Correlation of test results and influence of a mass balance constraint on risks in conformity assessment of a substance or material

When components of a substance or material are subject to a mass balance constraint, test results of the components’ contents are intrinsically correlated because of the constraint. This so-called ‘spurious’ correlation is observed in addition to possible metrologically-related correlation of test results, and natural and/or technological correlation of the components’ contents. Such correlations may influence understanding of test results and evaluation of risks of false decisions, due to measurement uncertainty, in conformity assessment of the substance or material. The objective of the present paper is the development of a technique for appropriate evaluation of the risks. A Bayesian multivariate approach to evaluate the conformance probability of materials or objects and relevant risks is discussed for different scenarios of the data modelling, taking into account all observed correlations. A Monte Carlo method, including the mass balance constraint, written in the R programming environment, is provided for the necessary calculations

Atrial fibrillation in healthy adolescents after highly caffeinated beverage consumption: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Energy drinks and highly caffeinated drinks comprise some of the fastest growing products of the beverage industry, often targeting teenagers and young adults. Cardiac arrhythmias in children related to high caffeine consumption have not been well described in the literature. This case series describes the possible association between the consumption of highly caffeinated drinks and the subsequent development of atrial fibrillation in the adolescent population.</p> <p>Case presentations</p> <p>We report the cases of two Caucasian adolescent boys of 14 and 16 years of age at the time of presentation, each without a significant cardiac history, who presented with palpitations or vague chest discomfort or both after a recent history of excessive caffeine consumption. Both were found to have atrial fibrillation on electrocardiogram; one patient required digoxin to restore a normal sinus rhythm, and the other self-converted after intravenous fluid administration.</p> <p>Conclusion</p> <p>With the increasing popularity of energy drinks in the pediatric and adolescent population, physicians should be aware of the arrhythmogenic potential associated with highly caffeinated beverage consumption. It is important for pediatricians to understand the lack of regulation in the caffeine content and other ingredients of these high-energy beverages and their complications so that parents and children can be educated about the risk of cardiac arrhythmias with excessive energy drink consumption.</p

Open issues in mucopolysaccharidosis type I-hurler

Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary follow-up with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H

Assessment of resistance mechanisms and clinical implications in patients with kras mutated-metastatic breast cancer and resistance to cdk4/6 inhibitors

Simple SummaryPalbociclib in combination with fulvestrant is used globally to treat metastatic breast cancer, but it was recognized that not all patients benefit from this combination of drugs. However, the predictive factors remain unknown. Here, we show KRAS ctDNA levels as predictive mechanisms of resistance to palbociclib and fulvestrant, and their association with the time to treatment discontinuation of the above treatment. These observations shed light on the potential clinical applications of ctDNA analysis in this setting of patients, in order to provide critical information about tumour dynamics, and to predict who will take advantage from CDK4/6 inhibitors.Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life

The ToF and Trigger electronics of the PAMELA experiment

The PAMELA satellite-borne experiment, scheduled to be launched in 2004, is designed to provide a better understanding of the antimatter component of the cosmic rays. Its ToF scintillator system will provide the primary experimental trigger and time-of-flight particle identification. The time resolution requested is σ, < 120 ps. To fulfill the detector requirements the digitization electronics should have a time resolution ≤ 50 ps and provide a wide dynamic range for charge measurements. The peculiarity of the developed electronics arises from the need to obtain such a time resolution operating in a satellite environment, which implies low-power consumption, radiation hardness, redundancy and high reliability

Time-resolving small angle X-Ray scattering analysis of melt crystallization of mixtures of regular and irregular isotactic polypropylene samples

The melting/crystallization properties of blends obtained by mixing two isotactic polypropylene (iPP) samples synthesized using single-site metallocene catalyst systems and containing a high and low concentration of rr triads as stereo-defects, are studied. The changes occurring at lamellar length scale during a heating/cooling cycle at constant scanning rate are followed in situ by performing time-resolved small angle X-ray scattering (SAXS) measurements. Data analysis demonstrates that the evolution of the SAXS intensity with increase/decrease of the temperature is controlled by the separate melting/crystallization of the two components, the differences in the thermal expansion (contraction) coefficient of the amorphous and crystalline phases and the role of thermal fluctuations in electron density. The two components give rise to different populations of intermixed lamellar stacks in the blends which originate from the good miscibility of the low and high stereoregular samples in the melt.info:eu-repo/semantics/publishedVersio

Double Heterozygous Mutations Involving Both HNF1A/MODY3 and HNF4A/MODY1 Genes: A case report

none9Abstract We describe the first MODY case with mutations involving both HNF4A and HNF1A genes. History and Examination. A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both parents (father at age 50, mother at age 54) and the sister (age 32 during pregnancy). Investigations. The genetic screening showed a double heterozygosity for the mutation p.E508K in HNF1A/MODY3 gene and the novel variant p.R80Q in HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister and her two children carried the MODY1 mutation. Conclusions. MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation, early need of insulin therapy to control hyperglycemia).mixedG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. MantovaniG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. Mantovan