Process capability indices and X , R control chart limit adjustments by taking into account measurement system errors

This paper investigates the effects of measurement system variability arising from evaluations of process capabilities. In this work, relationships between true process capability indices, Cp,True and Cpm,True, and their corresponding observed indices, Cp,Obs and Cpm,Obs, are developed depending on the levels of type I and II errors. Moreover, the method for adjusting control chart limits used to monitor the process is proposed based on measurement system variability. An industrial case study is used to highlight the findings of this investigation and to discuss the adjustment levels that should be conducted depending on the values of type I and type II errors

State of the art and challenges for occupational health and safety performance evaluation tools

In industrialized nations, occupational health and safety (OHS) has been a growing concern in many businesses for at least two decades. Legislation, regulation, and standards have been developed in order to provide organizations with a framework for practicing accident and illness prevention and placing worker well-being at the center of production system design. However, the occurrence of several accidents continues to show that OHS performance evaluation is subject to interpretation. In this review of the literature, we outline the scope of current research on OHS status and performance evaluation and comment on the suitability of the instruments being proposed for field use. This study is based on a keyword-based bibliographical search in the largest scientific databases and OHS-related websites, which allowed us to identify 15 OHS performance evaluation tools. Our principal conclusion is that researchers in the field have shown little interest in generalizing the instruments of OHS performance evaluation and that none of the 15 tools examined is properly applicable to any real organization outside of the sector of activity, economic scale, and jurisdiction for which it was designed

Two-Phase Ozonation for the Removal of Estrone, 17β-Estradiol and 17α-Ethinylestradiol in Water Using Ozone-Loaded Decamethylcyclopentasiloxane

Ozonation has been proven effective for the removal of endocrine disrupting chemicals (EDCs) in water. However, conventional ozonation processes are still limited by ozone low solubility and stability in water. These limitations may be overcome by mixing a prior ozone-loaded non-polar solvent with the aqueous solution. This two-phase ozonation process combines Liquid-liquid extraction and Ozonation (LLO). Decamethylcyclopentasiloxane (D5) was chosen as the solvent to be charged with ozone for its non-toxicity, reusability and high ozone solubility. A concurrent LLO column reactor was designed for the simultaneous degradation of three endocrine disrupting chemicals (EDCs) in water: Estrone (E1), 17β-estradiol (E2) and 17α-estradiol (EE2). Results showed that 98% of EDCs were removed effectively from a solution initially concentrated at 1 mg L−1. The efficacy of the degradation depends essentially of the column feeding flowrate, the ozone dose and the operating pH. The generation of by-products during EDCs degradation by LLO was also investigated in this study. For a complete removal of both EDCs and by-products, the dose of ozone had to be doubled

Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

<p>Abstract</p> <p>Background</p> <p>In Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV) infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR) and partial sequencing in the pre-S region.</p> <p>Results</p> <p>Three genotypes (D, B and A) were detected by the PCR-RFLP method and two (D and A) with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A) for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55%) and D7 (41%). Only one strain clustered with D3 subgenotype (3%).</p> <p>Conclusions</p> <p>Predominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variability may lead to wrong results in rapid genotyping methods and sequence analysis is needed to clarify atypical results.</p

Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1-/- mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/ = 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (−20–30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1-/- mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain

Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients

variations associated with enhanced drug toxicity. = 0.001; the attributable risk was 56.9%. Comparing tumor-type matched sets of samples, correlation of c.496A>G with toxicity was particularly present in patients with gastroesophageal and breast cancer, but did not reach significance in patients with colorectal malignancies. polymorphism strongly contributes to the occurrence of fluoropyrimidine-related drug adverse effects. Carriers of this variant could benefit from individual dose adjustment of the fluoropyrimidine drug or alternate therapies

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery