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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.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
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.
This paper concentrates on livestock production systems by introducing sustainable housing characteristics, and the type of information required to make an informed choice on environmentally sound materials and systems. It then compares energy use in two contrasting beef cattle systems, one a conventional straw-bedded court and roofed silo, with feed delivered by a side-delivery wagon, and the other a roofless woodchip corral and earth-bank silo, with feed delivered by fore-end loader. The woodchip corral system requires 70% less energy than the conventional bedded court, when the total energy inputs are analysed for preparation of the building materials, construction of the livestock accommodation with associated feed and waste storage, and manufacture and operation of machinery. However, when energy used in feed production is included this dominates the energy budget, accounting for 60% of all energy used in the conventional bedded court, and 85% of energy used in the woodchip corral system.
Gliricidia sepium (Jacq.) Steud. is widely used as a high-protein supplementary food for ruminants in many parts of the tropics. Native to Central America and Mexico, it has become widely naturalized elsewhere but the introduced populations are mostly of unknown origin and uncertain quality. Studies of the genetic resources from the native range, under a research programme at OFI, have shown great variation between populations in yield (Dunsdon and Simons, 1996). The objective of the research described here was to investigate whether there is also important genetic variation in fodder quality, to inform decisions on future distribution of ‘superior’ germplasm of G. sepium under the OFI programme.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
The solar magnesium II core-to-wing ratio has been a well-studied proxy for chromospheric activity since 1978. Daily measurements at high spectral (0.1 nm) resolution began with the launch of the Solar Radiation and Climate Experiment (SORCE) in 2003. The next generation of measurements from the Extreme Ultraviolet Sensor (EUVS) on the Geostationary Operational Environmental Satellite 16 (GOES-16) will add high time cadence (every 30 seconds) to the observational Mg II irradiance record. We present a comparison of the two measurements during the period of overlap.
Ultraviolet (UV) Solar spectral Irradiance (SSI) has been measured from orbit on a regular basis since the beginning of the space age. These observations span four Solar Cycles, and they are crucial for our understanding of the Sun-Earth connection and space weather. SSI at these wavelengths are the main drivers for the upper atmosphere including the production and destruction of ozone in the stratosphere. The instruments that measure UV SSI not only require good preflight calibration, but also need a robust method to maintain that calibration on orbit. We will give an overview of the catalog of current and former UV SSI measurements along with the calibration philosophy of each instrument and an estimation of the uncertainties in the published irradiances.
Boar taint is off-odours in cooked pork from uncastrated male pigs. It is caused by an excessive accumulation of skatole and androstenone in backfat. Accumulation of skatole is due to a low expression and activity of hepatic enzyme CYP2E1. The mechanism of androstenone accumulation is not clear. It could be due to low activity and expression of 3ß-hydroxysteroid dehydrogenase (HSD), an enzyme metabolising androstenone in liver. On the basis of our previous in vivo experiments with castrated animals we suggest that accumulation of skatole is regulated by androstenone. Castrated pigs manifest lower levels of skatole and androstenone and higher CYP2E1 expression. We hypothesise that high levels of androstenone inhibits CYP2E1 expression and hence, reduces the rate of hepatic skatole metabolism. The aims of the present study were (i) to investigate the expression of androstenone-metabolising enzyme HSD in liver of pigs with high and low skatole and androstenone deposition; (ii) to investigate the effect of androstenone on expression of the skatole-metabolising enzyme CYP2E1 in vitro (in cell culture).
Boar taint is a major meat quality defect, which affects about 10% of entire male pigs. It is due to an excessive accumulation of skatole and androstenone in adipose tissue. One of the reasons for accumulation of these compounds is a low rate of their metabolism. Androstenone is metabolised in liver via the enzyme 3-beta-hydroxysteroid dehydrogenase (HSD). This enzyme is well characterised in the testis, where it participates in the synthesis of steroids, while its properties in liver are unknown. The aim of the present study was to characterise and compare properties of HSD from pig liver versus pig testis when metabolising androstenone.
Raw materials used in feed manufacture are contaminated with high (>104 cfu/g) levels of enterobacteriaceae indicating the potential for contamination with pathogenic bacteria such as salmonella (Wood et al. 2001). There is urgent need to reduce the contamination of animal feed with zoonoses such as salmonella and campylobacter. During manufacture of feedingstuffs, heat and moisture are used to process and sterilise feed but this can also provide conditions for microbial growth. High temperature treatment used to sterilise feed will not protect feedingstuffs from recontamination, if residual microbial contamination remains in the feed mill. It is essential to understand the influence of feed processing and the feed mill environment on the microbial contamination of feed.
Bacteria belonging to the family Enterobacteriaceae enter the animal feed chain as normal contaminants of raw materials used in the manufacture of animal feeds. The family Enterobacteriaceae encompasses 30 established genera, including Salmonella spp, Escherichia spp, Shigella spp and Yersinia spp. Many of the genera exhibit pathogenicity towards man, animals, insects and plants and many of the pathogenic forms produce toxins. A number of the genera in this family occur regularly in association with animals; they are found as indigenous members of the gut microflora where they may either produce no harmful effects, or are capable of causing disease in both endothermic and ectothermic animals. There is a recognised association between the risk of isolation of salmonella and degree of Enterobacteriaceae contamination (Veldman et al. 1995). This has led to the consideration of recording Enterobacteriaceae contamination levels in feed stuffs as an indicator of feed hygiene and potential limits to the degree of contamination being set by the major retailers. This paper sets out data gathered from the routine analysis of feed raw materials examined for Enterobacteriaceae contamination.
Ruminant products are considered as a major source of saturated fatty acids (SFA) in the human diet and a reduction in the intake of SFA along with a concomitant increase in the intake of n-3 series PUFA is recommended by nutritionists (Department of Health, 1994). The major fatty acid classes in beef are the saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) and beef is a nutritionally important source of the beneficial n-3 series PUFA. Experiments investigating the effects of age on lipid composition in beef muscle have, in the main, used short time periods and also been subject to confounding effects of differences in growth rate (Rule et al., 1997). This study is part of a larger investigation into the effects of breed and diet, as well as age, on muscle lipids (Warren et al., 2003). This paper will focus on the effect of age.
Under controlled experimental conditions, ruminally protected lipid supplements (PLS) rich in 18:2n-6 and 18:3n-3 have been successful in creating large shifts in the fatty acid composition of beef muscle (Scollan et al., 2003). However, there is a need to test methodology under commercial conditions and with a wider range of breed types. This study was conducted at a Yorkshire Farm and used Charolais Cross and the Stabiliser breed, a mix of 5 breeds designed to combine efficient production and good carcass quality.
As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002–2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70–0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54–0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.