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Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
X-ray excitation causes rare-earth impurities in yttrium oxide and gadolinium oxide to emit intense and highly characteristic optical line fluorescence, which enables their analyses at low concentrations. The limits of detection for praseodymium, ncodymium, samarium, europium, gadolinium, terbium, dysprosium. holmium, erbium, thulium, and ytterbium in these two oxides range from 1 to 100 parts per billion (ppb). In other rare-earth oxides which have been investigated. the fluorescent intensities arc greatly reduced. Successful analyses can be made only by dilution in high-purity Y2O3. This dilution raises the detection limits for rare earths in these other oxides to the part per million range. X-rays from the chromium target of a cual-target X-ray tube are about two times more efficient in exciting rareeaith optical fluorescence than are the tungsten-target X-rays, even though the total energy output of the chromium target is only about one-third that of the tungsten target. With either target material, the rare-earth intensities vary linearly with the X-ray tube current, but a plot of intensity versus the square of the accelerating potential is not linear; it drops off at higher voltages.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
Following the B777 accident at Heathrow in 2008, the certification authorities required Boeing, Airbus, and Rolls-Royce to conduct icing analysis and tests of their Rolls-Royce Trent engined aircraft fuel systems. The experience and the test data gained from these activities were distilled and released by Airbus to the EASA ICAR project for research and analysis. This paper provided an overview of the Airbus ice accretion and release tests. Brief narratives on the test rigs, the test procedure and methodology were given and key findings from the ice release investigations were presented. The accreted ice thickness was non-uniform; however, it is found typically c.
thick. Analysis of the accreted ice collected from the rig tests showed the ice was very porous. The porosity is very much dependant on how the water was introduced and mixed in the icing test rigs. The standard Airbus method produced accreted ice of higher porosity compared to that produced by the injection method. The porosity of the accreted ice from Airbus icing investigations was found to be c. 0.90. The relationship of permeability with porosity was inferred from published data and models for freshly fallen snow in the atmosphere. Derived permeability
was then applied in the CFD analysis of pipe flow with a porous wall lining to determine the shear stress on the accreted ice. It showed that 25%, 50% and 75% of the accreted ice has interface shear strength of less than
This study compared the effect of feeding AmyPlus, a moist feed, as opposed to rolled wheat on the yield and composition of milk from dairy cows consuming grass silage based total mixed ration (TMR). Seventy-two Holstein-Friesian cows were distributed into AmyPlus (Treatment) and Wheat (Control) groups and loose housed on straw in an open shed. Each kg Wheat based concentrate contained 345g rolled wheat, 230g rapeseed meal, 115g sugarbeet pulp, 115g Molaferm 20, 115g soybean meal, 56g barley straw and 24g vitamin-minerals. In contrast, each kg AmyPlus based concentrate contained 501g AmyPlus (480g DM /kg), 105g rapeseed meal, 126g sugarbeet pulp, 126g Molaferm 20, 84g soybean meal, 41g barley straw and 17g vitamin-minerals. Here, AmyPlus was loaded directly into the mixer wagon to prepare fresh AmyPlus based TMR with a silage to concentrate ratio of 68:32. Each TMR was fed once daily to the corresponding group of cows also receiving 2kg of Distillers’ grains per cow in the parlour during milking. Daily milk yield and composition was recorded from November 1999 to February 2000. The overall daily Dry matter intake (DMI) of each TMR per cow remained uniform (20.19 vs 20.15 kg for Treatment and Control group respectively) across both groups. Daily milk yield and total cell counts per cow did not vary significantly (P>0.05) between groups during various months. While, milk fat and protein contents were greater in Treatment than Control group during each month, the differences were significant (P<0.05) only during November and December for fat and in January for protein. On average, the Treatment group tended to show a non-significant increase (P>0.05) in daily milk yield per cow by 0.144 kg than the Control group. The fat (46.2 vs 43.7) and protein (34.5 vs 33.5) contents in g /kg milk were also increased significantly (P<0.001) in Treatment compared with Control group. Total cell counts did not vary significantly (P>0.05) and remained within the acceptable limits. The cows consuming AmyPlus maintained their health as indicated by their intake, production, cell counts and general appearance. It would appear that AmyPlus can replace rolled wheat in TMR. However, it may be necessary to evaluate the storage, economic and environmental implications of using such moist co-products in silage based dairy rations.
In the tropics, fodder trees and shrubs are a very important source of nutrients, especially nitrogen. In vitro gas production methods used for food evaluation were originally developed for investigation of temperate forages and used a nitrogen-rich medium. Evaluation of fodder tree leaves in this medium may mask the effect of their nitrogen which it is important to understand. This trial studied the fermentation of a range of tropical fodder trees and shrubs in both nitrogen-rich and nitrogen-free media, in order to identify the main chemical entities contributing to gas production and the time within which such contributions were most important.
Previous work in animal nutrition has focused on single foods and assumed additivity during in vitro fermentation. In the tropics, farmers are likely to offer mixtures of foods, including tree fodders, which may not be simply additive in nutritional terms. There is little information about the nutritional interactions between tropical foods. The objective of this research was to test the existence of associative effects of mixtures of tropical fodder tree leaves.
