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The COVID-19 pandemic has produced significant psychological distress for college students due to the sudden proliferation of stressors. We examine whether and how self and parental immigration status contributes to Latina/o/x college students' mental health and pandemic stressors during the initial months of the pandemic. We draw on quantitative and qualitative survey data collected in March-June 2020 with 1,600 Latina/o/x University of California undergraduate students from three self-identified groups: undocumented students, US citizens with at least one undocumented parent, and US citizens with lawfully present parents. Quantitative analyses reveal that the pandemic produced widespread negative mental health effects but the severity of these effects did not differ by self/parental immigration status. Our qualitative analyses identify common pandemic-related stressors across our three student groups (financial insecurity, COVID-19 virus concerns, academic strains, and social dynamics); however, undocumented students and US citizens with undocumented parents identify unique aspects of these stressors due to legal vulnerabilities. Self and parental undocumented status also compromises the ability to manage common pandemic stressors because of immigration status-related exclusion from necessary resources. Ultimately, we argue that the high-stress nature of the pandemic elevated mental distress across all student groups, but the structural exclusion of undocumented immigrants contributes to unique experiences of stress among Latina/o/x undocumented students and US citizen students with undocumented parents.

Moving toward exascale computing, the size of data stored and accessed by applications is ever increasing. However, traditional disk-based storage has not seen improvements that keep up with the explosion of data volume or the speed of processors. Multiple levels of non-volatile storage devices are being added to handle bursty I/O, however, moving data across the storage hierarchy can take longer than the data generation or analysis. Asynchronous I/O can reduce the impact of I/O latency as it allows applications to schedule I/O early and to check their status later. I/O is thus overlapped with application communication or computation or both, effectively hiding some or all of the I/O latency. POSIX and MPI-I/O provide asynchronous read and write operations, but lack the support for non-data operations such as file open and close. Users also have to manually manage data dependencies and use low-level byte offsets, which requires significant effort and expertise to adopt. In this article, we present an asynchronous I/O framework that supports all types of I/O operations, manages data dependencies transparently and automatically, provides implicit and explicit modes for application flexibility, and error information retrieval. We implemented these techniques in HDF5. Our evaluation of several benchmarks and application workloads demonstrates it effectiveness on hiding the I/O cost from the application.

Background: Biologics and JAK inhibitors were the most effective innovative systemic treatments for moderate-to-severe atopic dermatitis (AD). However, their cost-effectiveness in China remains unclear. This study aims to compare both the short- and long-term cost-effectiveness of abrocitinib and dupilumab in adults with moderate-to-severe AD from the perspective of the Chinese healthcare system. Methods: A hybrid decision tree and Markov model were developed to simulate the costs and health outcomes of interventions on both short-term and long-term horizons. Short- and long-term horizons were employed to reflect the 26-week induction treatment and model the extended 10-year maintenance treatment period, respectively. The cost-effectiveness of strategies was measured by incremental cost-effectiveness ratios (ICERs), which were then compared with the willingness-to-pay threshold (WTP) that was equivalent to the gross domestic product (GDP) per capita of China in 2023 ($12,681 [€11,679.26]). One-way and probabilistic sensitivity analyses were conducted to validate the robustness of the model. Results: Over the short-term horizon, the QALYs (quality-adjusted life years) gained were 0.43 for the abrocitinib group and 0.42 for the dupilumab group, with the costs being $2,716.01 (€2,501.46) and $3,940.33 (€3,629.06), respectively. Over the long-time horizon, abrocitinib therapy yields higher QALYs (6.60 versus 6.53) and incurs a lower cost ($22,765.15 [€20,966.81] versus $30,683.38 [€28,259.54]) compared to dupilumab. The probability of abrocitinib being cost-effective was nearly 100% under the current WTP. Both short- and long-term results showed that abrocitinib was more effective and less costly than dupilumab, making abrocitinib the dominant option. Conclusions: Abrocitinib was dominant compared to dupilumab both over the short- and long-term horizon for moderate-to-severe AD in China. Future research incorporating real-world evidence and long-term efficacy outcomes could further refine these economic evaluations. [ABSTRACT FROM AUTHOR]

Aim: Dostarlimab plus carboplatin-paclitaxel (CP) significantly increased progression-free survival in patients with primary advanced or recurrent endometrial cancer (pA/rEC) vs CP alone in the RUBY trial (NCT03981796). This analysis estimated the per-member-per-month (PMPM) costs of introducing dostarlimab + CP as a treatment alternative from a third-party US payer perspective. Materials and methods: A budget impact model was developed to estimate the costs of introducing dostarlimab + CP into commercial and Medicare health plans over a 3-year time horizon (2023–2025). Costs were sourced from relevant literature and US-specific databases and were calculated using epidemiology data, clinical inputs, treatment costs, and market share estimates. Clinical inputs were sourced from primary clinical trials for each respective treatment (i.e. dostarlimab + CP, CP, pembrolizumab, pembrolizumab plus lenvatinib, bevacizumab + CP, and pembrolizumab + CP). Current and future market shares assumed dostarlimab + CP reduced the market share of CP only. Analyses were performed in mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) and overall populations using a US 2023 cost year. Results: For a commercial plan, the model estimated (dMMR/MSI-H and overall populations) that 7 and 26 patients would be treated with dostarlimab + CP, respectively; average annual budget impacts per patient treated were $118,257 and $116,094; average budget impacts per patient treated per month (PPPM) were $9,855 and $9,675; average budget impacts PMPM were $0.02 and $0.06. For a Medicare plan, the model estimated that 28 and 93 patients, respectively, would be treated with dostarlimab + CP. Average annual budget impacts per patient treated and PPPM were the same as those for the commercial plan in both populations; average budget impacts PMPM were $0.07 and $0.22, respectively. Conclusions: Introducing dostarlimab + CP as a first-line treatment for patients with pA/rEC results in minimal budget impact PMPM from a US third-party payer's perspective. Together with the efficacy and safety results from RUBY, these results support the use of dostarlimab + CP as a treatment option. PLAIN LANGUAGE SUMMARY: Dostarlimab with carboplatin–paclitaxel is a recently approved treatment for newly diagnosed advanced or recurrent endometrial cancer. This analysis was done to estimate the added costs that US commercial and Medicare health plans would have over 3 years if this treatment was covered. This analysis found that the budget increase for covering dostarlimab with carboplatin–paclitaxel was small ($0.02–$0.06 per commercial plan member per month; $0.07–$0.22 per Medicare plan member per month). [ABSTRACT FROM AUTHOR]

Aims: To provide an update on the cost-effectiveness of the chimeric antigen receptor (CAR) T-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL) among patients who have previously received ≥2 lines of systemic therapy using more mature clinical trial data cuts (60 months for axi-cel overall survival [OS] and 45 months for tisa-cel OS and progression-free survival [PFS]). Methods: A partitioned survival model consisting of three health states (pre-progression, post-progression and death) was used to estimate quality-adjusted life years (QALYs) and costs associated with axi-cel and tisa-cel over a lifetime horizon. PFS and OS inputs for axi-cel and tisa-cel were based on a previously published matching-adjusted indirect treatment comparison (MAIC). Long-term OS and PFS were extrapolated using parametric survival mixture cure models (PS-MCMs). Costs of CAR-T cell therapy drug acquisition and administration, conditioning chemotherapy, apheresis, CAR T-specific monitoring, stem cell transplant, hospitalization, adverse events, routine care, and terminal care were sourced from US cost databases. Health state utilities were derived from previous publications. Model inputs were varied using a range of sensitivity and scenario analyses. Results: Compared with tisa-cel, axi-cel resulted in 2.51 additional QALYs and $50,185 additional costs (an incremental cost-effectiveness ratio [ICER] of $19,994 per QALY gained). In probabilistic sensitivity analysis (PSA), the ICER for axi-cel versus tisa-cel was ≤$50,000/QALY in 99.4% of simulations and ≤$33,500 in 99% of simulations. Axi-cel remained cost-effective versus tisa-cel (assuming a willingness-to-pay threshold of $150,000 per QALY) across a range of scenarios. Conclusions: With longer-term survival data, axi-cel continues to represent a cost-effective option versus tisa-cel for treatment of r/r LBCL among patients who have previously received ≥2 lines of systemic therapy, from a US payer perspective. [ABSTRACT FROM AUTHOR]

Using observational data and model hindcasts produced by a coupled climate model, we examine the response of the East Asian winter monsoon (EAWM) to three types of El Niño: eastern Pacific (EP) and central Pacific I (CP-I) and II (CP-II) El Niños. The observational analysis shows that all three El Niño types weaken the EAWM with varying degrees of impact. The EP El Niño has the largest weakening effect, while the CP-II El Niño has the second largest, and the CP-I El Niño has the smallest. We find that diverse El Niño types impact the EAWM by altering the responses of two anomalous anticyclones during El Niño mature winter: the western North Pacific anticyclone (WNPAC) and Kuroshio anticyclone (KAC). The WNPAC responses are controlled by the Gill response and Indian Ocean warming processes that both respond to the eastern-to-central tropical Pacific precipitation anomalies. The KAC responses are controlled by a poleward wave propagation responding to the northwestern tropical Pacific precipitation anomalies. We find that the model hindcasts significantly underestimate the weakening effect during the EP and CP-II El Niños. These underestimations are related to a model deficiency in which it produces a too-weak WNPAC response during the EP El Niño and completely misses the KAC response during both types of El Niño. The too-weak WNPAC response is caused by the model deficiency of simulating too-weak eastern-to-central tropical Pacific precipitation anomalies. The lack of KAC response arises from the unrealistic response of the model’s extratropical atmosphere to the northwestern tropical Pacific precipitation anomalies.

In the observations, El Niño events initiated by a subtropical Pacific mechanism (SP-onset El Niños) show larger uncertainty in their decay evolution patterns than those initiated by a tropical Pacific mechanism. A 2,200-year simulation of Community Earth System Model reproduces this observed feature and its SP-onset El Niños are analyzed to understand the cause of the large uncertainty. Results show that the onset location of SP-onset El Niño, which interacts with the eastern edge of the western Pacific warm pool, is a key factor controlling its decay evolution. When the onset is located east (west) of 155°E, the event has a strong tendency to reverse (maintain) its phase, leading to cyclic (multiyear) evolution. These two onset locations respectively activate Indo-Pacific and tropical-subtropical Pacific interactions to give rise to the different evolution patterns. The findings offer a potential way to predict the evolution of SP-onset El Niños using their onset locations.

Applying statistical analyses to reanalysis products during the period 1900–2018, this study finds the 11-year solar cycle to have a significant correlation with sea surface temperature (SST) variations in the Northeastern Pacific. The solar influence is first manifested and amplified in the lower stratosphere, which then alters the strength of Hadley circulation in the troposphere. Lastly, the changes in the sinking branch of the Hadley circulation modulate surface heat fluxes to give rise to the SST footprint. The footprint has a structure similar to that of the Pacific meridional mode (PMM) that is known to be an important trigger of the central Pacific (CP) type of the El Niño-Southern Oscillation (ENSO). The 11-year solar cycle is thus shown to contribute to the slow modulation of the CP ENSO and, in particular, to be associated with more CP El Niño (La Niña) events during the active (inactive) phase of the cycle.

ObjectiveThe Wechsler Adult Intelligence Scale (WAIS) processing speed subtests are among the most ubiquitous indices of processing speed in the field. The aim of this study was to develop and examine demographically-adjusted normative data for Spanish language versions of the WAIS-III Digit Symbol Coding (DSC) and Symbol Search (SS) subtests for US-dwelling Spanish-speakers living in the US/Mexico border region.MethodsThe sample included 203 healthy participants who were part of the larger Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project (DSC: n = 201; SS: n = 200).ResultsOlder age and higher education were both related to lower scores on the DSC and SS subtests (all ps  .05). Raw-to-scaled score conversions were calculated for both subtests, and fractional polynomial equations were derived to compute demographically-adjusted T-scores accounting for age, education, and gender for each subtest and the Processing Speed Index. Published norms for English-speaking non-Hispanic white adults slightly overestimated impairment rates (T-scores

ObjectiveThis paper summarizes the findings of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project and offers a roadmap for future research.MethodsThe NP-NUMBRS project represents the largest and most comprehensive co-normed neuropsychological battery to date for native Spanish-speaking healthy adults from the U.S. (California/Arizona)-Mexico borderland region (N = 254; ages 19-60 years). These norms provide demographic adjustments for tests across numerous domains (i.e., verbal fluency, processing speed, attention/working memory, executive function, episodic memory [learning and delayed recall], visuospatial, and fine motor skills).ConclusionsThis project: 1) shows that the NP-NUMBRS norms consistently outperformed previously published norms for English-speaking non-Hispanic (White and African-American) adults in identifying impairment; 2) explores the role of Spanish-English bilingualism in test performance; and 3) provides support for the diagnostic validity of these norms in detecting HIV-associated neurocognitive impairment. Study limitations include the limited assessment of sociocultural variables and generalizability (e.g., other Latina/o populations, age limit [19 - 60 years]). Future research is needed to: 1) investigate these norms with U.S.-dwelling Spanish-speakers of non-Mexican heritage and other clinical subpopulations; 2) expand coverage of cognitive domains (e.g. language, visuospatial); 3) develop large normative datasets for children and older Latina/o populations; 4) examine how sociocultural factors impact performance (e.g., bilingualism, acculturation); 5) investigate these norms' diagnostic and ecological validity; and 6) develop norms for neurocognitive change across time. It is hoped that the NP-NUMBRS norms will aid researchers and clinicians working with U.S.-dwelling Spanish-speakers from the U.S.-Mexico borderland to conduct research and evidence-based neuropsychological evaluations in a more culturally responsive and ethical manner.

The objectives of this study were to (1) investigate the association between human blood type and COVID-19 in both inpatient and longitudinal populations and (2) identify the association between blood type and severity of COVID-19 via presence of cellular biomarkers of severe infection in hospitalized individuals at our institution in South Florida. This study consisted of (1) a single-center retrospective analysis of 669 out of 2741 COVID-19-positive, screened patients seen from 1 January 2020 until 31 March 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study ("CITY") at the University of Miami Miller School of Medicine, consisting of 185 survey participants. In an inpatient setting, blood type appeared to be associated with COVID-19 severity and mortality. Blood type O sustained less risk of COVID-19 mortality, and blood type O- demonstrated less risk of developing COVID-19 pneumonia. Inpatients with O- blood type exhibited less biomarkers of severe infection than did other blood types. In a longitudinal setting, there was no association found between blood type and SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Two-phase I/O is a well-known strategy for implementing collective MPI-IO functions. It redistributes I/O requests among the calling processes into a form that minimizes the file access costs. As modern parallel computers continue to grow into the exascale era, the communication cost of such request redistribution can quickly overwhelm collective I/O performance. This effect has been observed from parallel jobs that run on multiple compute nodes with a high count of MPI processes on each node. To reduce the communication cost, we present a new design for collective I/O by adding an extra communication layer that performs request aggregation among processes within the same compute nodes. This approach can significantly reduce inter-node communication contention when redistributing the I/O requests. We evaluate the performance and compare it with the original two-phase I/O on Cray XC40 parallel computers (Theta and Cori) with Intel KNL and Haswell processors. Using I/O patterns from two large-scale production applications and an I/O benchmark, we show our proposed method effectively reduces the communication cost and hence maintains the scalability for a large number of processes.

Copyright of Confluenze. Rivista di Studi Iberoamericani is the property of Universita di Bologna, Dipartimento di Lingue, Letterature e Culture Moderne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Linguistic Research / Dilbilim Arastirmalari Dergisi is the property of Bogazici University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Soletras is the property of Editora da Universidade do Estado do Rio de Janeiro (EdUERJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Scientific applications at exascale generate and analyze massive amounts of data. A critical requirement of these applications is the capability to access and manage this data efficiently on exascale systems. Parallel I/O, the key technology enables moving data between compute nodes and storage, faces monumental challenges from new applications, memory, and storage architectures considered in the designs of exascale systems. As the storage hierarchy is expanding to include node-local persistent memory, burst buffers, etc., as well as disk-based storage, data movement among these layers must be efficient. Parallel I/O libraries of the future should be capable of handling file sizes of many terabytes and beyond. In this paper, we describe new capabilities we have developed in Hierarchical Data Format version 5 (HDF5), the most popular parallel I/O library for scientific applications. HDF5 is one of the most used libraries at the leadership computing facilities for performing parallel I/O on existing HPC systems. The state-of-the-art features we describe include: Virtual Object Layer (VOL), Data Elevator, asynchronous I/O, full-featured single-writer and multiple-reader (Full SWMR), and parallel querying. In this paper, we introduce these features, their implementations, and the performance and feature benefits to applications and other libraries.

A technique is developed to identify the types of atmosphere-ocean interaction during El Niño-Southern Oscillation events using sea surface temperature, sea level pressure (SLP), and outgoing longwave radiation (OLR) data. Two pairs of indices are derived that separate the interactions into tropical and subtropical types and basin-wide and local types. The dominant interaction type for the observed El Niño events since 1980 is identified and shown to shift with time from the tropical to subtropical and from basin-wide to local. Thus, the 21st century El Niños have become dominated by subtropical and local interactions, in strong contrast to the 20th century El Niños that were dominated by the tropical and basin-wide interactions. These changes result in the 1997-98 and 2015-16 extreme El Niños being different in their evolutions and global impacts, despite having similar intensities. SLP is the key variable for separating the tropical and subtropical types of interactions, while OLR is the key variable for separating the basin-wide and local types of interactions.

To capture the economic and healthcare resource utilization (HCRU) burden in older adults due to respiratory syncytial virus (RSV) infection. An electronic literature search of PubMed, Embase, the Cochrane Library, PsycINFO, and EconLit was conducted for studies of the cost and HCRU outcomes of RSV infection in adult patients, with no language or country restrictions. The search dates for the primary studies were January 1, 2002–May 18, 2022. The methodological quality of included studies was assessed using a modification of the Critical Appraisal Skills Programme (CASP) checklist for economic studies and the Drummond checklist. Forty-two studies were identified that reported cost or HCRU data associated with RSV infections, with geographic locations across North America, South America, Europe, Asia, and Oceania. Generally, hospitalization costs were highest in the United States (US). Driving factors of increased cost included older age, comorbidities, and length of stay. US studies found that the national direct cost burden of RSV hospitalizations was $1.3 billion for all adults and $1.5–$4.0 billion for adults aged ≥60 years (estimates for other countries were not identified). Studies estimating incremental costs for RSV cases versus controls and costs pre- and post-RSV infection demonstrated higher costs for RSV cases. Hospitalizations accounted for the majority of total costs. The variability in definitions of cost outcomes, age groups, study seasons, and geographic locations was prohibitive of a meta-analysis and comparisons across studies. Cost and HCRU data were limited per country outside the US, per comorbidity, and in settings other than the inpatient setting. Only one study reported indirect costs, and only the US had national cost burden data. Despite several data gaps, the economic burden of RSV infections on healthcare systems and payers was found to be substantial, globally, underscoring the need for RSV preventive strategies for reducing this burden. [ABSTRACT FROM AUTHOR]

The landscape of treatment strategies for relapsed/refractory multiple myeloma (RRMM) has dramatically changed due to the emergence of chimeric antigen receptor T (CAR-T) cell therapy. The aim of this study was to evaluate the cost-effectiveness of two CAR-T cell treatments for RRMM patients from the perspective of the Chinese healthcare system. A Markov model was used to compare currently available salvage chemotherapy with Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) for treatment of patients with RRMM. The model was developed based on data from three studies: CARTITUDE-1, KarMMa, and MAMMOTH. The healthcare cost and utility of RRMM patients were collected from a provincial clinical center in China. In the base case analysis, 3.4% and 36.6% of RRMM patients were expected to be long-term survivors after 5 years of Ide-cel and Cilta-cel treatment, respectively. Compared to salvage chemotherapy, Ide-cel and Cilta-cel were associated with incremental QALYs of 1.19 and 3.31, and incremental costs of US$140,693 and $119,806, leading to ICERs of $118,229 and $36,195 per QALY, respectively. At an ICER threshold of $37,653/QALY gained, the probability that Ide-cel and Cilta-cel are cost-effective were estimated to be 0% and 72%, respectively. With younger target people entering the model, and a partitioned survival model in scenario analysis, the ICERs of Cilta-cel and Ide-cel changed rather mildly and their cost-effectiveness results were the same as base analysis. Based on the willingness-to-pay of 3-times China's per capita GDP in 2021, Cilta-cel was considered to be a more cost-effective option compared to salvage chemotherapy for RRMM in China, while Ide-cel was not. [ABSTRACT FROM AUTHOR]

This study estimated the "process utilities" of treatment options for patients with relapsed/refractory multiple myeloma (RRMM) in Japan using the time trade-off (TTO) method. Chimeric antigen receptor (CAR) T cell immunotherapy is available for patients with RRMM who are triple-class exposed (TCE) after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the impact of available treatment options on health state utilities has not been well characterized, particularly in relation to process utilities. Eight vignettes of health states and daily activity restrictions related to each of the following RRMM therapies were prepared: no treatment, CAR T cell therapy with idecabtagene vicleucel (ide-cel), regular intravenous infusion, and oral administration. A face-to-face survey of healthy Japanese adults who were representative of the general population was conducted. The TTO method was used to evaluate each vignette and to generate utility scores for each treatment regimen. Three hundred and nineteen respondents participated in the survey (mean age: 44 years [range: 20–64]; female: 50%). Utility scores for no treatment, ide-cel, oral pomalidomide, and dexamethasone (Pd) therapy ranged from ∼0.7 to 0.8. Utility scores for regular intravenous infusion regimens ranged from 0.50 to 0.56. There was a difference of ∼0.2 between the utility scores for no treatment/ide-cel/oral administration and regular intravenous infusions. Differences in treatment administration across RRMM therapies showed a substantial impact on health state utilities. When quantifying the value of treatments, process utility gains should be considered as an independent factor in health technology assessments. [ABSTRACT FROM AUTHOR]

The chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) is approved for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM) who have already received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have progressed on their last therapy. The objective of this study was to assess the cost-effectiveness of ide-cel versus conventional care in Canada and France. A partitioned survival model was used to estimate the cost-effectiveness of ide-cel (target dose 450 × 106 CAR T cells) in its approved indication in terms of life-years (LYs), quality-adjusted LYs (QALYs), and costs. Patient-level data from the KarMMa Phase II clinical trial (clinicaltrials.gov NCT03361748) and KarMMa-RW study were used to inform the model; overall and progression-free survival were extrapolated using standard parametric functions after the observed periods. The model adopted Canadian and French societal perspectives over a lifetime horizon. Costs, utilities, discounting (Canada: 1.5%, France: 2.5%), and general population mortality were country-specific. The base case demonstrated that ide-cel was associated with more additional LYs (+2.64 and +2.51) and QALYs (+2.31 and +2.54) than conventional care at incremental costs of CAN$588,490 and €392,251 in Canada and France, respectively. The resulting incremental cost-effectiveness ratio (ICER) for ide-cel was $255,245 per QALY in Canada, and €154,593 per QALY in France. Ide-cel was associated with significant survival improvements in terms of both LYs and QALYs in patients with progressive triple-class-exposed RRMM. The ICER for ide-cel was similar to that of other approved and reimbursed RRMM therapies. [ABSTRACT FROM AUTHOR]

Copyright of Journal History of Latin American Education / Revista Historia de la Educación Latinoamericana is the property of Universidad Pedagogica y Tecnologica de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Sex hormone-binding globulin (SHBG), testosterone and oestradiol have been associated with many diseases in observational studies; however, the causality of associations remains unestablished. Methods A phenome-wide Mendelian randomization (MR) association study was performed to explore disease outcomes associated with genetically proxied circulating SHBG, testosterone and oestradiol levels by using updated genetic instruments in 339 197 unrelated White British individuals (54% female) in the UK Biobank. Two-sample MR analyses with data from large genetic studies were conducted to replicate identified associations in phenome-wide MR analyses. Multivariable MR analyses were performed to investigate mediation effects of hormone-related biomarkers in observed associations with diseases. Results Phenome-wide MR analyses examined associations of genetically predicted SHBG, testosterone and oestradiol levels with 1211 disease outcomes, and identified 28 and 13 distinct phenotypes associated with genetically predicted SHBG and testosterone, respectively; 22 out of 28 associations for SHBG and 10 out of 13 associations for testosterone were replicated in two-sample MR analyses. Higher genetically predicted SHBG levels were associated with a reduced risk of hypertension, type 2 diabetes, diabetic complications, coronary atherosclerotic outcomes, gout and benign and malignant neoplasm of uterus, but an increased risk of varicose veins and fracture (mainly in females). Higher genetically predicted testosterone levels were associated with a lower risk of type 2 diabetes, coronary atherosclerotic outcomes, gout and coeliac disease mainly in males, but an increased risk of cholelithiasis in females. Conclusions These findings suggest that sex hormones may causally affect risk of several health outcomes. [ABSTRACT FROM AUTHOR]

A novel Tartaric acid derivative-based chiral resolving agent has been discovered for the enantiosepration of racemic Ibuprofen [(RS)-2-(4-(2-methyl propyl) phenyl) propanoic acid]. The processinvolves optimization of diastereomeric salt formed between (+) Ibuprofen and optically pure tartaric acid derivatives, followed by separating the individual enantiomer by acid salt preparation. Characterization of the synthesized compound has been carried out by elemental analysis, melting point, FT-IR, UV, HPLC, and ¹H NMR spectra. The developed separation method is simple, cost-effective, and industrially viable. [ABSTRACT FROM AUTHOR]

While effective asthma control medications reduce the burden of asthma, a significant subgroup of these treatments, namely metered-dose inhalers (MDIs), produce substantial greenhouse gas (GHG) emissions, thus contributing to climate change. This study quantified the global climate impact (i.e. carbon dioxide equivalent [CO2e] emissions) and costs of long-term status quo asthma inhaler use versus alternative scenarios substituting MDIs with propellant-free dry powder inhalers (DPIs). Three scenarios were evaluated across 10-year (2020–2030) and 50-year (2020–2070) time horizons: A (status quo inhaler use), B and C (2% and 5% year-over-year substitution of MDIs with DPIs, respectively). Global inhaler volumes and costs at baseline were sourced from IQVIA, then projected using UN and WHO trends in per capita GDP, urbanization, and asthma population growth. Inhaler spending was assumed to fall by 90% following generic entry in 2030. The carbon footprint per inhaler and health damage factors for disability-adjusted life years (DALYs) were derived from literature. The US government's central and high-impact estimates for the social cost of carbon (SCC) were used to calculate emissions costs. Over 50 years, scenario A resulted in 826 million tonnes of CO2e emissions globally, with an associated SCC between 21% and 65% of the projected global spending on asthma inhalers. In comparison, CO2e emissions were reduced by 38% and 58% in Scenarios B and C, respectively, and DALYs improved by 33 and 51%. Depending on SCC estimates, Scenarios B and C increased global costs by 7.3% and 16.5%, respectively (central SCC), or decreased costs by 4.2% and 2.6% (high-impact SCC) versus Scenario A. Over 10 years, Scenario A resulted in 97 million tonnes of CO2e emissions globally, with an associated SCC between 4.4% and 12.2% of projected spending. In comparison, Scenarios B and C were associated with 12% and 24% reductions in CO2e emissions and improvements in DALYs by 11.5% and 22.7%, respectively. Global efforts by environmental and health-policy decision-makers to substitute currently available MDIs with DPIs for asthma control would result in substantial reductions in GHG emissions with manageable costs, or potential cost savings, depending on the SCC. Policies that decrease use of MDIs warrant global attention. [ABSTRACT FROM AUTHOR]

This study evaluated from a US payer perspective the cost-effectiveness of two chimeric antigen receptor T (CAR T) cell therapies, axicabtagene ciloleucel (axi-cel) versus lisocabtagene maraleucel (liso-cel), for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following two or more systemic therapy lines. We developed a 3-state (i.e., pre-progression, post-progression, death) partitioned survival model to estimate patients' lifetime outcomes. Mixture cure models were used for survival extrapolation to account for long-term remission. Survival inputs were based on a matching-adjusted indirect comparison (MAIC) that reweighted the ZUMA-1 population (receiving axi-cel) to match patient characteristics in TRANSCEND-NHL-001 (assessing liso-cel). Costs included apheresis, drug acquisition, and administration for conditioning chemotherapy and CAR T therapies, monitoring, transplant, hospitalization, adverse events, routine care, and terminal care, per published literature and databases. Utilities were derived from ZUMA-1 and literature. Deterministic and probabilistic sensitivity analyses were conducted. In the base case, axi-cel was associated with more QALYs (7.76 vs. 5.94) and greater costs overall ($611,440 vs. $597,174) than liso-cel, at $7,843/QALY gained. The incremental costs (+$14,266) were largely driven by higher routine care costs (+$18,596) due to longer survival and hospitalization (+$10,993) but partially offset by reduced costs of CAR T acquisition (‒$11,300) and terminal care (‒$4,025). Sensitivity analyses consistently suggested robustness of base-case results. This study relied on an MAIC in which trial design differences and unobserved confounders could not be accounted for. Future real-world studies for recently approved CAR T are warranted to validate our results. Due to a lack of data, we assumed equivalent use of transplants and treatment for B-cell aplasia between the two therapies based on clinicians' opinions. In the US, axi-cel is a potentially cost-effective treatment option compared with liso-cel for adult patients with r/r LBCL after two or more systemic therapy lines. [ABSTRACT FROM AUTHOR]

