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A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.
Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.
A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.
Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.
The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.
Direct determination of barrier height (ΦBH) value between Ir and single crystal (001) hydrogen-terminated diamond with lightly boron doped has been performed using x-ray photoelectron spectroscopy technique. 70 nm Ir islands were formed on hydrogen-terminated diamond surface using anodic aluminum oxide. The ΦBH value for Ir/hydrogen-terminated diamond was −0.43 ± 0.14 eV, indicating that Ir was a suitable metal for ohmic contact with hydrogen-terminated diamond. The band diagram of Ir/hydrogen-terminated diamond was obtained. The experimental ΦBH was compared with the theoretical ΦBH in this work.
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.
In inertial confinement fusion experiments that involve short-laser pulses such as fast ignition (FI), diagnosis of neutrons is usually very challenging because high-intensity γ rays generated by short-laser pulses would mask the much weaker neutron signal. In this paper, fast-response scintillators with low afterglow and gated microchannel plate photomultiplier tubes are combined to build neutron time-of-flight (nTOF) spectrometers for such experiments. Direct-drive implosion experiments of deuterium-gas-filled capsules were performed at the Shenguang-II Upgrade (SG-II-UP) laser facility to study the compressed fuel areal density (〈ρR〉) and evaluate the performance of such nTOF diagnostics. Two newly developed quenched liquid scintillator detectors and a gated ultrafast plastic scintillator detector were used to measure the secondary DT neutrons and primary DD neutrons, respectively. The secondary neutron signals were clearly discriminated from the γ rays from (n, γ) reactions, and the compressed fuel areal density obtained with the yield-ratio method agrees well with the simulations. Additionally, a small scintillator decay tail and a clear DD neutron signal were observed in an integrated FI experiment as a result of the low afterglow of the oxygen-quenched liquid scintillator.
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.
Kaolinite can be used for many applications, including the underground storage of gases. Density functional theory was employed to investigate the adsorption of hydrogen molecules on the kaolinite (001) surface. The coverage dependence of the adsorption sites and energetics was studied systematically for a wide range of coverage, Θ (from 1/16 to 1 monolayer). The three-fold hollow site is the most stable, followed by the bridge, top-z and top sites. The adsorption energy of H2 decreased with increasing coverage, thus indicating the lower stability of surface adsorption due to the repulsion of neighbouring H2 molecules. The coverage has obvious effects on hydrogen adsorption. Other properties of the H2/kaolinite (001) system, including the lattice relaxation and changes of electronic density of states, were also studied and are discussed in detail.
Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.
Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5′UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.
Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).
Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.
Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).
Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.
We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.
A 2,000-bed tertiary-care psychiatric hospital.
Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.
The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.
WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.
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.
Cognition is multidimensional, and each domain plays a unique and crucial part in successful daily life engagement. However, less attention has been paid to multi-domain cognitive health for the elderly, and the role of lifestyle factors in each domain remains unclear.
We conducted a cross-sectional study of 3,230 older adults aged 60+ years in Xiamen, China, in 2016. The Montreal Cognitive Assessment (MoCA) was used to measure general cognition and six specific sub-domains. To account for educational effects, we adjusted the MoCA score and divided respondents into three education-specific groups (low, moderate, and high education groups with ≤5, 6~8, and ≥9 years of education, respectively). A series of proportional odds models were used to detect the associations between two categories of lifestyle factors – substance abuse (cigarette and alcohol) and leisure activity (TV watching, reading, smartphone use, social activity, and exercise) – and general cognition and the six sub-domains in those three groups.
Among the 3,230 respondents, 2,617 eligible participants were included with a mean age of 69.05 ± 7.07 years. Previous or current smoking/drinking was not associated with MoCA scores in the whole population, but unexpectedly, the ex-smokers in the low education group performed better in general cognition (OR = 2.22) and attention (OR = 2.05) than their never-smoking counterparts. Modest TV watching, reading, and smartphone use also contributed to better cognition among elderly participants in the low education group. For the highly educated elderly, comparatively longer reading (>3.5 hours/week) was inversely associated with general cognition (OR = 0.53), memory (OR = 0.59), and language (OR = 0.54), while adequate exercise (5~7 days/week) was positively related to these factors with OR = 1.48, OR = 1.49, and OR = 1.53, respectively. For the moderately educated elderly, only modest reading was significantly beneficial.
Lifestyle factors play different roles in multidimensional cognitive health in different educational groups, indicating that individual intervention strategies should be designed according to specific educational groups and different cognitive sub-domains.
