Top Management Evaluation in Italian Food & Beverage Industry

The standard ISO 9001: 2015 “Quality Management System. Requirements” states that the success of a company’s quality certification system is closely linked to the quality of its top management. The aim of the present work is to develop a model of top management quality evaluation useful for the ends of this certification. The model is calibrated for the Italian Food & Beverage Industry and it follows a multidisciplinary approach. The evaluation model is formed by two parts. In the first, the quality of top management is associated with an estimate of the probability of default and the related average expected life of a company in the Italian Food & Beverage Industry. These parameters are calculated using an original, easy-to-apply methodology that is especially useful for small and medium-sized companies that do not have an official rating. The second part of the model provides a system to estimate the quality of top managers' management styles based on seven qualitative organizational variables, which are then summarized by the attribution of a score ranging from 1 to 10. The judgments formulated in the two parts of the model must be considered as a system to arrive at an integrated final evaluation

Impact of DEL22q11, trisomy 21, and other genetic syndromes on surgical outcome of conotruncal heart defects

Objective: Genetic syndromes occur in more than 20% of patients with conotruncal heart defects. We investigated the impact of genetic syndromes on the surgical outcome of conotruncal anomalies in infancy. Methods: This retrospective study reviews the outcome of 787 patients (median age 6.3 months) who underwent primary (598) or staged (189) repair of a conotruncal defect between 1992 and 2007. Results: Proven genetic syndrome was diagnosed in 211 patients (26.8%), including del22q11 (91 patients), trisomy 21 (29 patients), VACTERL (18 patients), and other syndromes (73 patients). Primary repair was accomplished in 80.9% of nonsyndromic patients and 74.4% of syndromic patients (P ¼ .18) Fifteen-year cumulative survival was 84.3% 2.3% in nonsyndromic patients and 73.2% 4.2% in syndromic patients (P<.001). Primary and staged repair allowed similar 15-year survival (81.4% 4.5% vs 79.1% 5.1%, P ¼ .8). Freedom from noncardiac cause of death was significantly lower in syndromic patients (P ¼ .0056). Fifteen- year Kaplan–Meier survival was 87.6% 3.9% for del22q11, 95.8% 4.1% for trisomy 21, 56.8% 6.3% for VACTERL, and 62.3% 12.7% for patients with other syndromes (P ¼ .022). Total intensive care unit stay was 10.8 4.9 days in syndromic patients and 5.1 1.7 days in nonsyndromic patients (P<.001). Freedom from reintervention 15 years after repair was 79.6% 4.9%in nonsyndromic patients and 62.4% 7.4%in syndromic patients (P ¼ .007). Conclusion: Del22q11 and trisomy 21 do not represent risk factors for mortality after repair of conotruncal anomalies, whereas other syndromes adversely affect the surgical outcome for predominant noncardiac attrition. Higher morbidity and lower mid-term freedom from reintervention can be predicted in syndromic patients

Comparison of computational methods for the identification of topologically associating domains.

Chromatin folding gives rise to structural elements among which are clusters of densely interacting DNA regions termed topologically associating domains (TADs). TADs have been characterized across multiple species, tissue types, and differentiation stages, sometimes in association with regulation of biological functions. The reliability and reproducibility of these findings are intrinsically related with the correct identification of these domains from high-throughput chromatin conformation capture (Hi-C) experiments. Here, we test and compare 22 computational methods to identify TADs across 20 different conditions. We find that TAD sizes and numbers vary significantly among callers and data resolutions, challenging the definition of an average TAD size, but strengthening the hypothesis that TADs are hierarchically organized domains, rather than disjoint structural elements. Performances of these methods differ based on data resolution and normalization strategy, but a core set of TAD callers consistently retrieve reproducible domains, even at low sequencing depths, that are enriched for TAD-associated biological features. This study provides a reference for the analysis of chromatin domains from Hi-C experiments and useful guidelines for choosing a suitable approach based on the experimental design, available data, and biological question of interest

Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ¼ .16), nor did the choice to use a valved conduit (P ¼ .82). Primary correction (P ¼ .05) and lower weight at repair (P ¼ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention

Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ¼ .16), nor did the choice to use a valved conduit (P ¼ .82). Primary correction (P ¼ .05) and lower weight at repair (P ¼ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention

Whole-genome doubling drives oncogenic loss of chromatin segregation.

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies &lt;sup&gt;1-8&lt;/sup&gt; . However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotypes are currently unknown. Here we show that in p53-deficient cells, WGD induces loss of chromatin segregation (LCS). This event is characterized by reduced segregation between short and long chromosomes, A and B subcompartments and adjacent chromatin domains. LCS is driven by the downregulation of CTCF and H3K9me3 in cells that bypassed activation of the tetraploid checkpoint. Longitudinal analyses revealed that LCS primes genomic regions for subcompartment repositioning in WGD cells. This results in chromatin and epigenetic changes associated with oncogene activation in tumours ensuing from WGD cells. Notably, subcompartment repositioning events were largely independent of chromosomal alterations, which indicates that these were complementary mechanisms contributing to tumour development and progression. Overall, LCS initiates chromatin conformation changes that ultimately result in oncogenic epigenetic and transcriptional modifications, which suggests that chromatin evolution is a hallmark of WGD-driven cancer

Systematic inference and comparison of multi-scale chromatin sub-compartments connects spatial organization to cell phenotypes.

Chromatin compartmentalization reflects biological activity. However, inference of chromatin sub-compartments and compartment domains from chromosome conformation capture (Hi-C) experiments is limited by data resolution. As a result, these have been characterized only in a few cell types and systematic comparisons across multiple tissues and conditions are missing. Here, we present Calder, an algorithmic approach that enables the identification of multi-scale sub-compartments at variable data resolution. Calder allows to infer and compare chromatin sub-compartments and compartment domains in &gt;100 cell lines. Our results reveal sub-compartments enriched for poised chromatin states and undergoing spatial repositioning during lineage differentiation and oncogenic transformation

Comparison of anticoagulation quality between acenocoumarol and warfarin in patients with mechanical prosthetic heart valves: Insights from the nationwide PLECTRUM study

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p &lt; 0.001). A higher prevalence of TiTR (&lt;60%, &lt;65%, or &lt;70%) was found in acenocoumarol users than in warfarin ones (p &lt; 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies

Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease