Some reasoning on the RELM-CSEP likelihood-based tests

The null hypothesis is the essence of any statistical test: this is basically a comparison of what we observe with what we would expect to see if the null hypothesis was true. In this work, I explore the suitability of the null hypothesis of likelihood-based tests (LBTs), which are often adopted by the laboratories of the Collaboratory for the Study of Earthquake Predictability (CSEP), to check earthquake forecast models. First, I discuss the LBT in the wider context of classical statistical hypothesis testing. Then, I present some cases in which the null hypothesis of LBT is not appropriate for determining the merits of earthquake forecast models. I justify these results from a theoretical point of view, within the framework of point process theory. Finally, I propose a possible upgrade of LBT to enable the correct assessment of the forecasting capability of earthquake models. This study may provide new insights to the CSEP LBT

Probabilistic interpretationof «Bath's Law»

Assuming that, in a catalog, all the earthquakes with magnitude larger than or equal to a cutoff magnitude M c follow the Gutenberg-Richter Law, the compatibility of this hypothesis with «Baths Law» is examined. Consi-dering the mainshock M 0 and the largest aftershock M 1 of a sequence respectively as the first and the second largest order statistic of a sample of independent and identically distributed exponential random variables, the distribution of M 0 , M 1 and of their difference D 1 is evaluated. In particular, it is analyzed as the distribution of D 1 changes when only the sequences with the magnitude of the mainshock above a second threshold M c*M c are considered. It results that the distributions of M 0 , M 1 and D 1 depend on the difference M c*M c and on the number of events in the sequence. Moreover, the expected value of D 1 increases with increasing of M c*M c for every value of N. Then it is shown that «Baths Law» could be ascribed to selection of data caused by the two thresholds M c and M c* and that it has a qualitative agreement with the model proposed. Key words Assuming that, in a catalog, all the earthquakes with magnitude larger than or equal to a cutoff magnitude M c follow the Gutenberg-Richter Law, the compatibility of this hypothesis with «Baths Law» is examined. Consi-dering the mainshock M 0 and the largest aftershock M 1 of a sequence respectively as the first and the second largest order statistic of a sample of independent and identically distributed exponential random variables, the distribution of M 0 , M 1 and of their difference D 1 is evaluated. In particular, it is analyzed as the distribution of D 1 changes when only the sequences with the magnitude of the mainshock above a second threshold M c*M c are considered. It results that the distributions of M 0 , M 1 and D 1 depend on the difference M c*M c and on the number of events in the sequence. Moreover, the expected value of D 1 increases with increasing of M c*M c for every value of N. Then it is shown that «Baths Law» could be ascribed to selection of data caused by the two thresholds M c and M c* and that it has a qualitative agreement with the model propose

Meat intake and non-Hodgkin lymphoma: a meta-analysis of observational studies

Purpose: High intake of meat has been inconsistently associated with increased risk of NonHodgkin Lymphoma (NHL). We carried out a meta-analysis to summarise the evidence of published observational studies reporting association between red meat and processed meat intake and NHL risk. Methods: Analytical studies reporting relative risks with 95% confidence intervals (95% CI) for the association between intake of red and/or processed meat and NHL or major histological subtypes were eligible. We conducted random-effects meta-analysis comparing lowest and highest intake categories and dose-response meta-analysis when risk estimates and intake levels were available for more than three exposure classes. Results: Fourteen studies (4 cohort and 10 case-control) were included in the meta-analysis, involving a total of 10121 NHL cases. The overall relative risks of NHL for the highest versus the lowest category of consumption were 1.14 (95%CI: 1.03, 1.26) for red meat and 1.06 (95%CI: 0.98, 1.15) for processed meat. Significant associations were present when the analysis was restricted to case-control studies but not when restricted to cohort studies. No significant associations were found for major NHL etiological subtypes. Dose response meta-analysis could be based only on 8 studies that provided sufficient data and, compared to no meat consumption, the overall NHL relative risk increased not linearly with increased daily intake of red meat. Conclusion: The observed positive association between red meat consumption and NHL is mainly supported by the effect estimates coming from case-control studies and is affected by multiple sources of heterogeneity. This meta-analysis provided mixed and inconclusive evidences on the supposed relationship between red and processed meat consumption and NHL

A structure-function analysis in patients with prekallikrein deficiency.

To investigate the structure-function relation in prekallikrein (PK) deficiency. PK is one of the proteins of the contact phase of blood coagulation which at the present time is the object of a revival of interest.All patients with PK deficiency who had been investigated by molecular biology techniques are the object of the present investigation. Details of patients were obtained from personal files and a time-unlimited PubMed search. Only cases with a molecular-biology-based diagnosis were included.Twelve families were included. The total number of missense mutation was 10, together with 3 stop codons and 2 insertions. These mutations involved mainly exons 11 and 14. There were eight proved homozygotes and three compound heterozygotes. In one instance, homozygosity was probable but not proved. In nine cases, the defect was Type I, whereas it was Type II in the remaining three. No bleeding manifestations were present in 11 of the 12 probands. One proband had epistaxis, but she had hypertension. Altogether, four patients had hypertension and one of them had also two myocardial infarctions.Despite the paucity of cases, it was established that the majority of mutations involved the catalytic domain. It is auspicable that future reports of patients with this disorder should include molecular studies. This would certainly contribute to the understanding of the contact phase of blood coagulation

A New Mutation (Arg251 Trp) in the Ca2+ Binding Site of Factor X Protease Domain Appears to be Responsible for the Defect in the Extrinsic Pathway Activation of Factor X Padua

Factor X Padua, first described a few years ago, is characterized by a defect only in the extrinsic system. In this present paper, the molecular basis for this peculiar defect is investigated. Polymerase chain reaction amplification and direct sequencing of the entire FX coding sequence and of exon-intron junctions detected in the proposita a C-to-T translocation in exon 8 of nucleotide 875 at the homozygous level. This resulted in the substitution of tryptophan for arginine 251. A niece of the proposita was shown to be heterozygous for the abnormality. Molecular modeling suggested that the mutation does not alter significantly folding and stability of the protein but may be involved in the Ca2+ binding site

Malpractice and patient safety descriptors: an innovative grid to evaluate the quality of clinical records

Introduction: The medical record contains all the health information related to the patient’s clinical condition and its evolution during hospitalization. It was defined by the Italian Ministry of Health in 1992 as "The information tool designed to record all relevant demographic and clinical information about a patient during a single episode of hospitalization". The documents and information in a Medical Record must meet the following criteria: traceability, clarity, accuracy, authenticity, pertinence and completeness. The objectives of our study was to develop a tool capable of assessing the quality of the clinical record and pointed the critical point at the Organizational, Technical - Professional, Managerial level. Methods: To evaluate the quality of the medical documentation, we created an assessment grid composed of 4 sections with a total of 92 criteria. This grid was tested on 200 medical records that were randomly selected from 25 (18 medical and 7 surgical) wards of a teaching hospital in Rome. Results: The grid contains 4 sections. The first part regards administrative and clinical data; the second assesses the quality of hospital stay and surgical/invasive procedures; the third part is concerned with the discharge of the patient and the fourth aims to identify the presence of advisory reports given to the patient. This grid has been validated to verify internal consistency with Cronbach's Alpha = 0,743. Conclusions: Medical records were analyzed using a validated tool with grids to identify critical issues in care activities. Weaknesses in the system were identified in order to improve planning. The sample testing also in terms of ‘self-assessment' represents a tool to introduce activities to improve safety and quality of care, greatly reducing the costs of litigation

Quality assessment of medical record as a tool for clinical risk management: a three year experience of a teaching hospital Policlinico Umberto I, Rome

Introduction: The medical record was defined by the Italian Ministry of Health in 1992 as "the information tool designed to record all relevant demographic and clinical information on a patient during a single hospitalization episode". Retrospective analysis of medical records is a tool for selecting direct and indirect indicators of critical issues (organizational, management and technical). The project’s aim being the promotion of an evaluation and self-evaluation process of medical records as a Clinical Risk Management tool to improve the quality of care within hospitals. Methods: The Authors have retrospectively analysed, using a validated grid, 1,184 medical records of patients admitted to the Teaching Hospital “Umberto I” in Rome during a three-year period (2013-2015). Statistical analysis was performed using SPSS for Windows © 19:00. All duly filled out criteria (92) were examined. “Strengths” and "Weaknesses" were identified through data analysis and Best and Bad Practice were identified based on established criteria. Conclusion: The data analysis showed marked improvements (statistically significant) in the quality of evaluated clinical documentation and indirectly upon behaviour. However, when examining some sub-criteria, critical issues emerge; these could be subject to future further corrective action

Congenital prothrombin defects: they are not only associated with bleeding but also with thrombosis: a new classification is needed.

Congenital prothrombin deficiency is one of the rarest clotting disorders. It is commonly subdivided in Type I defects or cases of 'true' prothrombin deficiency characterized by a concomitant decrease in FII activity and antigen and in Type II or dysprothrombinemias, in which FII activity is low but FII antigen is normal or near normal. A bleeding tendency, often a severe one, is the hallmark of the two-defects even though the bleeding is usually less severe in the Type 2 defects or dysprothrombinemias.An extensive search of published cases of prothrombin deficiency was carried out in Pubmed and Scopus. The search started in 2012, after the publication of the first family with dysprothrombinemia and venous thrombosis. A few additional families were found.Recent studies have demonstrated that the Type 2 defects are heterogeneous. Several heterozygous mutations involving the Arg596 residue of exon 14 have been demonstrated not be associated with a bleeding tendency but, surprisingly, with venous thromboses. Mutations in close areas of prothrombin have failed to show the same pattern.These observations have required a reclassification of prothrombin defects. To the Type I and Type II defects, a Type III has to be added characterized by the absence of bleeding and the presence of venous thrombosis. It is not clear yet if this special variant of Type II defect is limited to the Arg596 mutations or if other residues may be involved

Bleeding manifestations in heterozygotes with congenital FVII deficiency: a comparison with unaffected family members during a long observation period.

To determine whether heterozygotes with FVII deficiency have a bleeding tendency or not.Eighty-four patients (OK) heterozygous for FVII deficiency, at the onset of the study, were paired with unaffected family members and followed for a long period of time (mean 22.6 years) for the occurrence of bleeding. Diagnosis of heterozygosis had to be based on family studies, clotting, immunological assays and genetic analysis.The mean FVII activity level was 0.51 IU/dl (range 35-65) and 94 IU/dl (range 88-118) in the heterozygotes and in the normal counterparts, respectively. Documented bleeding manifestations occurred in eight heterozygotes and in seven normal subjects. Statistical analysis of the difference was not significant. Bleeding manifestations were easy bruising, bleeding after tooth extractions, menorrhagia, epistaxis with no difference among the two groups. There was no strict correlation between bleeding and FVII activity levels.The study indicates that heterozygotes for FVII deficiency show rare bleeding manifestations which are also present in the unaffected family members with normal FVII levels. This indicates that Factor VII activity levels played no role in the occurrence of the bleeding symptoms. Furthermore, FVII levels of around 0.40 IU/dl are capable of assuring a normal hemostasis