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East Asia and Latin America are two regions of great similarities and trajectories. Struggling with poverty and underdevelopment, many analysts classified them as regions of developing states. Today, countries like Japan, Korea and Taiwan are among the fastest growing in the World while Brazil, Mexico and Argentina are still struggling with huge societal inequality, institutional corruption, and extreme poverty. The scope of this paper is to identify key factors that are attributed to different developmental outcomes between East Asia and Latin America. This will be accomplished through a comparative analysis of state policies, sectoral growth and relationship to external trade and market vulnerabilities, between three countries from each region, Argentina, Brazil and Mexico from Latin America and Japan, Korea, and Taiwan from East Asia. The paper argues that the model of developmentalism implemented in Latin America never aimed to achieve societal equality or technological growth and was tormented by political instability, elite-controlled systems, and protectionism that had no relativity with global trade. On the contrary, East Asia identified its internal market weaknesses and was committed to generating macroeconomic stability, creating an ideal atmosphere for private investment and political stability.

Background Thymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. Methods Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Results A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68–3.25]) or baseline high-flow oxygen (1.28 [.35–4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to Tα1. Conclusions Tα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Clinical Trials Registration NCT04487444.

“p-y” curves are used to simplify the pile response of laterally loaded piles at any given depth by describing the applied lateral soil reaction as a function of the lateral displacement. Simple analytical solutions in two-dimensions for system stiffness are available by modelling a segment of the pile surrounded by an annular zone of linear-elastic soil. Current solutions assume homogeneous soil conditions. However, installation of a bored pile in clay would result in a region of softened material immediately surrounding the pile-soil interface, which can be modelled using a function describing the variation of shear modulus with distance from the pile. Suchfunctions are available in the literature using linear and power-law variations. This paper derives an improved solution for the system stiffness considering the effects of pile installation. The previously discussed annular zone of soil is split into multiple rings with each able to define an independent shear modulus. A solution for the overall system stiffness is provided. Three-dimensional and parameter effects are discussed.

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose–Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

Introduction. Arachnoid cysts are benign lesions comprising about 1 % of all intracranial space occupying lesions. The majority are asymptomatic, while surgical intervention, consisting of fenestration, is suggested in the presence of mass phenomena.The aim of the study – to present the case of a patient with arachnoid cysts in the cerebellopontine angle and its treatment.Materials and methods. A 53‑years old female patient was referred to our Department of Neurosurgery for the surgical management of a cerebellopontine angle mass. The patient reported tingling sensation and causalgia of her left hemiface, dysarthria, hoarseness, difficulty swallowing solid food and liquids, tinnitus and pain distributed along the ophthalmic branch of the trigeminal nerve.Results. The patient was subjected to retrosigmoid craniotomy with fenestration of the cyst and concurrent placement of a Torkildsen shunt. No complete resection of the capsule of the cyst was attempted, due to its tight adhesions to the adjacent structures. Postoperatively, there was an improvement in the dysarthria and swallowing of the patient.Conclusions. Cerebellopontine angle cystic lesions while histologically benign, may become clinically apparent due to compression of adjacent structures. Simple fenestration of the cyst may be sufficient for the remission of symptoms.

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose–Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

Microbe entry through catheter ports can lead to biofilm accumulation and complications from catheter-related bloodstream infection and ultimately require antimicrobial treatment and catheter replacement. Although strides have been made with microbial prevention by applying standardized antiseptic techniques during catheter implantation, both bacterial and fungal microbes can present health risks to already sick individuals. To reduce microbial adhesion, murine and human catheters were coated with polyurethane and auranofin using a dip coating method and compared to non-coated materials. Upon passage of fluid through the coated material in vitro, flow dynamics were not impacted. The unique antimicrobial properties of the coating material auranofin has shown inhibitory activity against bacteria such as Staphylococcus aureus and fungi such as Candida albicans. Auranofin coating on catheters at 10mg/mL reduced C. albicans accumulation in vitro from 2.0 x 108 to 7.8 x 105 CFU for mouse catheters and from 1.6 x 107 to 2.8 x 106 for human catheters, showing an impact to mature biofilms. Assessment of a dual microbe biofilm on auranofin-coated catheters resulted in a 2-log reduction in S. aureus and a 3-log reduction in C. albicans compared to uncoated catheters. In vivo assessment in a murine subcutaneous model demonstrated that catheters coated with 10 mg/mL auranofin reduced independent S. aureus and C. albicans accumulation by 4-log and 1-log, respectively, compared to non-coated catheters. In conclusion, the auranofin-coated catheters demonstrate proficiency at inhibiting multiple pathogens by decreasing S. aureus and C. albicans biofilm accumulation.

The response of a two-storey RC school building in the town of Argostoli, Cephalonia Island, Greece, during the seismic sequence of January and February 2014, is examined. The structure was built following an older generation of seismic codes dating from the 1950s, which provide limited strength and ductility against lateral loads. Despite the severity of ground shaking and the two successive events, the building suffered relatively minor damage, like most of the RC buildings in the town. Following a short presentation of some basic seismological, structural and geotechnical aspects of the seismic sequence, the paper focuses on the seismic performance of the structure at hand. To this end, a series of detailed non-linear static and time-history dynamic analyses are reported, which highlight the interplay of soil, foundation and superstructure in modifying the seismic demand. It is demonstrated that SSI had an unexpectedly important (detrimental) role in the behaviour of the structure, increasing its natural period by about 25% and aggravating ductility demand in almost all columns, despite the moderately soft soil conditions (average VS = 180 m/s). The results shed light on the seismic performance of the building and help drawing conclusions on the engineering effects of the 2014 Cephalonia earthquake sequence.

There is evidence suggesting that infection with SARS-CoV-2 can lead to several long-term sequelae including diabetes. This mini-review examines the rapidly evolving and conflicting literature on new-onset diabetes after COVID-19, which we term NODAC. We searched PubMed, MEDLINE, and medRxiv from inception until December 1, 2022 using both MeSH terms and free text words including “COVID-19,” “SARS-CoV-2,” “diabetes,” “hyperglycemia,” “insulin resistance,” and “pancreatic β-cell.” We also supplemented searches by examining reference lists from retrieved articles. Current evidence suggests that COVID-19 increases the risk of developing diabetes, but the attributable risk is uncertain due to limitations of study designs and the evolving nature of the pandemic, including new variants, widespread population exposure to the virus, diagnostic options for COVID-19 and vaccination status. The etiology of diabetes after COVID-19 is likely multifactorial and includes factors associated with host characteristics (e.g., age), social determinants of health (e.g., deprivation index), and pandemic-related effects both at the personal (e.g., psychosocial stress) and the societal-community level (e.g., containment measures). COVID-19 may have direct and indirect effects on pancreatic β-cell function and insulin sensitivity related to: the acute infection and its treatment (e.g., glucocorticoids); autoimmunity; persistent viral residency in multiple organs including adipose tissue; endothelial dysfunction; and hyperinflammatory state. While our understanding of NODAC continues to evolve, consideration should be given for diabetes to be classified as a post-COVID syndrome, in addition to traditional classifications of diabetes (e.g., type 1 or type 2), so that the pathophysiology, natural history and optimal management can be studied.

Clinical management of Staphylococcus aureus infections presents a challenge due to the high incidence, considerable virulence, and emergence of drug resistance mechanisms.

Background Individuals who are immunocompromised (IC) are at high risk for severe coronavirus disease 2019 (COVID-19). Methods Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020–April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety of casirivimab plus imdevimab (CAS + IMD) versus placebo in IC versus overall study patients. Results Ninety-nine of 1940 (5.1%) patients were IC. IC versus overall patients were more frequently seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (68.7% vs 41.2%) and had higher median baseline viral loads (7.21 vs 6.32 log10 copies/mL). On placebo, IC versus overall patients had slower viral load declines. CAS + IMD reduced viral load in IC and overall patients; least-squares mean difference versus placebo in time-weighted average change from baseline viral load at day 7 was −0.69 (95% confidence interval [CI], −1.25 to −.14) log10 copies/mL for IC patients and −0.31 (95% CI, −.42 to −.20) log10 copies/mL for overall patients. For IC patients, the cumulative incidence of death or mechanical ventilation at day 29 was lower with CAS + IMD (11.0%) versus placebo (17.2%), consistent with overall patients (15.7% CAS + IMD vs 18.3% placebo). IC and overall patients receiving CAS + IMD exhibited similar rates of treatment-emergent adverse events (30.4% and 26.6%, respectively), grade ≥2 hypersensitivity or infusion-related reactions (1.4% and 2.5%), and deaths (8.7% and 12.2%). Conclusions IC patients were more likely to exhibit high viral loads and be seronegative at baseline. For susceptible SARS-CoV-2 variants, CAS + IMD reduced viral load and resulted in fewer death or mechanical ventilation events in IC and overall study patients. There were no new safety findings among IC patients. Clinical Trials Registration. NCT04426695.

Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes , inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti- C. acnes compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against C. acnes (ATCC 6919 and HM-513) of 1 μg/mL.

Background Clinical trials for coronavirus disease 2019 (COVID-19) have struggled to achieve diverse patient enrollment, despite underrepresented groups bearing the largest burden of the disease and, presumably, being most in need of the treatments under investigation. Methods To assess the willingness of patients to enroll into inpatient COVID-19 clinical trials when invited, we conducted a cross-sectional analysis of adults hospitalized with COVID-19 who were approached regarding enrollment. Associations between patient and temporal factors and enrollment were assessed by multivariable logistic regression analysis. Results A total of 926 patients were included in this analysis. Overall, Hispanic/Latinx ethnicity was associated with a nearly half-fold decrease in the likelihood to enroll (adjusted odds ratio [aOR], 0.60 [95% confidence interval {CI}, .41–.88]). Greater baseline disease severity (aOR, 1.09 [95% CI, 1.02–1.17]), age 40–64 years (aOR, 1.83 [95% CI, 1.03–3.25]), and age ≥65 years (aOR, 1.92 [95% CI, 1.08–3.42]) were each independently associated with higher likelihood to enroll. Over the course of the pandemic, patients were less likely to enroll during the summer 2021 wave in COVID-19–related hospitalizations (aOR, 0.14 [95% CI, .10–.19]) compared with patients from the first wave in winter 2020. Conclusions The decision to enroll into clinical trials is multifactorial. Amid a pandemic disproportionately affecting vulnerable groups, Hispanic/Latinx patients were less likely to participate when invited, whereas older adults were more likely. Future recruitment strategies must consider the nuanced perceptions and needs of diverse patient populations to ensure equitable trial participation that advances the quality of healthcare for all.

ObjectivesAntimicrobial resistance is global pandemic that poses a major threat to vision health as ocular pathogens, especially staphylococcal species, are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of a new class of synthetic retinoids in comparison to currently used antibiotics against clinically relevant ocular staphylococcal isolates.MethodsAntimicrobial susceptibility testing was performed by broth microdilution for 3 novel synthetic retinoids (CD1530, CD437, and a CD437 analogue) and 7 comparator antibiotics, against a collection of 216 clinical isolates.ResultsCD437 MIC50 and MIC90 were 2 µg/mL for Staphylococcus aureus, and 1 µg/mL and 2 µg/mL respectively, for coagulase-negative staphylococci (CoNS). CD1530 (MIC50 = 2 µg/mL for all species) also displayed good activity with an in vitro potency slightly lower (2-fold) for S. aureus (MIC90 = 4 µg/mL) when compared to CD437. A CD437 analogue also demonstrated good in vitro activity (MIC50 = 2 µg/mL for all species) and potency (MIC90 = 2 µg/mL for MRSA and 4 µg/mL for MSSA and CoNS). In vitro potencies were similar or higher than that of comparator agents, and were not impacted by multidrug resistance phenotypes.ConclusionOur results demonstrate that synthetic retinoids display potent in vitro activity against ocular staphylococcal species, including multidrug-resistant isolates.

Seismic earth pressures acting on basement walls and retaining walls are most commonly computed using limit state methods, in which the effects of earthquake shaking are represented by a horizontal body force in an active soil wedge. Limit state methods provide a poor physical representation of the fundamental mechanisms that give rise to seismic earth pressures, which depend on relative wall–soil displacements. Such displacements are a consequence of soil–structure interaction, which, in the absence of a strong inertial component (e.g. from a connected structure), are mainly sensitive to the ratio of wavelength-to-wall height and relative wall-to-soil flexibility. We present a simplified single-frequency procedure for computing seismic earth pressures applied to flexible retaining structures by vertically propagating shear waves. The procedure accounts for the first-order wavelength and wall flexibility effects while simplifying a number of secondary effects in a manner that produces a slightly conservative outcome. Input parameters to the proposed solution are readily attainable for engineering design applications. For typical earth retention systems, earth pressures computed using the proposed procedure are lower than those computed using limit state solutions. Predictions from the proposed solution compare well with results of numerical simulations and centrifuge modeling from literature, whereas limit state procedures either do not provide a physically meaningful solution or produce strongly biased predictions (overprediction of experiments, underprediction of available simulations).

This study focuses on the investigation of the factors that have limited, so far, the development of a consistent design and assessment approach for integral bridges (IBs). This paper presents a review of previous research and current design practices for IBs, followed by an overview of monitoring studies in the laboratory and in the field. As part of the UK Collaboratorium for Research on Infrastructure and Cities–Priming Laboratory EXperiments on Infrastructure and Urban Systems experimental campaign, a small-scale 1 g physical experiment is described. The test aimed to simulate the soil–structure interaction arising from seasonal expansion and contraction of the bridge deck and assess the performance of different monitoring techniques. Pressure cells were used to measure the lateral stresses behind the abutment wall, particle image velocimetry was employed to monitor the soil behaviour behind the abutment and linear variable differential transformers were used to monitor the backfill surface movements. By combining the data from these instruments, a preliminary assessment of the soil–structure interaction behaviour of the idealised integral abutment under seasonal thermal loading has been obtained. These monitoring methods and the associated understanding of IB behaviour gained from the tests provide definitive evidence for the development of monitoring systems for larger-scale physical tests and field monitoring systems for IBs.