A major focus for improving the diets in many less developed countries (LDCS) is the provision of rumen fermentable nitrogen (N) using protein supplements to complement N-deficient foods. However, in vitro digestibility methods usually use N-rich environments for the degradation of single foods. This conventional approach may give data which do not reflect the nutritive value of the N-deficient diets often on offer in LDCS, neither is it appropriate for using in vitro gas production to study protein supplementation. Our earlier study indicated that, by using a N-free medium, the gas production technique responded to added ammonium sulphate and urea. The ADAS standardized methodology, which used 10 ml of inoculum instead of the 5 ml used in the earlier study, was found not to be very responsive to N supplementation. The ADAS methodology was therefore investigated in order to develop a modified protocol for fermenting foods in an N-limited environment. The study involved using inocula diluted to different extents in N-free medium for fermenting N-deficient substrates in N-free and N-rich media. The modified protocol was then used for investigating the interactions between N-rich and N-deficient foods from north-west India.
There is increasing interest in the use of red clover (Trifolium pratense) as a high protein forage crop to finish growing lambs. Red clover contains the isoflavanoid compound formononetin which is converted to the non-steroidal oestrogen analogue equol by rumen micro-organisms. Equol is absorbed by the animal, and can have significant effects, such as suppressing reproductive cycling in ewes. Very few commercial red clover varieties have been bred with a low formononetin content to prevent this problem. Although human health benefits have been linked to the consumption of oestrogenically active compounds in foods such as soya (Kurzer and Xu, 1997), there is a need to investigate the presence of oestrogenically active compounds in animal products. The objective of this study was to investigate plasma metabolite and hormone concentrations, and the residual levels of equol in meat, of lambs grazing two varieties of red clover differing in their formononetin contents, compared to control animals grazing grass.
Attenuated positive symptom syndrome (APSS), characterized by ‘putatively prodromal’ attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of ‘true’ prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals.
Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis.
Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria.
Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.
More than 3000 radial velocity observations across the face of the Crab Nebula are used to investigate its 3-dimensional properties. In the standard model it consists of a thick hollow shell with synchrotron emission from within. We show that the thick shell is composed of bright inner and faint outer components
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
Robust time-averaged molecular dynamics has been developed to calculate finite-temperature elastic constants of a single crystal. We find that when the averaging time exceeds a certain threshold, the statistical errors in the calculated elastic constants become very small. We applied this method to compare the elastic constants of Pd and PdH0.6 at representative low (10 K) and high (500 K) temperatures. The values predicted for Pd match reasonably well with ultrasonic experimental data at both temperatures. In contrast, the predicted elastic constants for PdH0.6 only match well with ultrasonic data at 10 K; whereas, at 500 K, the predicted values are significantly lower. We hypothesize that at 500 K, the facile hydrogen diffusion in PdH0.6 alters the speed of sound, resulting in significantly reduced values of predicted elastic constants as compared to the ultrasonic experimental data. Literature mechanical testing experiments seem to support this hypothesis.
The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.
Charcoal is the result of natural and anthropogenic burning events, when biomass is exposed to elevated temperatures under conditions of restricted oxygen. This process produces a range of materials, collectively known as pyrogenic carbon, the most inert fraction of which is known as black carbon (BC). BC degrades extremely slowly and is resistant to diagenetic alteration involving the addition of exogenous carbon, making it a useful target substance for radiocarbon dating particularly of more ancient samples, where contamination issues are critical. We present results of tests using a new method for the quantification and isolation of BC, known as hydropyrolysis (hypy). Results show controlled reductive removal of non-BC organic components in charcoal samples, including lignocellulosic and humic material. The process is reproducible and rapid, making hypy a promising new approach not only for isolation of purified BC for 14C measurement but also in quantification of different labile and resistant sample C fractions.
The MACHO data base has been used to examine light curves of all red giant stars brighter than Mbol ∼ −2 in a 0.5° × 0.5° area of the LMC bar. Periods, often multiple, have been searched for in all stars found to be variable. Five distinct period-luminosity sequences have been found on the low mass (M ≲ 2.25M⊙) giant branch. Comparison of observed periods, luminosities and period ratios with theoretical models identifies Miras unambiguously as radial fundamental mode pulsators, while semi-regular variables can be pulsating in the 1st, 2nd or 3rd overtone, or even the fundamental. All these variables lie on just 3 of the 5 distinct sequences, and they all appear to be on the AGB.
The fourth sequence contains red giants on the first giant branch (FGB) or at the red end of the core-helium burning loops of intermediate mass stars (M ≳ 2.25M⊙). The light curves of these stars strongly suggest that they are contact binaries, and they make up ∼0.5% of stars within 1 mag. of the FGB tip. Stars on the fifth sequence show semi-regular, eclipse-like light curves. The light curves and periods of these stars suggest that they are in semi-detached binaries, transfering mass to an invisible companion via a stellar wind or Roche lobe overflow. They make up ∼25% of AGB stars. If the existence of these red giant contact and semi-detached binaries is confirmed, then extant theories of binary star evolution will require substantial modification.
We present the first results from multi-site observations of the δ Scuti star XX Pyx (CD–24°7599). The observations were carried out as the 17th run of the Delta Scuti Network. We collected 583 hr of B, V time-series photometry, resulting in a detection level (4σ) in the amplitude spectrum of 0.5 mmag. We detect 6 new pulsation frequencies, bringing the total number of frequencies known in this star up 19.