Mild Restriction Research Articles

Some new concepts related to fuzzy fractional calculus for up and down convex fuzzy-number valued functions and inequalities

The theory of convex mapping has a lot of applications in the field of applied mathematics and engineering. The fuzzy Riemann-Liouville fractional integrals are the most significant operator of fractional theory which permits to generalize the classical theory of integrals. This study considers the well-known Hermite-Hadamard type and associated inequalities. To full fill this mileage, some new versions of fuzzy Hermite-Hadamard type and Hermite-Hadamard-Fejér type inequalities for up and down convex fuzzy-number valued mappings have been obtained. Some new related fuzzy Hermite-Hadamard type inequalities are also obtained with the help of product of two up and down convex fuzzy-number valued mappings. Moreover, we have introduced some new important classes of fuzzy numbered valued convexity which are known as lower up and down convex (concave) and, upper up and down convex (concave) fuzzy numbered valued mappings by applying some mild restrictions on up and down convex (concave) fuzzy numbered valued mappings. By using these definitions, we have acquired many classical and new exceptional cases which can be viewed as applications of the main results. We also present three examples of fuzzy numbered valued convexity to demonstrate the validity of the fuzzy inclusion relations proposed in this paper.

On the BBM-Phenomenon in Fractional Poincaré–Sobolev Inequalities with Weights

Abstract In this paper, we unify and improve some of the results of Bourgain, Brezis, and Mironescu and the weighted Poincaré–Sobolev estimate by Fabes, Kenig, and Serapioni. More precisely, we get weighted counterparts of the Poincaré–Sobolev-type inequality and also of the Hardy type inequality in the fractional case under some mild natural restrictions. A main feature of the results we obtain is the fact that we keep track of the behavior of the constants involved when the fractional parameter approaches to $1$. Our main method is based on techniques coming from harmonic analysis related to the self-improving property of generalized Poincaré inequalities.

Unconditional error analysis of a linearized BDF2 virtual element method for nonlinear Ginzburg–Landau equation with variable time step

We consider a virtual element method in space for the nonlinear Ginzburg–Landau equation, while a linearized time-variable-step second order backward differentiation formula (BDF2) is adopted in time. The error splitting approach is used to prove the unconditional optimal error estimate of the derived scheme under the mild restriction on the ratio of adjacent time-steps ratios (similarly proposed in Liao and Zhang 2021, Zhang and Zhao 2021). By using the techniques of the discrete complementary convolution (DOC) kernels and the discrete complementary convolution (DCC) kernels, we obtain the boundedness and error estimates of the solution of time-discrete system. Moreover, the optimal convergence in L2-norm for the fully discrete scheme is finally derived. Numerical examples on a set of polygonal meshes are given to validate our theoretical results.

Pulmonary function tests in people with metabolic syndrome

Background: Metabolic syndrome is a cluster of cardio- metabolic risk factors characterized by abdominal obesity, insulin resistance, and chronic systemic inflammation. Objectives: i)To assess pulmonary function in people with metabolic syndrome ii)To assess whether each component of metabolic syndrome affects pulmonary function indices. Methodology: After a detailed history and physical examination, subjects underwent investigations like fasting lipid profile, fasting blood sugars, electrocardiogram, chest x-ray, pulmonary function tests, 2D echocardiography. Results:In both groups majority had normal pulmonary function tests.In metabolic syndrome group, most common abnormal PFT reported was mild restriction.The pattern of pulmonary function tests is mild restriction in metabolic syndrome subjects.In the overall study group, hypertension, fasting glucose, body mass index, waist circumference have significant negative correlation with both FEv1 and FVC and triglycerides have significant negative correlation with FVC whereas total cholesterol has significant negative correlation with FEV1.Only HDL-c has strong positive correlation with FVC .Conclusion: The findings in this study highlight the notion that FVC and FEV1 are inversely associated with the accumulation of metabolic syndrome components and also independently associated with each component of metabolic syndrome.

COVID-19-Associated Rhino-Mucormycosis and Pulmonary Aspergillosis Infection

In the current pandemic, the incidence of fungal infections-associated COVID-19 is surging. Diabetes mellitus, overzealous steroid, and antibiotic use for COVID-19 management may cause or exacerbate the fungal disease. In paranasal sinus (PNS), ethmoids followed by the maxillary sinus are commonly involved with the risk of intra-orbital or/and intracranial involvement is quite common. In lungs, COVID-19 infection has higher mortality rate, if there is an associated fungal infection. Aspergillus fumigates is the most common fungus that cause lung infection and present as discrete lesion different from COVID-19 manifestation. Two cases of COVID-associated fungal infections, i.e., rhino-mucormycosis and pulmonary aspergillosis are described here. In the first case, computed tomography (CT) of PNS was done for the complaints of mild right-sided facial swelling and mild restriction of the eye globe on day 27 of illness. CT showed hyperdense content involving the right-sided nasal sinus with the remodeling of bones with erosion and thinning of the inferior and medial orbital wall with the extension of soft tissue into the extraorbital space. The patient was treated with Amphotericin B and posaconazole oral suspension as the first-line antifungal monotherapy. In the second case, on complaints of cough with expectoration on the 20th day of illness, X-ray chest and CT chest were done which confirmed a thick-walled cavity in the right lung and other post COVID features. The tracheal aspirate culture was suggestive of Aspergillus fumigatus and Aspergillus antigen galactomannan was found positive in the fluid. The patient was treated for the same with antifungal therapy. Hence it is important to pay attention to the high probability of fungal infections in COVID-19 patients. The association of coronavirus with mucormycosis of the PNSs and aspergillosis of the lung must be given outmost consideration. Noncontrast CT of the PNSs is usually the first investigation of choice for PNS involvement, and CT chest help in the diagnosis of pulmonary fungal infection. Uncontrolled diabetes and use of steroids are two of the main factors for aggravating factors. Both early surgical intervention and anti-fungal treatment should be sought for the management.

Quantum regression theorem for multi-time correlators: A detailed analysis in the Heisenberg picture

The quantum regression theorem is one of the central results in open quantum systems and is extensively used for computing multi-point correlation functions. Traditionally it is derived for two-time correlators in the Markovian limit employing the Schr\"odinger picture. In this paper we make use of the Heisenberg picture to derive the quantum regression theorems for multi-time correlation functions, which in the special limit reduce to the well-known two-time regression theorem. For the multi-time correlation function we find that the regression theorem takes the same form as it takes for the two-time correlation function with a mild restriction that one of the times should be greater than all other time variables. Interestingly, the Heisenberg picture also allows us to derive an analog of regression theorem for out-of-time-ordered correlators. We further extend our study for the case of non-Markovian dynamics and report the modifications to the standard quantum regression theorem. We illustrate all of the above results using the paradigmatic dissipative spin-boson model.

Differences in body composition and growth persist postnatally in fetuses diagnosed with severe compared to mild fetal growth restriction.

Fetal growth restriction (FGR) is most commonly diagnosed in pregnancy if the estimated fetal weight (EFW) is < 10th%. Those with abnormal Doppler velocimetry, indicating placental insufficiency and pathological FGR, demonstrate reduced fat and lean mass compared to both normally growing fetuses and FGR fetuses with normal Dopplers. The aim of this study was to determine how severity of FGR and abnormal Doppler velocimetry impacts neonatal body composition. Among a cohort of fetuses with an EFW < 10th%, we hypothesized that those with abnormal Dopplers and/or EFW < 3rd% would have persistent reductions in lean body mass and fat mass extending into the neonatal period compared to fetuses not meeting those criteria. A prospective cohort of FGR fetuses with an estimated fetal weight (EFW) < 10th% was categorized as severe (EFW < 3rd% and/or abnormal Dopplers; FGR-S) versus mild (EFW 3-10th%; FGR-M). Air Displacement Plethysmography and anthropometrics were performed at birth and/or within the first 6-8 weeks of life. FGR-S versus FGR-M were born one week earlier (P = 0.0024), were shorter (P = 0.0033), lighter (P = 0.0001) with smaller weight-for-age Z-scores (P = 0.0004), had smaller head circumference (P = 0.0004) and lower fat mass (P = 0.01) at birth. At approximately 6-8 weeks postmenstrual age, weight, head circumference, and fat mass were similar but FGR-S neonates were shorter (P = 0.0049) with lower lean mass (P = 0.0258). Doppler velocimetry abnormalities in fetuses with an EFW < 10th% identified neonates who were smaller at birth and demonstrated catch-up growth by 6-8 weeks of life that favored fat mass accretion over lean mass and linear growth.

