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Moral reasoning and decision making help guide behavior and facilitate interpersonal relationships. Accounts of morality that position commonsense psychology as the foundation of moral development, (i.e., rationalist theories) have dominated research in morality in autism spectrum disorder (ASD). Given the well-documented differences in commonsense psychology among autistic individuals, researchers have investigated whether the development and execution of moral judgement and reasoning differs in this population compared with neurotypical individuals. In light of the diverse findings of investigations of moral development and reasoning in ASD, a summation and critical evaluation of the literature could help make sense of what is known about this important social-cognitive skill in ASD. To that end, we conducted a systematic review of the literature investigating moral decision making among autistic children and adults. Our search identified 29 studies. In this review, we synthesize the research in the area and provide suggestions for future research. Such research could include the application of an alternative theoretical framework to studying morality in autism spectrum disorder that does not assume a deficits-based perspective.
To update current estimates of non–device-associated urinary tract infection (ND-UTI) rates and their frequency relative to catheter-associated UTIs (CA-UTIs) and to identify risk factors for ND-UTIs.
Academic teaching hospital.
All adult hospitalizations between 2013 and 2017 were included. UTIs (device and non-device associated) were captured through comprehensive, hospital-wide active surveillance using Centers for Disease Control and Prevention case definitions and methodology.
From 2013 to 2017 there were 163,386 hospitalizations (97,485 unique patients) and 1,273 UTIs (715 ND-UTIs and 558 CA-UTIs). The rate of ND-UTIs remained stable, decreasing slightly from 6.14 to 5.57 ND-UTIs per 10,000 hospitalization days during the study period (P = .15). However, the proportion of UTIs that were non–device related increased from 52% to 72% (P < .0001). Female sex (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.50–2.50) and increasing age were associated with increased ND-UTI risk. Additionally, the following conditions were associated with increased risk: peptic ulcer disease (HR, 2.25; 95% CI, 1.04–4.86), immunosuppression (HR, 1.48; 95% CI, 1.15–1.91), trauma admissions (HR, 1.36; 95% CI, 1.02–1.81), total parenteral nutrition (HR, 1.99; 95% CI, 1.35–2.94) and opioid use (HR, 1.62; 95% CI, 1.10–2.32). Urinary retention (HR, 1.41; 95% CI, 0.96–2.07), suprapubic catheterization (HR, 2.28; 95% CI, 0.88–5.91), and nephrostomy tubes (HR, 2.02; 95% CI, 0.83–4.93) may also increase risk, but estimates were imprecise.
Greater than 70% of UTIs are now non–device associated. Current targeted surveillance practices should be reconsidered in light of this changing landscape. We identified several modifiable risk factors for ND-UTIs, and future research should explore the impact of prevention strategies that target these factors.
Gut cell losses contribute to overall feed efficiency due to the energy requirement for cell replenishment. Intestinal epithelial cells are sloughed into the intestinal lumen as digesta passes through the gastrointestinal tract, where cells are degraded by endonucleases. This leads to fragmented DNA being present in faeces, which may be an indicator of gut cell loss. Therefore, measuring host faecal DNA content could have potential as a non-invasive marker of gut cell loss and result in a novel technique for the assessment of how different feed ingredients impact upon gut health. Faecal calprotectin (CALP) is a marker of intestinal inflammation. This was a pilot study designed to test a methodology for extracting and quantifying DNA from pig faeces, and to assess whether any differences in host faecal DNA and CALP could be detected. An additional aim was to determine whether any differences in the above measures were related to the pig performance response to dietary yeast-enriched protein concentrate (YPC). Newly weaned (∼26.5 days of age) Large White × Landrace × Pietrain piglets (8.37 kg ±1.10, n = 180) were assigned to one of four treatment groups (nine replicates of five pigs), differing in dietary YPC content: 0% (control), 2.5%, 5% and 7.5% (w/w). Pooled faecal samples were collected on days 14 and 28 of the 36-day trial. Deoxyribonucleic acid was extracted and quantitative PCR was used to assess DNA composition. Pig genomic DNA was detected using primers specific for the pig cytochrome b (CYTB) gene, and bacterial DNA was detected using universal 16S primers. A pig CALP ELISA was used to assess gut inflammation. Dietary YPC significantly reduced feed conversion ratio (FCR) from weaning to day 14 (P<0.001), but not from day 14 to day 28 (P = 0.220). Pig faecal CYTB DNA content was significantly (P = 0.008) reduced in YPC-treated pigs, with no effect of time, whereas total faecal bacterial DNA content was unaffected by diet or time (P>0.05). Faecal CALP levels were significantly higher at day 14 compared with day 28, but there was no effect of YPC inclusion and no relationship with FCR. In conclusion, YPC reduced faecal CYTB DNA content and this correlated positively with FCR, but was unrelated to gut inflammation, suggesting that it could be a non-invasive marker of gut cell loss. However, further validation experiments by an independent method are required to verify the origin of pig faecal CYTB DNA as being from sloughed intestinal epithelial cells.
Todays demand for rapid trace element analysis in pollution control and resource materials has led to the development of a completely automatic, very sensitive and stable Si(Li) X-ray analyzer. The key element, a transmission target tube, which has inherently a very clean monochromatic X-ray output, has been studied in view of efficiency, sensitivity and stability. The transmission target tube requires different operating criteria than conventional X-ray tubes. An analysis was made to “explain” these differences using fundamental X-ray physics. Studies included various experiments directly applied to practical problems in analysis of pollutants and mineral resource materials.
This paper reports and discusses the results of a computer modeling study on powder diffraction profile analysis for crystallite size and strain of polycrystalline materials. The results of this computer modeling show that if the spans of diffraction profiles in reciprocal space (1/d) are not carefully chosen, an overestimation on size and an underestimation on strain may result in analysis by both the Warren-Averbach and the Hall-Williamson methods. A general way to eliminate such errors based on profile fitting and regeneration is presented and discussed in this paper.
Energy dispersive X-ray spectrometry has the potential for making very rapid analyses of multi-element samples. In order to fully exploit this capability several studies have been carried out with the goal of improving performance at high input count rates. A refined amplifier permits operation at input count rates up to 80000 per second with minimal peak shift and distortion. Optimum choice of tube parameters and filters permits utilization of a single Mo transmission target tube to analyze a broad range of elements in minimum time. Use of a pulsed tube further reduces the time required for analysis without sacrifice of precision or resolution. Dead time necessarily increases with increasing input count rate. It can be reduced by selecting a short amplifier time constant, but only with a loss of resolution. Digital processing permits recovery of the lost resolution. Some illustrations are given of spectra that have been processed on-line using a computer based multi-channel analyzer.
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.
Life span bias potentially alters species abundance in death assemblages through the overrepresentation of short-lived organisms compared with their long-lived counterparts. Although previous work found that life span bias did not contribute significantly to live–dead discordance in bivalve assemblages, life span bias better explained discordance in two groups: longer-lived bivalve species and species with known life spans. More studies using local, rather than global, species-wide life spans and mortality rates would help to determine the prevalence of life span bias, especially for long-lived species with known life spans. Here, we conducted a field study at two sites in North Carolina to assess potential life span bias between Mercenaria mercenaria and Chione elevata, two long-lived bivalve species that can be aged directly. We compared the ability of directly measured local life spans with that of regional and global life spans to predict live–dead discordance between these two species. The shorter-lived species (C. elevata) was overrepresented in the death assemblage compared with its live abundance, and local life span data largely predicted the amount of live–dead discordance; local life spans predicted 43% to 88% of discordance. Furthermore, the global maximum life span for M. mercenaria resulted in substantial overpredictions of discordance (1.4 to 1.6 times the observed live–dead discordance). The results of this study suggest that life span bias should be considered as a factor affecting proportional abundances of species in death assemblages and that using life span estimates appropriate to the study locality improves predictions of discordance based on life span compared with using global life span estimates.
Aeroacoustic measurements and analysis have been made for an unshrouded rotor partially immersed in a planar equilibrium turbulent boundary layer at low Mach number. This configuration provides an idealized model of inflow distortion effects seen when a rotor is mounted adjacent to the hull or fuselage of a vehicle. At low and moderate thrust conditions, the rotor produces broadband noise organized into haystacks produced by large eddies of the ingested turbulence being cut multiple times by successive rotor blades. At high thrust, however, the acoustic signature changes and becomes louder and more tonal. This change is accompanied by separation of the boundary layer from the wall in the vicinity of the rotor blade disk. The separation region is highly unsteady and populated by intense vortex structures. Acoustic analysis suggests that blade–vortex interactions with these structures are the source of the additional tonal noise at high thrust.
