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The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.
We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
We present a derivation that begins with the Navier–Stokes equation and ends with a prediction of multiple statistically stable states identical to those observed in a spanwise rotating plane Couette flow. This derivation is able to explain the presence of multiple states in fully developed turbulence and the selection of one state over another by differently sized computational domains and different initial conditions. According to the present derivation, two and only two statistically stable states are possible in an infinitely large plane Couette flow with spanwise rotation, and that multiple states are not possible at very slow or very rapid rotation speeds. We also show the existence of limit-cycle-like behaviours near statistically stable states.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
A certain degree of pulmonary stenosis after total correction of tetralogy of Fallot has been considered acceptable. But the long-term outcomes are not well understood. We observed the natural course of immediate pulmonary stenosis and investigated related factors for progression.
Fifty-two patients with acceptable pulmonary stenosis immediately after operation were enrolled. Acceptable pulmonary stenosis was defined as peak pressure gradient between 15 and 45 mmHg by Doppler echocardiography. Latent class linear mixed model was used to differentiate patients with progressed pulmonary stenosis, and the factors related to progression were analysed.
Pulmonary stenosis progressed in 14 patients (27%). Between the progression group and no progression group, there were no significant differences in operative age, sex, and the use of the transannular patch technique. However, immediate gradient was higher in the progression group (32.1 mmHg versus 25.7 mmHg, p = 0.009), and the cut-off value was 26.8 mmHg (sensitivity = 65.3%, specificity = 65.8%). Main stenosis at the sub-valve was observed more frequently in the progression group (85.7% versus 52.6%, p = 0.027). Despite no difference in the preoperative pulmonary valve z value, the last follow-up pulmonary valve z value was significantly lower in the progression group (−1.15 versus 0.35, p = 0.002).
Pulmonary stenosis immediately after tetralogy of Fallot total correction might progress in patients with immediate pulmonary stenosis higher than ≥26.8 mmHg and the main site was sub-valve area.
It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.
Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.
DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.
The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
The present study examined the relationship between the Lie scale scores and striatal D2/D3 receptor availability with respect to the cerebellum in 42 healthy community volunteers in Taiwan using single photon emission computed tomography (SPECT) with [123I]iodo-benzoaminde (IBZM). Even after controlling of age and educational level, subjects' Lie scale scores of the Maudsley personality inventory correlate negatively with D2/D3 receptor availability. Individual with higher Lie scale scores may have higher impulsivity due to lower dopaminergic availability.
We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after three weeks of repetitve transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.
We report six cases (four females) 15–21 years of age with treatment-resistant MDD. Participants had a mean age of 18.7 years and a mean IQ of 102.3. Short echo proton magnetic resonance spectroscopy (H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5cc) before and after rTMS treatment. rTMS was localized to the left DLPFC and applied for 15 consecutive weekdays. Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores (Ham-D).1H-MRS data was analyzed with LCModel to determine glutamate concentration.
Following rTMS, treatment responders (N=4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Ham-D score reduction). Treatment non-responders (N=2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (−10%). Procedures were generally well tolerated with no adverse events.
rTMS is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by Induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement. Transcranial Magnetic Stimulation for Adolescent Depression (TMSAD)
It is known that Sexual Dysfunction (SD) is higher in patient with depression than in the general population. Though antidepressant seems to worsen the situation, there are also indications that the gender may play a role on it.
Evaluate the gender effect of sexual function among unmedicated MDD, MDD receiving antidepressant, and healthy controls.
The sample was formed by male and female Taiwanese outpatients in three age and sex matched groups, with sixty nine participants per group: unmedicated MDD, MDD receiving antidepressant, and healthy controls. the diagnoses of depressions were performed according DSM-IV and Taiwanese Depression Questionnaire. SD was evaluated with the Chinese version of the Changes in Sexual Functioning Questionnaire. Finally, the data was analyzed using SPSS software v17. Mixed designed ANOVA was used.
There are significant differences between males and females CSFQ results (sex main effect F = 82.44, p < 0.001) and between groups (group main effect F = 3.48, p = 0.034). Additionally, the 2-way interaction between sex and group was also significant (F = 3.40, p = 0.036). Simple main effect analysis shows differences among male participants, between healthy and medicated males (F = 11.41, p = 0.002), but not in female (F = 1.58, p = 0.21). However the statistics weren’t different between females groups, the medicated expresses better results (similar to healthy group) than the unmedicated one.
SD is different between genders in each of the groups. Antidepressant seems to increase SD in man, while improves sexual satisfaction/function among depressive woman. We speculate that psychological improvement after treatment may have different impact between genders on sexual satisfaction.
Much of our theoretical understanding of statistically stable and unstable flows is from the classical Monin–Obukhov similarity theory: the theory predicts the scaling of the mean flow well, but its prediction of the turbulent fluctuation is far from satisfactory. This study builds on Monin–Obukhov similarity theory and Townsend’s attached-eddy hypothesis. We present a model that connects the mean flow and the streamwise velocity fluctuations in both neutral and unstable boundary-layer flows at both moderate and high Reynolds numbers. The model predictions are compared to direct numerical simulations of weakly unstable boundary layers at moderate Reynolds numbers, and large-eddy simulations of unstable boundary-layer flows at high Reynolds numbers. The flow is shear dominated. The range of stability parameter considered in this work is
is the Monin–Obukhov length, and
is the boundary-layer height. Reasonably good prediction of velocity fluctuations based on knowledge of the mean velocity profile is obtained.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
Until the past half-century, all agriculture and land management was framed by local institutions strong in social capital. But neoliberal forms of development came to undermine existing structures, thus reducing sustainability and equity. The past 20 years, though, have seen the deliberate establishment of more than 8 million new social groups across the world. This restructuring and growth of rural social capital within specific territories is leading to increased productivity of agricultural and land management systems, with particular benefits for those previously excluded. Further growth would occur with more national and regional policy support.
According to Townsend’s attached eddy hypothesis (AEH), a boundary layer flow is comprised of wall-attached eddies, but to extract the part of the flow whose statistical behaviours are well described by the AEH is not at all straightforward. The objective of this work is to extract the part of the flow that can be described by the AEH, and study the statistical behaviours of the other part, which cannot be described by the AEH. In this process, two types of eddies are identified in addition to the Kolmogorov-scale eddies, i.e. wall-attached eddies and wall-detached eddies. The statistical behaviours of the wall-attached eddies are shown to be very well described by the AEH, i.e. the eddies are wall-attached, self-similar and, importantly, Gaussian, whereas the wall-detached eddies cannot be modelled by the AEH. Specifically, a decomposition scheme is proposed following Townsend (The Structure of Turbulent Shear Flow, Cambridge University Press, 1976). We apply our decomposition scheme to three different flows, i.e. channel, boundary layer and atmospheric surface layer flows. The results are similar with only quantitative differences, suggesting possible universality in both the wall-attached eddies and the wall-detached eddies.
The aim was to assess the ability of post-treatment diffusion-weighted imaging (DWI) to predict 90-day functional outcome in patients with endovascular therapy (EVT) for large vessel occlusion in acute ischemic stroke (AIS).
We examined a retrospective cohort from March 2016 to January 2018, of consecutive patients with AIS who received EVT. Planimetric DWI was obtained and infarct volume calculated. Four blinded readers were asked to predict modified Rankin Score (mRS) at 90 days post-thrombectomy.
Fifty-one patients received endovascular treatment (mean age 65.1 years, median National Institutes of Health Stroke Scale (NIHSS) 18). Mean infarct volume was 43.7 mL. The baseline NIHSS, 24-hour NIHSS, and the DWI volume were lower for the mRS 0–2 group. Also, the thrombolysis in cerebral infarction (TICI) 2b/3 rate was higher in the mRS 0–2 group. No differences were found in terms of the occlusion level, reperfusion technique, or recombinant tissue plasminogen activator use. There was a significant association noted between average infarct volume and mRS at 90 days. On multivariable analysis, higher infarct volume was significantly associated with 90-day mRS 3–5 when adjusted to TICI scores and occlusion location (OR 1.01; CI 95% 1.001–1.03; p = 0.008). Area under curve analysis showed poor performance of DWI volume reader ability to qualitatively predict 90-day mRS.
The subjective impression of DWI as a predictor of clinical outcome is poorly correlated when controlling for premorbid status and other confounders. Qualitative DWI by experienced readers both overestimated the severity of stroke for patients who achieved good recovery and underestimated the mRS for poor outcome patients. Infarct core quantitation was reliable.
