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BackgroundPatients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life.MethodsThis was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions.ResultsIn the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p ConclusionsIn real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use. Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.

Currently, the debate surrounding the regulation of e-cigarettes focuses mainly on the size of e-cigarettes' potentially beneficial effects (i.e., adult cessation) versus their unwarranted effects (i.e., initiation among tobacco-naïve adolescents). Therefore, we investigated the relative scale of e-cigarette use transitions in the United States. We reported cross-sectional weighted prevalence estimates of past-month e-cigarette use by ever cigarette use from Waves 1-4 of the Population Assessment of Tobacco and Health study (2013-2018) among youth (12-17 years) and adults (≥ 18 years). We also examined past-month e-cigarette mono and dual transitions related to cigarette smoking and reported the longitudinal weighted prevalence across waves. Among youth new e-cigarette users, the proportion of never-cigarette smokers increased from 24.1 in Wave 1 (n = 418) to 51.4% in Wave 4 (n = 310) (p 0.0001 for trend). Of youth past-month e-cigarette mono-users in Wave 1 (n = 151), 15.2% transitioned to cigarette mono-use and 8.2% dual-use at Wave 2 or 3 or 4, compared to 60.2% no tobacco use and 16.4% e-cigarette mono-use. Among young adult past-month dual-users (18-24 years; n = 684), 22.6% transitioned to no tobacco use, 60.1% continued cigarette use, 11.4% dual use, and 5.9% e-cigarette mono-use. Among adult dual-users ≥ 25 years old (n = 1560), 13.6% transitioned to no tobacco use, 71.3% cigarette mono-use, 9.0% dual-use, and 6.1% e-cigarette mono-use. Transition to cigarette mono-use and continued dual-use were common among adult past-month e-cigarette users, while e-cigarette initiation was common among youth never-cigarette smokers. These findings contrast with data from other countries showing limited evidence of e-cigarette initiation among youth never cigarette smokers. Both e-cigarette and cigarette use should be addressed in youth and adults, given the potential for dual use in both populations.

Despite the general high fluorophilicity of boron, organoboranes such as BEt3 and 3,5-(CF3)2C6H3–BPin are shown herein for the first time, to our knowledge, to be effective (solid to solution) phase-transfer catalysts for the fluorination of certain organohalides with CsF. Significant (upto 30% e.e.) chiral induction during nucleophilic fluorination to form β-fluoroamines using oxazaborolidine (pre)catalysts and CsF also can be achieved. Screening different boranes revealed a correlation between calculated fluoride affinity of the borane and nucleophilic fluorination reactivity, with sufficent fluoride affinity required for boranes to react with CsF and form Cs[fluoroborate] salts, but too high a fluoride affinity leading to fluoroborates that are poor at transferring fluoride to an electrophile. Fluoride affinity is only one component controlling reactivity in this context; effective fluorination also is dependent on the ligation of Cs+ which effects both the phase transfer of CsF and the magnitude of the [Cs⋯F-BR3] interaction and thus the B-F bond strength. Effective ligation of Cs+ (e.g. by [2.2.2]-cryptand) facilitates phase transfer of CsF by the borane but also weakens the Cs⋯F-B interaction which in turn strengthens the B–F bond - thus disfavours fluoride transfer to an electrophile. Combined these findings indicate that optimal borane mediated fluorination occurs using robust (to the fluorination conditions) boranes with fluoride affinity of ca. 105 kJ mol-1 (relative to Me3Si+) under conditions where a signficant Cs⋯F–B interaction persists.

Myocardial work is an emerging tool in echocardiography that incorporates left ventricular afterload into global longitudinal strain analysis. Myocardial work correlates with myocardial oxygen consumption, and work efficiency can also be assessed. Myocardial work has been evaluated in a variety of clinical conditions to assess the added value of myocardial work compared to left ventricular ejection fraction and global longitudinal strain. This review showcases the current use of myocardial work in adult echocardiography and its possible role in cardiac pathologies.

Background Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of severe adult asthma patients eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods This was a prospective cohort study that included adult severe asthma patients from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance and hospital admissions. Results In the matched analysis (n=350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

Language is an important aspect of communication and language status is known to impact healthcare accessibility, its perceived suitability, and outcomes. However, its influence on treatment engagement and/or disengagement is unknown. Our study therefore sought to investigate the impact of language on service disengagement in an early intervention psychosis program in Montreal, Quebec (a province with French as the official language). We aimed to compare service disengagement between a linguistic minority group (i.e., English) vis-à-vis those whose preferred language was French and to explore the role of language in service engagement. Using a mixed methods sequential design, we tested preferred language and several sociodemographic characteristics associated with service disengagement in a time-to-event analysis with Cox proportional hazards regression models ( N = 338). We then conducted two focus groups with English (seven patients) and French speakers (five patients) to further explore differences between the two linguistic groups. Overall, 24% ( n = 82) disengaged from the service before the two-year mark. Those whose preferred language was English were more likely to disengage ( n = 47, 31.5%) than those whose preferred language was French ( n = 35, 18.5%; χ2 = 9.11, p

Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities is needed to inform clinical practice.To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA.Patients enrolled in the Australian Mepolizumab Registry (n=309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin exacerbated airway disease, asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), fungal sensitisation and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed.Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range 47-77%), maintenance oral corticosteroid use (dose reduction 4.2-13.3 mg/day), and improved symptom control (Asthma Control Questionnaire-5 score 1.9-2.4 point reduction) and lung function (mean 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1s). Peripheral blood eosinophils were reduced (mean 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO and fungal sensitisation) modified the baseline phenotype.Mepolizumab treatment is associated with comparable clinical improvements in in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

BACKGROUND People with HIV (PWH) are at an increased risk of both heart and kidney disease, but the relationship between kidney disease and cardiac structure and function in this population has not been well studied. In particular, whether the relationship between kidney disease and cardiac structure and function is stronger for PWH compared with uninfected controls is unknown. METHODS One hundred PWH on antiretroviral therapy were compared with 100 age-matched and sex-matched controls without HIV in Uganda. Multivariable regression models were used to examine associations between creatinine-based and cystatin C-based estimated glomerular filtration rate (eGFR), albumin-creatinine ratio, and echocardiographic measures of cardiac structure and function. RESULTS PWH had lower eGFRcr (β -7.486, 95% confidence interval: -13.868 to -1.104, P = 0.022) and a higher rate of albumin-creatinine ratio ≥30 (odds ratio 2.146, 95% confidence interval: 1.027 to 4.484, P = 0.042) after adjustment for traditional risk factors. eGFR was inversely associated with both left ventricular mass index and diastolic dysfunction in adjusted models but not with systolic function. Albuminuria was associated with more diastolic dysfunction among PWH but not controls (P for interaction = 0.046). The association of HIV with a higher left ventricular mass index (P = 0.005) was not substantially affected by adjusting for eGFRcr. CONCLUSION Among Ugandans, eGFR is associated with elevated LV mass and diastolic dysfunction. The association between albuminuria and diastolic dysfunction is particularly strong for PWH.

Prior work on controllable text generation has focused on learning how to control language models through trainable decoding, smart-prompt design, or fine-tuning based on a desired objective. We hypothesize that the information needed to steer the model to generate a target sentence is already encoded within the model. Accordingly, we explore a different approach altogether: extracting latent vectors directly from pretrained language model decoders without fine-tuning. Experiments show that there exist steering vectors, which, when added to the hidden states of the language model, generate a target sentence nearly perfectly (> 99 BLEU) for English sentences from a variety of domains. We show that vector arithmetic can be used for unsupervised sentiment transfer on the Yelp sentiment benchmark, with performance comparable to models tailored to this task. We find that distances between steering vectors reflect sentence similarity when evaluated on a textual similarity benchmark (STS-B), outperforming pooled hidden states of models. Finally, we present an analysis of the intrinsic properties of the steering vectors. Taken together, our results suggest that frozen LMs can be effectively controlled through their latent steering space., Accepted to ACL2022 Findings; 16 pages (9 pages plus references and appendices); Code: https://github.com/nishantsubramani/steering_vectors; Some text overlap with arXiv:2008.09049

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Patient: Male, 34-year-old Final Diagnosis: Infected atrial myxoma Symptoms: Chest pain Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Rare disease Background: Although left atrial myxoma is the most common benign primary cardiac tumor, infected atrial myxoma is rare. This report presents a case of infected left atrial myxoma with embolization to the left anterior descending (LAD) coronary artery, which was identified following an initial presentation with ST-elevation myocardial infarction (STEMI). Case Report: A 34-year-old man with a history of smoking tobacco and intravenous cocaine use presented to the emergency room with symptoms of a feeling of pressure on the chest and symptoms in the left arm. An electrocardiogram (ECG) showed ST elevation in leads II, III, aVF, and V3–V5, consistent with an anterior-inferior STEMI. He underwent percutaneous intervention (PCI) with two drug-eluting stents to the mid-distal LAD coronary artery. The patient also had fever, chills, a history of weight loss, and signs of peripheral emboli. Blood cultures identified Gram-positive Streptococcus parasanguinis, a member of the Streptococcus viridans group. Transesophageal echocardiogram (TEE) identified a large, mobile, pedunculated left atrial mass protruding into the mitral valve in diastole and mitral valve vegetations. Surgical excision and the histology confirmed a diagnosis of benign left atrial myxoma containing Gram-positive cocci. The patient required mitral valve replacement and a postoperative two-week course of gentamicin and a six-week course of ceftriaxone Conclusions: A rare case is reported of infected left atrial myxoma presenting as STEMI secondary to coronary artery embolization, which was treated with PCI, antibiotics, and mitral valve replacement.

