A state-level study of opioid use disorder treatment access and neonatal abstinence syndrome

Background Adult opioid use and neonatal abstinence syndrome (NAS) are growing public health problems in the United States (U.S.). Our objective was to determine how opioid use disorder treatment access impacts the relationship between adult opioid use and NAS. Methods We conducted a cross-sectional state-level ecologic study using 36 states with available Healthcare Cost and Utilization Project State Inpatient Databases in 2014. Opioid use disorder treatment access was determined by the: 1) proportion of people needing but not receiving substance use treatment, 2) density of buprenorphine-waivered physicians, and 3) proportion of individuals in outpatient treatment programs (OTPs). The incidence of NAS was defined as ICD-9 code 779.5 (drug withdrawal syndrome in newborn) from any discharge diagnosis field per 1000 live births in that state. Results Unmet need for substance use disorder treatment correlated with NAS (r = 0.54, 95% CI: 0.26–0.73). The correlation between adult illicit drug use/dependence and NAS was higher in states with a lower density of buprenorphine-waivered physicians and individuals in OTPs. Conclusions Measures of opioid use disorder treatment access dampened the correlation between illicit drug use/dependence and NAS. Future studies using community- or individual-level data may be better poised to answer the question of whether or not opioid use disorder treatment access improves NAS relative to adult opioid use

Performance of the PROMIS in Patients After Anterior Cruciate Ligament Reconstruction

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) is designed to advance patient-reported outcome (PRO) instruments by utilizing question banks for major health domains. Purpose: To compare the responsiveness and construct validity of the PROMIS physical function computer adaptive test (PF CAT) with current PRO instruments for patients before and up to 2 years after anterior cruciate ligament (ACL) reconstruction. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Initially, 157 patients completed the PROMIS PF CAT, Short Form-36 Health Survey (SF-36 physical function [PF] and general health [GH]), Marx Activity Rating Scale (MARS), Knee injury and Osteoarthritis Outcome Score (KOOS activities of daily living [ADL], sport, and quality of life [QOL]), and EuroQol-5 dimensions questionnaire (EQ-5D) at 6 weeks, 6 months, and 2 years after ACL reconstruction. Correlations between instruments, ceiling and floor effects, effect sizes (Cohen d), and standardized response means to describe responsiveness were evaluated. Subgroup analyses compared participants with and without additional arthroscopic procedures using linear mixed models. Results: At baseline, 6 weeks, and 6 months, the PROMIS PF CAT showed excellent or excellent-good correlations with the SF-36 PF (r = 0.75-0.80, P \u3c .01), KOOS-ADL (r = 0.63-0.70, P \u3c .01), and KOOS-sport (r = 0.32-0.69, P \u3c .01); excellent-good correlation with the EQ-5D (r = 0.60-0.71, P \u3c .01); and good correlation with the KOOS-QOL (r = 0.52-0.58, P \u3c .01). As expected, there were poor correlations with the MARS (r = 0.00-0.24, P \u3c .01) and SF-36 GH (r = 0.16-0.34, P \u3c .01 ). At 2 years, the PROMIS PF CAT showed good to excellent correlations with all PRO instruments (r = 0.42-0.72, P \u3c .01), including the MARS (r = 0.42, P \u3c .01), indicating frequent return to preinjury function. The PROMIS PF CAT had the fewest ceiling or floor effects of all instruments tested, and patients answered, on average, 4 questions. There was no significant difference in baseline physical function scores between subgroups; at follow-up, all groups showed improvements in scores that were not statistically different. Conclusion: The PROMIS PF CAT is a valid tool to assess outcomes after ACL reconstruction up to 2 years after surgery, demonstrating the highest responsiveness to change with the fewest ceiling and floor effects and a low time burden among all instruments tested. The PROMIS PF CAT is a beneficial alternative for assessing physical function in adults before and after ACL reconstruction

The Density of States of hole-doped Manganites: A Scanning Tunneling Microscopy/Spectroscopy study

Variable temperature scanning tunneling microscopy/spectroscopy studies on single crystals and epitaxial thin films of hole-doped manganites, which show colossal magnetoresistance, have been done. We have investigated the variation of the density of states, at and near the Fermi energy ($E_f$), as a function of temperature. Simple calculations have been carried out, to find out the effect of temperature on the tunneling spectra and extract the variation of density of states with temperature, from the observed data. We also report here, atomic resolution images, on the single crystals and larger range images showing the growth patterns on thin films. Our investigation shows unambiguously that there is a rapid variation in density of states for temperatures near the Curie temperature ($T_c$). While for temperatures below $T_c$, a finite DOS is observed at $E_f$, for temperatures near $T_c$ a hard gap opens up in the density of states near $E_f$. For temperatures much higher than $T_c$, this gap most likely gives way to a soft gap. The observed hard gap for temperatures near $T_c$, is somewhat higher than the transport gap for all the materials. For different materials, we find that the magnitude of the hard gap decreases as the $T_c$ of the material increases and eventually, for materials with a $T_c$ close to 400 K, the value of the gap approaches zero.Comment: 9 pages RevTeX, 12 postscript figures, 1 table included in text, submitted to Physical Review

Formation and Evolution of Planetary Systems: Cold Outer Disks Associated with Sun-like stars

We present the discovery of debris systems around three solar mass stars based upon observations performed with the Spitzer Space Telescope as part of a Legacy Science Program, ``the Formation and Evolution of Planetary Systems'' (FEPS). We also confirm the presence of debris around two other stars. All the stars exhibit infrared emission in excess of the expected photospheres in the 70 micron band, but are consistent with photospheric emission at <= 33 micron. This restricts the maximum temperature of debris in equilibrium with the stellar radiation to T < 70 K. We find that these sources are relatively old in the FEPS sample, in the age range 0.7 - 3 Gyr. Based on models of the spectral energy distributions, we suggest that these debris systems represent materials generated by collisions of planetesimal belts. We speculate on the nature of these systems through comparisons to our own Kuiper Belt, and on the likely planet(s) responsible for stirring the system and ultimately releasing dust through collisions. We further report observations of a nearby star HD 13974 (d =11 pc) that is indistinguishable from a bare photosphere at both 24 micron and 70 micron. The observations place strong upper limits on the presence of any cold dust in this nearby system (L_IR/L_* < 10^{-5.2}).Comment: 31 pages, 9 figures, accepted for publication in Ap

Formation and Evolution of Planetary Systems: Placing Our Solar System in Context with Spitzer

We summarize the progress to date of our Legacy Science Program entitled "The Formation and Evolution of Planetary Systems" (FEPS) based on observations obtained with the Spitzer Space Telescope during its first year of operation. In addition to results obtained from our ground-based preparatory program and our early validation program, we describe new results from a survey for near-infrared excess emission from the youngest stars in our sample as well as a search for cold debris disks around sun-like stars. We discuss the implications of our findings with respect to current understanding of the formation and evolution of our own solar system.Comment: 8 postscript pages including 3 figures. To appear in "Spitzer New Views of the Cosmos" ASP Conference Series, eds. L. Armus et al. FEPS website at http://feps.as.arizona.ed

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: Subset analysis of the ASPECT-NP randomized, controlled phase 3 trial

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757

Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A

TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy

Reflections from the Workshop on AI-Assisted Decision Making for Conservation

In this white paper, we synthesize key points made during presentations and discussions from the AI-Assisted Decision Making for Conservation workshop, hosted by the Center for Research on Computation and Society at Harvard University on October 20-21, 2022. We identify key open research questions in resource allocation, planning, and interventions for biodiversity conservation, highlighting conservation challenges that not only require AI solutions, but also require novel methodological advances. In addition to providing a summary of the workshop talks and discussions, we hope this document serves as a call-to-action to orient the expansion of algorithmic decision-making approaches to prioritize real-world conservation challenges, through collaborative efforts of ecologists, conservation decision-makers, and AI researchers.Comment: Co-authored by participants from the October 2022 workshop: https://crcs.seas.harvard.edu/conservation-worksho