Effective translational research requires engagement and collaboration between communities, researchers, and practitioners. We describe a community scientist academy (CSA) developed at the suggestion of our Clinical and Translational Science Awards’ (CTSA) community advisory board to engage and capacitate community members by (1) increasing community members’ and patients’ understanding about the research process and (2) increasing their access to opportunities to influence and participate in research. A joint CTSA/community planning committee developed this 8-hour workshop including sessions on: (1) research definitions and processes; (2) study design; (3) study implementation; and (4) ways to get involved in research. The workshop format includes interactive exercises, content slides and videos, and researcher and community presenters.
Community-based information sessions allowed assessment of community interest before piloting. Two pilots of the CSA were conducted with community members and patients. Participant data and a pre/post knowledge and feedback survey provide evaluation data.
The pilot included 24 diverse participants, over half of whom had not previously participated in research. Evaluation data suggest knowledge gains. Post-CSA, one-third have reviewed CTSA pilot grants and over 80% want to attend further training.
The CSA can demystify the research process for those underrepresented in research and facilitate their engagement and influence within CTSAs.
Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder with symptom onset early in childhood. Growing evidence suggests anomalous brain development across multiple brain regions is evident in school-aged children; however, few studies have examined whether such differences are notable in the preschool years when symptom onset typically occurs. Methods: High resolution anatomical (MPRAGE) images and cognitive and behavioral measures were analyzed in a total of 90 medication-naïve preschoolers, ages 4–5 years (52 with ADHD, 38 controls; 64.4% boys). Results: Results revealed reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children, with largest effect sizes noted for right frontal and left temporal lobe volumes. Examining frontal lobe sub-regions, the largest between group effect sizes were evident for left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. Conclusions: These findings represent the first comprehensive examination of cortical volume in preschool children with ADHD, providing evidence that anomalous brain structure in ADHD is evident very early in development. Furthermore, findings set the stage for developing our understanding of the way in which developmental trajectories of anomalous brain development are associated with the unfolding of symptoms in childhood ADHD. (JINS, 2018, 24, 531–539)
The occurrence of the minerals is reviewed. Consideration of their genesis leads to a tentative list of primary minerals, and of early diagenetie, later diagenetic and geothermal metamorphic, and late near-surface changes.
Tardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).
To evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.
ARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.
At Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).
Deutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.
Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.
These studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Week 54 open-labelresults are reported in this interim analysis.
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 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safetymeasures included incidence of adverse events (AEs), serious AEs (SAEs), drug-related AEs, and AEs leading to withdrawal, dose reduction, or dose suspension. This analysis reports results up to Week 54.
304 patients enrolled in the extension study. There were 215 patient-years of exposure in this analysis, and exposure-adjusted incidence rates (EAIRs) of AEs (incidence/patient-years) were comparable to or lower than those observed with short-term deutetrabenazine treatment and placebo. The frequency of SAEs (EAIR 0.14) was similar to rates observed with short-termplacebo (EAIR 0.33) and deutetrabenazine (EAIR range 0.06–0.33) treatment. AEs leading to study discontinuation (EAIR 0.08), dose reduction (EAIR 0.17), and dose suspension (EAIR 0.09) were uncommon.
Long-term treatment with deutetrabenazine was generally safe and well tolerated in patients with TD, and did not result in cumulative toxicity.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the efficacy and safety of long-term deutetrabenazine therapy in patients with TD.
Patients with TD who completed the ARM-TD or AIM-TD studies were eligible to enter this open-label, single-arm, long-term safety study after they completed the 1-week washout period and final evaluation in the blinded portion of the trial. Efficacy endpoints included the change in AIMS score from baseline, and treatment success (defined as “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). This analysis reports results up to Week 54.
304 patients enrolled in the extension study. At Week 54, the mean (standard error) change in AIMS score was –5.1 (0.52). After 6 weeks of deutetrabenazine treatment, the proportion of patients who achieved treatment success was 58% per the CGIC and 53% per the PGIC, and by Week 54 was 72% per the CGIC and 59% per the PGIC, thus demonstrating maintenance or enhancement of benefit over time. Deutetrabenazine was well tolerated for up to 54 weeks, and compared with the ARM-TD and AIM-TD studies, no new safety signals were detected.
54 weeks of deutetrabenazine treatment was generally efficacious, safe, and well tolerated in patients with TD.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Dietary protein is the main source of nitrous oxide and nitrates, harmful pollutants which are produced in pig units. So reducing the level of protein in the diet may be environmentally friendly. But will this compromise performance? This study compared three ‘nutritional strategies’ providing different protein and energy levels as pigs of two breeds grew from 40 to 120kg live weight.