It is a Frontiers tradition to herald the start of a new journal with an editorial that highlights the challenges and opportunities of the relevant field. For Frontiers in Bacteriology, the start of the journal coincides with a pivotal era for the field, with the slow-moving epidemic of antimicrobial resistance threatening medical progress.

Background: Remdesivir is widely used for the management of COVID-19 and several studies have reported bradycardia as a potential side effect associated with this agent. The aim of the present study was to evaluate the incidence rate, severity, and potential risk factors of remdesivir-associated bradycardia.Methods: We performed a retrospective cohort study among hospitalized adult patients with COVID-19 who were treated with remdesivir from March 2020 to October 2021. Our primary outcome of interest was the incidence rate and severity of bradycardia after remdesivir administration. We defined mild bradycardia as a heart rate of 51–59 beats per minute, moderate bradycardia as a heart rate of 41–50 beats per minute, and severe bradycardia as a heart rate of ≤40 beats per minute. We also performed univariable and multivariable regression analyses to determine potential bradycardia risk factors. Baseline characteristics were reported as means with standard deviations or medians with interquartile ranges (IQRs). All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs).Results: In total, 1,635 patients were included in this study. The median age with IQR was 68 (57–79) years and 51.7% of the patients were male. In total, 606 (37.1%) patients developed bradycardia. Among them, 437 patients (26.7%) developed mild bradycardia, 158 patients (9.7%) moderate bradycardia, while 11 patients (0.7%) experienced severe bradycardia. In our adjusted multivariate logistic regression, the odds of bradycardia development after remdesivir administration were higher among patients with age ≥65 years (OR 1.76, 95% CI: 1.04–2.99, p = 0.04), those with hypertension (OR 1.37, 95% CI: 1.07–1.75, p = 0.01), and obesity (OR 1.32, 95% CI: 1.02–1.68, p = 0.03).Conclusion: More than 1 out of 3 patients (37%) who received remdesivir for COVID-19 developed bradycardia with the majority of these patients developing mild or moderate bradycardia that is usually a benign manifestation not needing treatment in most cases. Age ≥65 years, hypertension, and obesity were potential risk factors for remdesivir-associated bradycardia among hospitalized COVID-19 patients. Clinicians should be aware of this adverse event and consider close clinical monitoring for patients at high risk for this adverse event.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p

Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17; P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%; P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g; P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU; P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g; P = 0.0313). In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%; P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.

Item does not contain fulltext BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

Communication is one of the most important and expensive resources in a network with different parts who desire to establish coordinated behavior. When the actions of some parts are distributed according to a probability distribution which is given by the nature of the problem, finding the minimum communication requirements to coordinate the actions of some other parts according to an empirical distribution can be posed as a network information theory problem. Two different notions of information theoretic coordination are studied in the literature: empirical and strong. This thesis deals with empirical coordination. In the standard empirical coordination framework, a mathematical criterion should be satisfied with perfect precision. This requirement can be restrictive in practice. A possible extension of the framework of empirical coordination is proposed in this thesis by introducing in the coordination requirement a fidelity parameter. Within the new framework, some new problems are stated and solved which can be useful in real applications. For example, they can be handled situations where the capacity of the network is not enough for the establishment of standard empirical coordination but is enough for the establishment of a weaker type of coordination; or situations where the quality of the coordination can vary according to the good or bad condition of the network (which is not known at the encoder). Two different classes of problems of empirical coordination subject to fidelity criteria are studied: empirical coordination of multi-agent systems, and interference coordination over noisy channels. In the first class, the nodes of a multi-agent system establish coordinated behavior by using the rate-limited communication links that are available between them. In the second class, two nodes control the interference created to an external observer while communicating over a noisy channel. For both classes of problems, the capacity region of two different setups is derived (fully or partially). Furthermore, the mathematical properties that the chosen fidelity metric should satisfy are discussed. One of the main conclusions of the thesis is that there is a connection between the proposed framework and the framework of empirical coordination. Specifically, it turns out that when we design optimal coding schemes that achieve empirical coordination according to an empirical distribution and subject to the fidelity criteria, it is necessary and sufficient (at least in some simple setups) to consider all coding schemes that achieve standard empirical coordination according to some empirical distribution, from a class of empirical distributions which is close enough to the desired empirical distribution. This observation allows us to separate the proofs of the proposed framework into two discrete steps: first, we derive the capacity region for the standard framework and, then, we apply an appropriate transformation to this capacity region to get the rate-distortion region for the framework of empirical coordination subject to fidelity criteria. Kommunikation är en av de viktigaste och mest kostsamma resurserna i ett nätverk där olika delar önskar koordinera sitt beteende. När beteendet i vissa delar av nätverket är fördelade enligt en viss sannolikhetsfördelning, som är givet av problemets natur, så är går det att hitta en lösning till det statistiska koordinationsproblemet som minimerar kommunikationskostnaden. Detta problem, vars lösning ska följa en given empirisk sannolikhetsfördelning, kan ställas upp som ett nätverksinformationsteoretiskt problem. I litteraturen studeras två typer av statistisk koordination: empirisk och stark. Denna avhandling undersöker empirisk statistisk koordinering. I det traditionella empiriska ramverket ska ett matematiskt kriterium uppfyllas med perfekt precision. Detta krav kan i praktiken vara restriktivt. En möjlig utvidgning av ramverket för empirisk statistisk koordinering föreslås i denna avhandling, nämligen en fidelitetsparameter i det statistiska koordinationskravet. Introduktionen av en fidelitetsparameter tillåter både formulering och lösning av nya problem, vilka kan vara användbara i praktiska tillämpningar. Exempel på situationer som kan hanteras av den nya problemformuleringen är dels situationer där nätverkskapaciteten inte räcker till för traditionell empirisk statistisk koordination, men där en lösning kan ges av ett svagare statistiskt koordinationskriterium, dels situationer där kvaliteten på koordineringen kan variera med god eller dålig nätverkskvalitet, vilket inte är känt hos avsändaren. Två olika klasser av empiriska statistiska koordinationsproblem, båda föremål för fidelitetskriterier, studeras: empirisk statistisk koordination för multiagentsystem, samt kommunikations- och interferenskoordination över brusiga kanaler. I den första klassen koordinerar noder i ett multiagentsystem sitt beteende genom att använda de bandbegränsade kommunikationskanaler som finns tillgängliga. I den andra klassen kontrollerar två noder den interferens som en extern observatör upplever under tiden noderna kommunicerar över en brusig kanal. I båda klasserna härleds kapacitetsregionen för två olika problem, antingen fullt eller delvis. Dessutom diskuteras de matematiska egenskaper som de valda fidelitetskriterierna bör uppfylla. En av avhandlingens huvudsakliga slutsatser är att det finns en koppling mellan de föreslagna ramverken och ramverket för empirisk statistisk koordination. Det visar sig att för att designa koder som når empirisk statistisk koordination enligt någon empirisk sannolikhetsfördelning under fidelitetskriterier, är det optimalt, åtminstone i några enkla situationer, att undersöka koder som når traditionell empirisk statistisk koordination givet en godtycklig empirisk sannolikhetsfördelning från en klass av empiriska fördelningar som i någon mening är nära nog den sanna empiriska fördelningen. Denna observation förenklar lösningen till det empiriska statistiska koordinationsproblemet under fidelitetskriterier: lösningen ges genom att tillämpa en lämplig transformation på lösningen till det traditionella ramverket. QC 20230303

The care for patients infected with COVID-19 requires a team approach, and dermatologists may collaborate with other specialties, especially infectious disease (ID) medicine and obstetrics and gynecology (ObGyn), at every stage of the infection process. A broad spectrum of cutaneous manifestations may occur early in COVID-19 infection, making appropriate dermatologic identification critical for an early diagnosis. There is prognostic value in appropriately identifying different types of COVID-19-associated skin manifestations, which have been linked to disease severity. Such observations emanated from dermatology research, especially large series and international registries of cutaneous manifestations relating to COVID-19, and impact COVID-19 care provided by most health care providers. Also, research based on international registries of skin reactions from the COVID-19 vaccines has an impact across disciplines. An increased risk for severe illness from COVID-19 is encountered during pregnancy, and dermatologists' role is to urge ObGyn and other clinicians to monitor and educate pregnant patients about the potential for eruptions as a manifestation of COVID-19. ID and ObGyn experts indicate that teledermatology enhanced the interaction among health care providers and improved COVID-19 care. More than 40% of all dermatology consultations at a tertiary care hospital were done via teledermatology. Future collaborative research involving dermatology and specialties, such as ID and ObGyn, could help delineate guidelines for dermatology consultations in patients infected with COVID-19 and determine cases appropriate for teledermatology.

Pipelines in the offshore sector make common use of polypropylene (and other polymer) coating systems to protect the infrastructure and provide thermal insulation. High pressure high temperature pipelines are subject to large axial loads due to restraint by seafloor soils of thermal strains in the pipe wall. Friction between pipe coating material and seafloor soil plays a defining role in the build-up of axial stress and the formation of lateral buckling. Accurate quantification of pipe–soil interface friction is key to robust pipeline stability design and possibilities to enhance or manipulate the friction coefficient may be attractive to designers. An extensive campaign of soil and interface tests using a range of granular materials and polypropylene surface specimens engineered to achieve varying surface textures was carried out. The results show that interface friction primarily depends on stress level and the magnitude of the surface texture in relation to the particle size. Herein, a new relative texture parameter, Ta, is developed that, unlike alternative relative roughness parameters, can be obtained using conventional profilometry measurement techniques. An expression for estimating the friction coefficient in relation to texture and stress level is proposed that can serve as a useful predictor of pipe–soil interface friction.

(1) Background: Respiratory co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses are common, but data on clinical outcomes and laboratory biomarkers indicative of disease severity are limited. We aimed to compare clinical outcomes and laboratory biomarkers of patients with SARS-CoV-2 alone to those of patients with SARS-CoV-2 and either rhinovirus or adenovirus. (2) Methods: Hospitalized patients co-infected with SARS-CoV-2 and rhinovirus and patients co-infected with SARS-CoV-2 and adenovirus were matched to patients infected with SARS-CoV-2 alone. Outcomes of interest were the cumulative incidences of mechanical ventilation use, intensive care unit (ICU) admission, 30-day all-cause mortality, and 30-day all-cause readmission from the day of discharge. We also assessed differences in laboratory biomarkers from the day of specimen collection. (3) Results: Patients co-infected with SARS-CoV-2 and rhinovirus, compared with patients infected with SARS-CoV-2, had significantly greater 30-day all-cause mortality (8/23 (34.8%) vs. 8/69 (11.6%), p = 0.02). Additionally, median alanine transaminase (13 IU/L vs. 24 IU/L, p = 0.03), aspartate transaminase (25 IU/L vs. 36 IU/L, p = 0.04), and C-reactive protein (34.86 mg/L vs. 94.68 mg/L, p = 0.02) on day of specimen collection were significantly lower in patients co-infected with SARS-CoV-2 and rhinovirus in comparison to patients infected with SARS-CoV-2 alone. Clinical outcomes and laboratory markers did not differ significantly between patients with SARS-CoV-2 and adenovirus co-infection and patients with SARS-CoV-2 mono-infection. (4) Conclusion: SARS-CoV-2 and rhinovirus co-infection, compared with SARS-CoV-2 mono-infection alone, is positively associated with 30-day all-cause mortality among hospitalized patients. However, our lack of significant findings in our analysis of patients with SARS-CoV-2 and adenovirus co-infection may suggest that SARS-CoV-2 co-infections have variable significance, and further study is warranted.

Background Immunocompromised (IC) individuals are at high risk for severe COVID-19, with high morbidity and mortality. CAS+IMD is a monoclonal antibody combination that neutralizes susceptible SARS-CoV-2 variants. We examined the natural history of COVID-19 and the efficacy and safety of CAS+IMD in IC patients (pts) hospitalized with COVID-19. Methods In a phase 1/2/3 double-blind trial (NCT04426695) conducted Jun 2020 to Apr 2021, prior to the emergence of Omicron-lineage variants, hospitalized COVID-19 pts were randomized 1:1:1 to a single 2.4 g or 8.0 g dose (combined for analyses) of CAS+IMD or placebo (P). Post hoc analyses assessed change in viral load (VL), clinical outcomes (death or mechanical ventilation [MV]), and safety for IC pts with B-cell deficiency or dysfunction (Table 1) vs all pts. Results 99/1940 (5.1%) treated pts were identified as IC (Table 2). At baseline, IC vs all pts were more likely to be seronegative for SARS-CoV-2 antibodies (68.7% vs 41.2%), and to have higher median VLs (7.21 vs 6.32 log10 copies/mL). Compared to all pts receiving P, IC pts receiving P had slower VL declines. Treatment with CAS+IMD led to a reduction in VL from baseline, with a least-squares mean time-weighted average change in VL difference vs P at Day 7 for IC pts of -0.69 (95% CI: -1.25, -0.41) vs -0.31 (CI: -0.42, -0.20) for all pts; treatment benefit persisted through Day 29 (Fig. 1). Although sample size was small for IC pts, trends in clinical outcomes of death or MV at Day 29 for IC pts (7/64 [11.0%] CAS+IMD vs 6/35 [17.2%] P) were consistent with those in all pts (200/1307 [15.3%] CAS+IMD vs 113/633 [17.9%] P). IC vs all pts treated with CAS+IMD exhibited similar rates of treatment emergent adverse events (TEAEs, 30.4% vs 26.6%), AEs of special interest (grade ≥2 hypersensitivity or infusion-related reactions; 1.4% vs 2.5%), and death (8.7% vs 12.2%; Table 3). IC and all pts exhibited fewer TEAEs with CAS+IMD vs P. Conclusion IC vs all pts hospitalized with COVID-19 were more likely to exhibit high VLs at baseline and to be seronegative. In the study, a single dose of CAS+IMD significantly reduced VL in IC pts (for variants circulating at the time, predominantly Alpha) and resulted in fewer events of death or MV. There were no new safety findings in IC pts vs all study pts. Disclosures Selin Somersan-Karakaya, PhD, BARDA: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Eleftherios Mylonakis, MD, PhD, Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH/NIAID, NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support|SciClone Pharmaceuticals: Grant/Research Support Ernesto Oviedo-Orta, MD, PhD, MBA, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Meagan P. O’Brien, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Veronica Mas Casullo, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Jenni Mou, PhD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Jing Xiao, PhD, Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Rafia Bhore, PhD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Adnan Mahmood, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Andrea T. Hooper, PhD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Mohamed Hussein, PhD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Shazia Ali, PharmD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Eduardo Forleo-Neto, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Gary A. Herman, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds Boaz Hirshberg, MD, MBA, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds David M. Weinreich, MD, Regeneron Pharmaceuticals, Inc.: Employement|Regeneron Pharmaceuticals, Inc.: Stocks/Bonds.

Objectives To assess the impact of aspiration on cytologic quality of fine-needle specimens obtained from lymph nodes of dogs and to compare the level of agreement of the cytologic diagnosis between the two sampling techniques. Materials and methods Fifty-three client-owned dogs were prospectively enrolled. Client-owned dogs were prospectively enrolled in the study if cytologic examination of lymph nodes was indicated in the course of their clinical diagnostic work-up. In each dog, two superficial, palpably accessible lymph nodes were sampled: one by fine-needle aspiration and the other by fine-needle non-aspiration, using a 21-Gauge needle with or without a 5-mL syringe. Cytologic quality was assessed in duplicate smears assessed by two observers who rated cellularity, blood contamination, thickness, cell preservation and cytoplasmic fragmentation using a predefined scoring system. Results Fifty-three client-owned dogs were included in the study. No significant difference was found in rating scores between the two sampling techniques for any of the cytologic quality parameters assessed. Cohen's kappa coefficient was 0.84 (95% confidence interval 0.68-1.00), indicating diagnostic agreement between the sampling techniques. Clinical significance In this study, both fine-needle aspiration and fine-needle non-aspiration techniques yielded lymph node specimens of comparable cytologic quality and with acceptable agreement in cytologic diagnosis.

Background Patients with multiple myeloma are at higher risk for infections due to disease pathogenesis and administered therapies. The purpose of this study was to estimate the risk for any grade and severe infections associated with the use of anti-CD38 monoclonal antibodies in patients with multiple myeloma. Methods We searched PubMed and EMBASE for randomized controlled trials (RCTs) that included patients with multiple myeloma who received CD38-targeting monoclonal antibody regimens and reported outcomes of infection and performed a random-effects meta-analysis to estimate the relative risk for infections. Results After screening 673 citations, we retrieved 17 studies providing data on 11 RCTs. Overall, the included reports evaluated 5316 patients (2797 in the intervention arm and 2519 in the control arm). The relative risk (RR) for both any grade or severe infections was 1.27 (95% CI, 1.17–1.37 and 1.14–1.41, respectively). The cumulative incidence of any grade infections for patients who received anti-CD38 agents was 77% (95% CI, 68%–86%), while for severe infections it was 28% (95% CI, 23%–34%). Patients treated with anti-CD38 agents had a 39% higher risk for any grade pneumonia (RR, 1.39; 95% CI, 1.12–1.72) and a 38% higher risk for severe pneumonia (RR, 1.38; 95% CI, 1.09–1.75). For upper respiratory tract infections, the relative risk was 1.51 and 1.71 for any grade and severe infections, respectively. Regarding varicella-zoster virus (VZV) reactivation, we found no evidence of increased risk (RR, 3.86; 95% CI, 0.66–22.50). Conclusions Patients with multiple myeloma treated with regimens that included an anti-CD38 monoclonal antibody were at higher risk for any grade or severe infections without an associated higher mortality rate during the follow-up period of the retrieved studies. No evidence of increased risk for VZV reactivation was noted, but there was a significant association between CD38-targeting treatment and pneumonia risk. Increased surveillance for infections, development of effective prophylactic strategies, and studies with long follow-up are needed for patients with multiple myeloma treated with anti-CD38-based regimens.

The clinical benefit of CAS+IMD in hospitalized seronegative patients with COVID-19 has previously been demonstrated, although these studies observed no clinical benefit in seropositive patients. As the prevalence of SARS-CoV-2-seropositive individuals rises due to both vaccination and previous infection, it is important to understand whether there is a subset of hospitalized patients with COVID-19 with antibodies against SARS-CoV-2 who could benefit from anti-SARS-CoV-2 monoclonal antibody treatment.

Background: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of opportunistic infections (OIs) in patients with PsA who were treated with these agents.Methods: We searched PubMed and EMBASE through 14 April 2022 for randomized clinical trials evaluating bDMARD or tsDMARD in the treatment of PsA. Trials were eligible if they compared the effect of a bDMARD or tsDMARD with placebo and provided safety data. We used the Revised Cochrane risk-of-bias tool to assess the risk of bias among trials, and stratified the studies by mechanism of action (MOA) of the agents studied.Results: We included 47 studies in this analysis. A total of 17,197 patients received at least one dose of an agent of interest. The cumulative incidence of OIs by MOA was as follows: 1) JAK inhibitors: 2.72% (95% CI: 1.05%–5.04%), 2) anti-IL-17: 1.18% (95% CI: 0.60%–1.9%), 3) anti-IL-23: 0.24% (95% CI: 0.04%–0.54%), and 4) anti-TNFs: 0.01% (95% CI: 0.00%–0.21%). Based on their MOA, these agents are known to increase the risk of certain serious infections. The cumulative incidence of herpes zoster infection following treatment with JAK inhibitors (JAKi) was 2.53% (95% CI: 1.03%–4.57%) and the cumulative incidence of opportunistic Candida spp. infections following treatment with anti-IL-17, was 0.97% (95% CI: 0.51%–1.56%).Conclusion: The overall incidence of OIs among patients with PsA who were treated with biologic and targeted synthetic agents is low. However, careful monitoring is warranted for specific OIs such as herpes zoster infection following JAKi treatment, mucocutaneous candidiasis following anti-IL-17 treatment, and Mycobacterium tuberculosis infection following anti-TNF treatment.

BackgroundLevels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.ObjectiveTo evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.DesignCross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.Setting114 centers in 10 countries.ParticipantsAdults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.MeasurementsBaseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively.ResultsPlasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity.LimitationsPlasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available.ConclusionElevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.Primary funding sourceU.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Background: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections.Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies.Methods: We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections.Results: Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%.Conclusion: Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies.Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number]

This paper discusses the main results of a full-scale shaking table test campaign carried out under the auspices of the EU funded research project SERA, whose objective is to investigate the seismic performance of three-leaf masonry walls with weak lime-mortar joints. These masonry walls are widely found in seismic prone regions in the Mediterranean area, thus assessing their behaviour under dynamic actions is an important pre-requisite for the seismic vulnerability evaluation of a plethora of historical centres. The first part of the paper presents a preliminary study on the mechanical properties of the wall component materials that was carried out through an ad-hoc experimental campaign. The outcomes are of particular interest for the characterization of the mortar and of the infill materials, that were designed to reproduce the low strength that is typically found in old masonry buildings. The design of the masonry wall that was tested and the test set-up are presented next. The applied loading protocol consisted of the horizontal component of a ground motion record that is repeatedly applied to the shaking table with increasing intensity. Finally, the main results of the experimental test are discussed. The damage patterns, drift ratios and base shear are presented for the ground motion sequence. The results are also discussed through a dynamic capacity curve that shows the attainment of different limit states with increasing ground motion intensity. A set of nonlinear numerical simulations, both static and dynamic, using a 3D FE model of the wall verify the experimental study as they report good agreement with the experimental tests and exhibit stable numerical behaviour.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR

BackgroundEnsovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.ObjectiveTo investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.DesignDouble-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).SettingMultinational, multicenter trial.ParticipantsAdults hospitalized with COVID-19.InterventionIntravenous ensovibep, 600 mg, or placebo.MeasurementsEnsovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.ResultsAn independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n=247) or placebo (n=238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P=0.68; OR>1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR>1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR&nbsp