IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination ...have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines—mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)—and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years IQR, 45-69; 2202 48.8% women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). CONCLUSIONS AND RELEVANCE: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.
In this work, a fully coupled thermo-mechanical meshfree approach is developed for the first time to simulate a solid-state layer-by-layer additive manufacturing process, Additive Friction ...Stir-Deposition (AFS-D). The meshfree method in this present work uses a Lagrangian reference frame, which permits tracking of material point history. A solid mechanics formulation is used, allowing the resolution of both elastic and plastic strains. An explicit dynamics time stepping scheme is used to ensure that the code is robust for the large level of non-linearity native to the AFS-D process. In this present work, a description of the meshfree method will first be described. Then a new thermo-mechanical joining contact algorithm will be introduced. Following that, a description of the experimental setup for the AFS-D model calibration experimental one layer deposition cases is explained. Subsequently, the simulation model and results for three different parameter sets will be detailed and compared against the experimental results. Finally, temperature and strain rate gradients are revealed across the entire deposition elucidating spatial-temporal flow phenomena in the AFS-D process.
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•Additive Friction Stir-Deposition simulations reveal inherent temperature and strain rate gradients.•Computationally efficient novel meshfree formulation facilitated by General-Purpose Computing on Graphics Processing Units.•Smoothed particle hydrodynamics simulations correlated to physical depositions representing acceptable and poor builds.•Simulations elucidate role of heat input on varying amounts of frictional heat generation influencing material flow.
Access to high quality abortion care is essential to women's health, as evidenced by the dramatic decrease in pregnancy-related morbidity and mortality since the legalization of abortion in the ...United States, and by high rates of maternal death and complications in those countries where abortion is still provided under unsafe conditions. The past two decades have brought important advances in abortion care as well as increasing cross-disciplinary use of abortion technologies in women's health care. Abortion is an important option for pregnant women who have serious medical conditions or fetal abnormalities, and fetal reduction techniques are now well-integrated into infertility treatment to reduce the risks of multiple pregnancies resulting from assisted reproductive technologies. Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care is the textbook of the National Abortion Federation, and serves as the standard, evidence-based reference text in abortion care. This state-of-the-art textbook provides a comprehensive overview of the public health implications of unsafe abortion and reviews the best surgical and medical practices for pregnancy termination, as well as managing ectopic and other abnormal pregnancies. Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care is the leading source for a comprehensive understanding of issues related to unintended and abnormal pregnancy. This textbook: is authored by internationally-known leaders in women's health care; addresses unintended pregnancy and abortion from historical, legal, public health, clinical, and quality care perspectives; includes chapters on pregnancy loss, ectopic pregnancy, gestational trophoblastic disease, and multifetal pregnancy reduction; covers treatment of pregnancies in the first and second trimester by both medical and surgical techniques; and provides resources for clinical, scientific, and social support for the abortion provider and patient.
In this study, the temperature and strain rate dependent physics of Additive Friction Stir Deposition (AFS-D) are elucidated for the first time. Candidate constitutive models are selected to account ...for the severe plastic deformation and wide ranges of temperature and strain rate inherent to AFS-D. Torsion mechanical tests are performed to capture AA6061 stress dependency on temperature and strain rate. Four constitutive models, including a low fidelity-calibrated one, are applied to single-layer AFS-D simulations. The robust meshfree method, smoothed particle hydrodynamics (SPH), provided the framework for constitutive model comparison. Utilizing the SPH simulations, peak values, temperature contours, effective stress contours, effective plastic strain contours, build profiles, and simulation run time are all compared to reveal hidden mechanisms of AFS-D processing. This work highlights the importance of constitutive model selection, which can lead to improved simulation results by accurately capturing plastic stress dependence on strain, strain rate, and temperature.
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•Temperature and strain rate mechanics of AFS-D revealed through SPH simulations.•Constitutive models investigated and calibrated against torsion mechanical testing.•AA6061-T6 and -O used to show flexibility of models for different tempers.•Constitutive models shown to have significant influences on simulation environment.
Background.
Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We ...delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan‐Kettering Cancer Center to determine the optimal therapy for patients with spine metastases.
Methods.
We provide a literature review of the integral publications that serve as the basis for the NOMS framework and report the results of systematic implementation of the NOMS‐guided treatment.
Results.
The NOMS decision framework consists of the neurologic, oncologic, mechanical, and systemic considerations and incorporates the use of conventional external beam radiation, spinal stereotactic radiosurgery, and minimally invasive and open surgical interventions. Review of radiation oncology and surgical literature that examine the outcomes of treatment of spinal metastatic tumors provides support for the NOMS decision framework. Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population.
Conclusion.
NOMS paradigm provides a decision framework that incorporates sentinel decision points in the treatment of spinal metastases. Consideration of the tumor sensitivity to radiation in conjunction with the extent of epidural extension allows determination of the optimal radiation treatment and the need for surgical decompression. Mechanical stability of the spine and the systemic disease considerations further help determine the need and the feasibility of surgical intervention.
摘要
背景. 癌症患者经常会发生肿瘤脊柱转移。现代肿瘤学提供了众多治疗方案，包括有效的系统治疗、放射治疗和手术治疗。我们描述并提供了解释神经病变学、肿瘤学、机械力学、以及系统（neurologic，oncologic，mechanical and systemic），NOMS决策框架的证据，该框架在斯隆‐凯特琳纪念癌症中心用于制定脊柱转移瘤患者的最佳治疗方案。
方法. 我们对以NOMS框架为基础的主要出版文献进行了文献综述，报告系统实施NOMS指导治疗的结果。
结果. NOMS决策框架包括对神经病变学、肿瘤学、机械力学以及系统原因的考量，综合应用常规外照射治疗、脊髓立体定向放射外科治疗、微创及开放性手术治疗。旨在调查脊柱转移瘤治疗结果的放射肿瘤学和外科学文献的综述为NOMS决策框架提供了支持。NOMS范例应用时综合多学科治疗以优化局部肿瘤控制、疼痛缓解，恢复或保留神经功能，并将此类容易系统性患病的患者人群的发病率降至最低。
结论. NOMS范例提供一种决策框架，该框架可汇总脊柱转移瘤治疗中的前哨决策点。针对肿瘤对放射治疗的敏感性结合肿瘤硬膜外侵犯程度的考量，可确定最佳放射治疗方案并符合外科减压手术的需求。针对脊柱的机械稳定性和系统性疾病的考虑更进一步有助于确定外科手术治疗的需求及其可行性。The Oncologist 2013;18:744–751
Spinal metastases frequently arise in patients with cancer. This article describes the neurologic, oncologic, mechanical, and systemic decision framework used at Memorial Sloan‐Kettering Cancer Center to determine the optimal therapy for patients with spinal metastases.
Abstract
Background
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness ...against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes.
Methods
In a multicenter case-control analysis of US adults hospitalized March 11–May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2.
Results
Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval CI, 80.7–91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18–49 years (97.4%; 95% CI, 79.3–9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8–82.6) than without immunosuppression (91.3%; 95% CI, 85.6–94.8).
Conclusion
During March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.
From March to May 2021, full vaccination using authorized mRNA products was associated with 87.1% (95% CI, 80.7–91.3) protection against COVID-19 hospitalization among US adults. Vaccine effectiveness was lower in adults with versus without immunosuppression (62.9% versus 91.3%).
AbstractObjectivesTo characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the ...effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.DesignCase-control study.Setting21 hospitals across the United States.Participants11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022).Main outcome measuresVaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression.ResultsEffectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85).ConclusionsmRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.
The thermodynamics and kinetics for the monofunctional binding of nitrogen mustard class of anticancer drugs to purine bases of DNA were studied computationally using guanine and adenine as model ...substrates. Mechlorethamine and melphalan are used as model systems in order to better understand the difference in antitumor activity of aliphatic and aromatic mustards, respectively. In good agreement with experiments that suggested the accumulation of a reactive intermediate in the case of mechlorethamine, our model predicts a significant preference for the formation of corresponding aziridinium ion for mechlorethamine, while the formation of the aziridinium ion is not computed to be preferred when melphalan is used. Two effects are found that contribute to this difference. First, the ground state of the drug shows a highly delocalized lone pair on the amine nitrogen of the melphalan, which makes the subsequent cyclization more difficult. Second, because of the aromatic substituent connected to the amine nitrogen of melphalan, a large energy penalty has to be paid for solvation. A detailed study of energy profiles for the two-step mechanism for alkylation of guanine and adenine was performed. Alkylation of guanine is ∼6 kcal mol–1 preferred over adenine, and the factors contributing to this preference were explained in our previous study of cisplatin binding to purine bases. A detailed analysis of energy profiles of mechlorethamine and melphalan binding to guanine and adenine are presented to provide an insight into rate limiting step and the difference in reactivity and stability of the intermediate in both nitrogen mustards, respectively.
The biotic ligand model: a historical overview Paquin, Paul R.; Gorsuch, Joseph W.; Apte, Simon ...
Comparative biochemistry and physiology. Toxicology & pharmacology,
09/2002, Letnik:
133, Številka:
1
Journal Article
Recenzirano
During recent years, the biotic ligand model (BLM) has been proposed as a tool to evaluate quantitatively the manner in which water chemistry affects the speciation and biological availability of ...metals in aquatic systems. This is an important consideration because it is the bioavailability and bioreactivity of metals that control their potential to cause adverse effects. The BLM approach has gained widespread interest amongst the scientific, regulated and regulatory communities because of its potential for use in developing water quality criteria (WQC) and in performing aquatic risk assessments for metals. Specifically, the BLM does this in a way that considers the important influences of site-specific water quality. This journal issue includes papers that describe recent advances with regard to the development of the BLM approach. Here, the current status of the BLM development effort is described in the context of the longer-term history of advances in the understanding of metal interactions in the environment upon which the BLM is based. Early developments in the aquatic chemistry of metals, the physiology of aquatic organisms and aquatic toxicology are reviewed first, and the degree to which each of these disciplines influenced the development of water quality regulations is discussed. The early scientific advances that took place in each of these fields were not well coordinated, making it difficult for regulatory authorities to take full advantage of the potential utility of what had been learned. However, this has now changed, with the BLM serving as a useful interface amongst these scientific disciplines, and within the regulatory arena as well. The more recent events that have led to the present situation are reviewed, and consideration is given to some of the future needs and developments related to the BLM that are envisioned. The research results that are described in the papers found in this journal issue represent a distinct milestone in the ongoing evolution of the BLM approach and, more generally, of approaches to performing ecological assessments for metals in aquatic systems. These papers also establish a benchmark to which future scientific and regulatory developments can be compared. Finally, they demonstrate the importance and usefulness of the concept of bioavailability and of evaluative tools such as the BLM.
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