Not All Children with Under-Control Asthma are Controlled

Subclinical lung function alterations can sometimes be discovered in asthmatic patients under clinical control. This study aimed to identify the burden of asthmatic children with subclinical airways abnormalities who may benefit from an adjustment in asthma therapy. 134 6-to-17-year-old asthmatic children were enrolled. Of them, 98 presented apparently under clinical control disease and all performed spirometry before and after bronchodilation: 17 (17.3%) had a positive bronchodilation test, in addition to significantly lower lung function indexes as compared to those with under-control asthma who had a negative bronchodilation test. These patients were randomized and re-evaluated: patients (n=8) receiving an adjustment in their therapy showed an improvement in lung function tests and quality of life indexes as compared to 7 without therapy adjustment. In conclusion, a substantial number of apparently-under-control asthmatic children show airways alterations that can be improved by adjusting their therapy, which also seems to enhance their quality of life

Comparison of blood and milk non-specific immune parameters in heifers after calving in relation to udder health

A practical protocol to study udder immune status in field conditions was planned with the aim to assess different non-specific immune parameters in milk samples from dairy heifers during the periparturient period. Five herds located in northern Italy were selected and overall 39 heifers were enrolled in the trial. Milk samples were taken at 7, 14, 21, 28, 45, 60, and 75 days after calving. The parameters assessed were N-acetyl-\u3b2-glucosaminidase (NAGase), lysozyme, respiratory burst (RB), somatic cell counts (SCC) and serum protein profile. SCC and NAGase were higher in the first sampling after calving, while lysozyme showed large variations during the observation period without a definite trend. The levels of RB observed in the first two weeks after calving, even if lower, were not statistically different from the values observed in samples taken over the following weeks. This study confirmed that the levels of immune components in milk are different from what is observed at blood level in the same cow. A significant decrease in RB in milk polymorphonuclear leukocytes (PMN) post-calving was not observed; milk PMN from healthy cows showed low RB levels, while the values from infected quarters were significantly higher. Significant differences between healthy and infected animals were also observed for milk NAG, lactoglobulin and albumin. These data suggest that udder immune response could be influenced both by the cow immune status and by external factors such as pathogens and management. Therefore, the reduction in immune defences, particularly in heifers, is not unavoidable and methods to boost PMN activity should be explored

In‐Depth Immunological Typization of Children with Sickle Cell Disease: A Preliminary Insight into Its Plausible Correlation with Clinical Course and Hydroxyurea Therapy

Sickle cell disease (SCD) is a condition of functional hypo‐/a‐splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune‐dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in‐depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case–control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi‐squared tests, t‐tests, and Pearson’s correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T‐cell depletion with prevalence of memory T‐cell compartment, NK and B‐naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched‐memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p‐value of <0.05). The mean CD4+ central‐memory T‐cell% count was the single independent variable showing a positive correlation with vaso‐occlusive crisis score in the SCD group (Pearson’s R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU‐related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo‐/a‐splenism immuno‐chemoprophylactic recommendations

Compact relaxations for polynomial programming problems

Reduced RLT constraints are a special class of Reformulation- Linearization Technique (RLT) constraints. They apply to nonconvex (both continuous and mixed-integer) quadratic programming problems subject to systems of linear equality constraints. We present an extension to the general case of polynomial programming problems and discuss the derived convex relaxation. We then show how to perform rRLT constraint generation so as to reduce the number of inequality constraints in the relaxation, thereby making it more compact and faster to solve. We present some computational results validating our approach

Elastic optical interface with variable baudrate: Architecture and proof-of-concept

Varying the symbol rate is an alternative or complementary approach to varying the modulation format or the channel spacing to turn optical networks into elastic networks. We propose to allocate just-enough bandwidth for each optical connection by adjusting the symbol rate such that the penalty originating from long cascades of optical filters is contained. This helps reduce overprovisioning for lightpaths where full capacity is not needed, by (i) eliminating unnecessary regenerators and (ii) reducing the power consumption of terminals, when the clock rate of electronics is reduced along with the baudrate. We propose a novel architecture for an elastic optical interface by combining a variable bitrate transceiver, paired with an elastic aggregation stage, with software-defined control. We then report a real-Time field-programmable-gate-Array-based prototype that delivers flexible transport frames to be sent with a polarization-division multiplexed quadrature phase-shift keying modulation format. We interconnect this prototype with a commercial optical transport network switch and a centralized controller. We demonstrate fast and hitless reconfiguration of the interface and measure the reconfiguration time of hardware logic ( < 450 μs), as well as end-To-end control and the data plane ( < 0.9 s)

