Polarization response of spin-lasers under amplitude modulation

Lasers with injected spin-polarized carriers show an outstanding performance in both static and dynamic operation. In addition to the intensity response of conventional lasers, without spin-polarized carriers, both intensity and polarization of light can be exploited for optical communication in spin-lasers. However, the polarization dynamics of spin-lasers under amplitude modulation has been largely overlooked. Here we reveal, analytically and numerically, a nontrivial polarization response that accompanies the well-known intensity dynamics of a spin-laser under amplitude modulation. We evaluate the polarization and intensity response under the same amplitude modulation, and further assess the capability of such a polarization response in digital data transfer with eye diagram simulations. Our results provide a more complete understanding of the modulation response in spin-lasers and open up unexplored opportunities in optical communication and spintronics.Comment: 7 pages, 4 figures, Applied Physics Letters in pres

Creating Markets for Captured Carbon: Retrofit of Abbott Power Plant and Future Utilization of Captured CO2

The successful implementation of CCUS requires the confluence of technology, regulatory, and financial factors. One of the factors that impact this confluence is the ability to utilize and monetize captured CO2. The generally accepted utilization approach has been CO2-based Enhanced Oil Recovery (EOR), yet this is not always feasible and/or a preferable approach. There is a need to be able to explore a multitude of utilization approaches in order to identify a portfolio of potential utilization mechanisms. This portfolio must be adapted based on the economy of the region. In response to this need, the University of Illinois has formed a Carbon Dioxide Utilization and Reduction (COOULR) Center. The open nature of the university, coupled with a university policy to reduce CO2 emissions, provides a model for the issues communities will face when attempting to reduce emissions while still maintaining reliable and affordable power. This Center is one of the key steps in the formation of a market for captured CO2. The goal of the Center is to not only evaluate technologies, but also demonstrate at a large pilot scale how communities may be able to adjust to the need to reduce GHG emissions.U.S. Department of Energy Award Number DE-FE0026588Ope

Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

IntroductionPirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.MethodsHere we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).ResultsOf 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.ConclusionsPirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

The Effect of Pleurotus ostreatus in Bioremediation of Escherichia coli Contaminated Water Grown on Various Substrates

Bacterial contaminant in water is a major issue that causes many deaths every year (Pini & Geddes, 2020).The type of substrate the fungi grows on can greatly affect which nutrients the fungi receives which in turn affect the enzymes that it makes (El-Ramady et al., 2022). Many different things in a substrate affect the remediation rate of the fungi, such as the carbon to nitrogen ratio (El-Ramady et al., 2022). The purpose of this study was to investigate which substrate coffee, sawdust, or wheat straws, would have the highest remediation capability. It was hypothesized that if Pleurotus ostreatus grown on wheat straws, would inhibit the growth of E. coli the greatest. Compared to coffee grounds and sawdust because wheat straws have the highest percentage composition of carbohydrates meaning that they would provide the most nutrients for the fungi to grow (Gashaw et al., 2020). The fungi was grown with the substrate for three weeks, before the E. coli broth was added. After 15 days, the bacterial growth was quantitated using a colony counter. Coffee and sawdust substrate was found to have the least number of colonies than wheat straw substrate; the one-way ANOVA test shows that the data was significant F(3,116) = 45.28, p=\u3c.0001. These findings did not support the hypothesis but rather support that sawdust and coffee provide P. ostreatus improved nutrition to inhibit E. coli growth. Therefore sawdust and coffee would be better substrates for P. ostreatus to remediation E. coli than wheat straw

Exploring a Future for PI3K Inhibitors in Chronic Lymphocytic Leukemia.

PURPOSE OF REVIEW: Treatment for chronic lymphocytic leukemia has changed substantially in the past decade with an increasing shift towards use of targeted therapies, in particular agents targeting the B cell receptor pathway. Inhibition of PI3K, downstream of the B cell receptor pathway, represents an active therapeutic strategy in CLL. Here, we explore the relevance of PI3K inhibition in CLL, examine efficacy and toxicity of approved PI3K inhibitors in CLL, examine barriers to use of PI3K inhibitors, and explore strategies to optimize use of PI3K inhibitors in CLL. RECENT FINDINGS: Current generation PI3K inhibitors are active agents in CLL but their use may be limited by immune-mediated toxicities. Clinical trials of next generation PI3K inhibitors are ongoing and early data suggests these agents are highly active with potentially differentiated toxicity profiles. Furthermore, alternative dosing schedules may reduce toxicities of these agents. Inhibition of PI3K remains an important strategy in management of CLL and novel approaches to limit toxicities of PI3K inhibitors represent an important area of clinical research in CLL