Significant Reduction In Variation Research Articles

Superpixel-ComBat modeling: A joint approach for harmonization and characterization of inter-scanner variability in T1-weighted images

Abstract T1-weighted imaging holds wide applications in clinical and research settings; however, the challenge of inter-scanner variability arises when combining data across scanners, which impedes multi-site research. To address this, post-acquisition harmonization methods such as statistical or deep learning approaches have been proposed to unify cross-scanner images. Nevertheless, how inter-scanner variability manifests in images and derived measures, and how to harmonize it in an interpretable manner, remains underexplored. To broaden our knowledge of inter-scanner variability and leverage it to develop a new harmonization strategy, we devised a pipeline to assess the interpretable inter-scanner variability in matched T1-weighted images across four 3T MRI scanners. The pipeline incorporates ComBat modeling with 3D superpixel parcellation algorithm (namely SP-ComBat), which estimates location and scale effects to quantify the shift and spread in relative signal distributions, respectively, concerning brain tissues in the image domain. The estimated parametric maps revealed significant contrast deviations compared to the joint signal distribution across scanners (p < 0.001), and the identified deviations in signal intensities may relate to differences in the inversion time acquisition parameter. To reduce the inter-scanner variability, we implemented a harmonization strategy involving proper image preprocessing and site effect removal by ComBat-derived parameters, achieving substantial improvement in image quality and significant reduction in variation of volumetric measures of brain tissues (p < 0.001). We also applied SP-ComBat to evaluate and characterize the performance of various image harmonization techniques, demonstrating a new way to assess image harmonization. In addition, we reported various metrics of T1-weighted images to quantify the impact of inter-scanner variation, including signal-to-noise ratio, contrast-to-noise ratio, signal inhomogeneity index, and structural similarity index. This study demonstrates a pipeline that extends the implementation of statistical ComBat method to the image domain in a practical manner for characterizing and harmonizing the inter-scanner variability in T1-weighted images, providing further insight for the studies focusing on the development of image harmonization methodologies and their applications.

Proficiency tests to evaluate the impact on assay outcomes of harmonized influenza-specific Intracellular Cytokine Staining (ICS) and IFN-ɣ Enzyme-Linked ImmunoSpot (ELISpot) protocols

The magnitude and quality of cell-mediated immune responses elicited by natural infection or vaccination are commonly measured by Interferon-ɣ (IFN-ɣ) Enzyme-Linked ImmunoSpot (ELISpot) and Intracellular Cytokine Staining (ICS). To date, laboratories apply a variety of in-house procedures which leads to diverging results, complicates interlaboratory comparisons and hampers vaccine evaluations. During the FLUCOP project, efforts have been made to develop harmonized Standard Operating Procedures (SOPs) for influenza-specific IFN-ɣ ELISpot and ICS assays. Exploratory pilot studies provided information about the interlaboratory variation before harmonization efforts were initiated. Here we report the results of two proficiency tests organized to evaluate the impact of the harmonization effort on assay results and the performance of participating FLUCOP partners.The introduction of the IFN-ɣ ELISpot SOP reduced variation of both background and stimulated responses. Post-harmonization background responses were all lower than an arbitrary threshold of 50 SFU/million cells. When stimulated with A/California and B/Phuket, a statistically significant reduction in variation (p < 0.0001) was observed and CV values were strongly reduced, from 148% to 77% for A/California and from 126% to 73% for B/Phuket. The harmonizing effect of applying an ICS SOP was also confirmed by an increased homogeneity of data obtained by the individual labs. The application of acceptance criteria on cell viability and background responses further enhanced the data homogeneity. Finally, as the same set of samples was analyzed by both the IFN-ɣ ELISpot and the ICS assays, a method comparison was performed. A clear correlation between the two methods was observed, but they cannot be considered interchangeable.In conclusion, proficiency tests show that a limited harmonization effort consisting of the introduction of SOPs and the use of the same in vitro stimulating antigens leads to a reduction of the interlaboratory variation of IFN-ɣ ELISpot data and demonstrate that substantial improvements for the ICS assay are achieved as comparable laboratory datasets could be generated. Additional steps to further reduce the interlaboratory variation of ICS data can consist of standardized gating templates and detailed data reporting instructions as well as further efforts to harmonize reagent and instrument use.

Multidimensional Analysis of Diversity in DH Lines and Hybrids of Winter Oilseed Rape (Brassica napus L.)

Limited genetic variability is a major problem in rapeseed breeding, whose strict selection, limited geographical range and a short period of domestication has led to a reduction in genetic and phenotypic diversity. Assessing specific populations for the greatest genetic diversity for many traits simultaneously, requires the evaluation of multi-feature characteristics. The aim of this study was to estimate the variability of DH (doubled haploid) lines and two generations of winter oilseed rape hybrids. In addition, the relationship between the Mahalanobis distances of parental forms and the effect of heterosis in hybrids was investigated. The results of MANOVA showed that the genotypes and years as well as genotype × year interaction were significantly different (p &lt; 0.001) for all eight observed traits. The first (V1) and the second (V2) canonical variate explained 38.57% and 27.55% of the total variation in 2015, and 50.19% and 31.84% in 2016, respectively Canonical variate analysis showed that the traits, flowering time and number of branches per plant had a very large influence on the differentiation of genotypes. Graphs demonstrated that the tested DH lines and hybrids are characterized by a similar, wide range of variability. It was observed, that when using a diverse population of DH lines for crossbreeding with only one CMS/Rfo line, there was no significant reduction of variation in hybrid generations and between these generations. The phenotypic distance values determined by the results of Mahalanobis analysis were similar in both years, but slightly wider in 2016. The observed minimum and maximum ranged from 1.324 to 22.356 in 2015, and from 1.105 to 27.792 in 2016, respectively. No significant correlation was observed between the hybrid heterosis effect and the Mahalanobis distance of the parental lines.

Impact of repeated hospital accreditation surveys on quality and reliability, an 8-year interrupted time series analysis

ObjectiveTo evaluate whether hospital re-accreditation improves quality, patient safety and reliability over three accreditation cycles by testing the accreditation life cycle model on quality measures.DesignThe validity of the life cycle...

An integrated approach to sustainability and delivery of improved health outcomes for Children’s Health Queensland community based services and programs

Introduction : A population health and locality based planning approach has been used to design and implement a digital reporting and monitoring platform to inform service improvement, guide strategic planning activity and support the implementation of CHQs key strategic priorities. The approach is framed within a Results Based Accountability (RBA) model that provides a stepped and disciplined approach to improving patient outcomes. Aim and theory of change : Taking a population health and locality based planning approach to the implementation of service improvement strategies ensures that child health services and programs are provided in the right location and consumers have improved outcomes. Targeted population and stakeholders : For all child health localities the service activity, workforce, consumer feedback and socio-demographic data were collated into a respository and was made available to all child health services and programs through an interactive digital dashboard. The information is rendered and presented via a series of performance indicators across five domains: Service activity; Economic sustainability; Healthy and engaged workforce; Experience of care; Results based accountability. The interactive dashboards are made available through ‘QlikView’ software and used to establish a baseline prior to implementing an intervention to improve service delivery. The same suite of tools are used to monitor the impact of the intervention. In each locality interventions were implemented to reduce the variation in specific performance indicators and the intent to increase home visiting, decrease failure to attend rates, increase new to review ratio, and increase partnerships with local services. Highlights : Each of the child health team accessing the dashboard has identified areas for improvement based on the digital dashboard reporting. Models of service delivery have been adjusted based on data e.g. Home visits to the consumers’ home have increased from 17% to 23% of all visiting with a target of 25%. Failure to attend rates across teams has decreased from 18% to 12% with significant reduction in variation with one team able to reduce from 30% to 14%. New to review ratio has improved across all teams to 1:4 with a reduction in repeat appointments. Consumers over a one month period have responded (n=652) to how well did we treat them, did we help them with their problems, why did they rate us this way, and is there any way we could have improved what we did. Comments and Conclusion : Child health services and program areas now have the capacity to make informed business decisions about clinical services, utilisation of resources and planning for longer term facility requirements with services and partners. Wider use of the dashboard reporting is now being used in Child Development Services, School Based Youth Health Nursing Service and other community based services.

Closing the Productivity Gap: Improving Worker Productivity Through Public Relative Performance Feedback and Validation of Best Practices

Public relative performance feedback (RPF) on an individual worker’s productivity metrics is used in various organizations with the hopes of improving worker productivity, but its effects are not well understood. We examine whether public RPF could be leveraged to facilitate adoption of best practices in an organization by enabling the validation of best practices shared by identifiable top performers. We use data from two emergency departments, both of which shared best practices for improving productivity and one of which changed from privately to publicly disclosing RPF to physicians. The public disclosure of RPF allowed workers to identify their top-performing coworkers, which in turn enabled the identification and validation of best practices within the work group. We find that the intervention is associated with a 10.9% improvement in physician productivity. We also find evidence for a significant reduction in variation in productivity across providers, which stems from bottom-ranked workers exhibiting differentially large improvements in productivity. These effects hold without sacrificing system-level performance, service quality, or worker attrition. Our results suggest that public disclosure of RPF, along with the validation of the best practices being shared, can improve worker productivity.The online supplement is available at https://doi.org/10.1287/mnsc.2017.2745 .This paper was accepted by Serguei Netessine, operations management.

Closing the Productivity Gap: Improving Worker Productivity through Public Relative Performance Feedback and Validation of Best Practices

Public relative performance feedback (RPF) on an individual worker’s productivity metrics is used in various organizations with the hopes of improving worker productivity, but its effects are not well understood. We examine whether public RPF could be leveraged to facilitate best practice adoption in an organization by enabling the validation of best practices shared by identifiable top performers. We use data from two emergency departments, both of which shared best practices for improving productivity and one of which changed from privately to publicly disclosing RPF to physicians. The public disclosure of RPF allowed workers to identify their top-performing coworkers, which in turn enabled the identification and validation of best practices within the work group. We find that the intervention is associated with a 10.9% improvement in physician productivity. We also find evidence for a significant reduction in variation in productivity across providers, which stems from bottom-ranked workers exhibiting differentially large improvements in productivity. These effects hold without sacrificing system-level performance, service quality, or worker attrition. Our results suggest that public disclosure of RPF, along with the validation of the best practices being shared, can improve worker productivity.

Hoof Conformation and Palmar Process Fractures of the Distal Phalanx in Warmblood Foals

This study evaluated onset and incidence of palmar process fractures in foals and investigated corresponding changes in hoof conformation. Radiographs of 17 warmblood foals were taken at 1 week and at 2, 4, 6, 8, and 12 months of age and examined for evidence of palmar process fractures. Hoof parameters were measured from the radiographs, and comparisons were made between fractured and nonfractured feet. All foals suffered at least one fracture during the study period, with an average age of 3.68 ± 0.20 months at fracture occurrence. Hoof conformation and fracture occurrence were not significantly correlated. Foals consistently demonstrated higher lateral heights in the right foot and higher medial heights in the left foot. Hoof angle increased until 3 months of age and then gradually dropped. Hoof-pastern axis exhibited a broken forward conformation, but approached a more correct conformation by 12 months of age. There was a significant reduction in variation of variables for hoof and pastern angle in both feet, and hoof-pastern axis in the right foot. Hoof conformation does not appear to be a causative factor of palmar process fractures. It is possible that these fractures are a normal part of bone remodeling.

