attention due to the rapid development in the field of both micro-electro-mechanical systems and high-performance engineering structure materials and the increasing demand for long-term fatigue reliability. Metallic NLCs have exhibited different damage behaviors due to the effect of high-density heterogeneous interface compared with bulk materials and thin metal films. In this review paper, the cyclic deformation damage behavior, fatigue cracking feature, and fatigue properties of some metallic NLCs are reviewed. Effects of length scales, including layer thickness and grain size, on fatigue damage behaviors of the NLCs are revealed, and the transition of the fatigue cracking behavior and the corresponding damage mechanism are discussed. Then, the fatigue properties of some typical metallic NLCs are presented and compared with that of bulk materials and metal thin films. The effect of interface type and grain boundary alignment is also discussed to correlate with fatigue cracking resistance of the NLCs. Finally, some prospective research topics on fatigue performance of metallic NLCs are addressed.
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.
We present for the first time the feasibility to recover the stiffness (here shear modulus) distribution of a three-dimensional heterogeneous sample using measured surface displacements and inverse algorithms without making any assumptions about local homogeneities and the stiffness distribution. We simulate experiments to create measured displacements and augment them with noise, significantly higher than anticipated measurement noise. We also test two-dimensional problems in plane strain with multiple stiff inclusions. Our inverse strategy recovers the shear modulus values in the inclusions and background well, and reveals the shape of the inclusion clearly.
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.
Stretchability of polyimide-supported nanocrystalline Au films with a thickness ranging from 930 to 20 nm was evaluated by uniaxial tensile testing. The results show that the fracture strain gradually decreased with decreasing the film thickness. Such degraded stretchability depends on plastic deformation mechanisms associated with the length scales. As the film thickness is larger than 90 nm, local thinning in the grown grains contributed to the high stretchability. Full dislocation behaviors including dislocation pileup in the 930 nm-thick film, the activation of Frank–Read dislocation source in the 170 nm-thick film and the grain boundary dislocation source in the 90 nm-thick film were dominated plastic deformation. As the film thickness is less than 40 nm, low stretchability of thin films resulted from intergranular fracture, and partial dislocation behaviors became prevailed. Evident grain growth happened in the films studied except for the 20 nm-thick film, which is expected to be involved in the stretchability of the nanocrystalline metal films on flexible substrates.
Ralstonia pickettii has caused contamination of pharmaceutical solutions in many countries, resulting in healthcare infections or outbreak events. We determined the source of the outbreak of R. pickettii bloodstream infection (BSI).
This study was conducted in a 3,000-bed tertiary referral medical center in Taiwan with >8,500 admissions during May 2015. Patients had been treated in the injection room or chemotherapy room at outpatient departments, emergency department, or hospital wards. All patients who were culture positive for R. pickettii from May 3 to June 11, 2015, were eligible for the study. The aim of the survey was to conduct clinical epidemiological and microbiological investigations to identify possible sources of infection.
We collected 57 R. pickettii–positive specimens from 30 case patients. We performed 24 blood cultures; 14 of these revealed >2 specimens and 6 used fluid withdrawn from Port-a-Cath implantable venous access devices. All patients received an injection of 20 mL 0.9% normal saline via catheter flushing. In addition, 2 unopened ampules of normal saline solution (20 mL) were confirmed positive for R. pickettii. The Taiwan Centers for Disease Control and Prevention performed sampling and testing of the same manufactured batch and identified the same strain of R. pickettii. Pulsed-field gel electrophoresis tests revealed that all clinical isolates had similarity of >90%, validating the outbreak of the same clone of R. pickettii.
R. pickettii can grow in saline solutions and cause bloodstream infections. Hospital monitoring mechanisms are extremely important measures in identifying and ending such outbreaks.
The prevalence and factors associated with delays in help seeking for people with dementia in China are unknown.
Within 1,010 consecutively registered participants in the Clinical Pathway for Alzheimer's Disease in China (CPAD) study (NCT01779310), 576 persons with dementia (PWDs) and their informants reported the estimated time from symptom onset to first medical visit seeking diagnosis. Univariate analysis of general linear model was used to examine the potential factors associated with the delayed diagnosis seeking.
The median duration from the first noticeable symptom to the first visit seeking diagnosis or treatment was 1.77 years. Individuals with a positive family history of dementia had longer duration (p = 0.05). Compared with other types of dementia, people with vascular dementia (VaD) were referred for diagnosis earliest, and the sequence for such delays was: VaD < Alzheimer's disease (AD) < frontotemporal dementia (FTD) (p < 0.001). Subtypes of dementia (p < 0.001), family history (p = 0.01), and education level (p = 0.03) were associated with the increased delay in help seeking.
In China, seeking diagnosis for PWDs is delayed for approximately 2 years, even in well-established memory clinics. Clinical features, family history, and less education may impede help seeking in dementia care.
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
To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.
An intervention trial.
Shenzhen City, Guangdong Province, China.
From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.
For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.
For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.
This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients.
From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status.
Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30–1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25–2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders.
We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.
