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The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth.
The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years.
Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other.
Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.
Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case-fatality rate that is caused by infection with the SFTS virus (SFTSV). Five electronic databases were systematically searched to identify relevant articles published from 1 January 2011 to 1 December 2019. The pooled rates with 95% confidence interval (CI) were calculated by a fixed-effect or random-effect model analysis. The results showed that 92 articles were included in this meta-analysis. For the confirmed SFTS cases, the case-fatality rate was 0.15 (95% CI 0.11, 0.18). Two hundred and ninety-six of 1384 SFTS patients indicated that they had been bitten by ticks and the biting rate was 0.21 (95% CI 0.16, 0.26). The overall pooled seroprevalence of SFTSV antibodies among the healthy population was 0.04 (95% CI 0.03, 0.05). For the overall seroprevalence of SFTSV in animals, the seroprevalence of SFTSV was 0.25 (95% CI 0.20, 0.29). The infection rate of SFTSV in ticks was 0.08 (95% CI 0.05, 0.11). In conclusion, ticks can serve as transmitting vectors of SFTSVs and reservoir hosts. Animals can be infected by tick bites, and as a reservoir host, SFTSV circulates continuously between animals and ticks in nature. Humans are infected by tick bites and direct contact with patient secretions.
In order to elucidate the physical connection between the propulsive performance and the unsteadiness of jet flow, the transient development of the impulse and thrust of laminar starting jets with finite fluid discharged is investigated numerically for cases with different velocity programmes and jet stroke ratios. The simulation quantitatively demonstrates that the impulse and thrust generated are highly sensitive to the jet kinematics and its near-wake dynamics. The momentum flux contribution to the jet impulse is found to be significant and is associated closely with the jet kinematics. On the other hand, although the over pressure effect at the jet initiation stage has been identified previously as the main reason for the enhanced propulsive performance of the starting jet, the current results indicate that its contribution is in fact weakened by the negative local pressure, induced by the formation of the leading vortex ring as well as jet development during the deceleration stage. Contrary to the effects of the leading vortex ring, the stopping vortex formed near the nozzle exit plane during the jet deceleration stage is found to contribute positively to the pressure impulse production, albeit it is relatively small. By augmenting the over pressure effect and mitigating the negative-pressure effect, the cases with the fast acceleration and slow deceleration velocity programme is capable of producing the maximum pressure impulse, leading to additional impulse production over what would be expected from the jet momentum flux alone.
Pollen-mediated gene flow (PMGF) refers to the transfer of genetic information (alleles) from one plant to another compatible plant. With the evolution of herbicide-resistant (HR) weeds, PMGF plays an important role in the transfer of resistance alleles from HR to susceptible weeds; however, little attention is given to this topic. The objective of this paper was to review reproductive biology, PMGF studies, and interspecific hybridization as well as potential for herbicide resistance alleles to transfer in the economically important broadleaf weeds including common lambsquarters, giant ragweed, horseweed, kochia, Palmer amaranth, and waterhemp. The PMGF studies involving these species reveal that transfer of herbicide resistance alleles routinely occurs under field conditions and is influenced by several factors such as reproductive biology, environment, and production practices. Interspecific hybridization studies within Amaranthus and Ambrosia spp. show that herbicide resistance allele transfer is possible between species of the same genus, but at relatively low levels. The widespread occurrence of HR weed populations and high genetic diversity is at least partly due to PMGF, particularly in dioecious species such as Palmer amaranth and waterhemp compared with monoecious species such as common lambsquarters and horseweed. Prolific pollen production in giant ragweed contributes to PMGF. Kochia, a wind pollinated species can efficiently disseminate herbicide resistance alleles via both PMGF and tumbleweed seed dispersal, resulting in widespread occurrence of multiple HR kochia populations. The review conducted for the aforementioned species verifies that intraspecific and interspecific gene flow can occur, and even at a low rate, could contribute to the rapid spread of herbicide resistance alleles. Further research is needed to determine the role of PMGF in transferring multiple herbicide resistance alleles at the landscape level.
Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.
In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.
We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.
These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.
The pandemic of coronavirus disease 2019 (COVID-19) has posed serious challenges. It is vitally important to further clarify the epidemiological characteristics of the COVID-19 outbreak for future study and prevention and control measures. Epidemiological characteristics and spatial−temporal analysis were performed based on COVID-19 cases from 21 January 2020 to 1 March 2020 in Shandong Province, and close contacts were traced to construct transmission chains. A total of 758 laboratory-confirmed cases were reported in Shandong. The sex ratio was 1.27: 1 (M: F) and the median age was 42 (interquartile range: 32–55). The high-risk clusters were identified in the central, eastern and southern regions of Shandong from 25 January 2020 to 10 February 2020. We rebuilt 54 transmission chains involving 209 cases, of which 52.2% were family clusters, and three widespread infection chains were elaborated, occurring in Jining, Zaozhuang and Liaocheng, respectively. The geographical and temporal disparity may alert public health agencies to implement specific measures in regions with different risk, and should attach importance on how to avoid household and community transmission.
The Shiji (史記 Records of the Grand Historian) is of great value for Chinese history before 90 BCE. Many online databases provide character-based search of the Shiji. We go beyond simple search by creating an word-based open-access database of the Basic Annals (本纪) of the Shiji that allows the exploration of relationships between persons and the relationships between persons and named places.
Biographies constitute the main historical record of China. The China Biographical Database (CBDB) is an important project that tackles this vast biographical material with digital technologies. With both online and offline versions, CBDB is meant to be useful for statistical, social network, and spatial analysis, as well as serving as biographical reference. Through the wide range of data it collects through mining historical texts and reference sources, CBDB offers multiple ways to examine the lives of past groups and individuals in Chinese history. The use of CBDB data for prosopographical and other types of analysis has generated important work that interprets Chinese history in new ways, and has also fostered new forms of digital humanities collaborations. This article introduces the history of the CBDB project and its methods for populating its biographical data. It also presents the ways that historians and other scholars could utilize its data for research and teaching.
Fat metabolism is an important and complex biochemical reaction in vivo and is regulated by many factors. Recently, the findings on high expression of fibroblast growth factor-16 (FGF16) in brown adipose tissue have led to an interest in exploring its role in lipogenesis and lipid metabolism. The study cloned the goat’s FGF16 gene 624 bp long, including the complete open reading frame that encodes 207 amino acids. We found that FGF16 expression is highest in goat kidneys and hearts, followed by subcutaneous fat and triceps. Moreover, the expression of FGF16 reached its peak on the 2nd day of adipocyte differentiation (P < 0.01) and then decreased significantly. We used overexpression and interference to study the function of FGF16 gene in goat intramuscular preadipocytes. Silencing of FGF16 decreased adipocytes lipid droplet aggregation and triglyceride synthesis. This is in contrast to the situation where FGF16 is overexpressed. Furthermore, knockdown of FGF16 also caused down-regulated expression of genes associated with adipocyte differentiation including CCAAT enhancer-binding protein beta (P < 0.01), fatty acid-binding protein-2 (P < 0.01) and sterol regulatory element binding protein-1 (P < 0.05), but the preadipocyte factor-1 was up-regulated. At the same time, the genes adipose triglyceride lipase (P < 0.01) and hormone-sensitive lipase (P < 0.05) associated with triglyceride breakdown were highly expressed. Next, we locked the fibroblast growth factor receptor-4 (FGFR4) through the protein interaction network and interfering with FGF16 to significantly reduce FGFR4 expression. It was found that the expression profile of FGFR4 in adipocyte differentiation was highly similar to that of FGF16. Overexpression and interference methods confirmed that FGFR4 and FGF16 have the same promoting function in adipocyte differentiation. Finally, using co-transfection technology, pc-FGF16 and siRNA-FGFR4, siRNA2-FGF16 and siRNA-FGFR4 were combined to treat adipocytes separately. It was found that in the case of overexpression of FGF16, cell lipid secretion and triglyceride synthesis showed a trend of first increase and then decrease with increasing interference concentration. In the case of interference with FGF16, lipid secretion and triglyceride synthesis showed a downward trend with the increase of interference concentration. These findings illustrated that FGF16 mediates adipocyte differentiation via receptor FGFR4 expression and contributed to further study of the functional role of FGF16 in goat fat formation.
OBJECTIVES/GOALS: Early age at menopause has been linked to increased risk of cardiovascular disease; however, there is limited evidence for a relationship between early menopause and heart failure (HF). We examined whether early menopause is associated with incident HF among women in the southeastern United States. METHODS/STUDY POPULATION: The Southern Community Cohort Study enrolled ~86,000 low-income black and white adults from 2002 to 2009. Participants for this analysis were 11,948 women who were postmenopausal at enrollment, had no history of HF, and were on Medicaid or Medicare. HF events were ascertained using ICD-9 codes 428.x via linkage of the cohort with CMS Research Identifiable Files through December 31, 2010. Early menopause was defined as self-reported age at menopause less than 45 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed from multivariable Cox regression models, overall and by race, adjusting for demographic, lifestyle, and reproductive factors, including reason for menopause. RESULTS/ANTICIPATED RESULTS: At baseline, mean age was 58±9 years, and 65% of participants were black. Among women with early menopause, 76% (n = 4,836) had menopause due to hysterectomy or oophorectomy. In women with later menopause, 74% (n = 4,102) reported natural menopause. During a median follow-up of 5.0 years (range 3.1-6.7), 2,157 incident HF events occurred. Compared with women with later onset of menopause, those with early menopause had increased HF risk (HR: 1.27, 95% CI: 1.10–1.47). Risk of HF associated with early menopause was similar in white and black women (p-value for interaction: 0.13). DISCUSSION/SIGNIFICANCE OF IMPACT: In this largely low-income population, early menopause was associated with an increased risk of developing HF. Women with early menopause represent a potential target population for future interventions to decrease risk of HF and cardiovascular risk factors.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Ovarian follicle selection is a natural biological process in the pre-ovulatory hierarchy in birds that drives growing follicles to be selected within the ovulatory cycle. Follicle selection in birds is strictly regulated, involving signaling pathways mediated by dietary nutrients, gonadotrophic hormones and paracrine factors. This study aimed to test the hypothesis that dietary Ca may participate in regulating follicle selection in laying ducks through activating the signaling pathway of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/extracellular signal-regulated kinase (ERK), possibly mediated by gonadotrophic hormones. Female ducks at 22 weeks of age were initially fed one of two Ca-deficient diets (containing 1.8% or 0.38% Ca) or a Ca-adequate control diet (containing 3.6% Ca) for 67 days (depletion period), then all birds were fed the Ca-adequate diet for an additional 67 days (repletion period). Compared with the Ca-adequate control, ducks fed 0.38% Ca during the depletion period had significantly decreased (P < 0.05) numbers of hierarchical follicles and total ovarian weight, which were accompanied by reduced egg production. Plasma concentration of FSH was decreased by the diet containing 1.8% Ca but not by that containing 0.38%. The ovarian content of cAMP was increased with the two Ca-deficient diets, and phosphorylation of PKA and ERK1/2 was increased with 0.38% dietary Ca. Transcripts of ovarian estradiol receptor 2 and luteinizing hormone receptor (LHR) were reduced in the ducks fed the two Ca-deficient diets (P < 0.05), while those of the ovarian follicle stimulating hormone receptor (FSHR) were decreased in the ducks fed 0.38% Ca. The transcript abundance of ovary gap junction proteins, A1 and A4, was reduced with the Ca-deficient diets (P < 0.05). The down-regulation of gene expression of gap junction proteins and hormone receptors, the increased cAMP content and the suppressed hierarchical follicle numbers were reversed by repletion of dietary Ca. These results indicate that dietary Ca deficiency negatively affects follicle selection of laying ducks, independent of FSH, but probably by activating cAMP/PKA/ERK1/2 signaling pathway.