Flow over aligned and staggered cube arrays is a classic model problem for rough-wall turbulent boundary layers. Earlier studies of this model problem mainly looked at rough surfaces with a moderate coverage density, i.e.
is the surface coverage density and is defined to be the ratio between the area occupied by the roughness and the total ground area. At lower surface coverage densities, i.e.
, it is conventionally thought that cubical roughness acts like isolated roughness elements; and that the single-cube drag coefficient, i.e.
is the drag force on one cubical roughness element,
is the fluid density,
is the height of the cube,
is the spatially and temporally averaged wind speed at the cube height, and
is the drag coefficient of an isolated cube. In this work, we conduct large-eddy simulations and direct numerical simulations of flow over wall-mounted cubes with very low surface coverage densities, i.e.
. The large-eddy simulations are at nominally infinite Reynolds numbers. The results challenge the conventional thinking, and we show that, at very low surface coverage densities, the single-cube drag coefficient may increase as a function of
. Our analysis suggests that this behaviour may be attributed to secondary turbulent flows. Secondary turbulent flows are often found above spanwise-heterogeneous roughness. Although the roughness considered in this work is nominally homogeneous, the secondary flows in our simulations are very similar to those observed above spanwise-heterogeneous surface roughness. These secondary vortices redistribute the fluid momentum in the outer layer, leading to high-momentum pathways above the wall-mounted cubes and low-momentum pathways at the two sides of the wall-mounted cubes. As a result, the spatially and temporally averaged wind speed at the cube height, i.e.
, is an underestimate of the incoming flow to the cubes, which in turn leads to a large drag coefficient
We conducted active surveillance of acute respiratory viral infections (ARIs) among residents and healthcare personnel (HCP) at a long-term care facility during the 2015–2016 respiratory illness season. ARIs were observed among both HCP and patients, highlighting the importance of including HCP in surveillance programs.
The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009–2010 to 2015–2016. We carried out weighted regression among young adults (20–39 years) and adults (40–59 years) separately. In total, 5230 men and 5794 women aged 20–59 years were included in the present analyses. In total, 0.8% men and 0.2% women were tested HIV-positive. Each increasing HIV risk behaviour was associated with elevated odds of being tested HIV-positive (1.15, 95% CI 1.15–1.15) among young adults and adults (1.61, 95% CI 1.61–1.61). Multi-faceted, community-based interventions are urgently required to reduce the incidence of HIV in the USA.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
This article considers the problem of testing for an explosive bubble in financial data in the presence of time-varying volatility. We propose a sign-based variant of the Phillips, Shi, and Yu (2015, International Economic Review 56, 1043–1077) test. Unlike the original test, the sign-based test does not require bootstrap-type methods to control size in the presence of time-varying volatility. Under a locally explosive alternative, the sign-based test delivers higher power than the original test for many time-varying volatility and bubble specifications. However, since the original test can still outperform the sign-based one for some specifications, we also propose a union of rejections procedure that combines the original and sign-based tests, employing a wild bootstrap to control size. This is shown to capture most of the power available from the better performing of the two tests. We also show how a sign-based statistic can be used to date the bubble start and end points. An empirical illustration using Bitcoin price data is provided.
We investigate the nonlinear phase-space dynamics of plane Couette flow and plane Poiseuille flow under the action of opposition control at low Reynolds numbers in domains close to the minimal unit. In Couette flow, the effect of the control is analysed by focussing on a pair of non-trivial equilibrium solutions. It is found that the control only slightly modifies the statistics, turbulent skin friction and phase-space projection of the lower-branch equilibrium solution, which, in this case, is in fact identical to the edge state. On the other hand, the upper-branch equilibrium solution and mean turbulent state are modified considerably when the control is applied. In phase space, they gradually approach the lower-branch equilibrium solution on increasing the control amplitude, and this results in an elevation of the critical Reynolds number at which the equilibrium solutions first occur via a saddle-node bifurcation. It is also found that the upper-branch equilibrium solution is stabilised by the control. In Poiseuille flow, we study an unstable periodic orbit on the edge state and find that it, too, is modified very little by opposition control. We again observe that the turbulent state gradually approaches the edge state in phase space as the control amplitude is increased. In both flows, we find that the control significantly reduces the fluctuating strength of the turbulent state in phase space. However, the reduced distance between the turbulent trajectory and the edge state yields a significant reduction in turbulence lifetimes for both Couette and Poiseuille flow. This demonstrates that opposition control greatly increases the probability of the trajectory escaping from the turbulent state, which takes the form of a chaotic saddle.