On the ISW-cluster cross-correlation in future surveys

We investigate the cosmological information contained in the cross-correlation between the Integrated Sachs-Wolfe (ISW) of the Cosmic Microwave Background (CMB) anisotropy pattern and galaxy clusters from future wide surveys. Future surveys will provide cluster catalogues with a number of objects comparable with galaxy catalogues currently used for the detection of the ISW signal by cross-correlation with the CMB anisotropy pattern. By computing the angular power spectra of clusters and the corresponding cross-correlation with CMB, we perform a signal-to-noise ratio (SNR) analysis for the ISW detection as expected from the eROSITA and the Euclid space missions. We discuss the dependence of the SNR of the ISW-cluster cross-correlation on the specifications of the catalogues and on the reference cosmology. We forecast that the SNRs for ISW-cluster cross-correlation are alightly smaller compared to those which can be obtained from future galaxy surveys but the signal is expected to be detected at high significance, i.e. more than $> 3\,\sigma$. We also forecast the joint constraints on parameters of model extensions of the concordance $\Lambda$CDM cosmology by combining CMB and the ISW-cluster cross-correlation.Comment: 12 pages, 10 figures. Matches version accepted in MNRA

Trastuzumab and Gemcitabine in Pretreated HER2 Overexpressing Metastatic Breast Cancer Patients: Retrospective Analysis of Our Series

Trastuzumab-based regimes improved clinical outcome in women with overexpressing HER2 metastatic breast cancer, mainly due to the availability of different combination therapies, clinically active and well tolerated. In this study we retrospectively evaluated clinical activity and toxicity of trastuzuamb plus gemcitabine regimen in heavily pretreated HER2 positive metastatic breast cancer patients. Although the observed population was heavily pretreated, the evaluated regimen was notably effective in terms of response rate, time to progression and survival, with very mild toxicity. These data suggest that in over expressing HER2 metastatic breast cancer patients, sequential trastuzumab based chemotherapeutic regimens can achieve good response rate with prolonged TTP in responding patients, even after other target therapy such as lapatinib based combinations

Relazioni tra geomorfologia, processi post-deposizionali e visibilità del suolo nella lettura dei dati di prospezione archeologica

This paper takes into examination two different districts of the vast area investigated by the archaeological survey of the hinterland of the Greek colony of Himera: the coastal area between the northern Imera and Roccella rivers and the hilly watershed zone located between the northern Imera, southern Imera and Platani rivers. The study examines the relationship between geomorphology, post-depositional processes and visibility of the ground and their impact on the interpration of data collected during the archaeological survey and, consequently, on the historical reconstruction of the population of the territory from Prehistory to the Middle Ages. Three aspects have been taken into consideration: a)the impact of geomorphology on the recognition of archaeological traces; b) the relationship betwween geomorphology and archaeological finds; c) the role of geomorphological and/or of the human factors in the selection of areas to be settled. It is shown that the geomorphological context assumes a major role in the selection of areas of settlement, while the visibility of the ground and/or the post-depositional processes usually are not determining factors for the discovery of a site, but seem to affect more their legibility and interpretation

An exploratory study on the effectiveness of virtual reality analgesia for children and adolescents with kidney diseases undergoing venipuncture

The current study evaluated the effectiveness of VR analgesia among pediatric and adolescent patients with kidney disease undergoing venipuncture. Patients at an Italian Children’s hospital (N = 82, age range 7–17 years) undergoing venipuncture were randomly assigned to a No VR group (non-medical conversation) vs. a Yes VR group (VR analgesia). After the procedure, patients gave 0–10 Verbal Numeric Pain Scale ratings. Compared with patients in the No VR Group, patients in the Yes VR group reported significantly lower “Pain intensity”(No VR mean = 2.74, SD = 2.76 vs. Yes VR mean = 1.56, SD = 1.83) and the VR group also rated “Pain unpleasantness” significantly lower than the No VR group (No VR mean = 2.41, SD = 0.94 vs. Yes VR mean = 1.17, SD = 1.80). Patients distracted with VR also reported having significantly more fun during the venipuncture procedure. No side effects emerged. In addition to reducing pain intensity, VR has the potential to make venipuncture a more fun and less unpleasant experience for children with CKD, as measured in the present study for the first time. Finally, in exploratory analyses, children aged 7–11 in the VR group reported 55% lower worst pain than control subjects in the same age range, whereas children aged 12 to 17 in the VR group only reported 35% lower worst pain than control subjects. Additional research and development using more immersive VR is recommended.info:eu-repo/semantics/publishedVersio

The microRNA-Processing Enzyme Dicer Is Essential for Thyroid Function

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions

Covid-19 and flattening the curve: a feedback control perspective

Many of the policies that were put into place during the Covid-19 pandemic had a common goal: to flatten the curve of the number of infected people so that its peak remains under a critical threshold. This letter considers the challenge of engineering a strategy that enforces such a goal using control theory. We introduce a simple formulation of the optimal flattening problem, and provide a closed form solution. This is augmented through nonlinear closed loop tracking of the nominal solution, with the aim of ensuring close-to-optimal performance under uncertain conditions. A key contribution of this letter is to provide validation of the method with extensive and realistic simulations in a Covid-19 scenario, with particular focus on the case of Codogno - a small city in Northern Italy that has been among the most harshly hit by the pandemic

Hemodynamic depression after carotid surgery: Incidence, risk factors and outcomes

Introduction: Hemodynamic Depression (HD) characterized by hypotension and bradycardia is a complication of carotid surgery due to direct autonomic stimulation in the carotid sinus. The authors believe the incidence of HD is high and possibly related to major cardiac complications. Methods: Analysis of patient records during admissions for carotid surgery between January 2014 and December 2018 in two hospitals. HD was defined as bradycardia or hypotension in the first 24 postoperative hours. Bradycardia was defined as heart rate < 50bpm; hypotension as systolic blood pressure < 90 mmHg, continuous use of vasopressors, or a drop in SBP > 20% compared to preoperative values. Myocardial infarction, stroke, and cardiovascular death were defined as adverse events. Results: Overall, 237 carotid surgeries (178 endarterectomies, 59 angioplasties) were studied, and the global incidence of HD was 54.4% (hypotension in 50.2%, bradycardia in 11.0%, and hypotension and bradycardia in 6.8%). The independent predictors of HD were asymptomatic carotid stenosis (OR = 1.824; 95% CI 1.014–3.280; p = 0.045), endovascular surgery (OR = 3.319; 95% CI 1.675–6.576; p = 0.001) and intraoperative hypotension or bradycardia (OR = 2.144; 95% CI 1.222–3.762; p = 0.008). Hypotension requiring continuous vasopressor infusion was the only factor independently associated with adverse cardiovascular events (OR = 5.504; 95% CI 1.729–17.529; p = 0.004). Discussion/conclusion: Incidence of Hemodynamic Depression after carotid surgery is high and independently associated with surgical technique, symptomatic repercussion of the carotid stenosis, and intraoperative hypotension or bradycardia. Hypotension requiring the continuous infusion of vasopressors was independently associated with the occurrence of MACE

Bayesian mixture models for phylogenetic source attribution from consensus sequences and time since infection estimates

In stopping the spread of infectious diseases, pathogen genomic data can be used to reconstruct transmission events and characterize population-level sources of infection. Most approaches for identifying transmission pairs do not account for the time that passed since divergence of pathogen variants in individuals, which is problematic in viruses with high within-host evolutionary rates. This is prompting us to consider possible transmission pairs in terms of phylogenetic data and additional estimates of time since infection derived from clinical biomarkers. We develop Bayesian mixture models with an evolutionary clock as signal component and additional mixed effects or covariate random functions describing the mixing weights to classify potential pairs into likely and unlikely transmission pairs. We demonstrate that although sources cannot be identified at the individual level with certainty, even with the additional data on time elapsed, inferences into the population-level sources of transmission are possible, and more accurate than using only phylogenetic data without time since infection estimates. We apply the approach to estimate age-specific sources of HIV infection in Amsterdam MSM transmission networks between 2010-2021. This study demonstrates that infection time estimates provide informative data to characterize transmission sources, and shows how phylogenetic source attribution can then be done with multi-dimensional mixture models

Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD

Estimativa de repetibilidade para caracteres de qualidade de frutos de laranjeira‑doce

The objective of this work was to determine the repeatability coefficient of fruit quality characteristics of sweet orange (Citrus sinensis) and the minimum number of evaluations that can provide levels of prediction certainty of the true genotype value. Thirty nine genotypes of sweet orange, collected in nine municipalities of the state of Acre, Brazil, were evaluated in five crop cycles. A randomized complete block design was used, with three replicates. The following were evaluated: average fruit weight, juice yield, peel thickness, soluble solids (SS), total acidity (TA), SS/TA ratio, and technological index. To estimate the repeatability coefficients, the methods of analysis of variance, principal component analysis, and structural analysis were used. All evaluated characters showed variability, except for juice yield. The evaluated characters showed a cyclic pattern, which was best captured by the multivariate methodologies for estimating the repeatability coefficient. Fifteen evaluations are needed to determine, with 90% certainty, the characters peel thickness and soluble solids, and 11, 6, 3, 2, and 1 evaluations, respectively for average fruit weight, total acidity, technological index, juice yield, and SS/TA ratio, respectively.O objetivo deste trabalho foi determinar o coeficiente de repetibilidade de características de qualidade do fruto de laranjeira‑doce (Citrus sinensis) e o número mínimo de avaliações capaz de proporcionar níveis de certeza da predição do valor real dos genótipos. Foram avaliados, em cinco safras, 39 genótipos de laranjeira‑doce, coletados em nove municípios do Estado do Acre. Utilizou-se o delineamento de blocos ao acaso, com três repetições. Foram avaliados: massa média de frutos, rendimento de suco, espessura de casca, sólidos solúveis (SS), acidez total (AT), relação SS/AT e índice tecnológico. Para a estimativa dos coeficientes de repetibilidade, foram utilizados os métodos da análise de variância, dos componentes principais e da análise estrutural. Todos os caracteres avaliados mostraram variabilidade, exceto o rendimento de suco. Os caracteres avaliados mostraram padrão cíclico, o que foi mais bem captado pelas metodologias multivariadas de estimativa do coeficiente de repetibilidade. São necessárias 15 avaliações para determinar, com 90% de certeza, os caracteres espessura de casca e sólidos solúveis, e 11, 6, 3, 2 e 1 avaliações, respectivamente para massa média de fruto, acidez total, índice tecnológico, rendimento de suco e relação SS/AT