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This paper derives a free analogue of the Euler-Maruyama method (fEMM) to numerically approximate solutions of free stochastic differential equations (fSDEs). Simply speaking, fSDEs are SDEs in the context of noncommutative random variables (e.g., large random matrices). By applying the theory of multiple operator integrals, we derive a free Itô formula from Taylor expansion of operator-valued functions. Iterating the free Itô formula allows us to motivate and define fEMM. Then we consider weak and strong convergence in the fSDE setting and prove strong convergence order of 1/2 and weak convergence order of 1. Numerical examples support the theoretical results and show solutions for equations where no analytical solution is known. [ABSTRACT FROM AUTHOR]

We introduce a cohomology set for groups defined by algebraic difference equations and show that it classifies torsors under the group action. This allows us to compute all torsors for large classes of groups. We also present an application to the Galois theory of differential equations depending on a discrete parameter. [ABSTRACT FROM AUTHOR]

Horses and humans share a close relationship that includes both species' viromes. Many emerging infectious diseases can be transmitted between horses and humans and can exhibit mortality rates as high as 90% in both populations. Antibody biologics represents an emerging field of rapidly discoverable and potent antiviral therapeutics. These biologics can be used to provide passive immunity, as well as blueprints for the rational design of novel active vaccine antigens. Here, we exploit the limited diversity of immunoglobulin variable genes used by horses to develop a rapid, high-throughput monoclonal antibody discovery pipeline. The antibodies isolated from two horses in this study were developed with near exclusivity from a few highly related germline genes within a single IgHV and IgλV gene family and could be recovered for cloning with just three primer pairs. This variable gene pairing was compatible with both horse and human immunoglobulin G isotypes, confirming the suitability of an equine antibody discovery pipeline for developing novel therapeutics to meet the One Health approach to infectious diseases. [ABSTRACT FROM AUTHOR]

Introduction/Background: Magnetic resonance imaging (MRI) misses a proportion of "clinically significant" prostate cancers (csPC) as defined by histopathology cr iter ia. The aim of this study was to analyze whether long-term oncologic outcomes differ between MRI-detectable and MRI-occult csPC. Patients and Methods: Retrospective analysis of 1449 patients with pre-prostatectomy MRI and csPC on prostatectomy specimens (ie, Grade group =2 or extraprostatic spread) between 2001-2006. T2-weighted MRIs were classified according to the Prostate Imaging Reporting and Data System into MRI-occult (categories 1, 2), MRI-equivocal (category 3), and MRI-detectable (categories 4, 5). Cumulative incidence of biochemical recurrence (BCR), metastatic disease, and cancer-specific mortality, estimated with competing risk models. The median follow-up in survivors was 11.0 years (IQR: 8.9-13.1). Results: In 188 (13%) cases, csPC was MRI-occult, 435 (30%) MRIs were equivocal, and 826 (57%) csPC were MRI-detectable. The 15-year cumulative incidence [95% CI] of BCR was 8.3% [2.2, 19.5] for MRI-occult cases, 17.4% [11.1, 24.8] for MRI-equivocal cases, and 43.3% [38.7, 47.8] for MRI-detectable cases (P < .001). The cumulative incidences of metastases were 0.61% [0.06, 3.1], 3.5% [1.5, 6.9], and 19.6% [15.4, 24.2] for MRI-occult, MRI-equivocal, and MRI-detectable cases, respectively (P < .001). There were no deaths from prostate cancer observed in patients with MRI-occult csPC, compared to an estimated 1.9% [0.54, 4.9], and 7.1 % [4.5, 10.6] for patients with MRI-equivocal and MRI-detectable cancer, respectively (P < .001). Conclusion: Oncologic outcomes after prostatectomy for csPC differ between MRI-occult and MRI-detectable lesions. Judging the clinical significance of a negative prostate MRI based on histopathologic surrogates alone might be misleading.Microabstract: Among 1449 patients with pre-prostatectomy MRI and clinically significant prostate cancer on prostatectomy histopathology, MRI-occult cancers (n = 188, 13%) were less likely to recur biochemically (8% vs. 43%, P < .001), metastasize (0.6% vs. 20%, P < .001), or lead to prostate cancer mortality (0% vs. 7%, P < .001) than MRI-detectable cancers (n = 826, 57%). MRI-occult cancers constitute a prognostically distinct subgroup among higher-grade prostate cancers. [ABSTRACT FROM AUTHOR]

We establish several finiteness properties of groups defined by algebraic difference equations. One of our main results is that a subgroup of the general linear group defined by possibly infinitely many algebraic difference equations in the matrix entries can indeed be defined by finitely many such equations. As an application, we show that the difference ideal of all difference algebraic relations among the solutions of a linear differential equation is finitely generated. [ABSTRACT FROM AUTHOR]

Background: Neck reflex points (NRPs) are 2 × 6 potentially tender areas of the neck, denominated NRP-C0 to NRP-C7. They are different from muscular trigger points and become tender in response to chronic trigeminal irritation. NRP examination has a high inter-rater reproducibility. We investigated the prevalence of NRPs in two populations to investigate their usefulness as a clinical test for trigeminal irritation. Methods: In total, 165 patients with chronic pain and 431 students were examined for NRP tenderness using a three-level pain scale: absent pain (PI = 0), mild tenderness (PI = 1), or marked tenderness (PI = 2). Results: In patients, we found more tender NRPs than in the student group (p < 0.001), and on the left side, more tender NRPs were found in NRP-C0–C4. Left and right NRPs appeared independently (kappa 0.1–0.4), except for NRP-C7 (kappa 0.55). Females had more tender NRPs (p < 0.001). Tenderness was independent of age, BMI, and pre-existing diseases. Conclusions: NRP tenderness occurs more frequently in patients than in students, independent from potential covariates. Our results, together with previous findings, support the use of NRP examination as a clinical test for chronic silent inflammation of the trigeminal region. These data provide a base for further studies investigating correlations of NRPs with clinical findings. [ABSTRACT FROM AUTHOR]

We lay the foundations for a model theoretic study of proalgebraic groups. Our axiomatization is based on the tannakian philosophy. Through a tensor analog of skeletal categories we are able to consider neutral tannakian categories with a fibre functor as many-sorted first order structures. The class of diagonalizable proalgebraic groups is analyzed in detail. We show that the theory of a diagonalizable proalgebraic group G is determined by the theory of the base field and the theory of the character group of G. Some initial steps towards a comprehensive study of types are also made. [ABSTRACT FROM AUTHOR]

Purpose: To explore associations between magnetic resonance imaging (MRI) features of prostate cancer and expression levels of cell cycle genes, as assessed by the Prolaris® test. Materials and methods: Retrospective analysis of 118 PCa patients with genetic testing of biopsy specimen and prostate MRI from 08/2013 to 11/2015. Associations between the cell cycle risk (CCR) score and MRI features [i.e., PI-RADSv2 score, extracapsular extension (ECE), quantitative metrics] were analyzed with Fisher's exact test, nonparametric tests, and Spearman's correlation coefficient. In 41 patients (34.7%), test results were compared to unfavorable features on prostatectomy specimen (i.e., Gleason group ≥ 3, ECE, lymph node metastases). Results: Fifty-four (45.8%), 60 (50.8%), and 4 (3.4%) patients had low-, intermediate-, and high-risk cancers according to American Urological Association scoring system. Patients with ECE on MRI had significantly higher mean CCR scores (reader 1: 3.9 vs. 3.2, p = 0.015; reader 2: 3.6 vs. 3.2, p = 0.045). PI-RADSv2 scores and quantitative MRI features were not associated with CCR scores. In the prostatectomy subset, ECE on MRI (p = < 0.001–0.001) and CCR scores (p = 0.049) were significantly associated with unfavorable histopathologic features. Conclusion: The phenotypic trait of ECE on MRI indicates a more aggressive genotype of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: We analysed socio-economic- and health-related quality of life (primary outcome) and radiological outcome (secondary outcome) 5 years after full time rigid bracing (FTRB) plus physiotherapeutic scoliosis-specific exercises (PSSE) in adolescent idiopathic scoliosis.Methods: We included 41 patients (38 female and 3 male) treated with FTRB (Chênau brace) and PSSE (Schroth) between 2001 and 2010. The study protocol included a clinical and radiological examination, the completion of the SRS-24 questionnaire and acquisition of data on socio-economic factors (educational and employment status) and physical activity. Descriptive statistics were used to analyse the data; differences between patients with mild (< 30°) and severe curves (30°-50°) regarding hrQoL outcomes were analysed using the Mann-Whitney U Test.Results: Primary outcomes showed full employment (higher education, 39%, and full-time work, 61%) and the majority of the patients (79.9%) performing moderate sports two to four times per week. The SRS-24 questionnaire produced a total mean score (MS) of 4.0 (79.9%). Patients with mild curves had a significantly better total score (MS 4.1 vs. MS 3.8, p = 0.020) and were more satisfied with the treatment (MS 4.3 vs MS 3.9, p = 0.020). As to the secondary outcomes, from start of bracing to follow-up (a mean of 6.7 years after brace weaning), the average Cobb angle changed from 28.6° to 25.6° (range 4°-48°); in 51.2% the curve angles could be maintained after weaning.Conclusions: Compared with the literature, our results showed similar curve development and hrQoL (pain, self-image and function) and better results regarding satisfaction with treatment. In comparison with the average population, there were no disadvantages as to occupation, education and sports. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

We introduce a class of strongly étale difference algebras , whose role in the study of difference equations is analogous to the role of étale algebras in the study of algebraic equations. We deduce an improved version of Babbitt's decomposition theorem and we present applications to difference algebraic groups and the compatibility problem. [ABSTRACT FROM AUTHOR]

Introduction. Indications discussed for the implantation of expandable prostheses in bone sarcoma patients are unclear. This survey aimed to analyse common practice with this implant type in orthopaedic oncology. Methods. A web-based survey was sent to 98 orthopaedic oncology surgeons. Factors reported in literature to influence the decision on the implantation of a growing prosthesis were covered in individual questions and three case scenarios. Results. The completion rate of the survey was 45% (n = 44). Twenty-seven of 44 surgeons (61%) had implanted between 1 and 15 expandable prostheses within three years. The minimum median patient age was 6.5 years, and 3–5 cm of predicted growth deficit was the minimum before implanting a growing prosthesis. One-third of surgeons do not use growth calculation methods. Two out of three surgeons would rather not implant a growing prosthesis in children with metastatic disease. Conclusions. Our survey confirmed the literature with 3-4 cm as the minimum estimated growth deficit. The minimum age for the implantation of a growing prosthesis is approx. 6.6 years, and therefore the patients are younger than those reported in previous publications. One-quarter of orthopaedic surgeons do not use growing prostheses at all. It remains unclear whether growing prostheses are indicated in patients with metastatic disease. [ABSTRACT FROM AUTHOR]

Background: Open conversions (OC) due to failed endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) are technically demanding because of preexisting prostheses and advanced aortic disease. This study evaluates the feasibility and outcomes of aorto-uniiliac endografting (AUI) as an alternative treatment option in acute failed EVAR.Methods: From March 1995 through February 2012, 26 patients underwent acute conversion of failed EVAR at our tertiary care university center. All data were prospectively entered in our institutional database. Outcomes included 30-day or in-hospital mortality, postoperative complications, and mid-term survival.Results: During the investigation period, a total of 692 patients received EVAR at our institution, while five of the 26 patients with acute conversion (19.2%) had an initial EVAR at an outlying institution and were referred for treatment. Therefore, our estimated institutional rate of acute conversions was 3% (21 of 692 EVAR). OC were performed in 14 patients (53.8%), while 12 patients underwent AUI (46.2%). An average time of 20.3 months (median: 18.6; interquartile range Q1-Q3: 0.0-38.6) elapsed between the initial EVAR and the acute conversion. All acute AUI conversion procedures were completed successfully. The 30-day mortality following acute conversions was 42.3% and since the use of AUI, it could be reduced to 33.3%. Kaplan-Meier estimates revealed a survival advantage for AUI at one year (p = 0.046), but the benefit was lost by mid-term follow-up (p = 0.103).Conclusions: AUI for the treatment of acute failed EVAR represents a feasible and less invasive alternative to OC, and is associated with better one-year survival rates. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design. [ABSTRACT FROM AUTHOR]

All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/ founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycandependent CD4 binding site B-cell lineage. [ABSTRACT FROM AUTHOR]

The added value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection, localization, and staging of primary prostate cancer has been extensively reported in original studies and meta-analyses. More recently, DW-MRI and related techniques have been used to noninvasively assess prostate cancer aggressiveness and estimate its biological behavior. The present article aims to summarize the potential applications of DW-MRI for noninvasive optimization of pretherapeutic risk assessment, patient management decisions, and evaluation of treatment response. [ABSTRACT FROM AUTHOR]

Background: Sarcomas infiltrating the knee joint require extraarticular resection to achieve wide margins. Opinions differ as to whether the superior tibiofibular joint (STFJ) is part of the knee joint and should be removed in the course of extraarticular resection. Thus, we investigated the frequency of communication between the tibiofemoral joint (TFJ) and the STFJ, and the reported local recurrence rates (LRR) following extraarticular knee resection. Methods: A systematic literature review on STFJ and TFJ communication and local recurrence rates following extraarticular knee resections was undertaken. Results: Cadaver studies detected communication between the TFJ and STFJ in 10-64 % of the cases. Direct arthrography with physical loading verified a 100 % communication rate. Regarding the extent of extraarticular knee resection, two institutions where the STFJ was resected had a LRR of 4-8 %, while studies from another three where the STFJ was not routinely resected reported a LRR of 0-21 %. Conclusions: Since the literature reports about a 100 % communication rate between the TFJ and the STFJ, resection of the STFJ in patients with sarcomas involving the knee joint would seem to be indicated, although it is not clear whether resection of the STFJ reduces local recurrence rates. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective cohort study.Objective: The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from spinal bone metastases Just (SBMs).Summary Of Background Data: On the basis of the estimated survival of patients with SBM, extent of treatment can be adjusted. To aid clinicians in the difficult task of assessing probability of survival, prognostic scoring systems have been developed by Tomita, Tokuhashi, Van der Linden, Bauer, Rades, and Bollen.Methods: All patients who were treated for SBM between 2000 and 2010 were included in this international, multicenter, retrospective study (n = 1379). Medical records were reviewed for all items needed to use the scoring systems. Survival time was calculated as the difference between start of treatment for SBM and date of death. Survival curves were estimated using the Kaplan-Meier method and accuracy was assessed with the c-statistic. Survival rates of the worst prognostic groups were evaluated at 4 months.Results: Median follow-up was 6.7 years [95% confidence interval (95% CI) 5.6-7.7] with a minimum of 2.3 years and a maximum of 12.3 years. The overall median survival was 5.1 months (95% CI 4.6-5.6). The most common primary tumors were breast (n = 388, 28%), lung (n = 318, 23%), and prostate cancer (n = 259, 19%). The Tokuhashi, Bauer, Tomita, and Van der Linden models performed similar with a c-statistic of 0.64 to 0.66 and a 4-month accuracy of 62% to 65%. The Rades model (c-statistic 0.44) and Bollen model (c-statistic 0.70) had a 4-month accuracy of 69% and 75%, respectively.Conclusion: The Bollen model performs better than the other models. However, improvements are still warranted to increase the accuracy.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

During physical exercise, pulse transit time (PTT), expressed as the interval between ventricular electrical activity and peripheral pulse wave, may provide a surrogate estimate for blood pressure by the use of specific calibration procedures. The objective of this study was to determine systolic blood pressure (SBP) values derived from the PTT method and from an established method of non-invasive continuous blood pressure measurement based on the volume clamp technique, and to compare their agreement with sphygmomanometry during exercise tests. In 18 subjects, electrocardiogram (ECG) and finger-photoplethysmography were continuously recorded during maximal cycle exercise tests. Intermittent and continuous blood pressure measurements were simultaneously taken using automated sphygmomanometry and a Portapres Model-2 device, respectively. PTT was calculated for each ECG R-wave and the corresponding steepest upstroke slope in the photoplethysmogram, and was transformed to a continuous blood pressure estimate using multipoint nonlinear regression calibration based on the individual subject's sphygmomanometer readings. Bland–Altman limits of agreement between PTT-derived SBP estimates and sphygmomanometer values were –24.7 to 24.1 mmHg, and between Portapres and sphygmomanometer SBP values were –42.0 to 70.1 mmHg. For beat-to-beat SBP estimation during exercise, PTT measurement combined with multipoint nonlinear regression calibration based on intermittent sphygmomanometry may be an alternative to volume clamp devices. [ABSTRACT FROM PUBLISHER]

Objectives: To investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS). Methods: One hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations. Results: PZ cancers (n = 143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values: <.0001-0.008). In TZ cancers (n = 43) we observed significant differences for all five texture features on the ADC map (all p-values: <.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225; 6 vs. >7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs. >7: p = 0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly different in GS ≤3 + 4 versus ≥4 + 3 cancers; ADC map Entropy remained significant after controlling for the median ADC (p = 0.0291). Conclusion: Several Haralick-based texture features appear useful for prostate cancer detection and GS assessment. Key Points: • Several Haralick texture features may differentiate non-cancerous and cancerous prostate tissue. • Tumour Energy and Entropy on ADC maps correlate with Gleason score. • T2w-image-derived texture features are not associated with the Gleason score. [ABSTRACT FROM AUTHOR]

Purpose: Estimating the survival time of patients with spinal metastases based on pre-treatment parameters is important for the best choice of therapy. Following two previous studies, this sequel analyzes possible changes in the impact of various parameters and scoring systems and includes a comparison to the previous dataset for the purpose to find the most predictive parameters and scores for this patient group.Methods: Included were 196 patients retrospectively with confirmed spinal metastases treated between 2005 and 2010 (35% surgery, 65% conservative). Possible prognostic factors [primary tumor, Karnofsky Performance Scale (KPS), visceral metastases, number of bone metastases, pathological fracture and neurologic status] and six scoring systems (Tokuhashi original/revised, Tomita, van der Linden, Bauer original and modified) were analyzed using Kaplan-Meier curves and Cox-regression models.Results: Median overall survival was 7 months with 9% of all patients alive at the time of analysis. Stepwise multivariate analysis showed significant influence on survival for visceral metastases (p<0.0001), primary tumor (p<0.0001), KPS (p<0.0001) and number of spinal metastases (p=0.0271). All scoring systems significantly predicted longer survival at a better score (absolute scores, p<0.001) in this dataset. Significant differentiation between the prognostic groups was seen only for the Tokuhashi original, the Bauer original and modified scores (p<0.001). In comparison to the previous dataset with varying age, gender and primary tumor distribution, the Bauer original and modified scores were the least influenced by the different patient collectives.Conclusions: The Bauer modified score has shown consistent impact on predicting the remaining survival in patients with spinal metastases and is simultaneously simple in clinical use. [ABSTRACT FROM AUTHOR]

We develop a Galois theory for systems of linear difference equations with an action of an endomorphism σ. This provides a technique to test whether solutions of such systems satisfy σ-polynomial equations and, if yes, then characterize those. We also show how to apply our work to study isomonodromic difference equations and difference algebraic properties of meromorphic functions. [ABSTRACT FROM AUTHOR]

Introduction Pulse transit time (PTT) is generally assumed to be a surrogate marker for blood pressure changes and arterial stiffness. The aim was to evaluate whether pulmonary PTT ( pPTT) may be noninvasively measured by Doppler echocardiography and whether it might be valuable for detecting pulmonary hemodynamic and vascular alterations. Methods We defined pPTT as the interval between R-wave in the ECG and the corresponding peak late systolic pulmonary vein flow velocity measured by pw-Doppler in the pulmonary vein. Twelve consecutive patients with pulmonary hypertension (PH) and 12 subjects without any cardiovascular or respiratory disease were included in the study. All patients underwent a standard echocardiography including pPTT measurement. Results In the PH group, 5 patients had idiopathic pulmonary arterial hypertension (WHO 1), 1 patient PH associated with connective tissue disease (CTD, WHO 1) without pulmonary fibrosis (PF), and 6 patients PH associated with PF either due to CTD (WHO 1) or other etiology (WHO 3). Mean pPTT was significantly shorter in the PH group (138.0 ± 16.78 msec; P < 0.0001) than in the control group (383.5 ± 23.84 msec). Within the PH group, the subgroup of patients with PF showed significantly shorter mean pPTT (93.50 ± 15.47 msec; P = 0.004) than the subgroup of patients with PH without PF (182.6 ± 14.35 msec). Conclusions The results of this study suggest that pPTT might be an interesting surrogate marker of pulmonary hemodynamic and vascular alterations in PH and PF. Further studies are warranted to evaluate the possible influence of other variables on pPTT. [ABSTRACT FROM AUTHOR]

We show that three problems involving linear difference equations with rational function coefficients are essentially equivalent. The first problem is the generalization of the classical Skolem-Mahler-Lech theorem to rational function coefficients. The second problem is whether or not for a given linear difference equation there exists a Picard-Vessiot extension inside the ring of sequences. The third problem is a certain special case of the dynamical Mordell-Lang conjecture. This allows us to deduce solutions to the first two problems in a particular but fairly general special case. [ABSTRACT FROM AUTHOR]

Unusual case of diffuse penile metastasis of prostate cancer on 68Ga PSMA PET/CT imaging and 177Lu PSMA posttherapy scintigraphy. This case highlights the diagnostic performance of SP 68 sp Ga-PSMA-11 PET/CT in localizing uncommon sites of metastatic spread in PCa patients with biochemical recurrence. [Extracted from the article]

We develop a Galois theory for difference ring extensions, inspired by Magid's separable Galois theory for ring extensions and by Janelidze's categorical Galois theory. Our difference Galois theorem states that the category of difference ring extensions split by a chosen Galois difference ring extension is classified by actions of the associated difference profinite Galois groupoid. In particular, difference locally étale extensions of a difference ring are classified by its difference profinite fundamental groupoid. The emergence of difference profinite spaces, viewed as discrete dynamical systems in the realm of topological dynamics, leads us to investigate the interaction of difference algebra and symbolic dynamics. As an application of this interaction, we prove the near-rationality of a certain difference zeta function counting solutions of systems of difference algebraic equations over algebraic closures of finite fields with Frobenius. [ABSTRACT FROM AUTHOR]

BACKGROUND: Reports of secondary modifications into aortouniiliac configuration to salvagefailed endovascular aneurysm repair (EVAR) are limited. We evaluated long-term results after these procedures and compared them with those after primary aortouniiliac endografting (AUE). METHODS: A retrospective review of all EVAR performed from March 1995 until July 2011 was conducted. Patients were included when primary AUE (group I) or modification into aortouniiliac configuration (group II) was done. RESULTS: Data analysis obtained 27 group I and 23 group II patients. Salvage of failed EVAR could be achieved in 96% of group II patients, and mortality was zero. Frequency of adverse events and amount of interventions to maintain aneurysm exclusion were not increased after secondary AUE. Kaplan- Meier estimates for long-term survival between groups were comparable (P = .36). CONCLUSIONS: Secondary AUE allows correction of graft-related endoleaks potentially leading to late aneurysm rupture. Complications and adverse events throughout long-term follow-up were not necessarily increased when compared with primary AUE. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy. Questions/purposes: We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients. Methods: Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores). Results: Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, −17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma. Conclusions: Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy. Level of Evidence: Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Abstract: We present a characterization of differential Picard–Vessiot extensions which is analogous to the field theoretic characterization of Galois extensions in classical Galois theory. [Copyright &y& Elsevier]

Identifying the targets of broadly neutralizing antibodies to HIV-1 and understanding how these antibodies develop remain important goals in the quest to rationally develop an HIV-1 vaccine. We previously identified a participant in the CAPRISA Acute Infection Cohort (CAP257) whose plasma neutralized 84% of heterologous viruses. In this study we showed that breadth in CAP257 was largely due to the sequential, transient appearance of three distinct broadly neutralizing antibody specificities spanning the first 4.5 years of infection. The first specificity targeted an epitope in the V2 region of gp120 that was also recognized by strain-specific antibodies 7 weeks earlier. Specificity for the autologous virus was determined largely by a rare N167 antigenic variant of V2, with viral escape to the more common D167 immunotype coinciding with the development of the first wave of broadly neutralizing antibodies. Escape from these broadly neutralizing V2 antibodies through deletion of the glycan at N160 was associated with exposure of an epitope in the CD4 binding site that became the target for a second wave of broadly neutralizing antibodies. Neutralization by these CD4 binding site antibodies was almost entirely dependent on the glycan at position N276. Early viral escape mutations in the CD4 binding site drove an increase in wave two neutralization breadth, as this second wave of heterologous neutralization matured to recognize multiple immunotypes within this site. The third wave targeted a quaternary epitope that did not overlap any of the four known sites of vulnerability on the HIV-1 envelope and remains undefined. Altogether this study showed that the human immune system is capable of generating multiple broadly neutralizing antibodies in response to a constantly evolving viral population that exposes new targets as a consequence of escape from earlier neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea ( OSA) is generally considered an etiologic factor in the development of hypertension ( HT), but the exact pathophysiological mechanisms remain incompletely explained. Portapres continuous non-invasive blood pressure ( BP) measurement during polysomnography ( PSG) might be a powerful tool for future research to better understand these mechanisms. However, the effect of overnight Portapres BP monitoring itself on sleep is unclear. The aim of this study was to analyze the impact of Portapres BP measurement on sleep quality during PSG. In a matched groups design, 40 patients with treated or suspected, untreated sleep apnea underwent one overnight PSG either with or without simultaneous Portapres BP measurement. Twenty PSG recordings with additional Portapres monitoring and 20 gender and treatment matched control PSGs were investigated. Total recording time was significantly lower in the Portapres group than in the control group (414.6 vs 443.4 min, P = 0.046). No statistically significant differences were observed in arousal index (20.6 vs 23.3 events/h), total sleep time (312.0 vs 324.6 min), sleep efficiency (75.2 vs 73.9%), sleep onset latency (20.4 vs 22.2 min), REM-sleep (16.1 vs 15.0%) and slow-wave sleep (8.9 and 11.5%) between the Portapres and the control group. The results of this analysis suggest that Portapres BP measurement during overnight PSG does not have a clinically relevant impact on sleep quality and might therefore be a good diagnostic tool for future research on dynamic BP changes in sleep apnea. [ABSTRACT FROM AUTHOR]

Background: The importance of clinical predictors in the treatment of non-small-cell lung cancer (NSCLC) has increased during the last decade. This retrospective study analyzed the combined patient-level data from two phase II trials that investigated the efficacy and safety of combination chemotherapy with vinorelbine and mitomycin in patients with locally advanced or metastatic NSCLC. The aim of this analysis was to determine if patients' baseline and disease characteristics, including histology, gender, smoking history, and expression of TTF-1, might be potential predictors of outcome. Methods: Response rates, unadjusted survival times, and Cox covariate-adjusted hazard ratios (HRs) were calculated. Results were reported separately for each subgroup in each individual trial and in the pooled data set. Results: A total of 175 patients were included in this analysis. Adjusted HRs for both overall survival (OS) and progression free survival (PFS) favored the nonadenocarcinoma histology subgroup, achieving a statistical significance for OS in the pooled data ( n = 175; HR 0.68; 95 % CI 0.49-0.94; p = 0.019). TTF-1-negative immunohistochemistry was associated with a significantly higher response rate (25 vs. 0 %; p = 0.04) and with a nonsignificant advantage in OS ( n = 33; HR 1.23; 95 % CI 0.56-2.73; p = 0.608). Gender and smoking history were not strongly related to outcome. Conclusions: The results of this analysis indicate that patients with nonadenocarcinoma histology might get superior benefit from combination chemotherapy with vinorelbine and mitomycin. These results should be confirmed in a prospective study. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this short note is to establish the existence of ∂-parameterized Picard–Vessiot extensions for systems of linear difference-differential equations over difference-differential fields with an algebraically closed field of constants. [Copyright &y& Elsevier]

Abstract: Introduction: Achilles tendon ruptures, especially ruptures caused by pathologic conditions and also by achillotendinitis are often attributed to the alleged hypovascularisation of the Achilles tendon. Anatomic studies often mention an avascular plane. The purpose of this study was to re-investigate the arterial supply of the Achilles tendon. Material and methods: Lower legs of 28 anatomic specimen were injected with a radiologic contrast agent and subsequently an arterial angiography was performed. Afterwards the legs were embalmed and later anatomically dissected. The origin of arteries entering the paratenon of the tendo calcanei branching off from either the anterior (TA) or the posterior tibial artery (TP) was determined. The distance between the points of commencement of these nutrient arteries and a specific reference point, i.e. the insertion of the Achilles tendon into the tuber calcanei, was measured digitally on the radiographs and again with a slide-gauge on the dissected specimens. Results: As revealed by angiographic analysis, the TA gave off 5 vessels (v) at a frequency and median distance to the tuber calcanei (in cm) of v1: 50%, 6.01cm; v2: 39.3%, 7.88cm; v3: 35.7%, 9.71cm; v4: 17.9%, 12.7cm; v5: 10.7%, 14.6cm. The TP contributed to the arterial supply of the Achilles tendon by means of 7 inserting arteries branching off at a frequency and mean distances of v1: 67.9%, 4.53cm; v2: 60.7%, 6.97cm, v3: 50%, 9.58cm; v4: 35.7%, 10.89cm; v5: 25%, 12.65cm; v6: 10.7%, 16.94cm; v7: 3.6%, 18.7cm proximal to the tuber calcanei. However, due to the small diameter of these branches, by anatomic dissection no nutrient arteries commencing from the TA could be detected. On the other hand, a maximum of 7 vessels originating from the TP, larger than the former vessels, had been also revealed by anatomic dissection (frequency and mean distances, v1: 100%, 6.8cm; v2: 82.1%, 7.7cm; v3: 71.4%, 9.5cm; v4: 35.7%, 11.3cm; v5: 17.9%, 9.9cm; v6: 7.1, 10.5cm; v7: 3.6%, 12.0cm). Conclusion: A dense net of small arteries inserts into the paratenon of the Achilles tendon in its lower 20cm. The angiographic method was more specific and showed vessels that could not be identified as arteries originating from the TA by macroscopic anatomic dissection. [Copyright &y& Elsevier]

Abstract: Purpose: To analyze the hazard and causes of death after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms during a complete ten year follow-up. Methods: This is a retrospective clinical study of 130 consecutive patients undergoing EVAR between 1995 and 1998. One-hundred twenty-one patients (93.1%) were treated with first-generation stentgrafts and nine patients (6.9%) received second-generation devices. All patients completed a follow-up of at least 10 years, unless death occurred before then. Time and causes of death were provided by the Austrian central register of deaths. Results: The median follow-up was 7.6 years, and the 130 patients had 968.5 person-years of follow-up. The ten-year mortality rate was 62.3%. Cardiovascular events were the most frequent causes of death, with a 3.9 incidence rate per 100 person-years. Cancer death and death due to other causes occurred in 2.1 and 1.8 cases per 100 person-years, respectively. Lethal late aneurysm rupture happened in 4.6% (n =6), which corresponds to an annual incidence rate of 0.6 per 100 person-years. All of those patients had been treated with first-generation devices. Conclusions: Cardiovascular events were the most frequent cause of death after EVAR, followed by malignancy and other diseases. The risk of dying from secondary rupture was clearly lower than that of death due to other reasons during ten years after EVAR, even in patients with first-generation stentgrafts. [Copyright &y& Elsevier]

Abstract: Purpose: To compare 64-multi-slice-CT angiography (64-MSCTA) to color-coded duplex sonography (CCDS) in the follow-up after carotid artery stenting (CAS). Methods: Thirty patients who had an MSCTA and CCDS examination prior and after CAS were included. Twelve closed-cell and 24 open-cell stents were implanted. Neointimal surface, in-stent-restenosis (ISR), stent expansion, and fracture were evaluated. In addition, the occurrence of atherosclerotic lesions leading to a >50% stenosis in supraaortic vessels was assessed. Results: With MSCTA, >50% ISR was found in 5.6% of cases during a mean follow-up of 41.7 months. Comparing MSCTA and CCDS, grading of ISR and absolute diameters of neointimal surface correlated moderately (Spearman=0.402, p =0.015; Pearson=0.404, p =0.03). Assessment of the neointimal surface was significantly better with MSCTA (100% vs. 80.6%; p =0.011). Stent expansion was significant, compared to the basic value, with both modalities and stent types (p <0.001). Of 237 additionally assessed vessel segments, a >50% stenosis was detected in 38 (16.0%) vessel segments. Findings were stable in 25 (10.5%) and progressed in 11 (4.6%) vessel segments. Five small intracranial aneurysms were detected in four (13.3%) patients. Of 21 incidental findings in 16 (51.6%) patients there was one with malignancy (4.8%). Conclusion: With regard to ISR and stent expansion, no significant difference was found, when MSCTA and CCDS were compared. CTA is quite applicable as a complementary imaging method for the follow-up of patients with carotid artery stents. Additional advantages are the detection of supraaortic vessel pathologies and incidental findings. [Copyright &y& Elsevier]

STUDY DESIGN.: Retrospective study. OBJECTIVE.: This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. SUMMARY OF BACKGROUND DATA.: Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. METHODS.: Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998-2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. RESULTS.: Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. CONCLUSION.: According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity. [ABSTRACT FROM AUTHOR]

Abstract: Possible effects of comorbidities and of different wound etiologies on the success of extracorporeal shock wave therapy (ESWT) of chronic soft tissue wounds were investigated. From September 2003 until February 2007, 282 patients, being previously treated unsuccessfully were enrolled. Treatment consisted of ESWT occurring at defined intervals. At each treatment session a wound bed score was recorded, also at initial presentation a detailed patient history and wound etiology. Observed comorbidities were pooled according to the chapters of the ICD-10 system. Two hunderd fifty-eight patients were analyzed (91.49%) and underwent follow-up for a median of 31.8 months. Wound closure occurred in 191 patients (74.03%) by a median of two treatment sessions. No wound reappeared at the same location. A multivariate logistic regression model showed that pooled comorbidities and wound etiologies did not have a significant influence on success. Comorbidities and wound etiologies have surprisingly no significant influence on the success of ESWT. [Copyright &y& Elsevier]

Abstract: Gröbner bases are the computational method par excellence for studying polynomial systems. In the case of parametric polynomial systems one has to determine the reduced Gröbner basis in dependence of the values of the parameters. In this article, we present the algorithm GröbnerCover which has as inputs a finite set of parametric polynomials, and outputs a finite partition of the parameter space into locally closed subsets together with polynomial data, from which the reduced Gröbner basis for a given parameter point can immediately be determined. The partition of the parameter space is intrinsic and particularly simple if the system is homogeneous. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the predictors of permanent ileostomy following proctocolectomy with ileal pouch-anal anastomosis (IPAA). An overview of the methodology used for the study is provided, along with information on the effectiveness of proctocolectomy with IPAA. Researchers found that age increased the need for a permanent ileostomy. Findings revealed that 3.9 per cent of patients aged 55 years or less needed a permanent ileostomy.

Background: Stricturing Crohn’s disease is accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Strictureplasty (SP) and endoscopic balloon dilatation (EBD) have been developed to prevent, or at least delay, the requirement for resection. The goal of this study was to compare the outcome of these two procedures with regard to complications and disease recurrence. Methods: We conducted a MEDLINE literature search to give a current overview about the safety and efficacy of EBD and SP. Results: The initial search yielded 744 articles. Case reports, reviews and meta-analyses were excluded. Finally, 63 articles (SP, 40 articles; EBD, 23 articles) were used for the review. None of the studies compared the two methods directly. A total of 2,532 patients (SP, n = 1,958; EBD, n = 574) were included. The incidence of perioperative complications after SP was 11% and the incidence of major complications was 5%. The median surgical recurrence rate was 24% after a median follow-up of 46 months. The median technical success for EBD was 90%. Major complications occurred in 3% of the cases. According to an intention-to-treat protocol, the median surgical recurrence rate was 27.6%. Per-protocol analysis revealed a median surgical recurrence rate of 21.4% after a median follow-up of 21 months. Conclusion: Due to the lack of comparable data, there is currently no reliable information on whether one treatment option is superior to the other. Regarding the limited applicability of EBD in strictures of the small bowel, only a controlled trial would provide evidence as a basis for clinical decision making in CD strictures that are potentially treatable by EBD and SP. [ABSTRACT FROM AUTHOR]

Background: Increasing incidence rates of soft tissue sarcomas (STS) have been reported. In the present study, the authors have analyzed the incidence of STS in Austria in a population-based study for the period 1984–2004. [ABSTRACT FROM PUBLISHER]

We study the inverse problem in the difference Galois theory of linear differential equations over the difference-differential field C (x) with derivation d d x and endomorphism f (x) ↦ f (x + 1). Our main result is that every linear algebraic group, considered as a difference algebraic group, occurs as the difference Galois group of some linear differential equation over C (x). [ABSTRACT FROM AUTHOR]

Background: Pompe disease (Glycogen storage disorder type II) is an inherited disease because of a lack or reduced activity of the enzyme α-1,4-glucosidase (acid maltase). Since 2006, an intravenous enzyme replacement therapy (ERT) with Myozyme™ (Genzyme Corporation, Cambridge, MA, USA) is available. Methods: Four adult patients aged between 39 and 68 years received ERT over a period of 6 months. Clinical and functional parameters were registered longitudinally. Results: In three patients, a considerable improvement of symptoms could be noticed, patients with pre-existing respiratory insufficiency seemed to profit most. In all patients, a continuous decrease of initially raised laboratory parameters (creatine kinase, lactic dehydrogenase, transaminases) was striking. Conclusions: Enzyme replacement therapy seems to be a long-term effective therapy in adult patients with Pompe disease. Whether all patients will profit from an improvement of symptoms or at least a stabilisation of the otherwise progressive disease is currently not definitively clear. [ABSTRACT FROM AUTHOR]