Asthma exacerbations are a primary driver of costs and health impacts from asthma. Despite research suggesting that asthma care has a disproportionate carbon footprint, emissions costs are not considered when evaluating its societal burden. To advance the understanding of greenhouse gas (GHG) emissions associated with asthma, we estimated the carbon footprint and associated costs of asthma exacerbation care by severity level among UK adults. Guidelines for asthma exacerbation treatment in UK adults were reviewed by severity level: mild, moderate, and severe/life-threatening. Components of care for each severity were evaluated for GHG emission potential and key drivers were identified. Carbon dioxide equivalent (CO2e) emissions of drivers were sourced from published literature and combined to estimate the carbon footprint per exacerbation, by severity level. Emissions were scaled up to the annual UK adult population based on the annual number of exacerbations at each severity. Costs associated with emissions were estimated using the UK government's 2020 nontraded price of carbon, at ₤71 per tonne CO2e (tCO2e). Overall, emissions drivers for exacerbations were medical services, including patient-travel, and quick-relief inhalers. The annual number of mild, moderate, and severe/life-threatening asthma exacerbations among UK adults were 118.9 M, 5.5 M, and 2.4 M. Associated annual carbon footprints were estimated to be 83,455 tCO2e, 192,709 tCO2e, and 448,037 tCO2e for mild, moderate, and severe/life-threatening exacerbations, respectively, with a total of 724,201 tCO2e. Total annual emissions costs from exacerbation care were £51.3 M; ₤5.9 M, ₤13.6 M, and ₤31.7 M for mild, moderate, and severe/life-threatening exacerbations, respectively. GHG emissions from asthma exacerbation management were the highest for severe/life-threatening events, followed by moderate exacerbations. Treatment to reduce the severity and occurrence of exacerbations, such as effective, long-term control therapy via lower-emission dry powder inhalers (DPIs), can help mitigate asthma care emissions. For mild exacerbations, the use of DPIs can eliminate associated emissions. [ABSTRACT FROM AUTHOR]

The Asian region has passed a long and rocky road during the past several decades to establish itself as the second leading regional biotech market globally. China has become the second largest pharmaceutical market while Japan holds a strong second position as the global hub for medical devices development and innovation. Pharmaceutical expenditure continues to outpace real GDP growth in most of these countries. The trend is likely to be continued for a decade ahead, driven by a myriad of factors ranging from aging populations, rapidly growing welfare and increased citizen expectations raising demand for novel medicines and technologies. Satisfaction of these unmet needs in terms of supply is coming from the large multinational companies in wealthier among these societies. Domestic born and largely state-owned manufacturing industries continue to play a crucial role in an array of middle-income countries. Global biotech hub of Singapore is hosting over 1.5 times more headquarters of large pharmaceutical companies than Beijing, Tokyo, Shanghai and Hong Kong combined together. Japanese Takeda, Astellas, Daiichi Sankyo and Otsuka and Chinese Sinopharm, Guangzhou Pharmaceuticals Corporation, SPH and Yunnan Baiyao are now enlisted in leading Top 25 pharmaceutical companies rankings as per their annual net revenues in 2020–2021. Global industry landscape is evolving with ever more Asian companies obtaining the sharp innovative competitiveness leading development of cutting-edge medical technologies. Asian societies demand for pharmaceuticals and medical services continue to be characterized with unmet needs and striving to increase supply capacities. Financial obstacles of affordability of life saving medicines to the ordinary citizens shall be gradually overcome with an array of reimbursement strategies and extended insurance coverage policies. Observing the broad landscape throughout Asian region, we may witness that optimism in terms of domestic real GDP growth and consecutive biotech industry forecasts remains firmly rooted in years to come. Biosimilars are not a focus of the paper. [ABSTRACT FROM AUTHOR]

Objective: Next Generation Sequencing (NGS) is increasingly used for the diagnosis of rare genetic disorders. The aim of this study is to review the different approaches for economic evaluations of Next Generation Sequencing (NGS) in pediatric care used to date, to identify all costs, effects, and time horizons taken into account.Methods: A systematic literature review was conducted to identify published economic evaluations of NGS applications in pediatric diagnostics, i.e. exome sequencing (ES) and/or genome sequencing (GS). Information regarding methodological approach, costs, effects, and time horizon was abstracted from these publications.Results: Twenty-eight economic evaluations of ES/GS within pediatrics were identified. Costs included were mainly restricted to direct in-hospital healthcare costs and varied widely in inclusion of sort of costs and time-horizon. Nineteen studies included diagnostic yield and eight studies included cost-effectiveness as outcome measures. Studies varied greatly in terms of included sort of costs data, effects, and time horizon.Conclusion: Large differences in inclusion of cost and effect parameters were identified between studies. Validity of outcomes can therefore be questioned, which hinders valid comparison and widespread generalization of conclusions. In addition to current health economic guidance, specific guidance for evaluations in pediatric care is therefore necessary to improve the validity of outcomes and furthermore facilitate comparable decision-making for implementing novel NGS-based diagnostic modalities in pediatric genetics and beyond. [ABSTRACT FROM AUTHOR]

Copyright of PODIUM- Revista de Ciencia y Tecnologia en la Cultura Física is the property of Universidad de Pinar del Rio and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this article is to compare the insulin cost-savings of the Medtronic Extended Infusion Set (or EIS, a.k.a. Extended Wear Infusion Set) designed and labeled for up to 7-day use with rapid-acting insulins to the current standard of care, 2- to 3-day infusion sets. There are three major improvements (reducing insulin waste, plastic waste, and adverse events) with the extended duration of infusion set wear. This analysis focuses on cost savings from reduced insulin wastage during set changes. Studies published on insulin infusion set survival and EIS clinical trial data (NCT04113694) were used to estimate device lifetime performance using a Markov chain Monte Carlo model, including the assessment of adverse effects and device failure. Total costs associated with infusion set change or failure were systematically found in published literature or estimated based on physical usage, and the direct impact on insulin costs was calculated. Based on the model and clinical data, EIS users can expect to change their infusion sets about 75 fewer times than standard set users each year. The costs related to unrecoverable insulin during an infusion set and reservoir change in the US were estimated to range from $19.79 to $22.48, resulting in approximately $1324 to $1677 in annual cost-savings for the typical user from minimizing insulin wastage. The study only assessed devices used within a monitored setting, that is, clinical trials. In addition, the variability associated with healthcare standards and costs and individual treatment variability including insulin dosages, contribute to the uncertainties with the calculations. Our analysis demonstrates that by extending the duration of infusion set wear, there may be substantial cost savings by reducing insulin wastage. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the predominant cause of dementia and a leading cause of death globally. With no cure or treatment to slow disease progression, AD-related healthcare costs are substantial and increase as the severity of the disease progresses. Given the complexity of this disease, including initial pathophysiological damage occurring decades before clinical manifestation, finding new impactful treatments for AD relies on highly innovative research and development. However, such sizable and sustained investments bring into question whether conventional value assessment models are fit for this purpose. In this article, we examine the importance and challenges of assimilating the perspectives of varied stakeholders, including patients, caregivers, health systems, payers, and society at large, into a comprehensive value assessment model that may be well suited for a breakthrough treatment for AD. [ABSTRACT FROM AUTHOR]

Introduction: Three strains of the FMD virus (A, O, and SAT 2) were recognised as causes of the FMD circulating in Egypt. The aims of this study were to trace the FMDV isolates from outbreaks in Egypt to understand their epidemiology and evolution and to understand the situation of the vaccine strains compared with the circulating serotypes. Material and Methods: A meta-analysis was carried out by using the data available for FMD outbreaks in Egypt from GenBank and the World Reference Laboratory for Foot-and-Mouth Disease (WRLFMD); a comparison was done with both data sets for the three serotypes. MEGA-X was used for the evolution analysis, through constructions of phylogenetic trees for all sequences recorded in GenBank for each serotype in different Egyptian outbreaks in different years and also within the same year. Additionally, nucleotide substitution rate, molecular clock, and mean evolutionary rates were estimated for the three serotypes to understand and compare their evolution. Results: Absence of some records of certain serotype outbreaks from the WRLFMD database was noted as were subsequent missing appropriate vaccine programmes. Genetic variation was recorded among the virus isolates within the same years and also the vaccine strain was associated with up to 26 amino acid substitutions. The evolution rate of the SAT2 strain was the highest of the circulating strains. SAT2 had high amino acid substitution per year at an important immunogenic site (130–170), serotype A had less, and serotype O the least. Conclusion: The need for different strategies for vaccine serotype selection is indicated. [ABSTRACT FROM AUTHOR]

The Wulong gold orefield is located in the eastern part of the Liaodong Peninsula, and contains the large Sidaogou and Wulong gold deposits, as well as several small gold deposits with a total of >100 tonnes of gold reserves. These deposits are hosted within Paleoproterozoic metamorphic rocks of the Liaohe Group and Mesozoic granitoids, and are structurally controlled by NNE–SSW‐ and NNW–SSE‐trending faults and interlayer fractures. The Sidaogou deposit is characterized by altered‐rock‐type mineralization occurring within interlayer fracture zones, whereas the mineralization in the Wulong deposit occurs as auriferous quartz veins along subsidiary faults. These two types of gold mineralization are representative of the mineralization in the Wulong orefield. The REE contents of quartz and calcite, together with previous studies of fluid inclusions, indicate that the ore‐forming fluids of the Sidaogou deposit were reduced NaCl–H2O–CO2 fluids. Quartz yielded δ18OH2O‐SMOW, δDSMOW, and δ13CCO2 values of +4.7‰ to +6.6‰, −82.2‰ to −79.0‰, and − 13.1‰ to −6.6‰, respectively, and calcite yielded δ13CCO2 and δ18OV‐SMOW values of −2.3‰ to −2.0‰ and + 7.4‰ to +7.9‰, respectively. These results indicate that the ore‐forming fluids of the Sidaogou deposit were derived primarily from magmatic water, and the C was sourced mainly from deep‐seated magma with a minor contribution from sedimentary organic matter. Pyrite crystals have δ34SCDT values of +4.9‰ to +12.9‰, indicating the S source was a combination of the magmatic system and ore‐bearing metamorphic rocks. Pyrite has 208Pb/204Pb ratios of 38.226–38.336, 207Pb/204Pb ratios of 15.606–15.683, and 206Pb/204Pb ratios of 18.345–18.492, suggesting that the Pb in the Sidaogou deposit was derived primarily from the upper crust, with minor input from the mantle. Taking into account previous studies of the Wulong deposit, we propose a metallogenic model for the Wulong gold orefield. Deep‐seated ore‐forming fluids were released from different intrusions hidden below the Wulong orefield for each of the deposits. The ore‐forming fluids moved through the metamorphic rocks of the Gaixian Formation along interlayer fracture zones, where intensive water–wallrock reactions, and episodic temperature and pressure drops resulted in the formation of altered‐rock‐type Sidaogou deposit. The fluids ascended to the Wulong and Sanguliu intrusions along NNE–SSW‐ and NNW–SSE‐trending faults, where temperature and pressure dropping, water–wallrock reactions, and fluid immiscibility generated the vein‐type Wulong deposit. The gold deposits in the Wulong orefield share many similarities with the Linglong‐ and Jiaojia‐type gold deposits in the Jiaodong Peninsula, including geological setting, mineralization style and age, and sources of ore‐forming fluids and metal. [ABSTRACT FROM AUTHOR]

