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Fernando J Martinez,1 Alberto Papi,2 Tobias Welte3,4 ,† Dave Singh,5 Dmitry V Galkin,6 Alessandro Guasconi,7 Stefania Pirondi,7 George Georges,7 Joseph Imperato,8 Ruben Hermans9 1Weill Cornell Medicine, New York–Presbyterian Hospital, New York, NY, USA; 2Research Center on Asthma and COPD, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 3Pneumonology and Infectiology, Member of the German Center of Lung Research, Hannover Medical School, Hannover, Germany; 4Biomedical Research in End Stage and Obstructive Lung Disease, German Center for Lung Research, Hannover Medical School, Hannover, Germany; 5Medicines Evaluations Unit, University of Manchester, Manchester University Foundation Hospitals Trust, Manchester, UK; 6Global Clinical Development, Chiesi USA, Cary, NC, USA; 7Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, Italy; 8Medical Affairs, IQVIA Inc, New York, NY, USA; 9Medical Affairs, IQVIA Inc, London, UK†Prof. Tobias We 50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53– 22.13% in 2019 to 9.94– 34.17% in 2021.Conclusion: Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.Keywords: COPD exacerbation, chronic obstructive pulmonary disease, COVID-19, electronic health records, real-world study

David Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif Şen,9 Dave Singh,10 Claus F Vogelmeier,11 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 Joan B Soriano,13 Maxim Kots,12 George Georges14 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Department of Health and Community Sciences, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Hospital and Institute (UMR1016), Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A, Parma, Italy; 13Respiratory Department, Hospital Universitario de La Princesa and Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; 14Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, ItalyCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Combined ICS and long-acting bronchodilators (LABD) more effectively reduce COPD exacerbations than LABD therapy alone. Corticosteroid-related adverse effects, including pneumonia, limit ICS use. Previous data suggest this risk is lower for extrafine beclometasone (ef-BDP). We compared pneumonia risk among new users of fixed dose ICS/LABD formulations containing ef-BDP, versus patients initiating LABD without any ICS.Methods: A propensity-matched historical cohort study design used data from OPCRD. COPD patients with ≥ 1 year of continuous data who initiated LABD or ICS/LABD formulations containing ef-BDP were matched. Primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions, with non-inferiority boundary of 15%.Results: 23,898 COPD patients were matched, who were 68± 11 years, 54.3% male and 56% current-smokers, while 43% were former-smokers. Initiation of ef-BDP/LABD was not associated with an increased risk of pneumonia versus LABD, for either a sensitive 0.89 (0.78– 1.02), P = 0.08 or a specific 0.91 (0.78– 1.05), P = 0.18 definition of pneumonia. The probability of remaining pneumonia free 1-year after ef-BDP/LABD was 98.4%, which was comparable to LABD at 97.7%, and was sustained up to 6 years of observation; non-inferiority criterion was met for both definitions. Initiation of ef-BDP/LABD was also associated with a reduced risk of developing LRTIs in the propensity matched cohort.Conclusion: Risk of pneumonia when using ICS for the management of COPD reported in several randomised controlled trials may not be relevant with ef-BDP in a diverse real-world clinical population.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclometasone, long-acting bronchodilators

Christian Gessner,1 Frederik Trinkmann,2,3 Sanaz Bahari Javan,4 Raimund Hövelmann,4 Valentina Bogoevska,4 George Georges,5 Elena Nudo,6 Carl-Peter Criée7 1Pneumologische Praxis Leipzig, Universitätsklinikum Leipzig, Institut für Klinische Immunologie, Leipzig, Germany; 2Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Translational Lung Research Center Heidelberg (TLRC), Member of German Center for Lung Research (DZL), Heidelberg, Germany; 3Department of Biomedical Informatics (DBMI) at the Center for Preventive Medicine and Digital Health Baden-Württemberg (CPD-BW), University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 4Department of Medical Affairs, Chiesi GmbH, Hamburg, Germany; 5Corporate R&D, Chiesi USA Inc., Cary, NC, USA; 6Global Medical Affairs, Chiesi Farmaceutici S.p.A., Parma, Italy; 7Department of Sleep and Respiratory Medicine, Evangelical Hospital Goettingen-Weende, Bovenden, GermanyCorrespondence: Christian Gessner, Pneumologische Praxis Leipzig, Universitätsklinikum Leipzig, Institut für Klinische Immunologie, Tauchaer Straße 12, Leipzig, 04357, Germany, Tel +49 341 60 20 960, Email ch.gessner@pneumologe-leipzig.dePurpose: Real-word evidence on the effectiveness of switching from dual therapies or triple therapies (multiple inhalers) to extrafine single-inhaler triple therapy (efSITT), which consists of the inhaled corticosteroid (ICS) beclomethasone, the long-acting β2-agonist (LABA) formoterol and the long-acting muscarinic antagonist (LAMA) glycopyrronium, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited. The impact of switching to efSITT on health-related quality of life (HRQoL), COPD specific symptoms, lung function and treatment adherence were assessed in routine clinical care.Patients and Methods: Patients were recruited at 148 sites in Germany between 2017 and 2020 in this multicenter, non-interventional observational study. Demographics, clinical data and treatment history were collected at baseline. HRQoL (measured by COPD Assessment Test [CAT]), lung function and adherence (measured by Test of Adherence to Inhalers [TAI]) were assessed at baseline and after six months. Descriptive analyses were conducted by prior treatment and GOLD groups as well as for the overall population.Results: 55.1% of the 2623 included patients were male. Mean age was 65.8 years. 57.5% of the patients were previously treated with ICS+LABA+LAMA (multiple inhalers), 23.9% with ICS/LABA (single or two inhalers) and 18.6% with LAMA/LABA (single or two inhalers). After six months, largest mean improvements in the total CAT score were observed in the ICS/LABA (− 3.9) and LAMA/LABA (− 3.9) prior treatment groups as well as in patients in GOLD group B (− 2.9). In the overall population, the CAT items for cough, phlegm, and dyspnea decreased on average by − 0.4 points each. After six months, FEV1 increased by 2.0 percentage points in relation to predicted values. The percentages of measured sRtot and RV of predicted values decreased by 24.5 and 4.4 percentage points, respectively. The percentage of patients with good adherence increased from 67.8% to 76.5%.Conclusion: Treatment switch to efSITT resulted in an improvement of HRQoL, COPD specific symptoms, lung function parameters and adherence under real-world conditions.Keywords: COPD, extrafine single inhaler triple therapy, treatment adherence, CAT score

David B Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif Şen,9 Dave Singh,10 Claus F Vogelmeier,11 Sara Barille,12 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 George Georges13 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Institute of Health Research, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Institute, Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A., Parma, Italy; 13Global Clinical Development, Chiesi Farmaceutici, S.p.A., Parma, ItalyCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Email dprice@opri.sgBackground: Inhaled corticosteroids (ICS) afford therapeutic benefits in some COPD patients, but their widespread use is cautioned due to an increased risk of developing pneumonia. Subclass variations exist, and the risk profile differs for individual ICS. Formulation particle size has been identified as a potential effect modifier. The present study compared the risk of pneumonia among new COPD users of fixed-dose combination inhalers containing fine-particle fluticasone (fp-FDC-F) versus extrafine particle beclometasone (ef-FDC-BDP).Methods: A propensity matched historical cohort study was conducted using data from the Optimum Patient Care Research Database. COPD patients aged ≥ 40 years with ≥ 1 year of continuous medical data who initiated fp-FDC-F or ef-FDC-BDP were compared. The primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions.Results: A total of 13,316 patients were matched. Initiation of fp-FDC-F (mean dosage furoate 99 μg; propionate 710 μg) was associated with an increased risk of pneumonia versus ef-FDC-BDP (mean beclometasone dose 395 μg), irrespective of definition (sensitive HR 1.38 95% CI 1.14– 1.68; specific HR 1.31 95% CI 1.05– 1.62).Conclusion: In the current investigation, we found that in comparison to extrafine beclomethasone, commencing a formulation containing fluticasone is associated with an increased risk of developing pneumonia. These observations support the idea that not all ICS are equal in their adverse effects and subclass variations exist and should be carefully considered in the treatment choice.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclomethasone, fluticasone

As radar sensors are being miniaturized, there is a growing interest for using them in indoor sensing applications such as indoor drone obstacle avoidance. In those novel scenarios, radars must perform well in dense scenes with a large number of neighboring scatterers. Central to radar performance is the detection algorithm used to separate targets from the background noise and clutter. Traditionally, most radar systems use conventional constant false alarm rate (CFAR) detectors but their performance degrades in indoor scenarios with many reflectors. Inspired by the advances in nonlinear target detection, In this article, we propose a novel high performance, yet low-complexity target detector and we experimentally validate our algorithm on a dataset acquired using a radar mounted on a drone. We experimentally show that our proposed algorithm drastically outperforms ordered statistics CFAR (OS-CFAR) (standard detector used in automotive systems) for our specific task of indoor drone navigation with more than 19% higher probability of detection for a given probability of false alarm. We also benchmark our proposed detector against a number of recently proposed multitarget CFAR detectors and show an improvement of 16% in probability of detection compared to censored harmonic averaging CFAR, with even larger improvements compared to both outlier-robust CFAR and truncated statistics log-normal CFAR in our particular indoor scenario. To the best of authors’ knowledge, this article improves the state-of-the-art for high-performance yet low-complexity radar detection in critical indoor sensing applications.

Kai-Michael Beeh,1 Piotr Kuna,2 Massimo Corradi,3 Isabelle Viaud,4 Alessandro Guasconi,4 George Georges4 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Łódź, Poland; 3Department of Medicine and Surgery, University of Parma, Parma, Italy; 4Global Clinical Development, Chiesi Farmaceutici SpA, Parma, ItalyCorrespondence: Kai-Michael BeehInsaf Respiratory Research Institute, Wiesbaden, GermanyTel +49 611 9854347Email k.beeh@insaf-wi.deBackground: Three 52-week studies in COPD have assessed the efficacy and safety of single-inhaler extrafine formulation triple therapy combining beclomethasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) delivered via pressurized metered-dose inhaler (pMDI). BDP/FF/G is now being developed for delivery via multi-dose dry-powder inhaler (DPI; NEXThaler). This study aimed to demonstrate non-inferiority of BDP/FF/G DPI vs pMDI for lung function.Methods: Multicenter, randomized, double-blind, double-dummy, active-controlled, three-way cross-over study in patients with COPD and post-bronchodilator forced expiratory volume in 1 second (FEV1) 30– 80% predicted. Patients received BDP/FF/G 100/6/10μg via DPI and pMDI, and BDP/FF 100/6μg via pMDI, all two inhalations twice daily for four weeks, with treatments separated by two-week washout. The two co-primary objectives were to demonstrate non-inferiority between the two BDP/FF/G formulations for FEV1 area under the curve between 0 and 12 hours post-dose (AUC0-12h) normalized by time and trough FEV1 at 24 hours, both on Day 28. EudraCT 2017– 004405-41.Results: Of 449 patients screened, 366 were randomized, with 342 (93.4%) completing all three treatment periods. The primary objectives were met, with changes from baseline in FEV1 AUC0– 12h and trough FEV1 on Day 28 similar for the two BDP/FF/G formulations, and the confidence intervals for the difference lying entirely within the pre-specified non-inferiority criterion (– 50mL): – 20 (– 35, – 6) mL and 3 (– 15, 20) mL for AUC0– 12h and trough FEV1, respectively. BDP/FF/G pMDI and DPI were statistically superior to BDP/FF for these endpoints (p< 0.001). A similar proportion of patients experienced adverse events with each treatment (15.5%, 18.7% and 15.4% with BDP/FF/G DPI and pMDI, and BDP/FF, respectively); the majority were mild or moderate, with few related to treatment.Conclusion: Extrafine BDP/FF/G DPI and pMDI demonstrated similar efficacy and safety in patients with COPD, supporting the DPI formulation as a valid alternative.Keywords: adrenergic beta-2 receptor agonists, muscarinic antagonists, steroids, respiratory function tests, chronic obstructive pulmonary disease

Omar S Usmani,1 Nicola Scichilone,2 Benjamin Mignot,3 Dennis Belmans,3 Cedric Van Holsbeke,3 Jan De Backer,3 Roberta De Maria,4 Erika Cuoghi,4 Eva Topole,4 George Georges4 1Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK; 2PROMISE Department of Medicine, University of Palermo, Palermo, Italy; 3FLUIDDA, Kontich, Belgium; 4Chiesi Farmaceutici, SpA, Parma, ItalyCorrespondence: George GeorgesChiesi USA Inc., 175 Regency Woods Place, Ste. 600, Cary, NC 27518, USATel +1 (919) 678 6611 x1536Email george.georges@chiesi.comIntroduction: There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.Materials and Methods: Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition.Results: HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were < 1, indicating greater peripheral than central deposition (0.48± 0.13, 0.48± 0.13 and 0.49± 0.13 for BDP, FF and GB, respectively; 1.96± 0.84, 0.97± 0.34 and 1.20± 0.48 for FluF, VI and UMEC, respectively).Conclusions: Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.Keywords: tomography, X-ray computed, metered dose inhalers, dry powder inhalers, inhaled corticosteroid, long-acting beta2 agonist, long-acting muscarinic antagonist

Se presenta un caso de hemobilia postraumática con fistula arteriobiliar; se comenta la sintomatología del cuadro étnico; se mencionan los medios diagnósticos para esta patología rara; se preconiza el tratamiento por embolización selectiva y se hace una revisión de la literatura sobre el tema, en In que se informa sobre 73 casos publicados hasta 1981 (4).

La quimiohipertermia intraperitoneal (IPCH) con Mitomicina C (MMC) fue usada en el tratamiento de 7 pacientes con cáncer gastrointestinal avanzado y carcinomatosis peritoneal. La resección primaria del tumor fue posible en 2 casos. La IPCH se realizó después del cierre de la pared abdominal durante 90 y 120 minutos bajo anestesia general con previa hipotermia a 320 Celsius, a través de un circuito cerrado formado con 3 drenajes de silicona intraperitoneal; se usó concentración de 10 mg/L de MMC en 6000 mL de liquido precalentado a 46-49° Celsius. No observamos ni mortalidad ni morbilidad. Otros autores han informado efectos biológicos secundarios ligeros y temporales; no hubo células malignas en el líquido ascítico después de la IPCH. Igualmente observamos en 6 pacientes un incremento en el índice de Karnofsky, 3 y 7 meses después de la IPCH. Estos resultados nos permiten confirmar que la IPCH con MMC es un método sin riesgo, que puede ser usado en el tratamiento del cáncer gastrointestinal avanzado con carcinomatosis peritoneal.

Abstract Background Knowledge of the conditions under which abortion is legal is important so that people can advocate for their right to abortion care. Yet minimal research has explored the association between women’s knowledge of abortion legality and the induced abortion care they receive, particularly using population-based survey data. Methods Using national survey data collected by Performance Monitoring for Action (PMA) in Côte d’Ivoire and Ghana, we aimed to compare the prevalence of accurate knowledge of abortion legality, factors associated with knowledge of the law, and the association between knowledge of abortion legality and the source of women’s induced abortion care in these two settings. We ran bivariate and multivariable logistic regressions to assess the relationships of interest. Results We found that awareness and knowledge of the abortion law were low in both Côte d’Ivoire and Ghana. In Cote d’Ivoire, women who were older, more educated, and with past abortion experience were more likely to be aware of the law. In Ghana, knowledge of the law did not vary significantly by demographic characteristics. However, in Ghana, knowledge of the law was correlated with women’s use of the formal healthcare system for abortion care, with greater use of clinical sources in rural areas. Conclusions It is possible that for populations with reduced access to abortion services, such as those in rural areas, knowledge of the law is advantageous for those seeking facility-based abortion care, particularly in settings where abortion is legal for a range of indications. Interventions seeking to improve access to facility-based abortion care in settings where abortion is legal on various grounds should incorporate education on the legal grounds for abortion.

Abstract Getting complementary physical information from a single image acquisition is particularly valuable for materials analysis. Grating based X-ray Phase Contrast Imaging (XPCI) methods allow decoupling attenuation, phase and scattering information. However, the phase and scattering extraction processes can easily suffer from artefacts, which is detrimental to implement this imaging technique in societal applications. In this paper, we demonstrate that grating based XPCI can provide a robust phase measurement in complex materials such as damaged composites. The technique allows the phase to be analysed using a self-assessment method that first identifies the artefacts from the imaging setup, and then can be used as an indicator to interpret the signal from a material. We focus on carbon fibre reinforced polymers which we subjected to laboratory-controlled lightning strikes. We evidence that the combined information from phase and attenuation allow identifying the type of defect induced by the lightning current. The phase information is converted into relative mass density variation within the sample and depicts areas with a loss in density up to 40%. We ensure that these results are valid by comparing them with an X-ray attenuation contrast tomographic reconstruction.

IntroductionThe gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics.MethodsFemale C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control). Caecal microbiota composition was assessed via 16S rRNA sequencing and caecal metabolites were quantified with NMR spectroscopy. Immune profiles of spleen and mesenteric lymph nodes (MLNs) were assessed by flow cytometry, and splenocytes assessed for ex vivo cytokine production. A generalised additive model approach was used to examine the relationship between global antibiotic consumption and IBD incidence.ResultsAntibiotics significantly altered gut microbiota composition, reducing alpha-diversity. Acetate and butyrate were significantly reduced in antibiotic groups, while propionate and succinate increased in Vancomycin and PmB-treated mice, respectively. The MLNs and spleen showed changes only to DC numbers. Splenocytes from antibiotic-treated mice stimulated ex vivo exhibited increased production of TNF. Epidemiological analysis revealed a positive correlation between global antibiotic consumption and IBD incidence.DiscussionOur findings demonstrate that antibiotic-mediated dysbiosis results in significantly altered short-chain fatty acid levels but immune homeostasis in spleen and MLNs at steady state is mostly preserved. Non-specific activation of splenocytes ex vivo, however, revealed mice with perturbed microbiota had significantly elevated production of TNF. Thus, this highlights antibiotic-mediated disruption of the gut microbiota may program the host towards dysregulated immune responses, predisposing to the development of TNF-associated autoimmune or chronic inflammatory disease.

Background and objectives: Intermittent androgen deprivation therapy (iADT) may result in measurable improvements in quality of life over continuous ADT in patients with advanced prostate cancer (aPC). Here, we studied time to castration and testosterone recovery in real-world patients with aPC undergoing iADT with relugolix. Methods and design: Eligibility criteria for this retrospective study were histologically confirmed through the diagnosis of aPC and initiation of iADT with relugolix. Primary endpoints were time to castrate level of testosterone after relugolix initiation and time to recovery to noncastrate levels after relugolix discontinuation. Results: Overall, 25 patients with aPC were treated with iADT and with relugolix. Median time to serum testosterone 50 ng/dL was 1.4 months [range 0.83–6.57 months] from holding treatment with relugolix. Conclusion: iADT with relugolix is associated with a rapid time to testosterone suppression and recovery. These results may guide patients’ counseling and monitoring of serum testosterone and PSA levels in patients wishing to pursue iADT for aPC.

Abstract Background Numerous factors at the individual, interpersonal, and societal levels are related to contraceptive use (or non-use) among adolescents and youth. Little is known about the role of religion as an individual and community-level influencer of contraceptive use among young women. Methods Using in-depth interviews with 24 young contraceptive users ages 18–24 who practice their Catholic, Protestant or Muslim religion in two cities in Burkina Faso, this study examines motivations and perceived consequences of contraceptive use. By including users of modern contraception who were both single and married, a range of perspectives are provided. Results Generally, the young women interviewed who practice their religion and use contraception perceived that their religion was not supportive of contraceptive use. A few exceptions were provided, including perceived acceptance of use of some methods for married women for spacing purposes; this was specifically identified as acceptable among Muslim respondents. Sexual activity and contraceptive use were not acceptable by any of the religions for unmarried young women. That said, young women, both married and unmarried, reported their motivations for use that often related to their and their children’s health and the realities of life. Contraceptive use was considered a private matter which meant that the religious community would not find out about women’s use. Conclusions Recognizing that some women are willing and able to use contraception even without the perceived support of their religious communities might help to push social norms to change and be more accepting of contraceptive use that meets young women’s and families’ circumstances.

The aim of the study is to analyze the aptitudes required for youth and activity leaders, which reflect the identity construction of people living in a prison environment. When caring for people in precarious situations, the needs of the situation and the needs of the individual must be taken into account (Kaës, 2022). Identifying the tutor's conceptualization in his management of interactions means taking into account the link between the objectives pursued and the rules of action, information gathering and control that he uses. The operational dimension of knowledge and the subjective involvement of the incarcerated person are necessary for this interpretation of the tutor's position. This raises the question of the skills required for support in order to successfully carry out the support system. An analysis of the results shows that, while support is a set of tools to facilitate self development and self-maintenance, this process requires the person handling it to have certain skills, such as neutrality, active listening, authenticity/congruence and awareness of their limits.

Summary: Background: Reproductive coercion (RC) is a type of abuse where a partner intentionally attempts to interfere with fertility through deception or violence, often by manipulating one’s contraceptive use or reproductive decision-making. Cross-sectional studies on the magnitude of RC across sub-Saharan Africa have noted associations with contraceptive use. No studies have longitudinally examined RC experiences as related to future contraceptive dynamics, including discontinuation or forgoing use altogether. Methods: Two rounds of longitudinal population-based cohorts across eight sites in sub-Saharan Africa, from November 2020 to January 2023, were used to prospectively examine past-year RC’s impact on future contraceptive dynamics (discontinuation and switching vs. continuation for contraceptive users at baseline; adoption vs. continued non-use for contraceptive non-users at baseline) using bivariate and multivariable multinomial and logistic regression. Findings: Minimal differences in women’s past-year RC experiences were observed over a two-year period. In many settings, RC prevalence decreased. Only in Uganda did past-year RC increase between rounds (15.8% to 17.8%). RC’s impact on contraceptive dynamics over one year differed by setting. In Burkina Faso, women with past-year RC had a three-fold increased risk of discontinuing contraception, as compared to continuing (RRR = 2.63; 95% CI = 1.28–5.42; p

X-ray imaging is widely used in non-destructive testing dedicated to industry, medical or security domain. In aircraft production, the aerospace industry increasingly integrates carbon fibre reinforced polymers (CFRP), which may develop defects from operational wear, like lightning strikes. To robustly characterize density changes resulting from induced lightning damage in CFRP, multilateral shearing interferometry (MLSI) – a phase imaging technique – have been incorporated on a X-ray laboratory bench. Indeed, such method provides higher contrasts than X-ray attenuation imaging for composite materials and brings complementary information of the imaged sample. However, extracting the phase signal requires conditions of the imaging system and algorithmic strategies, which can lead to the emergence of artifacts in phase images. This thesis work involved the characterisation of these artifacts in the context of MLSI applied to X-ray phase imaging, as well as the development of tracking methods and corrective strategies.

Recently, bulk drag coefficient (C˜D) formulations used to quantify wave energy dissipation by Rhizophora mangroves were developed from laboratory data; however, these formulations have not yet been validated with field data. Additionally, due to the complex geometry of mangrove trees within forests and spatial variability, common criteria for determining the adequate geometric characteristics of mangrove forests are lacking and are required to obtain accurate definitions for C˜D. This paper addresses these knowledge gaps by proposing a newly integrated C˜D formulation based on the comprehensive characterization of a Rhizophora mangle forest combined with wave measurements in field, and by using numerical modeling for the calibration process. The field campaign consisted of 23 continuous days of recorded wave data and spatial distribution observations of the geometric characteristics of the mangrove forest. The variation in frontal area per unit height per square meter (Ahm) along the mangrove forest was reported for three zones with different densities identified along the study transect, with decreasing root density from the vegetation edge to the forest interior. On average, the incident wave height decreased by 34% at 63 m in mangrove forests, and the wave attenuation ratios (r) varied between 0.001 and 0.01 m-1. To estimate the C˜D values associated with these wave height attenuation ratios, the Simulating Waves Nearshore (SWAN) numerical model was used to calibrate the model results with the field observations. The variation in the tree frontal area along the mangrove forest and the wave conditions at the site are considered during the calibration process. To further characterize C˜D for this type of mangrove species, the C˜D values acquired from the calibration together with the values reported in the literature from laboratory experiments are presented as a function of the Keulegan-Carpenter number (KC). Root diameter is defined as the characteristic length according to the inherent geometric characteristics of a Rhizophora sp. forest. The new formulation allows us to predictably estimate C˜D values that can be used as inputs in drag force-based models to estimate the attenuation of wave energy produced by Rhizophora sp. forests.

The development of future full-scale quantum computers (QCs) not only comprises the design of good quality qubits, but also entails the design of classical complementary metal–oxide semiconductor (CMOS) control circuitry and optimized operation protocols. The construction and implementation of quantum error correction (QEC) protocols, necessary for correcting the errors that inevitably occur in the physical qubit layer, form a crucial step in this design process. The steadily rising numbers of qubits in a single system make the development of small-scale quantum architectures that are able to execute such protocols a pressing challenge. Similar to classical systems, optimized simulation tools can greatly improve the efficiency of the design process. We propose an automated simulation framework for the development of qubit microarchitectures, in which the effects of design choices in the physical qubit layer on the performance of QEC protocols can be evaluated, whereas the focus in the current state-of-the-art design tools only lies on the simulation of the individual quantum gates. The hybrid Hamiltonian framework introduces the innovative combination of a hybrid nature that allows to incorporate several levels throughout the QC stack, with optimized embedded solvers. This provides the level of detail required for an in-depth analysis of the QEC protocol's stability.

Abstract Background Little is known about postabortion care (PAC) services in Burkina Faso, despite PAC’s importance as an essential and life-saving component of emergency obstetric care. This study aims to evaluate PAC service availability, readiness, and accessibility in Burkina Faso. Methods Data for this study come from the Performance Monitoring for Action (PMA) Burkina Faso project and the Harmonized Health Facility Assessment (HHFA) conducted by the Institut de Recherche en Sciences de la Santé and the Ministry of Health. PMA data from a representative sample of women aged 15–49 (n = 6,385) were linked via GPS coordinates to HHFA facility data (n = 2,757), which included all public and private health facilities in Burkina Faso. We assessed readiness to provide basic and comprehensive PAC using the signal functions framework. We then calculated distance to facilities and examined percent within 5 kms of a facility with any PAC, basic PAC, and comprehensive PAC overall and by women’s background characteristics. Results PAC services were available in 46.4% of health facilities nationwide; only 38.3% and 35.0% of eligible facilities had all basic and comprehensive PAC signal functions, respectively. Removal of retained products of conception was the most common missing signal function for both basic and comprehensive PAC, followed by provision of any contraception (basic) or any LARC (comprehensive). Nearly 85% of women lived within 5 km of a facility providing any PAC services, while 50.5% and 17.4% lived within 5 km of a facility providing all basic PAC and all comprehensive PAC signal functions, respectively. Women with more education, greater wealth, and those living in urban areas had greater odds of living within 5 km of a facility with offering PAC, basic PAC, or comprehensive PAC. Conclusions Results indicate a need for increased PAC availability and readiness, prioritizing basic PAC services at the primary level—the main source of care for many women—which would reduce structural disparities in access. The current deficiencies in PAC signal a need for broader strengthening of the primary healthcare services in Burkina Faso to reduce the burden of unsafe abortion-related morbidity and mortality while improving maternal health outcomes more broadly.

The shortest path problem is fundamental in graph theory and has been studied extensively due to its practical importance. Despite this aspect, finding the shortest path between two nodes remains a significant challenge in many applications, as it often becomes complex and time consuming. This complexity becomes even more challenging when constraints make the problem non-additive, thereby increasing the difficulty of finding the optimal path. The objective of this paper is to present a broad perspective on the conventional shortest path problem. It introduces a new method to classify cost functions associated with graphs by defining distinct sets of cost functions. This classification facilitates the exploration of line graphs and an understanding of the upper bounds on the transformation sizes for these types of graphs. Based on these foundations, the paper proposes a practical methodology for solving non-additive shortest path problems. It also provides a proof of optimality and establishes an upper bound on the algorithmic cost of the proposed methodology. This study not only expands the scope of traditional shortest path problems but also highlights their computational complexity and potential solutions.

The recent rise in telemedicine, notably during the COVID-19 pandemic, highlights the potential of integrating artificial intelligence tools in healthcare. This study assessed the effectiveness of ChatGPT versus medical oncologists in the telemedicine-based management of metastatic prostate cancer. In this retrospective study, 102 patients who met inclusion criteria were analyzed to compare the competencies of ChatGPT and oncologists in telemedicine consultations. ChatGPT’s role in pre-charting and determining the need for in-person consultations was evaluated. The primary outcome was the concordance between ChatGPT and oncologists in treatment decisions. Results showed a moderate concordance (Cohen’s Kappa = 0.43, p < 0.001). The number of diagnoses made by both parties was not significantly different (median number of diagnoses: 5 vs. 5, p = 0.12). In conclusion, ChatGPT exhibited moderate agreement with oncologists in management via telemedicine, indicating the need for further research to explore its healthcare applications.

We use the polynomials $m_s(t) = t^2 - 4 s$, $s \in \{-1, 1\}$, in an elementary process giving unlimited lists of {\it fundamental units of norm $s$}, of real quadratic fields, with ascending order of the discriminates. As $t$ grows from $1$ to an upper bound $\textbf{B}$, for each {\it first occurrence} of a square-free integer $M \geq 2$, in the factorization $m_s(t) =: M r^2$, the unit $\frac{1}{2} \big(t + r \sqrt{M}\big)$ is the fundamental unit of norm $s$ of $\mathbb{Q}(\sqrt M)$, even if $r >1$ (Theorem 4.2). Using $m_{s\nu}(t) = t^2 - 4 s \nu$, $\nu \geq 2$, the algorithm gives unlimited lists of {\it fundamental integers of norm $s\nu$} (Theorem~4.6). We deduce, for any prime $p>2$, unlimited lists of {\it non $p$-rational} quadratic fields (Theorems 6.3, 6.4, 6.5) and lists of degree $p-1$ imaginary fields with {\it non-trivial $p$-class group} (Theorems 7.1, 7.2). All PARI programs are given.

Abstract COVID‐19 hit Lebanon at the worst time, amid an economic downward spiral and national protests regarding living conditions and political corruption. The first case was found on February 21, 2020, and the first batch of vaccines arrived on March 24, 2021. Although neither natural infection nor mass vaccination truly provided herd immunity, the latter was a more effective way to handle the pandemic, and Lebanon fell short on that path. During the pandemic, a myriad of factors complicated its response to the virus. Thanks to the COVAX program, the country received 1086,720 doses donated and 1626,390 deliveries. All in all, over 5.8 million doses have been administered. A total of 2.74 million people received at least one dose, and 2.4 million had a complete primary vaccination series. However, around 98% of the population were infected with the virus. Issues that stopped the vaccination campaigns include a lack of trust in government officials and news media, leading to false information propagating and remaining unchallenged online. Other factors include the economic collapse, which led to the Lebanese currency losing over 98% of its initial worth. Some Lebanese people might find themselves either unable to reach proper health facilities or unwilling to adopt the narrative pushed by the political elite. Poverty also worsened affected infected individuals’ prognosis and mortality. A bigger emphasis must be put on reaching individuals with disabilities or in low‐income areas, as they were the most affected by the pandemic. Problems these communities face include the lack of funding for special education schools and the lack of accessibility to medical information promoted by the government. Lebanon must learn from the issues that arose during this pandemic and focus on fixing them in advance to prepare for any other health emergency that might turn up in the future.