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Compulsive behaviors in obsessive-compulsive disorder (OCD) have been related to impairment within the associative cortical-striatal system connecting the caudate and prefrontal cortex that underlies consciously-controlled goal-directed learning and behavior. However, little is known whether this impairment may serve as a biomarker for vulnerability to OCD.
Using resting-state functional magnetic resonance imaging (fMRI), we employed Granger causality analysis (GCA) to measure effective connectivity (EC) in previously validated striatal sub-regions, including the caudate, putamen, and the nucleus accumbens, in 35 OCD patients, 35 unaffected first-degree relatives and 35 matched healthy controls.
Both OCD patients and their first-degree relatives showed greater EC than controls between the left caudate and the orbital frontal cortex (OFC). Both OCD patients and their first-degree relatives showed lower EC than controls between the left caudate and lateral prefrontal cortex. These results are consistent with findings from task-related fMRI studies which found impairment in the goal-directed system in OCD patients.
The same changes in EC were present in both OCD patients and their unaffected first-degree relatives suggest that impairment in the goal-directed learning system may be a biomarker for OCD.
As a benchmark mortality model in forecasting future mortality rates and hedging longevity risk, the widely employed Lee–Carter model (Lee, R.D. and Carter, L.R. (1992) Modeling and forecasting U.S. mortality. Journal of the American Statistical Association, 87, 659–671.) suffers from a restrictive constraint on the unobserved mortality index for ensuring model’s identification and a possible inconsistent inference. Recently, a modified Lee–Carter model (Liu, Q., Ling, C. and Peng, L. (2018) Statistical inference for Lee–Carter mortality model and corresponding forecasts. North American Actuarial Journal, to appear.) removes this constraint and a simple least squares estimation is consistent with a normal limit when the mortality index follows from a unit root or near unit root AR(1) model with a nonzero intercept. This paper proposes a bias-corrected estimator for this modified Lee–Carter model, which is consistent and has a normal limit regardless of the mortality index being a stationary or near unit root or unit root AR(1) process with a nonzero intercept. Applications to the US mortality rates and a simulation study are provided as well.
Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression.
A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE.
Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores.
This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.
The aim of this study was to investigate the in vivo degradation mechanism and the mechanical properties of poly(lactide-co-glycolide)/beta-tricalcium phosphate (PLGA/β-TCP) composite anchors. Anchors composed of PLGA and β-TCP were implanted in the dorsal subcutaneous tissue of beagle dogs for 6, 12, 16, and 26 weeks. The degradation of the materials was evaluated by measuring the changes in thermal behavior, crystallinity, and mechanical properties. Scanning electron microscope (SEM) was used to observe the surface and longitudinal section of the material. The evaluation of mechanical strength retention and degradation properties suggest that the addition of β-TCP particles efficiently enhances their mechanical properties and thermal characteristics and delays their degradation rate. By analyzing the results of SEM, X-ray diffraction, and differential scanning calorimetry, we can infer that after 12 weeks, the connection between β-TCP and PLGA becomes less compact, which accelerates the decline of mechanical strength.
Many shorebird populations are in decline along the East Asian-Australasian Flyway. The rapid loss of coastal wetlands in the Yellow Sea, which provide critical stop-over sites during migration, is believed to be the cause of the alarming trends. The Yalu Jiang coastal wetland, a protected area in the north Yellow Sea, supports the largest known migratory staging populations of Bar-tailed Godwits Limosa lapponica (menzbieri and baueri subspecies) and Great Knots Calidris tenuirostris. Monitoring of the macrozoobenthos food for these shorebirds from 2011 to 2016 showed declines of over 99% in the densities of the bivalve Potamocorbula laevis, the major food here for both Bar-tailed Godwits and Great Knots. The loss of the bivalve might be caused by any combination of, but not limited to: (1) change in hydrological conditions and sediment composition due to nearby port construction, (2) run-off of agrochemicals from the extensive shoreline sea cucumber farms, and (3) parasitic infection. Surprisingly, the numbers of birds using the Yalu Jiang coastal wetland remained stable during the study period, except for the subspecies of Bar-tailed Godwit L. l. menzbieri, which exhibited a 91% decline in peak numbers. The lack of an overall decline in the number of bird days in Great Knots and in the peak numbers of L. l. baueri, also given the published simultaneous decreases in their annual survival, implies a lack of alternative habitats that birds could relocate to. This study highlights that food declines at staging sites could be an overlooked but important factor causing population declines of shorebirds along the Flyway. Maintaining the quality of protected staging sites is as important in shorebird conservation as is the safeguarding of staging sites from land claim. Meanwhile, it calls for immediate action to restore the food base for these beleaguered migrant shorebirds at Yalu Jiang coastal wetland.
For treatment of patients diagnosed with schizophrenia, comparative
long-term effectiveness of antipsychotic drugs to reduce relapses when
minimising adverse effects is of clinical interest, hence prompting this
To evaluate the comparative long-term effectiveness of antipsychotic
We systematically searched electronic databases for reports of randomised
controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing
relapse risks in schizophrenia. We conducted network meta-analysis of 18
antipsychotics and placebo.
Studies of 10 177 patients in 56 reports were included; treatment
duration averaged 48 weeks (range 4–156). Olanzapine was significantly
more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI
0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine
decanoate was more effective than chlorpromazine (OR=0.31, 95% CI
0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol,
haloperidol decanoate and trifluoperazine produced more extrapyramidal
adverse effects than olanzapine or quetiapine; and olanzapine was
associated with more weight gain than other agents.
Except for apparent superiority of olanzapine and fluphenazine decanoate
over chlorpromazine, most agents showed intermediate efficacy for relapse
prevention and differences among them were minor. Typical antipsychotics
yielded adverse neurological effects, and olanzapine was associated with
weight gain. The findings may contribute to evidence-based treatment
selection for patients with chronic psychotic disorders.
Motivated by a recent discovery that the two-step inference for the Lee–Carter mortality model may be inconsistent when the mortality index does not follow from a nearly integrated AR(1) process, we propose a test for a unit root in a Lee–Carter model with an AR(p) process for the mortality index. Although testing for a unit root has been studied extensively in econometrics, the method and asymptotic results developed in this paper are unconventional. Unlike a blind application of existing R packages for implementing the two-step inference procedure in Lee and Carter (1992) to the U.S. mortality rate data, the proposed test rejects the null hypothesis that the mortality index follows from a unit root AR(1) process, which calls for serious attention on using the future mortality projections based on the Lee–Carter model in policy making, pricing annuities and hedging longevity risk. A simulation study is conducted to examine the finite sample behavior of the proposed test too.
The effect of solution treatment (ST) on the microstructure and mechanical properties of cast Al–3Li–1.5Cu–0.2Zr alloy was investigated. Results showed that the volume fraction of secondary phases (Al2Cu, Al3Li) decreased obviously after ST. It was found that the strengthening of Al–3Li–1.5Cu–0.2Zr alloy was a balance of the precipitation strengthening, residual phase strengthening and fine grain strengthening. The residual phase strengthening and fine grain strengthening decreased with increasing the solution temperature and time, while precipitation strengthening increased. After ST at 560 °C for 40 h, the elongation of Al–3Li–1.5Cu–0.2Zr alloy reaches the highest value of 22.1%. In addition, the tensile properties are up to the highest values, ultimate tensile strength of 359 MPa and elongation of 3.5% after optimal ST at 560 °C for 40 h followed by aging treatment.
Objectives: Effective formulary management in healthcare institutions safeguards rational drug use and optimizes health outcomes. We implemented a formulary management program integrating the principles of health technology assessment (HTA) to improve the safe, appropriate, and cost-effective use of medicine in Singapore.
Methods: A 3-year formulary management program was initiated in 2011 in five public healthcare institutions. This program was managed by a project team comprising HTA researchers. The project team worked with institutional pharmacy and therapeutics (P&T) committees to: (i) develop tools for formulary drug review and decision making; (ii) enhance the HTA knowledge and skills of formulary pharmacists and members of P&T committees; (iii) devise a prioritization framework to overcome resource constraints and time pressure; and (iv) conceptualize and implement a framework to review existing formulary.
Results: Tools that facilitate drug request submission, drug review, and decision making were developed for formulary drug inclusion. A systematic framework to review existing formulary was also developed and tested in selected institutions. A competency development plan was rolled out over 2 years to enhance formulary pharmacists’ proficiency in systematic literature search and review, meta-analysis, and pharmacoeconomic evaluation. The plan comprised training workshops and on-the-job knowledge transfer between the project team and institutional formulary pharmacists through collaborating on selected drug reviews. A resource guide that consolidated the tools and templates was published to encourage the adoption of best practices in formulary management.
Conclusions: Based on the concepts of HTA, we implemented an evidence-based approach to optimize formulary management.
The late Quaternary sedimentary sequence in the northwestern part of the Sichuan Basin consists of five lithological units and with increasing depth include the: Chengdu Clay; Brown Clay; Red Clay; Sandy Silt; and basal Muddy Gravel. The genesis, provenance and age of the sediments, as well as the possible presence of hiatuses within this sequence are debated. Measurements of grain-size, magnetic susceptibility, quartz content, quartz δ18O values, element composition, and Sr–Nd isotopic concentrations of samples from a typical sedimentary sequence in the area provides new insights into the genesis and history of the sequence. The new data confirm that the sediments in study site are alluvial–aeolian in origin, with basal alluvial deposits overlain by aeolian deposits. Like the uppermost Chengdu Clay, the underlying Brown Clay and Red Clay are aeolian in origin. In contrast, the Silty Sand, like the basal Muddy Gravel, is an alluvial deposit and not an aeolian deposit as previously thought. Moreover, the succession of the aeolian deposits very likely contains two significant sedimentary hiatuses. Sedimentological analysis demonstrates that the source materials for the aeolian deposits in the northwestern part of the Sichuan Basin and those on the eastern Tibetan Plateau are different. Furthermore, the loess deposits on the eastern Tibetan Plateau are derived from heterogeneous local sources.
The effect of 0.5 wt% Mn addition on the microstructure and mechanical properties of cast Al–2Li–2Cu–0.8Mg–0.4Zn–0.2Zr (wt%) alloy was investigated. Results showed that the grain size of Mn-containing alloy was smaller than that of Mn-free alloy in both the as-cast and solution treated state. Al20Mn3Cu2 dispersoids were formed during solution treatment in the Mn-containing alloy. After aging at 175 °C for 32 h, a large volume fraction of coherent Al3Li/Al3(Li, Zr) particles were precipitated in both Mn-free and Mn-containing alloys, while more Guinier–Preston–Bagaratsky zones were observed in the Mn-free alloy. Mn addition improved the elongation significantly, which was 1.7% for Mn-free alloy and 3.3% for the alloy with 0.5 wt% Mn addition.
Based on SDSS and South Galactic Cap U-band Sky Survey (SCUSS) photometry, we try to study the photometric metallicity of the Sagittarius (Sgr) stream in the south Galactic cap. We find that the Sgr stream has a wider metallicity distribution, and that its median metallicity is richer than that of the field halo stars. The neighboring field halo stars in our studied fields can be modeled by a two-Gaussian model, with peaks at [Fe/H]= −1.9 and [Fe/H]= −1.5. The metallicity distribution function (MDF) of the mixed population (Sgr stream and halo stars) has peaks at [Fe/H]= −1.9, [Fe/H]= −1.5 and [Fe/H]= −0.5, respectively.
This paper presents the design and tests of a repetitive 800 kA fast linear transformer driver (LTD) stage aimed for the Z-pinch driven fusion-fission hybrid reactor (Z-FFR).The LTD stage consists of 34 parallel basic resistor R, inductor L, and capacitor C (RLC) circuits each made up of two 100 kV/40 nF capacitors, a multi-stage gas switch and Metglas magnetic cores. The stage can deliver about 800 kA current pulse with rise time of 100 ns into the matched liquid resistive load at a repetitive frequency 0.1 Hz. A novel method to trigger the stage via a continuous internal trigger bus composed by a single cable has been proposed and demonstrated. The experimental results show that the new trigger method is feasible and reliable. A 140 kV, 25 ns rising time trigger pulse, and a 5.2 kA, 30 μs width pre-magnetization current pulse which can operate at a repetition rate 0.1 Hz were used in this stage to insure the LTD stage generating a 80 kV/800 kA current pulse every 10 s. A multi-stage gas switch that has a lifetime in excess of 10,000 shots and a jitter less than 3 ns one sigma agrees well with the demand of Z-FFR. The electrical behavior of the stage can be predicted from a simple RLC circuit, which can simplify the design of various LTD-based accelerators.
Postnatal rapid growth by excess intake of nutrients has been associated with an increased susceptibility to diseases in neonates with intra-uterine growth restricted (IUGR). The aim of the present study was to determine whether postnatal nutritional restriction could improve intestinal development and immune function of neonates with IUGR using piglets as model. A total of twelve pairs of normal-birth weight (NBW) and IUGR piglets (7 d old) were randomly assigned to receive adequate nutrient intake or restricted nutrient intake (RNI) by artificially liquid feeding for a period of 21 d. Blood samples and intestinal tissues were collected at necropsy and were analysed for morphology, digestive enzyme activities, immune cells and expression of innate immunity-related genes. The results indicated that both IUGR and postnatal nutritional restriction delayed the growth rate during the sucking period. Irrespective of nutrient intake, piglets with IUGR had a significantly lower villous height and crypt depth in the ileum than the NBW piglets. Moreover, IUGR decreased alkaline phosphatase activity while enhanced lactase activity in the jejunum and mRNA expressions of Toll-like receptor 9 (TLR-9) and DNA methyltransferase 1 (DNMT1) in the ileum of piglets. Irrespective of body weight, RNI significantly decreased the number and/or percentage of peripheral leucocytes, lymphocytes and monocytes of piglets, whereas the percentage of neutrophils and the ratio of CD4+ to CD8+ were increased. Furthermore, RNI markedly enhanced the mRNA expression of TLR-9 and DNMT1, but decreased the expression of NOD2 and TRAF-6 in the ileum of piglets. In summary, postnatal nutritional restriction led to abnormal cellular and innate immune response, as well as delayed the growth and intestinal development of IUGR piglets.
Considerable controversy exists regarding the associations of dietary patterns with the risk of all-cause, CVD and stroke mortality. Therefore, a meta-analysis was conducted to elucidate the potential associations between dietary patterns and the risk of all-cause, CVD and stroke mortality. The PubMed database was searched for prospective cohort studies on the associations between dietary patterns and the risk of all-cause, CVD and stroke mortality published until February 2014. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest v. the lowest category of dietary pattern scores. Stratified analyses were conducted based on sex, geographical region, follow-up duration, and adjustment/non-adjustment for energy intake. A total of thirteen prospective cohort studies involving 338 787 participants were included in the meta-analysis. There was evidence of inverse associations between the prudent/healthy dietary pattern and the risk of all-cause (SRRE = 0·76, 95 % CI 0·68, 0·86) and CVD (SRRE = 0·81, 95 % CI 0·75, 0·87) mortality and an absence of association between this dietary pattern and stroke mortality (SRRE = 0·89, 95 % CI 0·77, 1·02). However, no significant associations were observed between the Western/unhealthy dietary pattern and the risk of all-cause (SRRE = 1·07, 95 % CI 0·96, 1·20), CVD (SRRE = 0·99, 95 % CI 0·91, 1·08) and stroke (SRRE = 0·94, 95 % CI 0·81, 1·10) mortality. In conclusion, the findings provide evidence that greater adherence to a prudent/healthy dietary pattern is associated with a lower risk of all-cause and CVD mortality and not significantly associated with stroke mortality and that the Western/unhealthy dietary pattern is not associated with all-cause, CVD and stroke mortality. Further studies are required to confirm these findings.
A novel micro in-pipe robot using an internally threaded profile for propulsion is proposed in this paper, and the dynamic model of the robot in the turbulent liquid pipeline is established, and the computational fluid dynamics method is used to solve the influence of environmental parameters and operating parameters on the robotic performance. By the orthogonal experimental optimization method, the optimal inner spiral structural parametrical combination is obtained. According to the working principle of the inner spiral robot, an inner spiral driving device is designed and fabricated, and the running experiment in the pipeline full of 201 methyl silicone oil verifies the feasibility of the proposed robot. Adopting the pulsating blood flow function as the inlet condition, in a pulsating period, the robotic performance is numerically analyzed.
An energy measurement system in a Large-aperture high power laser experiment platform
is introduced. The entire measurement system includes five calorimeters, which carry
out the energy measurement of the fundamental frequency before the frequency
conversion unit, remaining fundamental frequency, remain second-harmonics, third
harmonics, as well as the energy balance measurement after the frequency conversion
unit. Combinational indirect calibration and direct calibration are employed to
calibrate the sampling coefficients of the calorimeters. The analysis of the data
showed that, regarding the energy balance coefficients, combinational calibration
approach gives a higher precision, and leads to an energy balance with 1%; and
regarding the energy sampling coefficients for the various wavelengths after the
frequency conversion, the results from direct and combinational calibration are
consistent. The uncertainties for all energy sampling coefficients are within 3%,
which guarantees the reliability of the energy measurement for the laser
Clathrin heavy chain 1 (CLTC) has been considered a “moonlighting protein” which acts in membrane trafficking during interphase and in stabilizing spindle fibers during mitosis. However, its roles in meiosis, especially in mammalian oocyte maturation, remain unclear. This study investigated CLTC expression and function in spindle formation and chromosome congression during mouse oocyte meiotic maturation. Our results showed that the expression level of CLTC increased after germinal vesicle breakdown (GVBD) and peaked in the M phase. Immunostaining results showed CLTC distribution throughout the cytoplasm in a cell cycle-dependent manner. Appearance and disappearance of CLTC along with β-tubulin (TUBB) could be observed during spindle dynamic changes. To explore the relationship between CLTC and microtubule dynamics, oocytes at metaphase were treated with taxol or nocodazole. CLTC colocalized with TUBB at the enlarged spindle and with cytoplasmic asters after taxol treatment; it disassembled and distributed into the cytoplasm along with TUBB after nocodazole treatment. Disruption of CLTC function using stealth siRNA caused a decreased first polar body extrusion rate and extensive spindle formation and chromosome congression defects. Taken together, these results show that CLTC plays an important role in spindle assembly and chromosome congression through a microtubule correlation mechanism during mouse oocyte maturation.