Explore the vast range of titles available.

Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) (referred to hereafter as anti-PD-(L)1 agents) are approved to treat a variety of advanced-stage cancers. Incorporating these agents into neoadjuvant/adjuvant treatment regimens for early-stage cancers may provide health and economic benefits at the population level. A health outcomes projection model compared two scenarios in Switzerland: I) anti-PD-(L)1 agents used only for advanced/metastatic disease, and II) anti-PD-(L)1 agents starting in the neoadjuvant/adjuvant setting. The model focused on three cancers for which anti-PD-(L)1 agents are currently approved in Europe in early stages: melanoma, renal cell carcinoma (RCC), and triple-negative breast cancer (TNBC), projecting clinical evolution over 10 years. Estimated outcomes included life-years, quality-adjusted life-years (QALYs), recurrences/events, active treatments for metastatic disease, adverse events, and deaths. Of the estimated 10,659 eligible patients during 2022-2031, 9,050 were predicted to initiate neoadjuvant and/or adjuvant treatment with anti-PD-(L)1 agents for treatment of melanoma, RCC, or TNBC. Compared to anti-PD-(L)1 agents being available only in the metastatic setting, use of anti-PD-(L)1 agents in the neoadjuvant and/or adjuvant setting for these 3 cancers was projected to avoid 1,144 recurrences (a 27% decrease), prevent 1,577 active treatments in the metastatic setting (a 35% decrease), avoid 530 deaths (a 23% decrease), and increase life-years without recurrence by 3,416 (a 10% increase). The use of anti-PD(L)1 agents to treat early-stage cancers in Switzerland is anticipated to result in better outcomes by preventing recurrences/events, active metastatic treatments, and deaths.

Distinctive molecular characteristics of functionally diverse lymphocyte populations may represent novel pharmacological targets for immunotherapy. The intrinsic apoptosis pathway is differently regulated among conventional and regulatory T cells (Tregs). Targeted pharmacological modulation of this pathway with a small molecule Bcl-2/Bcl-xL inhibitor (ABT-737) caused a selective depletion of effector T cells and a relative enrichment of Tregs in vivo. Treatment with ABT-737 resulted in a tolerogenic milieu, which was exploited to alleviate graft-versus-host disease, to prevent allograft rejection in a stringent fully MHC-mismatched skin transplantation model and to induce immunological tolerance in combination with bone marrow transplantation. This concept has the potential to find various applications for immunotherapy, since it allows pharmacologic exploitation of the immunomodulatory properties of Tregs without the need for cell manipulation ex vivo.

Large language models have advanced the state-of-the-art in natural language processing and achieved success in tasks such as summarization, question answering, and text classification. However, these models are trained on large-scale datasets, which may include harmful information. Studies have shown that as a result, the models can exhibit social biases and generate misinformation after training. This dissertation discusses research on analyzing and interpreting the risks of large language models across the areas of fairness, trustworthiness, and safety. The first part of this dissertation analyzes issues of fairness related to social biases in large language models. We first investigate issues of dialect bias pertaining to African American English and Standard American English within the context of text generation. We also analyze a more complex setting of fairness: cases in which multiple attributes affect each other to form compound biases. This is studied in relation to gender and seniority attributes. The second part focuses on trustworthiness and the spread of misinformation across different scopes: prevention, detection, and memorization. We describe an open-domain question-answering system for emergent domains that uses various retrieval and re-ranking techniques to provide users with information from trustworthy sources. This is demonstrated in the context of the emergent COVID-19 pandemic. We further work towards detecting potential online misinformation through the creation of a large-scale dataset that expands misinformation detection into the multimodal space of image and text. As misinformation can be both human-written and machine-written, we investigate the memorization and subsequent generation of misinformation through the lens of conspiracy theories. The final part of the dissertation describes recent work in AI safety regarding text that may lead to physical harm. This research analyzes covertly unsafe text across various language modeling tasks including generation, reasoning, and detection. Altogether, this work sheds light on the undiscovered and underrepresented risks in large language models. This can advance current research toward building safer and more equitable natural language processing systems. We conclude with discussions of future research in Responsible AI that expand upon work in the three areas.

ABSTRACT Novice and experienced nurses are consistently concerned about their knowledge, skills and abilities to function appropriately in arrest situations. The clinical teachers at Mount Sinai Hospital in Toronto have established an innovative, creative, practical and cost-effective workshop that addresses nurses' code skills. The 500 evaluations received from nurses who have attended the workshops show the program is a resounding success. The 4-hour workshop concentrates on the nurses' role during cardiac arrests in four key areas: leadership, drug administration, suctioning, and airway management. The program is complete with goals and objectives, props, specific evaluation forms, and a take-home examination. The hands-on component of the workshop allows the application of new information under close observation and supervision of knowledgeable and skilled clinical teachers.

Annotation Contributors from rehabilitation medicine and physical therapy advise clinicians on the diagnosis and management of various pain syndromes in patients with primary disabling diseases, believing that managing pain in such patients will prevent physiological and functional decline. They discuss pain as it relates to various disease processes from the perspective of both rehabilitation specialists and primary care providers. They do not cover the neurophysiology of pain, surgical approaches to managing intractable pain, or other topics that are addressed adequately elsewhere. Annotation copyrighted by Book News, Inc., Portland, OR.

The Methodology Committee of the Patient Centered Outcomes Research Institute (PCORI) has released for public comment the draft of its first report recommending standards for the conduct of research leading to evidence-based, patient-centered health interventions. Health care in the United States has changed dramatically over the past several decades. Today, patients have more options than ever. Making the right choices, whether for prevention, diagnosis, or treatment, requires a critical appraisal of the potential benefits and harms of the options, within the context of the patient's characteristics, conditions, and preferences. Many of these choices are available thanks to advances in medical research. Yet most patients and many clinicians find research somewhat mysterious. They have difficulty sorting through the mountains of medical evidence to identify information that is reliable and actionable for their unique circumstances. Patient-centered outcomes . . .

A bstract Using the large-charge expansion, we prove a necessary condition for a CFT to exhibit conformal symmetry breaking, under the assumption that a continuous global symmetry is also broken on the moduli space: there must be a tower of charged local operators whose scaling dimensions are asymptotically linear in the charge. In supersymmetric theories with a continuous R-symmetry and a holomorphic moduli space, the existence of such a tower of operators follows trivially from a BPS condition: their scaling dimensions are then exactly linear in the R-charge. We illustrate the more general statement in several examples of three-dimensional N = 1 CFTs, where the leading linear behavior receives nontrivial corrections. By considering a suitable scaling limit, we also relate the spectrum of states with large charge on the cylinder (isomorphic to local operators) to the spectrum of massive particles on the moduli space.

In 2013, a Lancet Infectious Diseases Commission described the state of antimicrobial resistance worldwide. Since then, greater awareness of the public health ramifications of antimicrobial resistance has led to national actions and global initiatives, including a resolution at the high-level meeting of the UN General Assembly in 2016. Progress in addressing this issue has ranged from a ban on irrational drug combinations in India to commitments to ban colistin as a growth promoter in animals, improve hospital infection control, and implement better antimicrobial stewardship. Funds have been mobilised, and regulatory barriers to new antibiotic development have been relaxed. These efforts have been episodic and uneven across countries, however. Sustained funding for antimicrobial resistance and globally harmonised targets to monitor progress are still urgently needed. Except for in a few leading countries, antimicrobial resistance has not captured the sustained focus of national leaders and country-level actors, including care providers.

Following the emergency use authorisation of the Pfizer–BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6·5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine. We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84, and ≥85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant. During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72·1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95·3% (95% CI 94·9–95·7; incidence rate 91·5 per 100 000 person-days in unvaccinated vs 3·1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91·5% (90·7–92·2; 40·9 vs 1·8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97·0% (96·7–97·2; 32·5 vs 0·8 per 100 000 person-days) against symptomatic COVID-19, 97·2% (96·8–97·5; 4·6 vs 0·3 per 100 000 person-days) against COVID-19-related hospitalisation, 97·5% (97·1–97·8; 2·7 vs 0·2 per 100 000 person-days) against severe or critical COVID-19-related hospitalisation, and 96·7% (96·0–97·3; 0·6 vs 0·1 per 100 000 person-days) against COVID-19-related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94·5% among SARS-CoV-2 infections. Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. None.