Noncovariant gauge fixing in the quantum Dirac field theory of atoms and molecules

Starting from the Weyl gauge formulation of quantum electrodynamics (QED), the formalism of quantum-mechanical gauge fixing is extended using techniques from nonrelativistic QED. This involves expressing the redundant gauge degrees of freedom through an arbitrary functional of the gauge-invariant transverse degrees of freedom. Particular choices of functional can be made to yield the Coulomb gauge and Poincar\'{e} gauge representations. The Hamiltonian we derive therefore serves as a good starting point for the description of atoms and molecules by means of a relativistic Dirac field. We discuss important implications for the ontology of noncovariant canonical QED due to the gauge freedom that remains present in our formulation.Comment: 8 pages, 0 figure

Physician antipsychotic overprescribing letters and cognitive, behavioral, and physical health outcomes among people with dementia: a secondary analysis of a randomized clinical trial

Importance Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients’ health outcomes. Design, Setting, and Participants This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main Outcomes and Measures The primary outcome of this analysis was patients’ total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, –0.7 days; 95% CI, −1.3 to −0.1 days; P = .02) and community-dwelling patients (adjusted difference, −1.5 days; 95% CI, −1.8 to −1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, −0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, −0.2%; 95% CI −1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and Relevance This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care

Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p \u3c 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials

Model independent results for B→D1(2420)ℓνˉB\to D_1(2420)\ell\bar\nu and B→D2∗(2460)ℓνˉB\to D_2^*(2460)\ell\bar\nu at order ΛQCD/mc,b\Lambda_{QCD}/m_{c,b}

Exclusive semileptonic B decays into $D_1$ and $D_2^*$ mesons are investigated including order $\Lambda_{QCD}/m_{c,b}$ corrections using the heavy quark effective theory. At zero recoil, the $\Lambda_{QCD}/m_{c,b}$ corrections can be written in terms of the leading Isgur-Wise function for these transitions, $\tau$, and known meson mass splittings. We obtain an almost model independent prediction for the shape of the spectrum near zero recoil, including order $\Lambda_{QCD}/m_{c,b}$ corrections. We determine $\tau(1)$ from the measured $B\to D_1\ell\bar\nu$ branching ratio. Implications for B decay sum rules are discussed.Comment: 11 pages, revte

A global perspective on the trophic geography of sharks

Carbon isotopic analysis reveals global biogeographic traits in shark trophic interactions, and sheds light on the diverse foraging behaviour of sharks

Quantum-scissors device for optical state truncation: A proposal for practical realization

We propose a realizable experimental scheme to prepare superposition of the vacuum and one-photon states by truncating an input coherent state. The scheme is based on the quantum scissors device proposed by Pegg, Phillips, and Barnett [Phys. Rev. Lett. 81, 1604 (1998)] and uses photon-counting detectors, a single-photon source, and linear optical elements. Realistic features of the photon counting and single-photon generation are taken into account and possible error sources are discussed together with their effect on the fidelity and efficiency of the truncation process. Wigner function and phase distribution of the generated states are given and discussed for the evaluation of the proposed scheme.Comment: 11 pages, 12 figures, the final version to appear in Phys. Rev. A64, 0638xx (2001

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss

While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in chondrogenic and/or osteogenic precursors in vivo and found that the resulting increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis, but also by inhibiting osteoclast activity through increased osteoprotegerin secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the time of ovariectomy stemmed bone loss. Together, these data highlight roles for CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts