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In this paper the problem of a plane strain hydraulic fracture propagating in an elasto-plastic material is analyzed. A new stress redistribution model for the proximity of the fracture tip is formulated and a resulting plasticity-dependent crack propagation condition is introduced. A modified variant of the KGD problem that accounts for the plastic deformations in the near-tip zone only is proposed. It is demonstrated that this model can be a credible substitute for the full elasto-plastic hydraulic fracture problem in the case of moderate plastic deformation. The crack-tip shielding effect introduced by the plastic deformation is quantified. [ABSTRACT FROM AUTHOR]

SUMMARY In this article, we investigate the main parameters that influence the propagation of a fluid-driven fracture in a poroelastoplastic continuum. These parameters include the cohesive zone, the stress anisotropy, and the pore pressure field. The fracture is driven in a permeable porous domain that corresponds to weak formation by pumping of an incompressible viscous fluid at the fracture inlet under plane strain conditions. Rock deformation is modeled with the Mohr-Coulomb yield criterion with associative flow rule. Fluid flow in the fracture is modeled by the lubrication theory. The movement of the pore fluid in the surrounding medium is assumed to obey the Darcy law and is of the same nature as the fracturing fluid. The cohesive zone approach is used as the fracture propagation criterion. The problem is modeled numerically with the finite element method to obtain the solution for the fracture length, the fracture opening, and the propagation pressure as a function of the time and distance from the pumping inlet. It is demonstrated that the plastic yielding that is associated with the rock dilation in an elastoplastic saturated porous continuum is significantly affected by the cohesive zone characteristics, the stress anisotropy, and the pore pressure field. These influences result in larger fracture profiles and propagation pressures due to the larger plastic zones that are developing during the fracture propagation. Furthermore, it is also found that the diffusion process that is a major mechanism in hydraulic fracture operations influences further the obtained results on the fracture dimensions, plastic yielding, and fluid pressures. These findings may explain partially the discrepancies in net pressures between field measurements and conventional model predictions. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper investigates the main parameters that affect the propagation of a fluid driven-fracture in a poroelastic medium. The fracture results from the pumping of an incompressible Newtonian viscous fluid at the fracture inlet, and the flow in the fracture is modelled by the lubrication theory. Rock deformation is assumed as porous-elastic. Leak-off in the host rock is considered to account for the diffusion effects in the surrounding formation. The propagation criterion is of the cohesive type. Finite element analysis was performed to compute the fracturing pressure and fracture dimensions as a function of the time and length. It was found that higher pressures are needed to extend a fracture in a poroelastic medium than in an elastic medium, and the created profiles of poroelastic fracture are wider. It was found that grain compressibility plays a minor role and does not result any significant difference in the fluid pressures and fracture dimensions. Wider fracture profiles are obtained with higher injection rates. The fluid pressures and the fracture apertures are larger in the case of a high permeability formation. [ABSTRACT FROM AUTHOR]

In this paper the writers examine a borehole failure model that is based on fracture mechanics and layer buckling theories and compare its predictions with experimental data. The model assumes that the main failure mechanism of borehole collapse takes place in the form of (preexisting or formed) layers buckling. The model introduces a combination of fracture mechanics parameters with length dimension that scales the size of the holes, thus allowing for size effect predictions. The writers review the model and compare its predictions with available experimental data of hollow cylinder tests on weak rocks. The writers found for the model predictions and for the experimental data a strong correlation between hollow cylinder strength normalized by the rock strength and hole size normalized by the square of the ratio of fracture toughness over tensile strength. These findings can be used for constructing efficient mechanical models for predicting or interpreting failure of boreholes and perforations in mining and petroleum engineering. [ABSTRACT FROM AUTHOR]

This paper studies the importance of the cohesive zone in the modelling of a fluid driven fracture under plain strain conditions. The fracture is driven by pumping of an incompressible viscous fluid at the fracture inlet. Rock deformation is modeled for linear elastic and poroelastic solids. Fluid flow in the fracture is modeled by lubrication theory. The cohesive zone approach is used as the fracture propagation criterion. Finite element analysis was used to compute the solution for the crack length, the fracture opening and propagation pressure as a function of the time and distance from the wellbore. It is demonstrated that the crack profiles and the propagation pressures are larger in the case of elastic-softening cohesive model compared to the results of the rigid-softening cohesive model for both elastic and poroelastic cohesive solids. It is found that the results are affected by the slope of the loading branch of the cohesive model and they are nearly unaffected from the exact form of the softening branch. Furthermore, the size of the process zone, the fracture geometry and the propagation pressure increase with increasing confining stresses. These results may explain partially the discrepancies in net-pressures between field measurements and conventional model predictions. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the bifurcations of a circular cylinder within the context of the triaxial confining pressure test, for pressure sensitive solids. Background of the confining pressure triaxial calibration test; Problem formulation; Numerical results and conclusions.

Presents information on a study which focused on a linear bifurcation analysis for pressure sensitive elastoplastic hollow cylinders under radial surface loads. Derivation of perturbed equilibrium equations; Eigenmodes solution and constitutive specification; Numerical examples; Conclusions.

Introduction: Patients with depression are likely to eventually develop Cardiovascular disease(CVD) and have a higher mortality rate than general population. In addition, anxiety disorders, especially Generalized Anxiety Disorder (GAD), may be associated with mortality and other adverse cardiac outcomes. Objectives: Evaluation of depression and anxiety control in Greek patients with Major Depressive Disorder (MDD) with/without GAD and CVD, under 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin. Methods: 565 patients with MDD with/without GAD, enrolled in this observational, study (NCT03317262). The subgroup of 133 (24%) patients had CVD. Severity of MDD and GAD symptoms was evaluated using the HAM-D and HAM-A Scores at baseline (V1) and after 6 months (V3) respectively. Results: MeanHAM-Dscore in patientswith CVDwithoutGAD, at V1 and V3 was 23.94±7.51 and 8.14±4.65 respectively (p<0.0001). Similar results were observed in patients without CVDwithoutGAD (HAM-D score 26.67±8.79 atV1 and 7.44±4.40 atV3). MeanHAMAscore in patientswithCVDandGADatV1 andV3 was 25.64±6.38 and 8.98±3.93, respectively (p<0.0001). Same magnitude reduction in HAM-A score was observed in patients without CVD and GAD, 26.27±8.16 at V1 and 9.28±6.48 at V3 (p<0.0001). Patients' depression symptoms with/without CVD and GAD showed also a significant reduction between V1 and V3. Conclusions: MDD patients with CVD without GAD, had a marginally lower baseline HAM-D score versus patients with GAD. After 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin the improvement of depressive and anxiety symptoms was almost equal between MDD patients with/without GAD regardless of the presence of coexisting CVD. [ABSTRACT FROM AUTHOR]

To investigate serum prostate specific antigen (PSA) levels with age and sex in childhood. This prospective study included 205 children (123 boys, 82 girls; mean age 59.27 months, sd 3.78, range 2 days to 204 months) with no urogenital or endocrine disorders. PSA levels were measured using a highly sensitive, ‘third-generation’ PSA (time-resolved immunofluorometric) assay, able to detect PSA levels of ≥ 1 ng/L (0.001 ng/mL). Children were divided into four groups by age, i.e. A (0–12 months; 34 boys/20 girls); B (13–48, 37/21); C (49–144, 41/32); and D (> 144, 11/9). The data were analysed statistically using analysis of variance. An accurate measurement of PSA was possible in both sexes using the assay. The median ( sd, range) PSA level in boys was 38.41 (1.318, 1–2768) ng/L, and in girls 4.059 (1.392, 1–287) ng/L. There were no significant differences between girls at all age groups, or between the sexes for groups A–C, but levels were significantly higher in boys in group D (30 times that in girls), at 142.59 (1.53) and 4.85 (1.58) ng/L ( P < 0.01). PSA levels do not differ significantly between boys and girls until 12 years old, after which there is a significant and steep increase in PSA in boys, reflecting the development of the prostate. Assessing PSA in children could be used as a potential marker in the diagnosis and follow-up of urogenital disorders. [ABSTRACT FROM AUTHOR]

Background: Secukinumab has previously demonstrated sustained efficacy and favourable safety for up to 52 weeks in paediatric patients (children and adolescents aged 6 to <18 years) with severe chronic plaque psoriasis (NCT02471144). Objective: To investigate the long‐term (104 weeks) efficacy and safety of secukinumab. Methods: After 52 weeks, patients continued to receive secukinumab low dose (LD [75/150 mg]) or high dose (HD [75/150/300 mg]). Patients on etanercept (0.8 mg/kg) until Week 52 entered follow‐up. Data for patients receiving secukinumab LD from the beginning and those switching to secukinumab LD from placebo ('Any secukinumab' LD) and patients receiving secukinumab HD from the beginning and those switching to secukinumab HD from placebo ('Any secukinumab' HD) are presented. Assessments: Psoriasis Area and Severity Index (PASI) score, PASI (75/90/100) responses, Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children's Dermatology Life Quality Index (CDLQI) score and CDLQI 0/1 response up to Week 104, and, safety up to Week 104 for all patients and up to 4 years for some patients (~320 patient‐years [PY] of treatment). Results: Secukinumab‐treated patients showed sustained PASI 75/90/100 and IGA mod 2011 0/1 responses up to Week 104. Throughout the second year of treatment, efficacy was similar for the 'Any secukinumab' LD and HD groups for PASI 75 and IGA mod 2011 0/1 responses. PASI 90/100 responses were mostly comparable between the dose groups up to Week 88, but higher in the 'Any secukinumab' HD than the 'Any secukinumab' LD group at Week 104. Patients achieved a sustained CDLQI 0/1 response that was similar between the 'Any secukinumab' LD (61.1%) and HD (65.0%) groups. Safety data were consistent with the established safety profile of secukinumab. Conclusion: Secukinumab demonstrated sustained long‐term efficacy (up to 2 years) and a favourable safety profile (~320 PY of treatment) in paediatric patients with severe chronic plaque psoriasis. [ABSTRACT FROM AUTHOR]

Sand production is a complex physical process that depends on the external stress and flow rate conditions as well as on the state of the material. Models developed for the prediction of sand production are usually solved numerically because of the complexity of the governing equations. Testing of new sand production models can very well be performed through calibration with laboratory experiments, which by construction possess geometric symmetry facilitating explicit mathematical analysis. We introduce an erosion model that is built upon the physics (poro-mechanical coupling of the fluid-solid system) usually incorporated in erosion models for the prediction of sand production. Around this model, we set up a mathematical framework in which sand production models because of erosion can be tested and calibrated without having to resort to complex numerical work or specialised software. The model is validated by data of volumetric sand production from a hollow cylinder test on synthetic sandstone. Generalisations of the model, which are naturally incorporated in the same framework and have useful phenomenological features, are discussed. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We present results of a parametric study on shearband formation in geomaterials, examining the influence of material dilatancy on shearband properties. The study is based on a new higher order continuum theory, called gradient elastoplasticity, developed to model localization of deformation. We present results for two problems with different initial stress fields: The biaxial test and the hollow cylinder test. We show that nonassociativity promotes bifurcation at lower deformation, leading to localized deformation and more abrupt final failure. Both the inclination and thickness of the calculated shearbands decrease with increasing nonassociativity. Gradient elastoplasticity is capable of reproducing the experimentally observed localized failure modes, including details such as reorientation of shearband close to a free boundary. [ABSTRACT FROM AUTHOR]

Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1-58 months (mean=13.4±1.7 and median=8.0 months). A cutoff value of 0.2?µg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2-7a were histologically categorized as low malignant (LM) and PC with GS 7b-10 as high malignant (HM). The immunohistochemical method of streptavidin-biotin-peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P=0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P=0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.Prostate Cancer and Prostatic Diseases (2003) 6, 223-227. doi:10.1038/sj.pcan.4500674 [ABSTRACT FROM AUTHOR]

Background: Secukinumab has demonstrated sustained long‐term efficacy with a favourable safety profile in various psoriatic disease manifestations in adults. Objectives: Here, the efficacy and safety of two secukinumab dosing regimens [low dose (LD) and high dose (HD)] in paediatric patients with severe chronic plaque psoriasis over one year are reported. Methods: In this multicentre, double‐blind study (NCT02471144), patients aged 6 to <18 years with severe chronic plaque psoriasis were stratified and randomized by weight (<25 kg, 25 to <50 kg, ≥50 kg) and age (6 to <12 years, 12 to <18 years) to receive low‐dose (LD: 75/75/150 mg) or high‐dose (HD: 75/150/300 mg) subcutaneous secukinumab or placebo or etanercept 0.8 mg/kg (up to a max of 50 mg). Results: Overall, 162 patients were randomized to receive secukinumab LD (n = 40) or HD (n = 40), etanercept (n = 41) or placebo (n = 41). The co‐primary objectives of the study were met with both secukinumab doses (LD and HD) showing superior efficacy compared to placebo (P < 0.0001) with respect to PASI 75 response (80.0%, 77.5% vs. 14.6%) and IGA mod 2011, 0 or 1 response (70%, 60% vs. 4.9%) at Week 12. Both secukinumab doses were superior to placebo (P < 0.0001) with respect to PASI 90 response at Week 12 (72.5%, 67.5% vs. 2.4%). The efficacy of both doses was sustained to Week 52 with secukinumab achieving higher responses vs. etanercept (PASI 75/90/100: LD, 87.5%/75.0%/40.0% and HD, 87.5%/80.0%/47.5.% vs. etanercept, 68.3%/51.2%/22.0% and IGA 0 or 1: LD, 72.5% and HD, 75.0% vs. etanercept, 56.1%). The safety profile of secukinumab was consistent with the adult Phase 3 studies, with no new safety signals identified. Conclusions: Both doses of secukinumab demonstrated high and sustained efficacy up to Week 52 with a favourable safety profile in paediatric patients with severe chronic plaque psoriasis. [ABSTRACT FROM AUTHOR]

Background User satisfaction is an important factor associated with treatment adherence in chronic diseases including moderate-to-severe psoriasis. Objective To evaluate the efficacy, safety and patient acceptability of 300 and 150 mg secukinumab - a fully human anti-interleukin-17A monoclonal antibody that has demonstrated efficacy in the treatment of patients with moderate-to-severe plaque psoriasis - self-administered by autoinjection. Methods Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg or placebo self-administered by autoinjection at baseline, Weeks 1, 2 and 3 and then every 4 weeks from Week 4 to Week 48. Efficacy responses [≥75/90/100% improvement in Psoriasis Area and Severity Index ( PASI 75/90/100) and clear/almost clear skin by Investigator's Global Assessment 2011 modified version ( IGA mod 2011 0/1)] were measured at Week 52. Patient-reported usability of the autoinjector was evaluated by the self-injection assessment questionnaire to Week 48. Results At Week 52 with secukinumab 300 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 81.4/64.1/38.8% and 69.6% of patients, respectively, by multiple imputation. At Week 52 with secukinumab 150 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 75.2/57.4/33.1% and 60.2% of patients, respectively, by multiple imputation. Patient-assessed acceptability of the autoinjector remained high to Week 48. The proportion of patients experiencing adverse events was greater with secukinumab 300 mg (88.6%) than with secukinumab 150 mg (78.7%). Conclusion Self-administration of secukinumab using an autoinjector was associated with robust and sustained efficacy, a good safety profile and high acceptability. [ABSTRACT FROM AUTHOR]

