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Many orogens on the planet result from plate convergence involving subduction of a continental margin. The lithosphere is strongly deformed during mountain building involving subduction of a plate composed generally of accreted continental margin units and some fragments of downgoing oceanic crust and mantle. A complex deformation involving strong partitioning of deformation modes and kinematics produces crustal shortening, accompanied by crustal thickening. Partitioning depends on three main factors: (1) rheologic layering of the lithosphere; (2) interaction between tectonics and surface processes; (3) subduction kinematics and 3D geometry of continental margins (oblique convergence, shape of indenters). Here we present an original view and discussion on the impact of deformation partitioning on the structure and evolution of orogens by examining the Taiwan mountain belt as a case study. Major unsolved questions are addressed through geological observations from the Taiwan orogen and insights from analogue models integrating surface processes. Some of these questions include: What is the role played by décollements or weak zones in crustal deformation and what is the impact of structural heterogeneities inherited from the early extensional history of a rifted passive continental margin? What is the relationship between deep underplating, induced uplift and flow of crustal material during erosion (finite strain evolution during wedge growth)? Are syn-convergent normal faults an effect of deformation partitioning and erosion? What is the role of strain partitioning on the location of major seismogenic faults in active mountain belts? What can be learned about the long-term and the present-day evolution of Taiwan?
Emotional distress during pregnancy is likely influenced by both maternal history of adversity and concurrent prenatal stressors, but prospective longitudinal studies are lacking. Guided by a life span model of pregnancy health and stress sensitization theories, this study investigated the influence of intimate partner violence (IPV) during pregnancy on the association between childhood adversity and prenatal emotional distress. Participants included an urban, community-based sample of 200 pregnant women (aged 18–24) assessed annually from ages 8 to 17 for a range of adversity domains, including traumatic violence, harsh parenting, caregiver loss, and compromised parenting. Models tested both linear and nonlinear effects of adversity as well as their interactions with IPV on prenatal anxiety and depression symptoms, controlling for potential confounds such as poverty and childhood anxiety and depression. Results showed that the associations between childhood adversity and pregnancy emotional distress were moderated by prenatal IPV, supporting a life span conceptualization of pregnancy health. Patterns of interactions were nonlinear, consistent with theories conceptualizing stress sensitization through an “adaptive calibration” lens. Furthermore, results diverged based on adversity subdomain and type of prenatal IPV (physical vs. emotional abuse). Findings are discussed in the context of existing stress sensitization theories and highlight important avenues for future research and practice.
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.
Introduction: Emergency department (ED) congestion is an ongoing threat to quality care. Traditional measures of ED efficiency use census and wait times over extended time intervals (e.g. per year, per day), failing to capture the hourly variations in ED flow. Borrowing from the traffic theory framework used to describe cars on a freeway, ED flow can instead be characterized by three fundamental parameters: flux (patients traversing a care segment per unit time), density (patients in a care segment per unit time), and duration (length of stay in a care segment). This method allows for the calculation of near-instantaneous ED flux and density. To illustrate, we examined the association between stretcher occupancy and time to physician initial assessment (PIA), seeking to identify thresholds where flux and PIA deteriorate. Methods: We used administrative data as reported to government agencies for 115,559 ED visits from April 1, 2014 to March 31, 2016 at a tertiary academic hospital. Time stamps collected at triage, PIA, and departure were verified by nosologists and used to define two care segments: awaiting assessment or receiving care. Using open-source software developed in-house, we calculated flow measures for each segment at 90-minute intervals. Graphical analysis was supplemented by regression analysis, examining PIA times of high (CTAS 1-3) or low (CTAS 4-5) acuity patients against ED occupancy (=density/staffed stretchers) adjusting for the day of the week, season and fiscal year. Results: At occupancy levels below 50%, PIA times remain stable and flux increases with density, reflecting free flow. Beyond 50% occupancy, PIA times increase linearly and flux plateaus, indicating congestion. While PIA times further deteriorate above 100% occupancy, flow is maintained, reflecting care delivery in non-traditional spaces (e.g. hallways). An inflection point where flux decreased with increased crowding was not identified, despite lengthening queues. Conclusion: The operational performance of a modern ED can be captured and visualized using techniques borrowed from the analysis of vehicular traffic. Unlike cars on a jammed roadway, patients behave more like a compressible fluid and ED care continues despite high degrees of crowding. Nevertheless, congestion begins well below 100% occupancy, presumably reflecting the need for stretcher turnover and saturation in subsegmental work processes. This methodology shows promise to analyze and mitigate the many factors contributing to ED crowding.