Summary: Background: Aim of this study was to evaluate efficacy, toxicity and tolerability of chemotherapy with a combination of mitomycin and vinorelbine (M/V) in patients with advanced non-small cell lung cancer (NSCLC). Methods: We enrolled 110 patients (median age 67 years) with locally advanced or metastatic NSCLC, who had no prior chemotherapy or progressive disease after at least one prior chemotherapy regimen. 45 patients (41%) were ≥70 years old. All patients received vinorelbine 25mg/m2 (d1,8) and mitomycin 8mg/m2 (d1) every 3–4 weeks. Restaging was performed by CT-scan after every two courses M/V according to RECIST criteria. Results: M/V was well tolerated, even in patients with a poor performance status or ≥70 years Median progression free survival was 4.4 months. Median overall survival was 9.0 months with a 1-year survival rate of 39%. Partial response was observed in 15% and stable disease in 51% of patients. Both hematological and non-hematological toxicities were generally mild. CTC grade 3 toxicities observed included neutropenia in 3%, anemia in 3%, thrombocytopenia in 1% and suspected pneumonitis in 2% of patients. Except neutropenia in 2% and acute dyspnea in 1%, there were no other grade 4 toxicities and no treatment associated casualties. There was no relevant difference in outcome or toxicity between patients ≥70 and <70 years. Conclusions: M/V seems to be a well-tolerated and effective chemotherapy regimen with low toxicity in patients with advanced NSCLC. It seems to be an interesting option even for patients ≥70 years or with a reduced performance status. [Copyright &y& Elsevier]

Abstract: Let be an ideal of the polynomial ring over the commutative, Noetherian ring . Geometrically, defines a family of affine schemes, parameterized by : For , the fibre over is the closed subscheme of the affine space over the residue field , which is determined by the extension of under the canonical map . If is homogeneous, there is an analogous projective setting, but again the ideal defining the fibre is . For a chosen term order, this ideal has a unique reduced Gröbner basis which is known to contain considerable geometric information about the fibre. We study the behavior of this basis for varying and prove the existence of a canonical decomposition of the base space into finitely many, locally closed subsets over which the reduced Gröbner bases of the fibres can be parametrized in a suitable way. [Copyright &y& Elsevier]

Simple Summary: For patients with newly diagnosed prostate cancer, it is important to detect tumor growth beyond the prostate, as this can affect a patient's prognosis, influence management decisions, and alter treatment strategies. It is recognized that on prostate MRI, some instances of extraprostatic tumor growth can be missed. In this study, we merged patient data from multiple hospitals in different countries and developed a type of mathematical formula called "nomogram" that combines MRI findings with other available patient data. The results of our study allow physicians to more accurately diagnose extraprostatic tumor growth by combining clinical, biopsy, and MRI-derived information according to their relative statistical importance. Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models. [ABSTRACT FROM AUTHOR]

We introduce a notion of dimension for the solution set of a system of algebraic difference equations that measures the degrees of freedom when determining a solution in the ring of sequences. This number need not be an integer, but, as we show, it satisfies properties suitable for a notion of dimension. We also show that the dimension of a difference monomial is given by the covering density of its set of exponents. [ABSTRACT FROM AUTHOR]

We assessed correlation between hazard ratios of imaging-based intermediate endpoints (IBIEs) and overall survival among 28 Prostate Cancer Working Group 2-based phase II-III randomized trials evaluating systemic treatments in 16,511 metastatic castration-resistant prostate cancer patients. The overall correlation was good (R2 = 0.57). Trials using radiographic progression-free survival showed higher correlation than those using a composite IBIE (including clinical factors in the definition of progression): R2 = 0.58 vs. 0.00. Introduction/Background: Radiographic progression-free survival (rPFS) based on Prostate Cancer Working Group 2 (PCWG2) has been increasingly used as a meaningful imaging-based intermediate endpoint (IBIE) for overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). In randomized phase III trials, rPFS showed good correlation with OS at the individual trial level. We aimed to assess the correlation between the hazard ratios (HR) of IBIE and OS among PCWG2-based randomized trials. Materials and Methods: PubMed and EMBASE databases were systematically searched for randomized trials evaluating systemic treatments on mCRPC using PCWG2 up to April 15, 2020. Hazard ratios for OS and IBIEs were extracted and their correlation was assessed using weighted linear regression. Subgroup analyses were performed according to var ious clinical settings: pr ior chemotherapy, dr ug category, type of IBIE (rPFS vs. composite IBIE, latter defined as progression by imaging and one or a combination of PSA, pain, skeletal-related events, and performance status), and publication year. Results: Twenty-eight phase II-III randomized trials (16,511 patients) were included. Correlation between OS and IBIE was good (R² = 0.57, 95% confidence interval [CI], 0.35-0.78). Trials using rPFS showed substantially higher correlation than those using a composite IBIE (R² = 0.58, 95% CI, 0.32-0.82 vs. 0.00, 95% CI, -0.01 to 0.01). Correlations between OS and IBIE in other subgroups were at least moderate in nearly all subgroups (R² = 0.32-0.91). Conclusion: IBIEs in the era of PCWG2 correlate well with OS in randomized trials for systemic drugs in patients with mCRPC. PCWG2-based rPFS should be used instead of a composite IBIE that includes PSA and other clinical variables. [ABSTRACT FROM AUTHOR]

We consider pairs of automorphisms acting on fields of Laurent or Puiseux series: pairs of shift operators .W x 7 x C h1; W x 7 x C h2/, of q-difference operators .W x 7 q1x, W x 7 q2x/, and of Mahler operators .W x 7 xp1 ; W x xp2 /. Given a solution f to a linear -equation and a solution g to an algebraic -equation, both transcendental, we show that f and g are algebraically independent over the field of rational functions, assuming that the corresponding parameters are sufficiently independent. As a consequence, we settle a conjecture about Mahler functions put forward by Loxton and van der Poorten in 1987. We also give an application to the algebraic independence of q-hypergeometric functions. Our approach provides a general strategy to study this kind of question and is based on a suitable Galois theory: the -Galois theory of linear -equations. [ABSTRACT FROM AUTHOR]