Febrile Neutropenia Duration Is Associated with the Severity of Gut Microbiota Dysbiosis in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Febrile neutropenia (FN) is a common complication in pediatric patients receiving al-logeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella, Megasphaera, Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called “healthy” GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications

FGF trapping inhibits multiple myeloma growth through c-Myc degradation-induced mitochondrial oxidative stress

Multiple myeloma (MM), the second most common hematological malignancy, frequently relapses because of chemotherapeutic resistance. Fibroblast growth factors (FGFs) act as pro-angiogenic and mitogenic cytokines in MM. Here, we demonstrate that the autocrine FGF/FGFR axis is essential for MM cell survival and progression by protecting MM cells from oxidative stress-induced apoptosis. In keeping with the hypothesis that the intracellular redox status can be a target for cancer therapy, FGF/FGFR blockade by FGF trapping or tyrosine kinase inhibitor impaired the growth and dissemination of MM cells by inducing mitochondrial oxidative stress, DNA damage and apoptotic cell death that were prevented by the antioxidant vitamin E or mitochondrial catalase overexpression. In addition, mitochondrial oxidative stress occurred as a consequence of proteasomal degradation of the c-Myc oncoprotein that led to glutathione depletion. Accordingly, expression of a proteasome-non-degradable c-Myc protein mutant was sufficient to avoid glutathione depletion and rescue the pro-apoptotic effects due to FGF blockade. These findings were confirmed on Bortezomib-resistant MM cells as well as on bone marrow-derived primary MM cells from newly diagnosed and relapsed/refractory patients, including plasma cells bearing the t(4;14) translocation obtained from high-risk MM patients. Altogether, these findings dissect the mechanism by which the FGF/FGFR system plays a non-redundant role in MM cell survival and disease progression, and indicate that FGF targeting may represent a therapeutic approach for MM patients with poor prognosis and advanced disease stage

Error bounds for monomial convexification in polynomial optimization

Convex hulls of monomials have been widely studied in the literature, and monomial convexifications are implemented in global optimization software for relaxing polynomials. However, there has been no study of the error in the global optimum from such approaches. We give bounds on the worst-case error for convexifying a monomial over subsets of $[0,1]^n$. This implies additive error bounds for relaxing a polynomial optimization problem by convexifying each monomial separately. Our main error bounds depend primarily on the degree of the monomial, making them easy to compute. Since monomial convexification studies depend on the bounds on the associated variables, in the second part, we conduct an error analysis for a multilinear monomial over two different types of box constraints. As part of this analysis, we also derive the convex hull of a multilinear monomial over $[-1,1]^n$.Comment: 33 pages, 2 figures, to appear in journa

Risk of SARS-CoV-2 infection, hospitalization, and death for COVID-19 in people with Parkinson disease or parkinsonism over a 15-month period: A cohort study

Background and purpose: The patterns of long-term risk of SARS-CoV-2 infection, hospitalization for COVID-19, and related death are uncertain in people with Parkinson disease (PD) or parkinsonism (PS). The aim of the study was to quantify these risks compared to a control population cohort, during the period March 2020–May 2021, in Bologna, Northern Italy. Methods: ParkLink Bologna cohort (759 PD, 192 PS) and controls (9226) anonymously matched (ratio&nbsp;=&nbsp;1:10) for sex, age, district, and comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March–May 2020 and October 2020–May 2021). Results: Adjusted hazard ratio of SARS-CoV-2 infection was 1.3 (95% confidence interval [CI] = 1.04–1.7) in PD and 1.9 (95% CI&nbsp;=&nbsp;1.3–2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID-19 was 1.1 (95% CI&nbsp;=&nbsp;0.8–1.7) in PD and 1.8 (95% CI&nbsp;=&nbsp;0.97–3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30-day mortality risk after hospitalization was higher (p&nbsp;= 0.048) in PS (58%) than in PD (19%) and controls (26%). Conclusions: Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS-CoV-2 infection throughout the first 15 months of the pandemic. COVID-19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization