132,733 research outputs found
The fractional variation and the precise representative of functions
No full textWe continue the study of the fractional variation following the distributional approach developed in the previous works Brue et al. (2021), Comi and Stefani (2019), Comi and Stefani (2019). We provide a general analysis of the distributional space BV alpha,p(R-n) of L-p functions, with p is an element of [1, +infinity], possessing finite fractional variation of order alpha is an element of (0, 1). Our two main results deal with the absolute continuity property of the fractional variation with respect to the Hausdorff measure and the existence of the precise representative of a BV alpha,p function
The fractional variation and the precise representative of BV alpha,p functions
No full textWe continue the study of the fractional variation following the distributional approach developed in the previous works Bruè et al. (2021), Comi and Stefani (2019), Comi and Stefani (2019). We provide a general analysis of the distributional space BVα,p(Rn) of Lp functions, with p∈ [1 , + ∞] , possessing finite fractional variation of order α∈ (0 , 1). Our two main results deal with the absolute continuity property of the fractional variation with respect to the Hausdorff measure and the existence of the precise representative of a BVα,p function
Validity and responsiveness of the Core Outcome Measures Index (COMI) for the neck
No full textPatient-orientated outcome questionnaires are essential to evaluate treatment success. To compare different treatments, hospitals, and surgeons, standardised questionnaires are required. The present study examined the validity and responsiveness of the Core Outcome Measurement Index for neck pain (COMI-neck), a short, multidimensional outcome instrument
Asymptotic homogenization of metamaterials elastic plates
No full textThe asymptotic homogenization technique is applied to evaluate the effective properties of thin plates with periodic heterogeneity. The effect of shear deformation in the homogenization process is evidenced and the role of cell slenderness, besides that of the plate, is clarified by several numerical analyses
Development of a mapping function ("crosswalk") for the conversion of scores between the Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI).
No full textINTRODUCTION
The Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI) are two commonly used self-rating outcome instruments in patients with lumbar spinal disorders. No formal crosswalk between them exists that would otherwise allow the scores of one to be interpreted in terms of the other. We aimed to create such a mapping function.
METHODS
We performed a secondary analysis of ODI and COMI data previously collected from 3324 patients (57 ± 17y; 60.3% female) at baseline and 1y after surgical or conservative treatment. Correlations between scores and Cohen's kappa for agreement (κ) regarding achievement of the minimal clinically important change (MCIC) score on each instrument (ODI, 12.8 points; COMI, 2.2 points) were calculated, and regression models were built. The latter were tested for accuracy in an independent set of registry data from 634 patients (60 ± 15y; 56.8% female).
RESULTS
All pairs of measures were significantly positively correlated (baseline, 0.73; 1y follow-up (FU), 0.84; change-scores, 0.73). MCIC for COMI was achieved in 53.9% patients and for ODI, in 52.4%, with 78% agreement on an individual basis (κ = 0.56). Standard errors for the regression slopes and intercepts were low, indicating excellent prediction at the group level, but root mean square residuals (reflecting individual error) were relatively high. ODI was predicted as COMI × 7.13-4.20 (at baseline), COMI × 6.34 + 2.67 (at FU) and COMI × 5.18 + 1.92 (for change-score); COMI was predicted as ODI × 0.075 + 3.64 (baseline), ODI × 0.113 + 0.96 (FU), and ODI × 0.102 + 1.10 (change-score). ICCs were 0.63-0.87 for derived versus actual scores.
CONCLUSION
Predictions at the group level were very good and met standards justifying the pooling of data. However, we caution against using individual values for treatment decisions, e.g. attempting to monitor patients over time, first with one instrument and then with the other, due to the lower statistical precision at the individual level. The ability to convert scores via the developed mapping function should open up more centres/registries for collaboration and facilitate the combining of data in meta-analyses
Novel network pharmacology methods for drug mechanism of action identification, pre-clinical drug screening and drug repositioning
No full textThe high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Here we present two methodology innovations on network pharmacology modeling. (1) We hypothesize that the gene network associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. We proposed a novel in vivo genetic interaction between genes as ‘synergistic outcome determination’, in a similar way to ‘synthetic lethality’. We scanned above genetic interactions based on microarray profiling for cancer prognosis, and identified a cluster of important yet epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to this network, we could define a perturbation index for each drug based upon its characteristic perturbation pattern. Finally, by using this index, we significantly discriminated successful drugs from the candidate pool, and revealed the mechanisms of drug combinations. Thus, the prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies. Part of this work was published, and we will present new results on this project. (2) MicroRNAs (miRNAs) play a key role in the regulation of the transcriptome and have been identified as a key mediator in human disease and drug response. we introduced a novel concept, the Context-specific MiRNA activity (CoMi activity), to reflect a miRNA’s regulation effect on a context specific gene set .Using breast cancer as an example, we examined the CoMi activity based on a Gene Ontology (GO) term as context. Interestingly, we found that chemotherapeutic drug treatment can counteract the dis-regulated CoMi activity in the cancer-specific network. For instance, 100% of down-regulated CoMi activities in a “core” breast cancer network contains apoptosis-related GO terms that could be counteracted by Paclitaxel treatment. By defining a Stability Index for in silico drug screening, we found CoMi activity signatures strikingly outperformed the traditional CMAP method or mRNA-based signatures. Thus, the dynamic remodeling of context-specific miRNAs regulation network could reveal the hidden miRNAs that act as key mediators of drug action and facilitate in silico cancer drug screening
The CoMi pattern used to predict pCR in clinical trials involving Paclitaxel.
No full text<p>(a) Graphical summary of correlation analysis between the CoMi pattern across samples and the outcome of pCR status. The edges represent activities pattern where green lines indicate highly negative correlations, red lines indicate positive correlations. (b) The expression distribution of the gene ESR1 in the two groups of pCR and no pCR patients. (c.) The distribution of the CoMi index (hsa-miR-18a on “Regulation of transcription, DNA-dependent”) in two the groups of patients. (d.) The fold change of the average expression from the patients without pCR to the group of people has pCR of the gene ESR1 and the CoMi pattern. The blue bar represents the average value of CoMi Index of patients without pCR, while the red bar is the average value of the group of patients with pCR. (e.) The regulation network of two CoMi activities with its target gene. Gene ESR1 is the target of the CoMi pattern of hsa-miR-18a's regulation on the GO term “Regulation of transcription, DNA-dependent”, it is also the target of the CoMi pattern of hsa-miR-33a's regulation on the GO term “Regulation of transcription, DNA-dependent”.</p
Impact absorption in auxetic damageable materials
No full textIn this work we study the behaviour of elastic and quasi-brittle auxetic metamaterial under impact. Particular reference is made
to the use of these structured materials for facial protector devices for sport activities. Impact analyses of a ball over an auxetic and a non-
auxetic honeycomb material show the potential benefit of the densification mechanism occurring in the auxetic material below the
impacted region. Moreover, when the bulk material is assumed to have a brittle behaviour, the auxetic lattice in compression develops a
smaller damage with respect to the honeycomb, non-auxetic lattice. This can be another advantage in impact absorption applications
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