Patterns of genetic diversity and candidate genes for ecological divergence in a homoploid hybrid sunflower,Helianthus anomalus

Natural hybridization accompanied by a shift in niche preference by hybrid genotypes can lead to hybrid speciation. Natural selection may cause the fixation of advantageous alleles in the ecologically diverged hybrids, and the loci experiencing selection should exhibit a reduction in allelic diversity relative to neutral loci. Here, we analyzed patterns of genetic diversity at 59 microsatellite loci associated with expressed sequence tags (ESTs) in a homoploid hybrid sunflower species, Helianthus anomalus. We used two indices, ln RV and ln RH, to compare variation and heterozygosity (respectively) at each locus between the hybrid species and its two parental species, H. annuus and H. petiolaris. Mean values of ln RV and ln RH were significantly lower than zero, which implies that H. anomalus experienced a population bottleneck during its recent evolutionary history. After correcting for the apparent bottleneck, we found six loci with a significant reduction in variation or with heterozygosity in the hybrid species, compared to one or both of the parental species. These loci should be viewed as a ranked list of candidate loci, pending further sequencing and functional analyses. Sequence data were generated for two of the candidate loci, but population genetics tests failed to detect deviations from neutral evolution at either locus. Nonetheless, a greater than eight-fold excess of nonsynonymous substitutions was found near a putative N-myristoylation motif at the second locus (HT998), and likelihood-based models indicated that the protein has been under selection in H. anomalus in the past and, perhaps, in one or both parental species. Finally, our data suggest that selective sweeps may have united populations of H. anomalus isolated by a mountain range, indicating that even low gene-flow species may be held together by the spread of advantageous alleles.

Imageless navigation for insertion of the acetabular component in total hip arthroplasty

In a prospective randomised clinical study acetabular components were implanted either freehand (n = 30) or using CT-based (n = 30) or imageless navigation (n = 30). The position of the component was determined post-operatively on CT scans of the pelvis. Following conventional freehand placement of the acetabular component, only 14 of the 30 were within the safe zone as defined by Lewinnek et al (40 degrees inclination sd 10 degrees ; 15 degrees anteversion sd 10 degrees ). After computer-assisted navigation 25 of 30 acetabular components (CT-based) and 28 of 30 components (imageless) were positioned within this limit (overall p < 0.001). No significant differences were observed between CT-based and imageless navigation (p = 0.23); both showed a significant reduction in variation of the position of the acetabular component compared with conventional freehand arthroplasty (p < 0.001). The duration of the operation was increased by eight minutes with imageless and by 17 minutes with CT-based navigation. Imageless navigation proved as reliable as that using CT in positioning the acetabular component.

Sequence variation in the dihydrofolate reductase-thymidylate synthase ( DHFR-TS) and trypanothione reductase ( TR) genes of Trypanosoma cruzi

Dihydrofolate reductase-thymidylate synthase ( DHFR-TS) and trypanothione reductase ( TR) are important enzymes for the metabolism of protozoan parasites from the family Trypanosomatidae (e.g. Trypanosoma spp., Leishmania spp.) that are targets of current drug-design studies. Very limited information exists on the levels of genetic polymorphism of these enzymes in natural populations of any trypanosomatid parasite. We present results of a survey of nucleotide variation in the genes coding for those enzymes in a large sample of strains from Trypanosoma cruzi, the agent of Chagas’ disease. We discuss the results from an evolutionary perspective. A sample of 31 strains show 39 silent and five amino acid polymorphisms in DHFR-TS, and 35 silent and 11 amino acid polymorphisms in TR. No amino acid replacements occur in regions that are important for the enzymatic activity of these proteins, but some polymorphisms occur in sites previously assumed to be invariant. The sequences from both genes cluster in four major groups, a result that is not fully consistent with the current classification of T. cruzi in two major groups of strains. Most polymorphisms correspond to fixed differences among the four sequence groups. Two tests of neutrality show that there is no evidence of adaptive divergence or of selective events having shaped the distribution of polymorphisms and fixed differences in these genes in T. cruzi. However, one nearly significant reduction of variation in the TR sequences from one sequence group suggests a recent selective event at, or close to, that locus.

Early newborn discharge: a tale of two hospitals.

This study reviews physician documentation of compliance with The American Academy of Pediatrics (AAP) policy RE9539 regarding early newborn hospital discharge and follow-up. All pediatricians in Kalamazoo, MI, were educated at a grand rounds regarding the AAP early newborn discharge policy. Newborns are seen at 2 community hospitals. One of them simultaneously instituted a Quality Improvement/Feedback (QI/F) program regarding early newborn discharge, (intervention) and the other 1 did not (control). This is a retrospective chart analysis that compares performance of 4 pediatric practices seeing newborns at each hospital. Each practice was compared at each hospital for appropriateness of discharge orders before and after the educational grand rounds and the QI/F initiative. Statistical analysis was done using the chi square test and the Breslow-Day test for homogeneity, and the Fisher's Exact Test. Odds ratios with a 95% confidence interval based on Taylor's approximation were used. There were no significant differences between the pediatric practices' performance before and after the educational initiative at the control hospital. There were significant differences before and after the educational initiative in the intervention hospital with the QI/F initiative. There was a significant reduction in variation among the practices after the QI/F initiative at the intervention hospital. When both hospitals were compared after the educational initiative, there was a significant difference between compliance among the same practices at each hospital, with better compliance at the intervention hospital with the QI/F initiative. There were significant differences in physicians' performance at the intervention hospital before and after the educational and QI/F initiatives. However, it was noted that the very same physicians did not comply as well in the control hospital without the QI/F initiative, thus still raising questions as to whether QI measures alter physician "culture." It is possible that the driving force for change in physician behavior was more intragroup peer pressure than an external QI/F initiative.

Genetic variation in a human immunodeficiency virus type 2 live-virus Macaca nemestrina vaccine model.

Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2KR) and subsequently challenged with a highly pathogenic strain, HIV-2287, together with two naive control animals. After challenge, two animals inoculated with a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity in protection, fragments of the env gene were amplified from peripheral blood mononuclear cell DNA and plasma RNA of challenged animals by PCR, examined by using a heteroduplex tracking assay (HTA), and sequenced. By HTA, variation was detected principally within the V1 and V2 regions of envelope. Extent of variation in viral DNA clones as assessed by HTA correlated with inoculum size, as did the degree of variation in sequences of clones derived from viral DNA. Conversely, a rapid reduction in the number of plasma viral RNA variants was noted by HTA at 8 weeks postinfection in protected animals; this reduction was not present in naive or unprotected macaques. Sequences derived from plasma viral RNA were found to be more closely related than corresponding viral DNA sequences, and protection correlated with a significant reduction in variation in plasma RNA sequences in animals given the identical inocula of HIV-2287. Nonsynonymous mutations were significantly less prevalent in the protected animals. An additional potential glycosylation site was predicted to be present in the V2 region in all but one clone, and amino acid signatures related to protection were identified in viral DNA and RNA clones within both the V1 and V2 regions. Examination of the role of viral variation in this HIV-2 live-virus vaccine model may provide valuable insights into immunopathogenesis.

The MAR-Mediated Reduction in Position Effect Can Be Uncoupled from Copy Number-Dependent Expression in Transgenic Plants.

To study the role of matrix-associated regions (MARs) in establishing independent chromatin domains in plants, two transgenes were cloned between chicken lysozyme A elements. These transgenes were the neomycin phosphotransferase (NPTII) gene under control of the nopaline synthase (nos) promoter and the [beta]-glucuronidase (GUS) gene controlled by the double cauliflower mosaic virus (dCaMV) 35S promoter. The A elements are supposed to establish an artificial chromatin domain upon integration into the plant DNA, resulting in an independent unit of transcriptional regulation. Such a domain is thought to be characterized by a correlated and position-independent, hence copy number-dependent, expression of the genes within the domain. The presence of MARs resulted in a higher relative transformation efficiency, demonstrating MAR influence on NPTII gene expression. However, variation in NPTII gene expression was not significantly reduced. The selection bias for NPTII gene expression during transformation could not fully account for the lack of reduction in variation of NPTII gene expression. Topological interactions between the promoter and A element may interfere with the A element as a domain boundary. In contrast, the GUS gene on the same putative chromatin domain showed a highly significant reduction in variation of gene expression, as expected from previous results. Surprisingly, no copy number-dependent GUS gene expression was observed: all plants showed approximately the same GUS activity. We concluded, therefore, that dCaMV 35S-GUS gene expression in mature tobacco plants is regulated by some form of dosage compensation.

Effects of Short‐Term Selection Along Environmental Gradients on Variation in Populations of Amaranthus Retroflexus and Abutilon Theophrasti

This study examines the effects of short—term selection along resource gradients on variation within plant populations. Populations of Amaranthus retroflexus and Abutilon theophrasti were subjected to four generations of selection in the following treatments: soil moisture (low, moderate, or high), diversity of competitor species (low, moderate, or high), and density (low or high). In several cases such selection resulted in significant divergence of the population from its original configuration. The changes occurred in such characters as photosynthetic rate, reproductive allocation, flowering time, root/shoot allocation, and shoot biomass. In all cases where significant changes in overall level of variation occurred, these were in the direction of reduced variation. The rapidity and nature of these changes differed according to the level and type of treatment. Reductions in variation occurred almost uniformly in the density treatments. In contrast, changes in variation were most unpredictable in the diversity treatments, owing to a high level of variability in the competitive background that was apparently associated with generation—to—generation variability in light and temperature. In some generations Abutilon theophrasti was greatly suppressed by heterosopecific competitors. This resulted in a significant reduction in variation in spite of high levels of environmental variability. Thus environmental variation in itself may not be sufficient to maintain variation in the population of extreme fluctuation in population size results in genetic bottlenecks. Levels of morphological and physiological variation were maintained in all but a low— and a moderate—moisture line of Amaranthus retroflexus, but the diversity of electrophoretically marked genotypes declined in all moisture treatments. The loss of variation at moderate soil moistures may be due to an overlying gradient of conspecific competition, a situation which cannot be avoided in even the simplest of gradients. Despite significant changes in several characters and in levels of overall variation, technological and analytical tools were found to be inadequate to determine if these changes led to significant and consistent differences in the response patterns of the species along these gradients.

A CASE OF DARWINIAN SELECTION IN BEARS

Differential or mortality is one aspect of selection, not the only one but of great importance. It is the same concept as Darwin's and Wallace's survival of the fittest and may properly be styled Darwinian selection. Such differential may favor variants close to the population mode, while weeding out more extreme variants through higher mortality rates than the population average. This is stabilizing selection, as it is sometimes called; centripetal selection (Simpson, 1954) would seem to be a happier expression. A population in this situation is, on an average, well-adapted; the selection tends only to promote the central or most frequent type in the population. As another possibility, a linear component (ibid.) may enter into the complex. The selection is then directed towards an optimum different from the population mode, within or outside the realized population range of variation. Such instances are apparently less common, because a population of this type is not optimally adapted, and will tend to adapt by utilization of its genetic variability; if no suitable variability is available, it is rather likely to become extinct. Instances of differential affecting mammalian teeth have been given in Kurten (1953, 1955 b). The study of differential mortality is particularly easy on mammalian tooth crowns, because variation caused by growth does not occur. If care is taken to select a mensuration system not affected by the wear or by the disposition of the tooth in the jaw, any significant reduction of variation or change of mean in a cohort, with increasing age, is therefore due to differential survival, or Darwinian selection. A necessary prerequisite for study of this kind is the existence of large and homogeneous samples, because the changes in variances and means are generally subtle, and only a large material can be used for the statistical establishing of such trends. It should also be possible to make some kind of age grouping, even if only a crude distinction between young and old individuals, with unworn and worn tooth crowns, respectively.