Despite the general high fluorophilicity of boron, simple organoboranes such as BEt3 and 3,5-(CF3)2C6H3–BPin are shown herein for the first time, to our knowledge, to be effective phase-transfer catalysts for the fluorination of organohalides with CsF. Significant chiral induction during nucleophilic fluorination to form -fluoroamines using oxazaborolidine (CBS) (pre)catalysts and CsF also can be achieved. Screening different boranes revealed a correlation between calculated fluoride affinity of the borane and nucleophilic fluorination reactivity, with sufficent fluoride affinity required for boranes to react with CsF and form Cs[fluoroborate] salts, but too high a fluoride affinity leading to fluoroborates that are poor at transferring fluoride to an electrophile. Fluoride affinity is only one component controlling reactivity in this context; effective fluorination also is dependent on the ligation of Cs+ which effects the [Cs⋯F⋯BR3] interaction and thus the B–F bond strength. Effective ligation of Cs+ (such as by [2.2.2]-cryptand) weakens the Cs⋯FB interaction which strengthens the B–F bond - thus disfavours fluoride transfer to an electrophile. Combined these findings enables optimal fluorination outcomes to be expected using robust (to the fluorination conditions) boranes with fluoride affinity of ca. 110 kJ mol-1 (relative to Me3Si+) under conditions where a signficant Cs⋯F–B interaction persists.

Controlled text perturbation is useful for evaluating and improving model generalizability. However, current techniques rely on training a model for every target perturbation, which is expensive and hard to generalize. We present Tailor, a semantically-controlled text generation system. Tailor builds on a pretrained seq2seq model and produces textual outputs conditioned on control codes derived from semantic representations. We craft a set of operations to modify the control codes, which in turn steer generation towards targeted attributes. These operations can be further composed into higher-level ones, allowing for flexible perturbation strategies. We demonstrate the effectiveness of these perturbations in multiple applications. First, we use Tailor to automatically create high-quality contrast sets for four distinct natural language processing (NLP) tasks. These contrast sets contain fewer spurious artifacts and are complementary to manually annotated ones in their lexical diversity. Second, we show that Tailor perturbations can improve model generalization through data augmentation. Perturbing just 2% of training data leads to a 5.8-point gain on an NLI challenge set measuring reliance on syntactic heuristics.

Density functional theory (DFT) calculations show that it is essential to consider the magnetic contribution to the total energy for the end-members of the σ phase. A more straightforward method to use the DFT results in a CALPHAD (Calculation of phase diagrams) description has been applied in the present work. It was found that only the results from DFT calculations considering spin-polarization are necessary to obtain a reliable description of the σ phase. The benefits of this method are: the DFT calculation work can be reduced and the CALPHAD description of the magnetic contribution is more reliable. A revised thermodynamic description of the Co-Cr system is presented which gives improved agreement with experimental phase boundary data for the σ phase.

RationaleProgressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results.MethodsThis historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory.ResultsWe studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional −1.34 L/min PEF per year (95% CI −1.23 to –1.50) were lost. Patients with AERs >2/year and aged 18–24 years at baseline lost an additional −5.95 L/min PEF/year (95% CI −8.63 to –3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above.ConclusionTo our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

PbSe is a promising thermoelectric that can be further improved by nanostructuring, band engineering, and carrier concentration tuning; therefore, a firm understanding of the defects in PbSe is necessary. The formation energies of point defects in PbSe are computed via first-principles calculations under the dilute-limit approximation. We find that under Pb-rich conditions, PbSe is an n-type semiconductor dominated by doubly-charged Se vacancies. Conversely, under Se-rich conditions, PbSe is a p-type semiconductor dominated by doubly-charged Pb vacancies. Both of these results agree with previously performed experiments. Temperature- and chemical potential-dependent Fermi levels and carrier concentrations are found by enforcing the condition of charge neutrality across all charged atomic and electronic states in the system. The first-principles-predicted charge-carrier concentration is in qualitative agreement with experiment, but slightly varies in the magnitude of carriers. To better describe the experimental data, a CALPHAD assessment of PbSe is performed. Parameters determined via first-principles calculations are used as inputs to a five-sublattice CALPHAD model that was developed explicitly for binary semiconductors. This five sublattice model is in contrast to previous work which treated PbSe as a stoichiometric compound. The current treatment allows for experimental carrier concentrations to be accurately described within the CALPHAD formalism. In addition to the five-sublattice model, a two-sublattice model is also developed for use in multicomponent databases. Both models show excellent agreement with the experimental data and close agreement with first-principles calculations. These CALPHAD models can be used to determine processing parameters that will result in an optimized carrier concentration and peak zT value.

Multiple active regions connected in series with low-resistance tunnel junctions enable a new class of high-brightness VCSEL arrays that enhance the capability for 3DS sensing applications. Multiple photons can be generated by each injected electron which proportionally increases the power and brightness of the VCSEL with additional benefit of reduced inductance penalty at the same output power. Two and three junction VCSEL arrays have been demonstrated for mobile Time-of-Flight applications with +30% module efficiency. Five junction VCSEL arrays reach 100W at 25A and 400W at 100A for automotive LIDAR applications. Preliminary reliability data appears promising.

This cross-sectional study evaluates the outcomes of universal COVID-19 testing following discovery of incident cases in 11 long-term care facilities in the US.