Childhood exposure to stress can induce prolonged negative effects on health, which in turn confer risks for the next generation, but greater specificity is needed to inform intervention. A first step is to measure individual differences in emotional reactivity to stress early in life in ways that can account for heterogeneity in child exposure. The present study tested the hypothesis that mothers’ childhood exposure to stress would be differentially associated with patterns of positive and negative emotional reactivity in their offspring, suggesting transmission of stress response across generations. Participants were 268 young mothers (age 14–23 years) followed longitudinally since childhood, and their infants aged 3–9 months. Latent class analysis of infant emotions expressed before and during the still-face paradigm yielded five subgroups that varied in valence, intensity, and reactivity. After accounting for sociodemographic factors, infant temperament, and postpartum depression, multinomial regression models showed that, relative to an emotionally regulated still-face response, infants showing low negative reactivity were more likely to have mothers exposed to childhood emotional abuse, and infants showing high and increasing negative reactivity were more likely to have mothers exposed to childhood emotional neglect. Mechanisms by which early maternal stress exposure influences emotional reactivity in offspring are discussed.
Let q be a power of a prime p and let U(q) be a Sylow p-subgroup of a finite Chevalley group G(q) defined over the field with q elements. We first give a parametrization of the set Irr(U(q)) of irreducible characters of U(q) when G(q) is of type G2. This is uniform for primes p ≥ 5, while the bad primes p = 2 and p = 3 have to be considered separately. We then use this result and the contribution of several authors to show a general result, namely that if G(q) is any finite Chevalley group with p a bad prime, then there exists a character χ \in Irr(U(q)) such that χ(1) = qn/p for some n \in Z≥0 . In particular, for each G(q) and every bad prime p, we construct a family of characters of such degree as inflation followed by an induction of linear characters of an abelian subquotient V(q) of U(q).
In September 2008, the United States Trade Representative (USTR) announced the United States’ intention to join Singapore, New Zealand, Brunei, and Chile in what was then called the Trans-Pacific Strategic Economic Partnership Agreement, a preferential trade agreement. Since then, the agreement has grown in scope and ambition. The negotiations to create what is now known as the Trans-Pacific Partnership (TPP) have expanded to include seven other nations. The USTR wants the TPP to be “an ambitious, next-generation, Asia-Pacific trade agreement that reflects U.S. economic priorities and values.” According to the USTR's webpage dedicated to the agreement, the administration is “working in close partnership with Congress and with a wide range of stakeholders, in seeking to conclude a strong agreement that addresses the issues that U.S. businesses and workers are facing in the 21st century.”
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.
Using the flow method, we prove some existence results for the problem of prescribing the mean curvature on the unit ball. More precisely, we prove that there exists a conformal metric on the unit ball such that its mean curvature is f, when f possesses certain reflection or rotation symmetry.
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.
Childhood maltreatment robustly predicts adolescent externalizing behaviors (EB; e.g., violence, delinquency, substance use) and may crystalize patterns of EB by influencing sensitivity to the social environment (e.g., parenting, friendships). In a nationally representative sample of 9,421 adolescents, we modeled latent growth curves of EB from age 13 to 32 years. Next, we explored whether maltreated youth differed from nonmaltreated youth in their sensitivity to parental closeness, friendship involvement, and polymorphisms from dopamine genes linked to EB (dopamine receptors D2 and D4, dopamine transporter). Overall, maltreated youth had significantly higher levels of EB across adolescence and adulthood; however, maltreated and nonmaltreated youth showed similar patterns of EB change over time: violent behavior decreased in adolescence before stabilizing in adulthood, whereas nonviolent delinquency and substance use increased in adolescence before decreasing in the transition to adulthood. Maltreatment reduced sensitivity to parental closeness and friendship involvement, although patterns varied based on type of EB outcome. Finally, none of the environmental effects on EB were significantly moderated by the dopamine polygenic risk score after accounting for multiple testing. These findings underline the enduring effects of early maltreatment and implicate that maltreatment may contribute to long-term risk for EB by influencing children's sensitivity to social relationship factors in adolescence.
