Systems approach to assessing and improving local human research Institutional Review Board performance.

ObjectiveTo quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.MethodsOver 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.ResultsStaffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.ConclusionsUnderstanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics

Knock: A Century of Research

Knock is one of the main limitations on increasing spark-ignition (SI) engine efficiency. This has been known for at least 100 years, and it is still the case today. Knock occurs when conditions ahead of the flame front in an SI engine result in one or more autoignition events in the end gas. The autoignition reaction rate is typically much higher than that of the flame-front propagation. This may lead to the creation of pressure waves in the combustion chamber and, hence, an undesirable noise that gives knock its name. The resulting increased mechanical and thermal loading on engine components may eventually lead to engine failure. Reducing the compression ratio lowers end-gas temperatures and pressures, reducing end-gas reactivity and, hence, mitigating knock. However, this has a detrimental effect on engine efficiency. Automotive companies must significantly reduce their fleet carbon dioxide (CO2) values in the coming years to meet targets resulting from the 2015 Paris Agreement. One path towards meeting these is through partial or full electrification of the powertrain. However, the vast majority of automobiles in the near future will still feature a gasoline-fueled SI engine; hence, improvements in combustion engine efficiency remain fundamental. As knock has been a key limitation for so long, there is a huge amount of literature on the subject. A number of reviews on knock have already been published, including in recent years. These generally concentrate on current understanding and status. The present work, in contrast, aims to track the progress of research on knock from the 1920s right through to the present day. It is hoped that this can be a useful reference for new and existing researchers of the subject and give further weight to occasionally neglected historical activity, which can still provide important insights today

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease.

BackgroundScreening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation.AimTo determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.MethodsInformation generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed.ResultsNon-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%.ConclusionsScreening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner

Large-Eddy simulation analysis of spark configuration effect on cycle-to-cycle variability of combustion and knock

Cycle-to-cycle variability is numerically simulated for high-speed, full-load operation of a turbocharged gasoline direct injection engine. Large-Eddy simulation is adopted to replicate the fluctuations of the flow field affecting the turbulent combustion. Experimental data were provided at knock onset, and large-Eddy simulation was validated for the same condition. In the original engine configuration, the spark plug is displaced toward the exhaust side, while the electrodes orientation is arbitrary. A 90 rotation is imposed to evaluate the effects of the aerodynamic obstruction caused by the electrode with respect to the flow field and the flame kernel growth. A second speculative analysis is performed modifying the position of the spark plug. The electrodes are shifted 2mm toward the intake side since this variation is compatible with the cylinder head layout. For both variations in orientation and position, the effects on the flow field around the spark plug are investigated. Statistical analysis is carried out on early flame kernel formation and knock tendency. The results highlight that the orientation of the electrodes affects the flow field for each cycle but plays a negligible role on the statistical cyclic variability, indirectly justifying the lack of an imposed orientation. As for the spark plug position, the numerical analysis indicate that the shifting of the electrodes toward the intake side slightly improves the knock limit mainly because of a reduction in in-cylinder peak pressure. In general, it is inferred that improvements may be achieved only through a simultaneous modification of the fuel jet orientation and phasing

Identification of mutations in the bovine KIT gene, a candidate for the Spotted locus in cattle

AbstractIn mammals, abnormal migration of melanoblasts from the neural crest during embryonic development may be the reason of the pielbaldism phenotype that is a mixture of pigmented and unpigmented areas in the coat. Several cattle breeds, like for example Holstein, show the piebald spotted coat colour phenotype, that, according to crossbreeding studies, is due to a recessive allele (s), member of the allele series of the Spotted (S) locus. Dominant alleles at this locus act as suppressors of the spotted pattern and produce uniformly pigmented animals while others determine the colour-sided pattern known, for example, in the Hereford breed. The bovine v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene (KIT) gene was localized in the region of chromosome 6 where the Spotted locus was mapped. KIT plays a major role during the embryonic development in directing the migration of the melanoblasts from the neural crest. Mutations in this gene cause different coat colour patterns in mouse and human. In pigs..

Knock Tendency Prediction in a High Performance Engine Using LES and Tabulated Chemistry

The paper reports the application of a look-up table approach within a LES combustion modelling framework for the prediction of knock limit in a highly downsized turbocharged DISI engine. During experimental investigations at the engine test bed, high cycle-to-cycle variability was detected even for relatively stable peak power / full load operations of the engine, where knock onset severely limited the overall engine performance. In order to overcome the excessive computational cost of a direct chemical solution within a LES framework, the use of look-up tables for auto-ignition modelling perfectly fits with the strict mesh requirements of a LES simulation, with an acceptable approximation of the actual chemical kinetics. The model here presented is a totally stand-alone tool for autoignition analysis integrated with look-up table reading from detailed chemical kinetic schemes for gasoline. The look-up table access is provided by a multi-linear interpolating routine internally developed at the \u201cGruppo Motori (GruMo)\u201d of the University of Modena and Reggio Emilia. As the experimental tests were conducted operating the engine at knock-limited spark advance, the tool is at first validated for three different LES cycles in terms of knock tolerance, i.e. the safety margin to knock occurrence. As a second stage, the validation of the methodology is performed for discrete spark advance increases in order to assess the sensitivity of the modelling strategy to variations in engine operations. A detailed analysis of the unburnt gas physical state is performed which confirms the knock-limited condition suggested by the experimental tests

Shotgun sequencing of honey DNA can describe honey bee derived environmental signatures and the honey bee hologenome complexity

Honey bees are large-scale monitoring tools due to their extensive environmental exploration. In their activities and from the hive ecosystem complex, they get in close contact with many organisms whose traces can be transferred into the honey, which can represent an interesting reservoir of environmental DNA (eDNA) signatures and information useful to analyse the honey bee hologenome complexity. In this study, we tested a deep shotgun sequencing approach of honey DNA coupled with a specifically adapted bioinformatic pipeline. This methodology was applied to a few honey samples pointing out DNA sequences from 191 organisms spanning different kingdoms or phyla (viruses, bacteria, plants, fungi, protozoans, arthropods, mammals). Bacteria included the largest number of species. These multi-kingdom signatures listed common hive and honey bee gut microorganisms, honey bee pathogens, parasites and pests, which resembled a complex interplay that might provide a general picture of the honey bee pathosphere. Based on the Apis mellifera filamentous virus genome diversity (the most abundant detected DNA source) we obtained information that could define the origin of the honey at the apiary level. Mining Apis mellifera sequences made it possible to identify the honey bee subspecies both at the mitochondrial and nuclear genome levels

Whole genome sequencing identifies candidate genes and mutations that can explain diluted and other colour varieties of domestic canaries (Serinus canaria)

The domestic canary (Serinus canaria) is one of the most common pet birds and has been extensively selected and bred over the last few centuries to constitute many different varieties. Plumage pigmentation is one of the main phenotypic traits that distinguish canary breeds and lines. Feather colours in these birds, similarly to other avian species, are mainly depended on the presence of two major types of pigments: carotenoids and melanins. In this study, we exploited whole genome sequencing (WGS) datasets produced from five canary lines or populations (Black Frosted Yellow, Opal, Onyx, Opal × Onyx and Mogno, some of which carrying different putative dilute alleles), complemented with other WGS datasets retrieved from previous studies, to identify candidate genes that might explain pigmentation variability across canary breeds and varieties. Sequencing data were obtained using a DNA pool-seq approach and genomic data were compared using window-based FST analyses. We identified signatures of selection in genomic regions harbouring genes involved in carotenoid-derived pigmentation variants (CYP2J19, EDC, BCO2 and SCARB1), confirming the results reported by previous works, and identified several other signatures of selection in the correspondence of melanogenesis-related genes (AGRP, ASIP, DCT, EDNRB, KITLG, MITF, MLPH, SLC45A2, TYRP1 and ZEB2). Two putative causative mutations were identified in the MLPH gene that may explain the Opal and Onyx dilute mutant alleles. Other signatures of selection were also identified that might explain additional phenotypic differences between the investigated canary populations

Application of next generation semiconductor-based sequencing for the identification of apis mellifera complementary sex determiner (Csd) alleles from honey dna

The complementary sex determiner (csd) gene plays an essential role in the sex determination of Apis mellifera L. Females develop only if fertilized eggs have functional heterozygous genotypes at this gene whereas males, being haploids, are hemizygous. Two identical csd alleles produce non vital males. In light of the recent decline in honey bee populations, it is therefore important to monitor the allele variability at this gene. In this study, we tested the application of next generation semiconductor-based sequencing technology (Ion Torrent) coupled with environmental honey DNA as a source of honey bee genome information to retrieve massive sequencing data for the analysis of variability at the hypervariable region (HVR) of the csd gene. DNA was extracted from 12 honey samples collected from honeycombs directly retrieved from 12 different colonies. A specifically designed bioinformatic pipeline, applied to analyze a total of about 1.5 million reads, identified a total of 160 different csd alleles, 55% of which were novel. The average number of alleles per sample was compatible with the number of expected patrilines per colony, according to the mating behavior of the queens. Allele diversity at the csd could also provide information useful to reconstruct the history of the honey