Introduction: Emergency department (ED) flow is a strong predictor of patient safety, quality of care and provider satisfaction. Throughput interventions have been shown to improve flow metrics, yet few studies have considered MD leadership roles and evaluated provider experience. Our objective was to evaluate the emergency physician lead (EPL) role, a novel MD staffing initiative. Methods: This mixed-method observational time series analysis evaluated ED metrics at two tertiary EDs including ED length of stay (LOS), EMS Park LOS and physician initial assessment (PIA) time as well as 72-hour readmit and left without being seen (LWBS) rates. Data was collected from the ED information system database for control (Dec 6, 2017-Feb 28, 2018 SITE1 and Mar 1–May 31, 2018 SITE2), pre (Sept 3-Nov 30, 2018 SITE 1 and Dec 3, 2018-Feb 28, 2019 SITE2) and post (Dec 3, 2018 –Feb 28, 2019 SITE1, Mar 1- May 31, 2019 SITE2) periods for adult patients presenting to each site. Site data was analyzed independently using descriptive and inferential statistics to calculate differences in means, and means were compared using t-tests. A survey elicited provider feedback from ED physicians, nurses, and EMS professionals on the effect of the EPL on throughput, timeliness of admissions and discharges, provider workload, and the EPL as a resource to other professionals. Results: The number of ED visits at SITE1 were 13136 (Ctrl), 13236 (Pre) and 13137 (Post), and at SITE2 were 14371(Ctrl), 13866 (Pre) and 14962 (Post). Mean ED LOS was decreased by 17 min in post vs control and 20 min vs pre at SITE1 (p < 0.01). SITE2 saw an increase in ED LOS by 7 min vs control and 8 min vs pre (p < 0.01). EMS LOS at SITE1 was decreased by 21 min vs control and 22 min vs pre (p < 0.01), but was increased at SITE2 by 2 min vs control (p = 0.09) and 14 min vs pre (p < 0.01). PIA time at SITE1 was decreased by 15 min vs control (p < 0.01) and 13 min vs pre and increased by 5 min vs control and 12 min vs pre at SITE2 (p < 0.01). 72 hour readmit and LWBS rates were unchanged at both sites. Qualitative feedback from ED providers highlighted the early provision of treatments and investigations by the EPL, and many felt the EPL was an important resource. Conclusion: The inclusion of both quantitative and qualitative data in this study provided a robust analysis of the impact of the EPL role and demonstrated modest but important improvements. A site-dependent, carefully considered implementation of the EPL role may improve ED metrics and provider experiences.
