Dupilumab efficacy in uncontrolled, moderate-to-severe asthma with self-reported chronic rhinosinusitis

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P \u3c .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS

Riesz transforms, Cauchy-Riemann systems and amalgam Hardy spaces

In this paper we study Hardy spaces $\mathcal{H}^{p,q}(\mathbb{R}^d)$, $0<p,q<\infty$, modeled over amalgam spaces $(L^p,\ell^q)(\mathbb{R}^d)$. We characterize $\mathcal{H}^{p,q}(\mathbb{R}^d)$ by using first order classical Riesz transforms and compositions of first order Riesz transforms depending on the values of the exponents $p$ and $q$. Also, we describe the distributions in $\mathcal{H}^{p,q}(\mathbb{R}^d)$ as the boundary values of solutions of harmonic and caloric Cauchy-Riemann systems. We remark that caloric Cauchy-Riemann systems involve fractional derivative in the time variable. Finally we characterize the functions in $L^2(\mathbb{R}^d) \cap \mathcal{H}^{p,q}(\mathbb{R}^d)$ by means of Fourier multipliers $m_\theta$ with symbol $\theta(\cdot/|\cdot|)$, where $\theta \in C^\infty(\mathbb{S}^{d-1})$ and $\mathbb{S}^{d-1}$ denotes the unit sphere in $\mathbb{R}^d$.Comment: 24 page

Exploring the ethical considerations of using Chat GPT in university education

This study investigates the moral dilemmas that arise with incorporating Chat GPT into higher education, with a focus on the situation in Latinoamerican institutions of higher learning. The study surveyed 220 people via online questionnaire to learn more about their experiences with and motivations for using AI-powered conversational agents. An overview of the demographics of the participants was provided through descriptive statistics. This investigation of the subject at hand lays the groundwork for further research. It also reveals the hidden meanings of the observed phenomena, and it suggests possible solutions to the problems that have been uncovered. This research looks at how AI systems and chatbots can supplement human knowledge and judgment, as well as their potential drawbacks. The results showed that participants thought Chat GPT integration was moderately accessible and had moderately positive social attitudes. They understood the value and responsibility of Chat GPT in creating individualized educational opportunities. Participants stressed the necessity for explicit institutional standards regarding privacy and data security. Gender, age, sense of accessibility, social attitude, opinions, and personal experience, privacy and data security, institutional guidelines, and individualized learning were also found to affect participants' reliance on AI through regression analysis. The findings shed light on how the integration of Chat GPT into Latinoamerican higher education is complicated by factors such as individual beliefs, cultural norms, and ethical problems. The busy schedules of students may be accommodated and the resources they need to succeed can be made available thanks to this adaptability. In addition, natural language processing models can offer students instantaneous help via text chat, voice, or video. To fully grasp the ethical consequences and lead the creation of responsible implementation techniques, the research proposes that additional qualitative investigations, longitudinal studies, and comparative research across diverse contexts is required. Closing these knowledge gaps will help move the conversational AI field forward in ways that are ethical and beneficial to the classroom

Effective Talent Management Practices of Small and Medium-Size Businesses

Effective Talent management strategies to acquire, develop, and retain employees are essential, as 73% of business leaders in the United States identified that good human resources practices favorably affect the efficiency and effectiveness of business operations. Based on the people capability maturity model and transformational leadership theory, the purpose of this qualitative multiple case study was to explore the successful strategies that leaders of small and medium-size businesses (SMBs) used to acquire, develop, and retain employees. The case population comprised five SMBs’ leaders who had successfully used talent management strategies to acquire, develop, and retain employees for more than 5 years, and four employees who had worked with the SMBs for more than 5 years. The selected leaders participated in face-to-face semistructured interviews while the employees participated in a focus group. The data analysis process followed Yin’s five-phase analysis cycle; entailed an analysis of interview responses from individual interviews, the focus group interview, and a review of related documents. Four themes emerged from the data analysis: conducting management assessments, following recruitment and selection guidelines, empowering and enabling employees, and fostering workplace loyalty. A recommendation is that SMBs’ leaders prepare training manuals from their successful procedures for internal use and benchmarking with other SMBs. The study’s findings could contribute to positive social change by enabling leaders to improve employee development and retention for more productive employees and higher revenues to benefit society through employees becoming mentors and volunteers in local communities

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

Clinical epigenomics: Genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders

PURPOSE: We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested. METHODS: We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. We describe the clinical validation of EpiSign using 211 specimens and assess the test performance and diagnostic yield in the first 207 subjects tested involving two patient subgroups: the targeted cohort (subjects with previous ambiguous/inconclusive genetic findings including genetic variants of unknown clinical significance) and the screening cohort (subjects with clinical findings consistent with hereditary neurodevelopmental syndromes and no previous conclusive genetic findings). RESULTS: Among the 207 subjects tested, 57 (27.6%) were positive for a diagnostic episignature including 48/136 (35.3%) in the targeted cohort and 8/71 (11.3%) in the screening cohort, with 4/207 (1.9%) remaining inconclusive after EpiSign analysis. CONCLUSION: This study describes the implementation of diagnostic clinical genomic DNA methylation testing in patients with rare disorders. It provides strong evidence of clinical utility of EpiSign analysis, including the ability to provide conclusive findings in the majority of subjects tested

De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy

PURPOSE: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene. METHODS: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher. RESULTS: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay. CONCLUSION: Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients