Objectives

This study aimed to evaluate whether the Families First Coronavirus Response Act (FFCRA) modified the association between pre-existing state paid sick leave (PSL) and weekday workplace mobility between February 15 and July 7, 2020.

Study design

This was a longitudinal, observational study.

Methods

The 50 US states and Washington, D.C., were divided into exposure groups based on the presence or absence of pre-existing state PSL policies. Derived from Google COVID-19 Community Mobility Reports, the outcome was measured as the daily percent change in weekday workplace mobility. Mixed-effects, interrupted time series regression was performed to evaluate weekday workplace mobility after the implementation of the FFCRA on April 1, 2020.

Results

States with pre-existing PSL policies exhibited a greater drop in mobility following the passage of the FFCRA (β = -8.86, 95% confidence interval: -11.6, -6.10, P < 001). This remained significant after adjusting for state-level health, economic, and sociodemographic indicators (β = -3.13, 95% confidence interval: -5.92, -0.34; P = .039).

Conclusions

Pre-existing PSL policies were associated with a significant decline in weekday workplace mobility after the FFCRA, which may have influenced local health outcomes. The presence of pre-existing state policies may differentially influence the impact of federal legislation enacted during emergencies.

We describe improvements in CCD performance that have been achieved on 4k×4k, (15 μm)2-pixel, fully depleted CCDs for the Dark Energy Spectroscopic Instrument (DESI) [1]. With respect to our previous work on CCDs for the Dark Energy Camera and the Baryon Oscillation Spectroscopic Survey, our goals for the DESI CCD development were to improve read noise and quantum efficiency, improve the astrometric precision, and decrease pixel-size variations. We report experimental results on recently fabricated CCDs to be used in DESI.

Background

There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes.

Patients and methods

This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy).

Results

Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97).

Conclusion

The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.

Clinicaltrialsgov id

NCT00736619.

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.