Some New Estimates on Coordinates of Generalized Convex Interval-Valued Functions

The theory of convex and nonconvex mapping has a lot of applications in the field of applied mathematics and engineering. The Riemann integrals are the most significant operator of interval theory, which permits the generalization of the classical theory of integrals. This study considers the well-known coordinated interval-valued Hermite–Hadamard-type and associated inequalities. To full fill this mileage, we use the introduced coordinated interval left and right preinvexity (LR-preinvexity) and Riemann integrals for further extension. Moreover, we have introduced some new important classes of interval-valued coordinated LR-preinvexity (preincavity), which are known as lower coordinated preinvex (preincave) and upper preinvex (preincave) interval-valued mappings, by applying some mild restrictions on coordinated preinvex (preincave) interval-valued mappings. By using these definitions, we have acquired many classical and new exceptional cases that can be viewed as applications of the main results. We also present some examples of interval-valued coordinated LR-preinvexity to demonstrate the validity of the inclusion relations proposed in this paper.

Root components for tensor product of affine Kac-Moody Lie algebra modules

Let g \mathfrak {g} be an affine Kac-Moody Lie algebra and let λ , μ \lambda , \mu be two dominant integral weights for g \mathfrak {g} . We prove that under some mild restriction, for any positive root β \beta , V ( λ ) ⊗ V ( μ ) V(\lambda )\otimes V(\mu ) contains V ( λ + μ − β ) V(\lambda +\mu -\beta ) as a component, where V ( λ ) V(\lambda ) denotes the integrable highest weight (irreducible) g \mathfrak {g} -module with highest weight λ \lambda . This extends the corresponding result by Kumar from the case of finite dimensional semisimple Lie algebras to the affine Kac-Moody Lie algebras. One crucial ingredient in the proof is the action of Virasoro algebra via the Goddard-Kent-Olive construction on the tensor product V ( λ ) ⊗ V ( μ ) V(\lambda )\otimes V(\mu ) . Then, we prove the corresponding geometric results including the higher cohomology vanishing on the G \mathcal {G} -Schubert varieties in the product partial flag variety G / P × G / P \mathcal {G}/\mathcal {P}\times \mathcal {G}/\mathcal {P} with coefficients in certain sheaves coming from the ideal sheaves of G \mathcal {G} -sub-Schubert varieties. This allows us to prove the surjectivity of the Gaussian map.

Genome-wide characterization of Salmonella Typhimurium genes required for the fitness under iron restriction

BackgroundIron is a crucial element for bacterial survival and virulence. During Salmonella infection, the host utilizes a variety of mechanisms to starve the pathogen from iron. However, Salmonella activates distinctive defense mechanisms to acquire iron and survive in iron-restricted host environments. Yet, the comprehensive set of the conditionally essential genes that underpin Salmonella survival under iron-restricted niches has not been fully explored.ResultsHere, we employed transposon sequencing (Tn-seq) method for high-resolution elucidation of the genes in Salmonella Typhimurium (S. Typhimurium) 14028S strain required for the growth under the in vitro conditions with four different levels of iron restriction achieved by iron chelator 2,2′-dipyridyl (Dip): mild (100 and 150 μM), moderate (250 μM) and severe iron restriction (400 μM). We found that the fitness of the mutants reduced significantly for 28 genes, suggesting the importance of these genes for the growth under iron restriction. These genes include sufABCDSE, iron transport fepD, siderophore tonB, sigma factor E ropE, phosphate transport pstAB, and zinc exporter zntA. The siderophore gene tonB was required in mild and moderate iron-restricted conditions, but it became dispensable in severe iron-restricted conditions. Remarkably, rpoE was required in moderate and severe iron restrictions, leading to complete attenuation of the mutant under these conditions. We also identified 30 genes for which the deletion of the genes resulted in increased fitness under iron-restricted conditions.ConclusionsThe findings broaden our knowledge of how S. Typhimurium survives in iron-deficient environments, which could be utilized for the development of new therapeutic strategies targeting the pathways vital for iron metabolism, trafficking, and scavenging.

Sublinear Convergence of a Tamed Stochastic Gradient Descent Method in Hilbert Space

In this paper, we introduce the tamed stochastic gradient descent method (TSGD) for optimization problems. Inspired by the tamed Euler scheme, which is a commonly used method within the context of stochastic differential equations, TSGD is an explicit scheme that exhibits stability properties similar to those of implicit schemes. As its computational cost is essentially equivalent to that of the well-known stochastic gradient descent method (SGD), it constitutes a very competitive alternative to such methods. We rigorously prove (optimal) sub-linear convergence of the scheme for strongly convex objective functions on an abstract Hilbert space. The analysis only requires very mild step size restrictions, which illustrates the good stability properties. The analysis is based on a priori estimates more frequently encountered in a time integration context than in optimization, and this alternative approach provides a different perspective also on the convergence of SGD. Finally, we demonstrate the usability of the scheme on a problem arising in a context of supervised learning.

Direct serendipity and mixed finite elements on convex polygons

We construct new families of direct serendipity and direct mixed finite elements on general planar, strictly convex polygons that are H1 and H(div) conforming, respectively, and possess optimal order of accuracy for any order. They have a minimal number of degrees of freedom subject to the conformity and accuracy constraints. The name arises because the shape functions are defined directly on the physical elements, i.e., without using a mapping from a reference element. The finite element shape functions are defined to be the full spaces of scalar or vector polynomials plus a space of supplemental functions. The direct serendipity elements are the precursors of the direct mixed elements in a de Rham complex. The convergence properties of the finite elements are shown under a regularity assumption on the shapes of the polygons in the mesh, as well as some mild restrictions on the choices one can make in the construction of the supplemental functions. Numerical experiments on various meshes exhibit the performance of these new families of finite elements.

Study of Multiple Target Defense Differential Games Using Receding Horizon-Based Switching Strategies

In this article, we study a variation of the active target-attacker-defender (ATAD) differential game involving multiple targets, an attacker, and a defender. Our model allows for 1) a capability of the defender to switch roles from <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rescuer</i> (rendezvous with all the targets) to <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">interceptor</i> (intercepts the attacker) and vice versa and 2) the attacker to continuously pursue the closest target (which can change during the course of the game). We assume that the mode of the defender (rescue or interception) defines the mode of the game itself. Using the framework of Games of a Degree, we first analyze the game within each mode. More specifically, the objectives of the players are taken as a combination of weighted Euclidean distances and penalties on their control efforts. We model the interaction of the players within each mode as a linear quadratic differential game (LQDG) and obtain the open-loop Nash equilibrium strategies. We then use the receding horizon approach to enable switching between the modes to obtain switching strategies for the players. By partitioning the matrices associated with the Riccati differential equations we obtain geometric characterization of the trajectories of the players. Furthermore, under mild restrictions on the problem parameters and for a particular choice of the defender’s switching function we show that interception mode is invariant. We illustrate our results with numerical simulations. Experimental results involving multiple autonomous differential drive mobile robots are presented.

Self-Reported Emotional Health and Social Support but not Executive Function Predict Participation After Mild Stroke

Abstract Date Presented 03/31/2022 Stroke rehabilitation prioritizes restoring basic self-care functions. Yet, community-dwelling survivors of mild stroke report persistent participation restrictions. This study examined the extent to which executive function, emotional health, and social support contribute to poststroke participation. We discuss how targeted interventions to address emotional health and social support may enable meaningful participation. Primary Author and Speaker: Corinne Ianni Additional Authors and Speakers: Laura Magee, Lisa Connor Contributing Authors: Marjorie Nicholas

Investigating the relationship between interventions, contact patterns, and SARS-CoV-2 transmissibility

BackgroundAfter a rapid upsurge of COVID-19 cases in Italy during the fall of 2020, the government introduced a three-tiered restriction system aimed at increasing physical distancing. The Ministry of Health, after periodic epidemiological risk assessments, assigned a tier to each of the 21 Italian regions and autonomous provinces. It is still unclear to what extent these different sets of measures altered the number of daily interactions and the social mixing patterns. Methods and findingsWe conducted a survey between July 2020 and March 2021 to monitor changes in social contact patterns among individuals in the metropolitan city of Milan, Italy, which was hardly hit by the second wave of the COVID-19 pandemic. The number of daily contacts during periods characterized by different levels of restrictions was analyzed through negative binomial regression models and age-specific contact matrices were estimated under the different tiers of restrictions. By relying on the empirically estimated mixing patterns, we quantified relative changes in SARS-CoV-2 transmission potential associated with the different tiers.As tighter restrictions were implemented during the fall of 2020, a progressive reduction in the mean number of daily contacts recorded by study participants was observed: from 15.9 % under mild restrictions (yellow tier), to 41.8 % under strong restrictions (red tier). Higher restrictions levels were also found to increase the relative contribution of contacts occurring within the household. The SARS-CoV-2 reproduction number was estimated to decrease by 17.1 % (95 %CI: 1.5–30.1), 25.1 % (95 %CI: 13.0–36.0) and 44.7 % (95 %CI: 33.9–53.0) under the yellow, orange, and red tiers, respectively. ConclusionsOur results give an important quantification of the expected contribution of different restriction levels in shaping social contacts and decreasing the transmission potential of SARS-CoV-2. These estimates can find an operational use in anticipating the effect that the implementation of these tiered restriction can have on SARS-CoV-2 reproduction number under an evolving epidemiological situation.

Optimal vaccine roll-out strategies including social distancing for pandemics

SummaryNon-pharmacological interventions (NPIs), principally social distancing, in combination with effective vaccines, aspire to develop a protective immunity shield against pandemics and particularly against the COVID-19 pandemic. In this study, an agent-based network model with small-world topology is employed to find optimal policies against pandemics, including social distancing and vaccination strategies. The agents’ states are characterized by a variation of the SEIR model (susceptible, exposed, infected, recovered). To explore optimal policies, an equation-free method is proposed to solve the inverse problem of calibrating an agent’s infection rate with respect to the vaccination efficacy. The results show that prioritizing the first vaccine dose in combination with mild social restrictions, is sufficient to control the pandemic, with respect to the number of deaths. Moreover, for the same mild number of social contacts, we find an optimal vaccination ratio of 0.85 between older people of ages compared to younger ones.

Overweight Management through Mild Caloric Restriction in Multigenerational Long-Tailed Macaque Breeding Groups.

Caloric restriction (CR) is an effective method to reduce overweight in captive non-human primates (NHPs). CR has been applied to individually- and pair-housed NHPs, but whether applying CR can be effective and safe in group-housed NHPs has not yet been assessed. This study investigates the effect of mild (20%) CR on adult overweight and biochemical parameters, immature growth, veterinary consultations, and reproductive success in multigenerational long-tailed macaque (Macaca fascicularis) breeding groups. Data were derived from anthropometric measurements and blood samples during yearly health checks, complemented with retrospective data on veterinary consultations and reproductive success. Adult body measures decreased after CR, with heavier individuals and females losing more weight compared to leaner individuals and males. CR lowered cholesterol levels in adults but had no overall effect on other biochemical parameters. Yet, biochemical parameters of individuals with high baseline values were reduced more compared to individuals with low baseline values. Immature growth, veterinary consultations and reproductive success were not influenced by CR. Thus, CR targeted the right individuals, i.e., overweight adults, and had no adverse effects on the variables examined in this study. This implies that mild CR can be a valuable overweight management strategy in group-housed NHPs.

