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We present the second data release (DR2) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia, using six optical filters: u, v, g, r, i, z. DR2 is the first release to go beyond the
) limit of the Shallow Survey released in the first data release (DR1), and includes portions of the sky at full survey depth that reach
mag in g and r filters. The DR2 photometry has a precision as measured by internal reproducibility of 1% in u and v, and 0.7% in griz. More than 21 000
have data in some filters (at either Shallow or Main Survey depth) and over 7 000
have deep Main Survey coverage in all six filters. Finally, about 18 000
have Main Survey data in i and z filters, albeit not yet at full depth. The release contains over 120 000 images, as well as catalogues with over 500 million unique astrophysical objects and nearly 5 billion individual detections. It also contains cross-matches with a range of external catalogues such as Gaia DR2, Pan-STARRS1 DR1, GALEX GUVcat, 2MASS, and AllWISE, as well as spectroscopic surveys such as 2MRS, GALAH, 6dFGS, and 2dFLenS.
The Stac Fada Member of the Stoer Group, within the Torridonian succession of NW Scotland, is a melt-rich, impact-related deposit that has not been conclusively correlated with any known impact structure. However, a gravity low approximately 50 km east of the preserved Stac Fada Member outcrops has recently been proposed as the associated impact site. We investigate the location of the impact structure through a provenance study of detrital zircon and apatite in five samples from the Stoer Group. Our zircon U–Pb data are dominated by Archaean grains (> 2.5 Ga), consistent with earlier interpretations that the detritus was largely derived from local Lewisian Gneiss Complex, whereas the apatite data (the first for the Stoer Group) display a single major peak at c. 1.7 Ga, consistent with regional Laxfordian metamorphism. The almost complete absence of Archaean-aged apatite is best explained by later heating of the > 2.5 Ga Lewisian basement (the likely source region) above the closure temperature of the apatite U–Pb system (c. 375–450°C). The U–Pb age distributions for zircon and apatite show no significant variation with stratigraphic height. This may be interpreted as evidence that there was no major change in provenance during the course of deposition of the Stoer Group or, if there was any significant change, the different source regions were characterized by similar apatite and zircon U–Pb age populations. Consequently, the new data do not provide independent constraints on the location of the structure associated with the Stac Fada Member impact event.
Valbenazine is approved for tardive dyskinesia (TD) in adults based on clinical trials that included patients with mood disorders (e.g., bipolar disorder, major depressive disorder). In two long-termphase 3 trials, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091), sustained TD improvements were found in participants who received once-daily treatment with valbenazine (40 or 80mg). Data from these studies were analyzed post hoc to evaluate changes in psychiatric status of patients with a primary mood disorder.
Data were pooled from participants with mood disorders in KINECT 3 (6-week double-blind, placebo-controlled period; 42-week double-blind extension period; 4-week drug-free washout) and KINECT 4 (48week open-label treatment; 4-week drug-free washout). At screening, patients must have had a Brief Psychiatric Rating Scale total score <50. Mood changes were evaluated after long-term treatment (Week 48) and washout (Week 52) using the Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS). For each scale, mean changes from baseline in the total score and individual item scores were analyzed descriptively.
Of the 95 participants with a primary mood disorder (40mg , n=32; 80mg , n=63), 59 (62.1%) were diagnosed with bipolar disorder, 32 (33.7%) with major depressive disorder, and 4 (4.2%) with another mood disorder. A majority of all mood participants received concomitant antidepressants (84.2%) and/or antipsychotics (76.8%) during treatment; other common concomitant medications included antiepileptics (47.4%), anxiolytics (38.9%), and anticholinergics (22.1%). Mean YMRS and MADRS total scores in all mood participants indicated mood symptom stability at baseline (YMRS, 2.7; MADRS, 5.9). This stability was maintained during the studies, as indicated by minimal changes from baseline in mean total scores (YMRS: Week 48, 1.0; Week 52, –1.0; MADRS: Week 48, 0.3; Week52,0.9). Changes in individual items on both scales were also small (<±0.3), indicating no clinically significant changes or worsening in specific mood symptoms or domains.
Mood symptom stability was maintained in patients with TD and a primary mood disorder who received up to 48 weeks of treatment with once-daily valbenazine in addition to their psychiatric medication(s).
Funding Acknowledgements: Neurocrine Biosciences, Inc.
Although polyphenols inhibit glucose absorption and transport in vitro, it is uncertain whether this activity is sufficient to attenuate glycaemic response in vivo. We examined this using orange juice, which contains high levels of hesperidin. We first used a combination of in vitro assays to evaluate the potential effect of hesperidin and other orange juice components on intestinal sugar absorption and then tested whether this translated to an effect in healthy volunteers. Hesperidin attenuated transfer of 14C-labelled glucose across differentiated Caco-2/TC7 cell monolayers. The involvement of the sugar transporter GLUT2 was demonstrated by experiments carried out in the absence of Na to exclude the contribution of sodium-glucose linked transporter 1 and further explored by the use of Xenopus laevis oocytes expressing human GLUT2 or GLUT5. Fructose transport was also affected by hesperidin partly by inhibition of GLUT5, while hesperidin, even at high concentration, did not inhibit rat intestinal sucrase activity. We conducted three separate crossover interventions, each on ten healthy volunteers using orange juice with different amounts of added hesperidin and water. The biggest difference in postprandial blood glucose between orange juice and control, containing equivalent amounts of glucose, fructose, sucrose, citric acid and ascorbate, was when the juice was diluted (ΔCmax=–0·5 mm, P=0·0146). The effect was less pronounced when the juice was given at regular strength. Our data indicate that hesperidin can modulate postprandial glycaemic response of orange juice by partial inhibition of intestinal GLUT, but this depends on sugar and hesperidin concentrations.
While the importance of political appointments is a matter of consensus, theorists and empiricists generally focus on different considerations, such as ideology and confirmation duration, respectively. More recently, there have been efforts to integrate empirical and theoretical scholarship but, to date, no empirical analysis assesses theoretical expectations about the relationship between temporal concerns and nominee ideologies. We fill this gap by examining theoretical predictions and related expectations about how the passage of time affects the President’s choices of nominees. We find that executives are disadvantaged as days pass and Presidents propose nominees with whom they are less ideologically compatible over time.
Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. Methods: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. Results: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. Conclusions: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
Educational tools for application of team science competencies in clinical research are needed. Our interdisciplinary group developed and evaluated acceptability of a virtual world game-based learning tool simulating a multisite clinical trial; performance hinges on effective intrateam communication. Initial implementation with clinical research trainees (n=40) indicates high satisfaction and perceived relevance to team science and research career goals. Game-based learning may play an important role in team science training.
Loess is widespread over Alaska, and its accumulation has traditionally been associated with glacial periods. Surprisingly, loess deposits securely dated to the last glacial period are rare in Alaska, and paleowind reconstructions for this time period are limited to inferences from dune orientations. We report a rare occurrence of loess deposits dating to the last glacial period, ~19 ka to ~12 ka, in the Yukon-Tanana Upland. Loess in this area is very coarse grained (abundant coarse silt), with decreases in particle size moving south of the Yukon River, implying that the drainage basin of this river was the main source. Geochemical data show, however, that the Tanana River valley to the south is also a likely distal source. The occurrence of last-glacial loess with sources to both the south and north is explained by both regional, synoptic-scale winds from the northeast and opposing katabatic winds that could have developed from expanded glaciers in both the Brooks Range to the north and the Alaska Range to the south. Based on a comparison with recent climate modeling for the last glacial period, seasonality of dust transport may also have played a role in bringing about contributions from both northern and southern sources.
To quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.
Over 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.
Staffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.
Understanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics.