Introduction: Calgary's introduction of rentable electronic scooters (e-scooters) in July of 2019 was met with wild popularity, representing the third most popular launch after Tel-Aviv and Paris. The present study aims to characterize the injury burden seen in all Calgary Emergency Departments (EDs) and Urgent Care Centres (UCCs) attributable to e-scooters since their 2019 introduction. Methods: We retrospectively reviewed all electronic medical records of patients presenting to Calgary EDs or UCCs with the term “scooter” in the triage note, where exclusion criteria are considered for non e-scooter injuries (e.g: non-motorized scooters). Trends in scooter injuries will be compared between April - October 2018 (control arm preceding e-scooter introduction) and April - October 2019. Injury incidence, types, patient demographics, and relative risk compared to bicycle-related injuries will be determined. Descriptive statistics will be calculated. Moreover, 33 ED visits were brought in by EMS and provide information about injury types and locations of injuries involving EMS transport. Results: Preliminary data reveals 540 scooter-related visits (3.10% admitted/transferred) between July 8th and September 30th 2019 (mean age of 28, 56.30% male). Conversely, the number of bicycle-related visits and motor vehicle related injuries were 1482 and 586 (9.90% and 9.70% admitted/transferred) respectively over the same time period suggesting a greater burden but likely a lower per-ride incidence of injury requiring ED or UCC care. Moreover, between July 8th to October 1st 2019, 33 e-scooter presentations involved EMS (21.21% admitted to hospital), where 12.12% involved upper extremity injury, 21.21% were lower extremity injuries, and 6.06% were head injuries (mean age of 34, 48.48% male). Conversely, estimated EMS transfers to EDs or UCCs for bicycle injuries and motor vehicle injuries were 197 and 463 respectively over the same time period. ICU admissions or fatality were not recorded. Conclusion: Representing the most comprehensive study of e-scooter injury patterns in Canada to date, we here demonstrate a significant injury burden attributable to e-scooters following their introduction in Calgary in 2019. Bicycle-related and motor vehicle injuries were both more prevalent in this time period, and required more EMS visits. Further characterization of injury types, injuries and comparison with injury patterns prior to e-scooter introduction is yet to be determined.
We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
In recent years, men who have sex with men (MSM) constitute a major group of HIV transmission in China. High primary drug-resistance (PDR) rate in MSM also represents a serious challenge for the Chinese antiretroviral therapy (ART) program. To assess the efficiency of ART in controlling HIV/AIDS infection among MSM, we developed a compartmental model for the annually reported HIV/AIDS MSM from 2007 to 2019 in the Zhejiang Province of China. R0 was 2.3946 (95% CI (2.2961–2.4881)). We predict that 90% of diagnosed HIV/AIDS individuals will have received treatment till 2020, while the proportion of the diagnosed remains as low as 40%. Even when the proportion of the diagnosed reaches 90%, R0 is still larger than the level of AIDS epidemic elimination. ART can effectively control the spread of HIV, even in the presence of drug resistance. The 90-90-90 strategy alone may not eliminate the HIV epidemic in Chinese MSM. Behavioural and biologic interventions are the most effective interventions to control the HIV/AIDS epidemic among MSM.
Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition.
Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms.
At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = −2.17, p = 0.03, d = −0.32) and WL conditions(t(207) = −2.33, p = 0.02, d = −0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms.
Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.
Accretionary orogens contain key evidence for the conversion of oceanic to continental crust. The late tectonic history and closure time of the Palaeo-Asian Ocean are recorded in the Mazongshan subduction–accretion complex in the southern Beishan margin of the Central Asian Orogenic Belt. We present new data on the structure, petrology, geochemistry and zircon U–Pb isotope ages of the Mazongshan subduction–accretion complex, which is a tectonic mélange with a block-in-matrix structure. The blocks are of serpentinized peridotite, basalt, gabbro, basaltic andesite, chert and seamount sediments within a matrix that is mainly composed of fore-arc-trench turbidites. U–Pb zircon ages of two gabbros are 454.6 ± 2.5 Ma and 434.1 ± 3.6 Ma, an andesite has a U–Pb zircon age of 451.3 ± 3.5 Ma and a tuffaceous slate has the youngest U–Pb zircon age of 353.6 ± 5.1 Ma. These new isotopic ages, combined with published data on ophiolitic mélanges from central Beishan, indicate that the subduction–accretion of Beishan in the southernmost Central Asian Orogenic Belt lasted until Late Ordovician – Early Carboniferous time. Structure and age data demonstrate that the younging direction of accretion was southwards and that the subduction zone dipped continuously to the north. Accordingly, these results record the conversion of oceanic to continental crust in the southern Beishan accretionary collage.
The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.
Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + mood stabilizer or placebo + mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test).
127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively).
These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.