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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.
Real-time Precise Point Positioning (PPP) has been evolved as a cost-effective technique for highly precise maritime positioning. For a long period, maritime PPP technology has mainly relied on the Global Positioning System (GPS). With the revitalisation of GLONASS and the emerging BeiDou navigation satellite system (BDS), it is now feasible to investigate real-time navigation performance of multi-constellation maritime PPP with GPS, BDS and GLONASS. In this contribution, we focus on maritime PPP performance using real world maritime kinematic data and real-time satellite correction products. The results show that BDS has lower position accuracy and slower convergence time than GPS. The BDS and GPS combination has the best performance among the dual-constellation configurations. Meanwhile, the integration of BDS, GLONASS and GPS significantly improves the position accuracy and the convergence time. Some outliers in the single constellation configuration can be mitigated when multi-constellation observations are utilised.
A high power laser system was used to drive the ignition of inertial confinement fusion (ICF), of which the high energy, the uniform focal spot, the accurate laser waveform, and the synchronization between the laser beams are key parameters. To accomplish this, global laser characteristics control should be assured, which was the main purpose of the injection laser system. In this paper, the key technological progress involved in the improvement of the performance of the injection laser of SG-II is reported, including frequency domain control, time domain control, near-field spatial shaping, pre-amplifier technology, and the optical parametric chirped pulse amplification pump source.
An optically addressed liquid crystal modulator for wavefront control of 1053 nm laser beam is reported in this paper. Its working principle, control method and spatial phase modulation capability are mainly introduced. A new method of measuring the relationship between gray level and phase retardation is proposed. The rationality of the curve is further confirmed by designing special experiments. According to the curve, several spatial phase distributions have been realized by this home-made device. The results show that, not only the maximum phase retardation is larger than
for 1053 nm wavelength, but also the control accuracy is high. Compared with the liquid crystal on silicon type spatial light modulator, this kind of modulator has the advantages of generating smooth phase distribution and avoiding the black-matrix effect.
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.
This study aimed to investigate the effects of dietary live yeast (LY) supplementation on growth, intestinal permeability and immunological parameters of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets weaned at 21 d were allocated into three treatments with six pens and six piglets per pen, receiving the control diet (CON), diets supplemented with antibiotics plus zinc oxide (ANT–ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407), respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected as control without ETEC (CON), CON–ETEC, ANT–ZnO–ETEC and LY–ETEC groups challenged with ETEC until day 10 for sample collections. Piglets fed ANT–ZnO diet had the highest average daily gain and average daily feed intake (P<0·05) during the 1st week, but ADG of piglets fed the ANT–ZnO diet was similar as piglets fed LY diet during the second week. Piglets with LY–ETEC or ANT–ZnO–ETEC had markedly lower diarrhoea score (P<0·05) than piglets with CON–ETEC during the 24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli, urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA abundances of innate immunity-related genes in ileum and mesenteric lymph node tissues were increased (P<0·05), whereas the villous height of jejunum and relative protein expression of ileum claudin-1 were decreased (P<0·05) in piglets with CON–ETEC; however, these parameters did not markedly change in piglets with LY–ETEC or ANT–ZnO–ETEC. In summary, dietary LY supplementation could alleviate the severity of diarrhoea in piglets with ETEC, which may be associated with the improved permeability, innate immunity and bacterial profile.
In this study, we present clay mineral records from a late Pleistocene loess-paleosol sequence in the Ili Basin, Central Asia, and assess their significance for paleoclimatic reconstruction. The results show that the clay minerals are mainly illite (average 60%) and chlorite (28%), with minor kaolinite (9%) and smectite (3%). Illite was of detrital origin with no obvious modification to its crystal structure. Increases in illite content in the loess are ascribed to wind intensity rather than pedogenesis. High proportions of illite in the clay fraction, and of muscovite in the bulk samples of the paleosol units, may lead to an overestimation of the weathering intensity. Kaolinite was likely inherited from the sedimentary rocks, while chlorite might have been inherited from both sedimentary and metamorphic rocks. The paleoclimatic signals of kaolinite and chlorite were unclear, due to reworking by both fluvial and eolian systems. Smectite was more likely formed by the transformation of biotite and illite, and its variation in the loess sequence was also controlled by wind intensity; this was largely due to aggregation and is unlikely to reflect moisture changes. Although the interpretation of paleoclimate evolution may contain some uncertainties, clay mineralogy does provide the possibility of tracing dust provenance.
To develop a theoretical model explaining the longitudinal changes in the caregiving process for family caregivers of persons with mild cognitive impairment (MCI) in Taiwan.
A longitudinal, grounded theory approach using in-depth face-to-face interviews and an open-ended interview guide. We conducted 42 interviews over a two-year period; each participant was interviewed at least once every six months. All participants were interviewed in their home. The participants total of 13 family caregivers of persons with MCI.
One core theme emerged: “protective preparation.” This reflected the family caregiving process of preparation for a further decline in cognitive function, and protection from the impact of low self-esteem, accidents, and symptoms of comorbidities for the family member with MCI. Protective preparation contained three components: ambivalent normalization, vigilant preparation, and protective management.
Interventions to help family caregivers manage the changes in persons with MCI can reduce caregiver burden. Our findings could provide a knowledge base for use by healthcare providers to develop and implement strategies to reduce caregiver burden for family caregivers of persons with MCI.
The purpose of this paper was to examine whether glaucoma could be a non-memory manifestation of Alzheimer's disease in older people.
We conducted a population-based, retrospective, case-control study to analyze the database of the Taiwan National Health Insurance Program. There were 1,351 subjects ≥65 years old with newly diagnosed Alzheimer's disease as the cases, and 5,329 subjects without any type of dementias as the controls during 2000–2011. The odds ratio (OR) and 95% confidence interval (CI) for the risk of Alzheimer's disease associated with glaucoma was estimated by the multivariable unconditional logistic regression model.
After controlling for confounders, the multivariable logistic regression model demonstrated that the adjusted OR of Alzheimer's disease was 1.50 in subjects with glaucoma (95% CI 1.19, 1.89), compared to subjects without glaucoma.
Older people with glaucoma are associated with 1.5-fold increased odds of Alzheimer's disease in Taiwan. Glaucoma may be a non-memory manifestation of Alzheimer's disease in older people. Further research is needed to confirm this issue.
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased Mn superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase in malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expressions of heat shock factor 1 (HSF1) and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels compared with those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions in the tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance the heart’s antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.
The classical dynamic recrystallization (DRX) kinetics models, such as Avrami equation, are often used to describe the DRX behaviors of alloys. However, it is found that the classical DRX kinetics models cannot be directly applied to evaluate DRX volume fractions under inconstant deformation conditions, such as at fluctuant deformation temperature and strain rate. It obviously limits their application in the practical industrial production. Therefore, an improved DRX kinetics model is proposed based on the hypothesis that the derivatives of DRX volume fraction with respect to strain only depends on the current deformation temperature, strain rate, and DRX volume fraction. To verify the improved DRX kinetics model, the hot compressive tests in which the strain rate is inconstant are carried out on a solution-treated Ni-based superalloy. Experimental results indicate that the improved DRX kinetics model can well predict the DRX behavior under inconstant deformation conditions.
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a serious hospital and community-acquired infection and some strains are associated with greater severity. We investigated the clinical variability and molecular characteristics of MRSA infections in Shenzhen, China through a study at nine sentinel hospitals from January to December 2014. MRSA infections were classified as community-associated (CA-MRSA), healthcare-associated (HA-MRSA), and healthcare-associated community-onset (HACO-MRSA). In total, 812 MRSA isolates were collected and 183 of these were selected for further study. Patients with HA-MRSA infections were generally of greater age compared to other groups. Distinct body site and clinical presentations were evident in infected patients, e.g. CA-MRSA (skin and soft tissue, 53%), HA-MRSA (respiratory tract, 22%; surgical site, 20%; trauma wounds, 20%) and HACO-MRSA (mastitis, 47%). In contrast to HA-MRSA, other categories of strains were significantly more susceptible to gentamicin, sulfamethoxazole/trimethoprim, and tetracycline. No resistance to vancomycin or linezolid was recorded. The predominant clonal lineage within each strain category was CC59-t437-SCCmec IV/V-agr I (CA, 51·4%; HA, 28·9%; HACO, 52·9%) which exhibited characteristics of a traditional CA clone together with agr I which is more often associated with HA clones. In conclusion, for the three categories of MRSA infections, there were significant differences in clinical characteristics of patients, but the predominant clone in each category shared a similar genetic background which suggests that transmission of MRSA strains has occurred between the community and hospitals in Shenzhen.
Bulk nanocrystalline (NC) silvers were fabricated by spark plasma sintering process. The effects of sintering temperature on physical and mechanical properties of the NC silvers were investigated. The results indicate that no impurities were introduced into the bulk compacts during the preparation procedure. Both the density and the electrical conductivity of the NC Ag increase with an increase in sintering temperature. However, the micro-hardness and ultimate tensile strength (UTS) of the bulk compacts increase initially and then decrease with increasing sintering temperature. The NC Ag sintered at 500 °C exhibits the highest micro-hardness of 85.3 HV along with the best compression yield strength of 379 MPa and the highest UTS of 534 MPa. The deterioration of the mechanical properties of the NC Ag sintered at 550 °C should be attributed to the rapid grain growth.
To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.