Previous studies have suggested that the daidzein metabolite equol rather than daidzein itself contributes to the beneficial effect of soya foods in the prevention of CVD. The aim of the present study is to examine the proportion of equol excretion in Chinese adults and compare plasma lipids and carotid artery intima–media thickness (IMT) between equol excretors and non-excretors, and to evaluate the effect of soya isoflavone intakes on serum lipids and IMT in either equol excretors or non-excretors. Subjects (n 572; women n 362, men n 210) were recruited for the present study. An overnight urine sample was provided by each subject on their usual diet to quantify urinary concentrations of daidzein and equol. Far-wall IMT was determined by B-mode ultrasound in the right carotid at two sites, carotid bulb (CB-IMT) and common carotid artery (CCA-IMT), and fasting serum lipids were measured. Habitual dietary intakes were estimated with a FFQ, and soya isoflavone intake derived from the FFQ was assessed. Of the 572 subjects, the proportion of equol excretors on their usual diet was 25·0 % (n 143). Compared with non-excretors, equol excretors showed significantly lower serum TAG ( − 38·2 (95 % CI − 70·4, − 5·9) %, P = 0·012) and CCA-IMT ( − 4·9 (95 % CI − 9·7, − 0·3) %, P = 0·033). Equol excretors with higher daily isoflavone intakes ( − 5·4 mg/d) had significantly lower IMT ( − 16·2 %, P = 0·035) and tended to have higher HDL-cholesterol (P = 0·055) than did those with lower daily isoflavone intakes (1·5 mg/d), while no association was observed between soya isoflavone intakes and serum lipids or IMT in non-excretors. In conclusion, the benefits of soya isoflavones in preventing CVD may be apparent among equol excretors only.
The aim of this study was to evaluate the therapeutic effects of osteopontin neutralization treatment on schistosome-induced liver injury in BALB/C mice. We randomly divided 100 BALB/C mice into groups A, B, C, D and group E. Mice in all groups except group A were abdominally infected with schistosomal cercariae to induce a schistosomal hepatopathological model. Mice in group C, D and group E were respectively administered with praziquantel, praziquantel plus colchicine and praziquantel plus neutralizing osteopontin antibody. We extracted mouse liver tissues at 3 and 9 weeks after the ‘stool-eggs-positive’ day, observed liver histopathological changes by haematoxylin-eosin and Masson trichrome staining and detected the expression of osteopontin, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β1) by immunohistochemistry, RT-PCR and Western blot. We found that praziquantel plus neutralizing osteopontin antibody treatment significantly decreased the granuloma dimension, the percentage of collagen and the expression of osteopontin, α-SMA and TGF-β1 compared to praziquantel plus colchicine treatment in both the acute and chronic stage of schistosomal liver damage (P<0·05). So we believe that the combined regimen of osteopontin immunoneutralization and anti-helminthic treatment can reduce the granulomatous response and liver fibrosis during the schistosomal hepatopathologic course.
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.
Male and female Schistosoma japonicum worms have dissimilar appearances in their final host. In this study, a morphometric and morphological assessment of whole worms derived from unisexual and mixed infections in mice was conducted using confocal laser scanning microscopy. Worms from mixed infections showed significant morphological changes between 15 and 25 days post-infection (PI). On the fifteenth day PI, 33% of males had formed the conspicuous gynecophoric canal, but only 8% of them had testicular lobes containing a few germinative cells; 13% of females had incipient ovaries with a few immature ovarian cells inside. On the twentieth day PI, the testicular lobes contained more germinative cells in all male worms, while female worms presented vitelline glands. On the twenty-fifth day PI, more germinative cells were observed in the male testicular lobes, and differentiated cells were present in the female ovaries. All worms had fully developed reproductive organs from 30 days PI onwards. Morphometric analysis showed significant differences between mixed and unisexual infections at 35 days PI. Ovaries of worms from unisexual infections contained cells in one stage of maturation and vitelline glands had undifferentiated cells. Our study of S. japonicum provides a detailed comparison of different morphological traits from worms of mixed and unisexual infections throughout development.
Continuous-wave (cw) indium-gallium nitride (InGaN) multiple-quantum-well (MQW) laser diodes (LDs) were successfully transferred from sapphire onto copper and diamond substrates using a two-step laser lift-off (LLO) process. Reduced threshold currents and increased differential quantum efficiencies were measured for LDs on Cu due to a 50% reduction of the thermal impedance. Light output for LDs on Cu was three times greater than comparable LDs on sapphire with a maximum output of 30 mW. Increased light output for LDs on diamond were also measure with a maximum output of 80 mW.
Impedance spectroscopy (IS) has been used to characterise the degradation of thermal barrier coatings (TBCs) due to thermal treatments at 1100°C for a period up to 200 hrs. The growth of the oxide layer at the yttria stabilised zirconia (YSZ)/bond coat interface in TBCs can be examined by measuring the impedance diagrams. From the analysis of the impedance diagrams of TBCs, the electrical properties of YSZ were found to be nearly constant during the thermal treatments, indicating there was little change in the microstructure and composition of YSZ. However, there was a clear change in the electrical properties of the oxide layer in the TBCs after thermal treatments, suggesting both microstructural and composition changes occurred in the oxide layer. These studies indicate that the IS is a very useful method in non-destructive characterisation of the degradation of TBCs.