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Paul Matthews

Publications and source records attributed to Paul Matthews.

8 recordsLinked to original sources
PubMed2026

Refining the Multivariable Predictive-Prognostic PREDICTR-OPC Model for Survival in Surgical Escalation for Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: The PREDICTR-OPC model is the only prognostic classifier for oropharyngeal squamous cell carcinoma (OPSCC) also predictive of surgical outcomes. Of the four biomarkers included, survivin contributes minimally and presents practical limitations. This study aimed to refine and simplify the model by removing survivin, then re-assess its prognostic predictive performance compared to the original. METHODS: This retrospective cohort study analyzed a multi-center training cohort (n&#x2009;=&#x2009;600) and an external validation cohort (n&#x2009;=&#x2009;385) of OPSCC patients. Tumor biopsies were stained for p16, high-risk human papillomavirus (HR-HPV) DNA, tumor-infiltrating lymphocytes (TILs), and survivin and independently scored by at least three certified pathologists. Cox proportional hazards models assessed overall survival (OS), comparing three-biomarker (p16, HR-HPV, TILs) and four-biomarker models. Hazard ratios (HRs) for OS were estimated in the validation cohort, adjusting for covariates. Discrimination, calibration, and decision curve analysis (DCA) evaluated performance and clinical utility. RESULTS: Among 985 patients (median age: 57&#x2009;years), median OS&#x2009;=&#x2009;8.8&#x2009;years (95% CI: 6.9-10.5). The three-biomarker model yielded HR&#x2009;=&#x2009;4.10 (95% CI: 2.41-6.98, p&#x2009;<&#x2009;0.001) for high- vs. low-risk groups in the validation cohort, comparable to the four-biomarker model (HR&#x2009;=&#x2009;4.24, p&#x2009;<&#x2009;0.001). Surgery was associated with improved OS in high-risk (HR&#x2009;=&#x2009;0.45, p&#x2009;=&#x2009;0.001) but not low-risk (HR&#x2009;=&#x2009;0.83, p&#x2009;=&#x2009;0.72) patients, consistent with the original model. The models performed similarly across all metrics (e.g., Concordance Index: 0.71 vs. 0.72; Brier Score: 0.22 for both) as was model fit (Likelihood Ratio Test: p&#x2009;=&#x2009;0.066). DCA revealed comparable clinical benefit. CONCLUSION: Removing survivin preserves PREDICTR-OPC's predictive performance, offering a more cost-effective, easier-to-implement tool for OPSCC treatment recommendations.

Humans↗
PubMed2002

Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

Amino Acid Sequence↗
PubMed2002

Evidence for asymmetric frontal-lobe involvement in episodic memory from functional magnetic resonance imaging and patients with unilateral frontal-lobe excisions.

Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.

Female↗
PubMed2002

Activity in the fusiform gyrus predicts conscious perception of Rubin's vase-face illusion.

We localized regions in the fusiform gyrus and superior temporal sulcus that were more active when subjects viewed photographs of real faces than when they viewed complex inanimate objects and other areas in the parahippocampal gyrus and the lateral occipital lobe that showed more activity during the presentation of nonface objects. Event-related functional magnetic resonance imaging was then used to monitor activity in these extrastriate visual areas while subjects viewed Rubin's vase-face stimulus and indicated switches in perception. Since the spontaneous shifts in interpretation were too rapid for direct correlation with hemodynamic responses, each reported percept (faces or vase) was prolonged by suddenly adding subtle local contrast gradients (embossing) to one side or the other of the figure-ground boundary, stabilizing the percept. Under these conditions, only face-selective areas in the fusiform gyrus responded more strongly during the perception of faces. To control for effects of the physical change to Rubin's stimulus (i.e., addition of embossing), we compared activity when the face contours were embossed after the subject had just reported the onset of perception of either faces or vase. Activity in the fusiform face area responded more strongly under the first condition, despite the fact that the physical stimulus sequences were identical. Moreover, on a trial-to-trial basis, the activity was statistically predictive of the subjects' responses, suggesting that the conscious perception of faces could be made explicit in this extrastriate visual area.

Adult↗
PubMed2002

Asymmetric growth of models of avascular solid tumours: exploiting symmetries.

In this paper a mathematical model of avascular tumour growth is studied. Attention focuses on the stability of radially symmetric model solutions to perturbations involving spherical harmonics Ylm (theta, phi). Linear theory is used to identify bifurcation points at which the radially symmetric steady state loses stability. The first modes to become unstable are shown to correspond to the l = 2 spherical harmonics. Results from group theory and weakly nonlinear analysis indicate the structure of the l = 2 bifurcation point is a transcritical bifurcation in which all nontrivial solution branches are unstable. By proceeding to third order and focusing on a special set of parameter values for which the quadratic terms are negligible, it is shown that the system's behaviour in a neighbourhood of the l = 2 bifurcation point is governed by a subcritical bifurcation. In consequence, the nontrivial asymmetric solution branches in a neighbourhood of the bifurcation point are unstable. The branches of asymmetric solutions bound the domain of attraction of the radially symmetric tumour configuration where it is locally stable. The analytical results that are derived lead us to conjecture that any stable asymmetric tumour structures will involve spherical harmonics of order l > or = 3.

Cell Division↗