The problem of determining the steady state pressure field for single and multi-well configurations with non-trivial wellbore boundary conditions is considered in this work as an integral equation problem. The aquifer, where the well configuration resides, is assumed to have different vertical and horizontal intrinsic permeabilities and it is bounded above and below by impermeable geological settings. The solutions of the integral equation, known as density functions, are studied from two points of view. First, the singular behavior of the density function is investigated by studying the singular part of the kernel of the integral equation; on this basis the density function is suitably expressed in terms of a non-singular counterpart, the reduced density function, for which a polynomial approximation is formulated and constructed numerically. The convergence of the approximation is studied with respect to the order of the polynomial and shown to be adequately fast. Second, the density functions for large depth to radius ratio and/or large horizontal to vertical permeability ratio exhibit similarity. The density functions depend on the parameters of the single-well problem through a single similarity parameter c . For large values of c , corresponding to the physical limits just mentioned, the density functions are reduced to essentially a single function, modulo a factor ( log c ) - 1 . This property simplifies considerably the analysis of all the large c cases. Considering the case of two wells, as an illustrative example, we also show that the properties of the single well case are also exhibited by the multi-well density functions. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a decoupled Arbitrary Lagrangian–Eulerian (ALE) approach for the large deformation analysis of plane-strain elastoplastic problems. In this decoupled approach, the Eulerian step consists of first remeshing the deformed continuum and then remapping the state variables at the new quadrature points. Remeshing is performed without altering the element topology of the original mesh with the aid of the Spring Analogy Method enhanced with torsional springs. Before remeshing, nodes at free boundaries are relocated using an analytical approach, in order to preserve a good node distribution throughout the analysis. State variable remapping is achieved through the Radial Basis Point Interpolation Functions scheme. Large deformation elastoplastic analyses of two plane strain example problems are conducted using the presented ALE approach to test its robustness and effectiveness. The continuum is modeled as a Tresca or Mohr–Coulomb elastic–perfectly plastic material, while the meshes consist of second-order finite elements. The numerical results demonstrate that the present methodology is capable of predicting with adequate accuracy the load–displacement response even in analyses involving very large translations of the loaded boundary. [Copyright &y& Elsevier]

Summary: This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction: In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods: Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤3 months) subpopulations] were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results: At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤74 years ( P < 0.05) in the treatment and 65-74 years ( P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P < 0.05), cumulative prednisone dose (all P < 0.01), and postmenopausal status (all P < 0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P < 0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention ( P = 0.0189) and osteopenic patients in the treatment subpopulation ( P = 0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions: This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients [ABSTRACT FROM AUTHOR]

Introduction: GINA (Global Initiative for Asthma) 2018 guidelines for asthma management include, among others, assessment of asthma symptom control and any comorbidities that could affect symptom burden and Quality of Life (QoL). Objectives: Assessment of asthma symptom control and QoL in a subgroup of asthmatic patients with psychiatric disorders residing in Greece, who were treated for 6 months with a Fixed Dose Combination (FDC) of Budesonide/Formoterol (Elpenhaler®). Methods: Multicenter, prospective, non-interventional, observational study(NCT03033758) of 1,230 asthmatic patients, not previously treated with ICS/LABA. 713(57.97%) patients had at least one comorbidity. Weevaluated asthma control andQoL in a subgroup of 73 patients with depression and anxiety disorders using validated Greek versions of Asthma Control Questionnaire (ACQ) and mini-Asthma Quality of Life Questionnaire (mini-AQLQ), respectively. Results: For this subgroup, at baseline, the median (IQR) ACQ and mini-AQLQ scores were 2.37(1.43, 3.43) and 4.05(3.07, 5.13), respectively. After 6 months, we noticed a significant decrease in ACQ score(Z=-6.06, p<0.001), a significant increase in mini-AQLQ score(Z=-6.68, p<0.001) and a significant, strong, negative, linear correlation between the change in ACQ(-1.48) and mini-AQLQ(1.95) scores(rs=-0.88, p<0.001) among visits. Conclusions: At baseline, asthmatic patients with psychiatric disorders were less controlled and had worse QoL than the rest of study population (without comorbidities/with at least one). Six months of treatment with FDC Budesonide/Formoterol, Elpenhaler® resulted in a significant improvement both in asthma control and QoL. [ABSTRACT FROM AUTHOR]