Glioblastomas are the most frequent and aggressive primary brain tumor in adults and despite recent therapeutic advances, they are resistant to treatment. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumor vasculature, leading to insufficient blood supply, hypoxic areas, and ultimately to the formation of necrosis. Hypoxia induces direct or indirect changes in the biology of solid tumor and their microenvironment through the activation of HIF transcription factors, leading to increased aggressiveness and tumor resistance to therapy. Not much is known about the epigenetic alterations induced by hypoxia and how they could alter tumor biology. In the present study, we have utilized PIMO as a specific marker of hypoxia in glioblastoma patients, treated with PIMO preoperatively. We have estimated PIMO positivity in each tumor (5-45%) and determined that it positively correlates with the hypoxia marker CA IX (r=0.57). In addition, 10 surgical PIMO cases were dissociated, immune labeled using PIMO antibody, followed by DNA isolation and methylation profiling. Our analysis of differentially top 4000 differentially methylated probes suggests that PIMO-positive (hypoxic) cells are differentially methylated compared to the PIMO-negative cells and these changes are associated with genes involved in hypoxic cellular response. We will validate these findings in additional glioblastoma cases and assess the mechanism of these epigenetic alterations in vitro in glioma stem cell culture conditions and upon exposure of the cells hypoxic conditions.
As the 1991 Paris Peace Accords brought an end to the Cambodian conflict, the normalization of Vietnam's relations with China appeared to be just a matter of time. Yet, China's seizure of the Paracels in 1974 and its encroachment into the Spratlys in 1988 continued to complicate the Sino–Vietnam relationship. Therefore, while trying to promote friendly relations with China, Vietnam remained vigilant and endeavoured to enhance its comprehensive national power to cope with the latter's territorial and maritime ambitions. Against this backdrop, some scholars argued that if Vietnam became an Association of Southeast Asian Nation (ASEAN) member, Hanoi could improve its strategic position vis-à-vis China as Beijing would have to deal with not only Vietnam, but also ASEAN as a whole (Johnston 2003, p. 28; Tuan 1994). It was therefore possible that Hanoi did have China in mind while pursuing ASEAN membership, which seemed to be even more sensible given the rising “China threat” thesis in the early 1990s (Betts 1995; Betts and Christensen 2000; Brown 1997).
This chapter, based on Vietnam's diplomatic archive and interviews with Vietnamese foreign policymakers and diplomats, traces thoughts of policymakers in Hanoi as to whether, while considering to join ASEAN, they were serious about enlisting ASEAN's support to bolster Vietnam's position in the South China Sea disputes with China. The chapter also examines if Hanoi viewed its bid for ASEAN membership as a measure to improve ties with the United States, thereby gaining leverage vis-à-vis China in the South China Sea.
The chapter contends that although the South China Sea disputes became an increasingly central security concern for Vietnam in the 1990s, Hanoi did not seriously consider its prospective ASEAN membership as a strategic tool to counter China's expansion in the South China Sea.1 This was because Hanoi realized that ASEAN was indeed not a military organization, and ASEAN members, as well as the United States, did not want to antagonize China by supporting Vietnam in the South China Sea disputes.
The chapter is divided into three sections. The first analyses shifts in Vietnam's perception of the China threat in the late 1980s and early 1990s when Vietnam was pursuing ASEAN membership.
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.
Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity.
Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS.
Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0–1, 2–4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions.
The prevalence of food insecurity was 27·8 %. Compared with those having 0–1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2–4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37).
A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.