Successful university–industry collaborations require high levels of trust among participants, yet achieving this goal is complex. In this study, we provide a fine-grained qualitative analysis of thirty interviews from four collaborative, government-funded case studies over a 2-year period to analyze how trust can facilitate and/or impede project outcomes. We identified two levels of trust (individual and organizational), at multiple stages of the collaboration. Scientists' reputation and shared values about information sharing helped build trust among individual scientists, while organizational-level trust centered on efficiency, including alignment with contract provisions and time commitment to the project. Our analysis shows that only one project had a positive outcome, demonstrating that the interaction of trust across levels and over time helps explain collaborative success or lack thereof. Such a holistic perspective can widen understanding of the outcomes of university–industry collaborative efforts. [ABSTRACT FROM AUTHOR]

The low solubility of the iron, manganese and zinc oxides in the pH range of calcareous soils contributes, among other factors, to the low availability of these nutrients to plants. The aim of this work was study the efficacy of the application of Fe, Mn, Zn and Cu chelates to correct the deficiencies in soybean in hydroponic solution in the presence of CaCO3. Fe was applied as o,oEDDHA/Fe3+ in all the cases while Mn, Zn and Cu were applied as o,pEDDHA, EDDS, EDTA, HEDTA or DTPA chelates, with the same chelating agent for the three metals in the same treatment and two additional treatments with Mn and Cu chelated by EDTA and Zn chelated by o,pEDDHA or EDDS. Three controls with no Mn, no Zn and no Mn and Zn with the others chelated by EDTA were tested too. Results indicate that the content of Fe in leaf was similar in all the treatments due the same chelated was applied. The treatments that presented the higher levels for Mn and Zn in leaf, especially for Zn, was the one with the application of Mn and Zn as o,pEDDHA. The higher level for Cu was produced in the treatment with EDTA. It seems that the less stable phenolic chelates for Mn and Zn, like o,pEDDHA, are adequate for the nutrition of Mn and Zn in hydroponics due the low competence of this chelating agent with the plant for the metals.

Herein, a kind of hydroxyl and sulfonyl-containing diamine 2,2-bis[4-(3-hydroxy-4-aminophenoxy)phenyl]sulfone (BHAPS) was first synthesized and polymerized with pyromellitic dianhydride (PMDA) to obtain poly(amic acid) (PAA) solution. Then, the PAA nanofibers were fabricated by electrospinning technology, which were further thermally treated at 300 °C for imidization, 450 °C for rearrangement and a certain final temperature for carbonization to obtain carbon nanofibers (CNFs). The PAA concentration, carbonization temperature and thermal rearrangement time were separately optimized, and the HPI-CNF-20-2-800 exhibited better electrochemical properties. Next, the HPI-CNF-20-2-800 was chemically activated with KOH to enhance specific surface area. The preferred A-HPI–CNF–1/3 demonstrated a specific capacitance maximum of 335.0 F g−1 at 0.5 A g−1, with a 73 % capacitance retention at 10 A g−1. Furthermore , the SC device was symmetrically assembled with self-supporting A-HPI–CNF–1/3 membranes, which showed a maximum energy density of 10.42 Wh kg−1 at a power density of 250.0 W kg−1. In addition, the capacitance retention rate of the SC reached 99.94 % even after 50,000 charge/discharge cycles at a current density of 1 A g−1. Thus, this work reports a new precursor to prepare N, O, S co-doped active CNFs with better electrochemical performance, which will provide a reference for the preparation of co-doped self-supporting SC electrodes. • A new kind of diamine monomer containing hydroxyl and sulfonyl was synthesized. • The N, O, S co-doped activated carbon nanofibers were prepared. • The capacitive performance of self-supporting electrode was effectively boosted. [ABSTRACT FROM AUTHOR]

In theories with multiple vacua, reheating to a temperature greater than the height of a barrier can stimulate transitions from a desirable metastable vacuum to a lower energy state. We discuss the constraints this places on various theories and demonstrate that in a class of supersymmetric models this transition does not occur even for arbitrarily high reheating temperature.

As a promising electrode material for supercapacitors, porous carbon has received widespread attention. However, taking into account of the capacitive performance, the cost and environmental protection, the practicability of the carbon previously reported is still unsatisfactory. Therefore, it is meaningful and challenging to develop a proper carbon material. In the present work, N, O, P co-doped porous carbon materials are prepared from poplar catkin biomass wastes with a two-step chemical activation method by using H 3 PO 4 and K 2 CO 3 , separately. Specifically, the optimal HKPC-1-2.0 possesses a multi-level pore structure with an ultra-high specific surface area (2133 m2 g−1) and a suitable micropore percentage (52.8 %). As a result, HKPC-1-2.0 displays a specific capacitance of 296.2 F g−1 at 1.0 A g−1 in the three-electrode system by using 6.0 M KOH as electrolyte. More importantly, the symmetrical HKPC-1-2.0//HKPC-1-2.0 device exhibits a high capacity retention rate of 100.1 % even after 40,000 charge-discharge cycles at 1.0 A g−1. The co-doping of the heteroatoms and the hierarchical network with suitable pore size distribution are advantageous for the storage and transportation of ions, therefore leading to the encouraging capacitive performance. This work not only offers a low-cost and high-performance carbon electrode material for supercapacitors but also develops an environmentally-friendly strategy for effectively conversing biomass wastes to high value-added products. [Display omitted] • Facilely preparing poplar catkin-derived N, O, P co-doped porous carbon by a co-activation method • Constructing a multi-level pore structure with large surface area and suitable pore distribution • Delivering superior energy density (26.85 Wh kg−1 at 135 W kg−1) to many previous data • Presenting outstanding capacitance retention (100.1 % after 40,000 cycles) [ABSTRACT FROM AUTHOR]

Copyright of Plural - Revista de Ciências Sociais is the property of Revista Plural and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)