We present the first data release of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction, and database schema. The first data release dataset includes over 66 000 images from the Shallow Survey component, covering an area of 17 200 deg2 in all six SkyMapper passbands uvgriz, while the full area covered by any passband exceeds 20 000 deg2. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our griz point-source photometry with Pan-STARRS1 first data release and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia first data release. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries.
Valbenazine (INGREZZA; VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is approved for the treatment of tardive dyskinesia (TD) in adults. The randomized, double-blind, placebo (PBO)-controlled trials of VBZ evaluated the treatment of TD in patients with a primary psychiatric diagnosis (schizophrenia/schizoaffective disorder or mood disorder) while on concomitant psychiatric medications to manage these disorders. Since treatment-emergent depression and suicidal ideation/behavior are important clinical concerns in psychiatric patient populations, data from these trials were analyzed to assess the effectsof once-daily VBZ on depression and suicidality.
Data were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Outcome data were analyzed in the safety population by pooled VBZ doses (40 mg, 80 mg) and PBO. Outcomes of interest included: treatment-emergent adverse events (TEAEs) related to depression or suicidality; mean score change from baseline to Week 6 in the Calgary Depression Scale for Schizophrenia (CDSS, for participants with schizophrenia/schizoaffective disorder) or the Montgomery-Åsberg Depression Rating Scale (MADRS, for participants with mood disorder); and, worsening from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation scores. All outcomes were analyzed descriptively.
There were 400 total participants in the pooled safety population; 286 participants had schizophrenia/schizoaffective disorder (40 mg, n=82; 80 mg, n=70; PBO, n=134) and 114 had a mood disorder (40 mg, n=28; 80 mg, n=42; PBO, n=44). Over one-third of participants had a lifetime history of suicidal ideation or behavior (40 mg, 45%; 80 mg, 39%; PBO, 37%). Few participants had a depression- or suicide-related TEAE, with no apparent differences between VBZ and PBO: suicidal ideation (40 mg, 3.6%; 80 mg, 0.9%; PBO, 2.2%); depression (40 mg, 0%; 80 mg, 1.8%; PBO, 1.1%); depressive symptom (40 mg, 0.9%; 80 mg, 0%; PBO, 0.6%); suicide attempt (40 mg, 0%; 80 mg, 0.9%; PBO, 0%). Mean changes from baseline to Week 6 in depression scale scores were generally small and similar across treatment groups: CDSS total score (40 mg, -0.5; 80 mg, -0.6; PBO, -0.3); MADRS total score (40 mg, -0.2; 80 mg, -1.7; PBO, 0.6). Few participants had a shift from no suicidal ideation at baseline (C-SSRS score=0) to any suicidal ideation during treatment (C-SSRS score=1-5): 40 mg, 3.9% (4/103); 80 mg, 0.9% (1/111); PBO, 2.9% (5/174).
Data from 3 double-blind, placebo-controlled trials indicate that once-daily VBZ treatment was not associated with a worsening in depression-related symptoms or an increased risk of suicidal ideation or behavior.
This study was funded by Neurocrine Biosciences, Inc.
The approval of valbenazine (INGREZZA; VBZ) for the treatment of tardive dyskinesia (TD) in adults was based on results from double-blind, placebo (PBO)-controlled trials. These studies demonstrated the efficacy of once-daily VBZ based on intent-to-treat analyses. However, because many different types ofpatients can develop TD, subgroup analyses describing treatment outcomes by various patient factors were also conducted.
Data were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558), with outcomes analyzed by VBZ dose (80 mg, 40 mg) and PBO. Descriptive analyses conducted using the Abnormal Involuntary Movement Scale (AIMS) total score included: mean change from baseline to Week 6; and AIMS response, defined as 50% improvement from baseline to Week 6. Subgroups were defined as follows: age (<55 years, ≥55 years), sex (male, female), psychiatric diagnosis (schizophrenia/schizoaffective disorder, mood disorder), CYP2D6 genotype (poor metabolizer [PM], non-PM), body mass index (BMI) (<18.5, 18.5 to <25, 25 to <30, ≥30 kg/m2), concomitant antipsychotic (yes, no); type of antipsychotic (atypical, typical/both); lifetime history of suicidality (yes, no); concomitant anticholinergic (yes, no); TD duration (<7 years, ≥7 years).
The pooled population included 373 participants (VBZ 80 mg, n=101; VBZ 40 mg, n=114; PBO, n=158). Mean improvements from baseline to Week 6 in AIMS total score were greater overall with VBZ compared to PBO. Within subgroup categories, AIMS score improvement with VBZ 80 mg (recommended dose) was greater in CYP2D6 PMs (n=17; 80 mg, -6.8; 40 mg, 2.4; PBO, 0.5), participants taking no concomitant antipsychotics (n=64; 80 mg, -4.9; 40 mg, -3.0; PBO, 0.0), and overweight participants (BMI 25 to <30 kg/m2, n=115; 80 mg, -4.2; 40 mg, 2.7; PBO, -0.7). Overweight participants also had the highest AIMS response rates at Week 6 (80 mg, 57.7%; 40 mg, 31.6%; PBO, 11.8%), followed by participants taking typical/both antipsychotics (n=67; 80 mg, 57.1%; 40 mg, 20.0%; PBO, 25.0%), and those taking anticholinergics (n=126; 80 mg, 52.9%; 40 mg, 22.7%; PBO, 6.3%).
These preliminary analyses indicate that TD improvements were generally greater with VBZ than PBO across most subgroups. However, the small sizes of some subgroups may need to be considered when interpreting results. Additional analyses within subgroup categories are ongoing and will be presented at the meeting.
This study was funded by Neurocrine Biosciences, Inc.
Objectives: This study investigated the relationship between on-field, objective signs immediately following sport-related concussion and self-reported symptom endorsement within 1 day post injury. Methods: A retrospective case series of 237 concussed high school athletes was performed. On-field signs were evaluated immediately post injury. Self-reported symptoms (2 clusters) were collected within 1 day post injury. A two-step structural equation model and follow-up bivariate regression analyses of significant on-field signs and symptom clusters were performed. Results: Signs of immediate memory, β=0.20, p=.04, and postural instability, β=0.19, p < .01, significantly predicted a greater likelihood of endorsing the cognitive-migraine-fatigue symptom cluster within 1 day post injury. Regarding signs correlated with specific symptoms, immediate memory was associated with symptoms of trouble remembering, χ2=37.92, p < .001, odds ratio (OR)=3.89 (95% confidence interval (CI) [2.47, 6.13]), and concentration difficulties, χ2=10.84, p=.001, OR=2.13 (95% CI [1.37, 3.30]). Postural instability was associated with symptom endorsement of trouble remembering, χ2=12.08, p < .001, OR=1.76 (95% CI [1.29, 2.40]). Conclusions: Certain post-concussion on-field signs exhibited after injury were associated with specific symptom endorsement within 1 day post injury. Based on these associations, individualized education-based interventions and academic accommodations may help reduce unanticipated worry from parents, students, and teachers following a student-athlete’s sport-related concussion, especially in cases of delayed onset symptoms. (JINS, 2018, 24, 476–485)
Ni-based bulk metallic glasses and composites with high absolute densities exceeding 11 g/cm3 were synthesized via spark plasma sintering of Ni45Co10Ta25Nb20 powders produced from pulverized, melt-spun amorphous ribbons. Optimizing the synthesis via selection of sintering temperature, uniaxial load pressure, and powder mechanical screening yielded samples with relative densities of nearly 100% and hardness values in excess of 12.5 GPa without cracking. Mechanical testing included Weibull modulus determination for hardness and compression testing at 10-3 s-1 and 103 s-1 strain rates. The capability of using spark plasma sintering to fabricate high hardness, high density, large scale metallic glasses is demonstrated. The mechanical properties of these compacted comminuted melt-spun glass ribbons are presented.