This paper presents the design of all dielectric non-absorptive phase gradient reflective surfaces that can be used to manipulate the reflected electromagnetic waves at millimeter-wave regime. Compared with a bare perfect electrical conductor reflector which obeys the classical Snell's law of reflection, the presented design can effectively alter both the shape and level of the backscattered energy and thus radar cross section (RCS) reduction is achieved in the specular direction. One- and two-dimensional phase gradient reflective dielectric surfaces of phase change about 72° across their apertures are designed and their ability to manipulate the reflected waves under normal incidence are investigated both by means of full-wave simulations and experimentally tested for validation. More than 6 dB of specular RCS reduction is achieved from about 66.5–78.2 GHz.
Bovine mastitis, an inflammation of the udder, results in reduced milk production and poor milk quality. Mastitis is usually, but not always, a response to pathogen infection. High milk yield can produce oxidative stress in the mammary tissue. High milk yield is also known to be associated with bovine mastitis. Thus, in the current study, we hypothesised that oxidative stress increases inflammatory responses in bovine mammary cells. To examine the hypothesis, we produced cellular oxidative stress and investigated resulting inflammatory responses in bovine mammary alveolar cells (MAC-T). To produce oxidative stress, cells were treated with the reactive oxygen species (ROS; e.g., superoxide anion)-producing agent, menadione (MD; 0–10 µm; 6 h). To ensure the ROS-induced responses, cells were pretreated with an antioxidant NAC (0–10 mm; 1 h). Results showed that MD elevated intracellular ROS levels and protein expression of cyclooxygenase-2 (COX-2), a biomarker of inflammation. Pretreatment of cells with NAC attenuated MD-induced COX-2 expression by scavenging intracellular ROS and enhancing intracellular glutathione levels. MD-induced COX-2 expression was mediated by activation of extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, and nuclear factor-kappa B (NF-κB). NAC attenuated activation of these intracellular signalling molecules. Treatment of cells with pharmacological inhibitors for ERK1/2, Akt, and NF-κB confirmed the association of these signalling pathways in MD-induced COX-2 expression. These results support our hypothesis that oxidative stress, which is found in high-yielding dairy cows, can produce cellular inflammation in bovine mammary alveolar cells and prevention of oxidative stress can attenuate such pathological responses. This may be relevant for cases of clinical mastitis for which no pathogen can be isolated.
Two middle Permian (Capitanian) to Early Triassic (Griesbachian) rugosochonetidae brachiopod genera, Fusichonetes Liao in Zhao et al., 1981 and Tethyochonetes Chen et al., 2000, have been regarded as two distinct taxa and used as such for a wide range of discussions including biostratigraphy, paleoecology, paleobiogeography, and the Permian-Triassic boundary mass extinction. However, the supposed morphological distinctions between the two taxa are subtle at best and appear to represent two end members of a continuum of morphological variations. In this study, we applied a range of quantitative and analytical procedures (bivariate plots, Kolmogorov-Smirnov test, categorical principle component analysis, and cladistic analysis) to a dataset of 15 quantified morphological variables, integrating both key external and internal characters, measured from 141 specimens of all well-known Fusichonetes and Tethyochonetes in order to test whether or not these two genera could be distinguished in view of the chosen characters. The results indicate that these two genera are morphologically indistinguishable and that the species classification previously applied to these two genera appears to represent polyphyletic groupings within the genus Fusichonetes. Consequently, Tethyochonetes is concluded to be a junior synonym of Fusichonetes. The diagnosis and key characteristics of Fusichonetes are clarified and refined based on a new suite of well-preserved specimens from the Permian−Triassic Xinmin section in South China.
Integration of photonic devices on silicon (Si) substrates is a key method in enabling large scale manufacturing of Si-based photonic–electronic circuits for next generation systems with high performance, small form factor, low power consumption, and low cost. Germanium (Ge) is a promising material due to its pseudo-direct bandgap and its compatibility with Si-CMOS processing. In this article, we present our recent progress on achieving high quality germanium-on-silicon (Ge/Si) materials. Subsequently, the performance of various functional devices such as photodetectors, lasers, waveguides, and sensors that are fabricated on the Ge/Si platform are discussed. Some possible future works such as the incorporation of tin (Sn) into Ge will be proposed. Finally, some applications based on a fully monolithic integrated photonic–electronic chip on an Si platform will be highlighted at the end of this article.
Proton radiography is a key diagnostics to measure and image the electric/magnetic field in laser-produced plasmas. A thin solid target is irradiated with an intense laser pulse to produce a proton beam. The accelerated proton can achieve higher energy with thinner target. In order to produce an extremely thin target, we have developed a large-area suspended graphene as a laser target for energetic ion sources. We describe the manufacturing process of the suspended graphene, and show the results of quality evaluations.