EXPERIMENTAL DETERMINATION OF LAMINAR BURNING VELOCITY OF BIOGAS AT PRESSURES UP TO 5 BAR

This paper presents a very detailed description of a new cylindrical constant volume combustion chamber designed for laminar burning velocity determination of gaseous mixtures at ambient temperature and initial pressure up to 6 bar. The experimental setup, the experimental procedure and the determination of the range of flame radius for laminar burning determination are all described in details. The laminar burning velocity of twelve synthetic biogas mixtures has been studied. Initial pressure varying between 1 and 5 bar, equivalence ratios, f, between 0.7 and 1.1 and percentage dilution, with a mixture of CO2 and N2, between 35 and 55% have been considered. Five experiments were run for each mixture providing a maximum percentage standard deviation of 8.11%. However, for two third of the mixtures this value is lower than 3.55%. A comparison with simulation using PREMIX for both GRI-Mech 3.0 and San Diego mechanisms has provided closer agreement for mixtures with equivalence ratio closer to stoichiometry whereas for f = 0.7 the deviation is larger than 15% for all pressures. Mixtures with lower equivalence ratio, higher dilution percentage and higher initial pressure presents the lower values of laminar burning velocity

A FMEA clinical laboratory case study: how to make problems and improvements measurable

The authors have experimented the application of the Failure Mode and Effect Analysis (FMEA) technique in a clinical laboratory. FMEA technique allows: a) to evaluate and measure the hazards of a process malfunction, b) to decide where to execute improvement actions, and c) to measure the outcome of those actions. A small sample of analytes has been studied: there have been determined the causes of the possible malfunctions of the analytical process, calculating the risk probability index (RPI), with a value between 1 and 1,000. Only for the cases of RPI > 400, improvement actions have been implemented that allowed a reduction of IPR values between 25% to 70% with a costs increment of <1%. FMEA technique can be applied to the processes of a clinical laboratory, even if of small dimensions, and offers a high potential of improvement. Nevertheless, such activity needs a thorough planning because it is complex, even if the laboratory already operates an ISO 9000 Quality Management System

Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline

Molecular analysis of BRCA1 (MIM# 604370) and BRCA2 (MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the OncomineTM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features

Triple positive breast cancer. A distinct subtype?

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets

CLASH-VLT: Testing the Nature of Gravity with Galaxy Cluster Mass Profiles

We use high-precision kinematic and lensing measurements of the total mass profile of the dynamically relaxed galaxy cluster MACS J1206.2-0847 at $z=0.44$ to estimate the value of the ratio $\eta=\Psi/\Phi$ between the two scalar potentials in the linear perturbed Friedmann-Lemaitre-Robertson-Walker metric.[...] Complementary kinematic and lensing mass profiles were derived from exhaustive analyses using the data from the Cluster Lensing And Supernova survey with Hubble (CLASH) and the spectroscopic follow-up with the Very Large Telescope (CLASH-VLT). Whereas the kinematic mass profile tracks only the time-time part of the perturbed metric (i.e. only $\Phi$), the lensing mass profile reflects the contribution of both time-time and space-space components (i.e. the sum $\Phi+\Psi$). We thus express $\eta$ as a function of the mass profiles and perform our analysis over the radial range $0.5\,Mpc\le r\le r_{200}=1.96\,Mpc$. Using a spherical Navarro-Frenk-White mass profile, which well fits the data, we obtain \eta(r_{200})=1.01\,_{-0.28}^{+0.31} at the 68\% C.L. We discuss the effect of assuming different functional forms for mass profiles and of the orbit anisotropy in the kinematic reconstruction. Interpreting this result within the well-studied $f(R)$ modified gravity model, the constraint on $\eta$ translates into an upper bound to the interaction length (inverse of the scalaron mass) smaller than 2 Mpc. This tight constraint on the $f(R)$ interaction range is however substantially relaxed when systematic uncertainties in the analysis are considered. Our analysis highlights the potential of this method to detect deviations from general relativity, while calling for the need of further high-quality data on the total mass distribution of clusters and improved control on systematic effects.Comment: 18 pages, 3 figures, submitted to JCA

Non-invasive diagnostic imaging of colorectal liver metastases

Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver- directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs

Microfluidic tools for enhanced characterization of therapeutic stem cells and prediction of their potential antimicrobial secretome

Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advan-tageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms

PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines

PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR)

Financial Analysis of Dalbavancin for Acute Bacterial Skin and Skin Structure Infections for Self-Pay Patients

© 2020, The Author(s). Introduction: Acute bacterial skin and skin structure infections (ABSSSI) are an increasing cause of admission in the self-pay population. We previously reported that patients with ABSSSI discharged to receive dalbavancin showed a decreased length of stay (LOS) and total direct costs without increasing 30-day readmission rate. For patients who are financially eligible, a dalbavancin vial replacement program can offset costs. The objective of this study was to determine cost differences in treating ABSSSI in self-pay inpatients discharged to receive dalbavancin compared to standard of care (SOC). Methods: This retrospective cohort within a community health system compared self-pay adult inpatients with ABSSSI from February 3, 2016 to August 5, 2019 discharged to receive dalbavancin at an outpatient infusion center with SOC intravenous antibiotics. Patients were included with cellulitis, abscess, or postoperative wound infections diagnoses on the basis of International Classification of Disease, Tenth Revision (ICD-10) codes. Excluded populations were patients without dalbavancin vial replacement performed, pregnant, infections caused exclusively by gram-negative bacteria or fungi, or ICD-10 codes not consistent with ABSSSI. The primary outcome was direct cost of hospital stay. Secondary outcomes included length of stay (LOS), 30-day readmission rates, adverse events (AE), and indirect hospital costs. On the basis of previous studies, a one-sided Student’s t test was performed on financial data. Results: Twelve dalbavancin and 263 SOC patients met inclusion criteria. Direct cost ($2758 vs$4010, p = 0.105) and indirect hospital cost ($2913 vs$3646 , p = 0.162) per patient were less in the dalbavancin group. There was no significant difference between median LOS (4 vs 4, p = 0.888), AE (0% vs 14.8%), and 30-day readmission rates for dalbavancin vs SOC group (8.3% vs 7.2%, p = 0.604). Conclusion: Self-pay patients with ABSSSI discharged to receive dalbavancin with vial replacement resulted in decreased direct and indirect costs per patient with similar 30-day readmission rates, AE, and LOS. More studies targeted toward this population are warranted to determine ultimate benefit