0242 Intraindividual Variability in Sleep Duration Blunts Response to Academic Stressors

Abstract Introduction Cross-sectional studies indicate that greater intra-individual variability (IIV) in sleep is correlated with poorer cognitive-emotional outcomes. Yet, the causal direction of these relationships is unclear. Therefore, we conducted an experimental study to compare cognitive and stress outcomes following random assignment to normal sleep, sleep restriction, and irregular/IIV sleep conditions. Methods Ninety college students (mean age=19.16, SD=0.98; 77.78% female) completed an Organic Chemistry virtual lecture during session 1. Then, for the next five days, participants were randomly assigned to the following conditions: normal sleep (8h in bed every night), sleep restriction (6h in bed every night), or IIV sleep (nightly oscillation between 6.5h and 9.5h in bed, with mean of 8h/night). Adherence was confirmed using actigraphy. On the sixth day (session 2), participants took a test on the Organic Chemistry lecture (retention measure) and then completed a new lecture and test (acquisition measure). Participants reported their stress levels across the lectures and tests. Results ANCOVA tests showed that sleep condition did not affect retention (F=0.50, p=.611) or acquisition of Organic Chemistry knowledge (F=1.33, p=.275; adjusted for Grade Point Average). Interestingly, participants in the IIV condition reported lower stress levels throughout session 2 than students in the normal sleep condition, adjusting for baseline stress levels (p=.025). Furthermore, when collapsing across conditions, correlation analyses confirmed that greater IIV in TST predicted lower stress throughout session 2, after adjusting for mean TST and baseline stress level (r=-.33, p=.014). This “blunted” stress response following nightly sleep fluctuations was in contrast to the heightened stress levels that were associated with shorter mean TST (r=-.22, p=.051). Conclusion Brief sleep variability and mild sleep restriction had minimal impact on laboratory measures of STEM knowledge retention and acquisition. However, greater sleep IIV blunted reactivity to academic stressors, which may reflect altered hypothalamic–pituitary–adrenal axis functions and have implications for student metacognition and course persistence. Future research should investigate the chronic effect of maintaining irregular sleep patterns and whether improving regularity of sleep across longer time intervals promotes cognitive and emotional functioning. Support (If Any) American Psychological Association, APAGS, Psi Chi, National Science Foundation (1920730, 1943323)

POS1377 LUNG INVOLVEMENT IN VEXAS SYNDROME

BackgroundVacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently identified disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic findings is lacking.ObjectivesTo describe lung involvement in VEXAS syndrome.MethodsA retrospective cohort study was conducted of all patients identified at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed.ResultsOur cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with polyangiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glucocorticoids (GC) (median duration of treatment was 2.6 years); 21 (96%) received conventional immunosuppressive agents (methotrexate, azathioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5; 3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3; pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died; 3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immunosuppressive regimen.ConclusionPulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecific and characterized predominantly by inflammatory parenchymal involvement.Disclosure of InterestsNone declared

Connecting the Dots: Numerical Randomized Hamiltonian Monte Carlo with State-Dependent Event Rates

Numerical generalized randomized Hamiltonian Monte Carlo is introduced, as a robust, easy to use and computationally fast alternative to conventional Markov chain Monte Carlo methods for continuous target distributions. A wide class of piecewise deterministic Markov processes generalizing Randomized HMC (Bou-Rabee and Sanz-Serna) by allowing for state-dependent event rates is defined. Under very mild restrictions, such processes will have the desired target distribution as an invariant distribution. Second, the numerical implementation of such processes, based on adaptive numerical integration of second order ordinary differential equations (ODEs) is considered. The numerical implementation yields an approximate, yet highly robust algorithm that, unlike conventional Hamiltonian Monte Carlo, enables the exploitation of the complete Hamiltonian trajectories (hence, the title). The proposed algorithm may yield large speedups and improvements in stability relative to relevant benchmarks, while incurring numerical biases that are negligible relative to the overall Monte Carlo errors. Granted access to a high-quality ODE code, the proposed methodology is both easy to implement and use, even for highly challenging and high-dimensional target distributions. Supplementary materials for this article are available online.