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Airfoil boundary forces caused by unsteady, incompressible, inviscid flow were studied using the simulation methods of artificial compressibility. Simulated convection of a compact vortex through a diverging/converging channel was generated through both the finite difference method (FDM) and discrete vortex method (DVM). The compact flows were then investigated by applying the different formulas for boundary forces. Results indicate that both DVM and FDM allow accurate solutions of the equations governing incompressible flow problems.

Background Serum macrophage inhibitory cytokine-1 ( MIC-1/ GDF15) concentration has been associated with colonic adenomas and carcinoma. Aims To determine whether circulating MIC-1/ GDF15 serum concentrations are higher in the presence of adenomas and whether the level decreases after excision. Methods Patients were recruited prospectively from a single centre and stratified into five groups: no polyps ( NP); hyperplastic polyps ( HP); sessile serrated ademona ( SSA); adenomas ( AP); and colorectal carcinoma ( CRC). Blood samples were collected immediately before and 4 weeks after colonoscopy. MIC-1/ GDF15 serum levels were quantified using ELISA. Results Participants (n=301) were stratified as: NP; n=116 (52%), HP; n=37 (12%), SSA; n=19 (7%), AP; n=68 (23%); and CRC; n=3 (1%). Patients were excluded from the study due to nondiagnostic pathology (n=9, 3%) and exclusion criteria (n=20, 6%). In the 272 remaining subjects (M=149; F=123), age ( P=.005), history of colonic polyps ( P=.003) and family history of colonic polyps ( P=.002) were associated with presence of adenomas. Baseline median MIC-1/ GDF15 serum levels increased significantly from NP 609 (460-797) pg/ mL, HP 582 (466-852) pg/ mL, SSA 561 (446-837) pg/ mL to AP 723 (602-1122) pg/ mL and CRC 1107 (897-1107) pg/ mL; ( P<.001). In the pre- and postpolypectomy paired adenoma samples median MIC-1/ GDF15 reduced significantly from 722 (603-1164) pg/ mL to 685 (561-944) pg/ mL ( P=.002). A ROC analysis for serum MIC-1/ GDF15 to identify adenomatous polyps indicated an area under the curve of 0.71. Conclusions Our data suggest that serum MIC-1/ GDF15 has the diagnostic characteristics to increase the detection of colonic neoplasia and improve screening. [ABSTRACT FROM AUTHOR]

Background: Physicians dedicate approximately a quarter of daily work to documentation. Completeness and speed of medical documentation processes are important parameters, because they can affect quality of healthcare.Objectives: A generic method to monitor these quality parameters is proposed and its utility is demonstrated in two examples.Methods: Based on a generic event-driven process chain of a medical documentation process, completeness functions for created and finalized documents (available versus required documents by time) are defined. The 95%-quantile of process time is applied as performance indicator of documentation speed. A plotting function for these parameters is provided: completeness and speed of medical documentation (CSMD)-plot. Open source code and a sample data set are available in the Supplement.Results: This methodology is applied to analyze the effect of an electronic dictation system on discharge letter documents. CSMD-plot detects significant differences regarding speed and completeness of the process before and after implementation of electronic dictation; in addition, it pinpoints differences regarding these quality parameters in documentation processes between different clinical departments. In a second example, CSMD-plot is used to analyze follow-up documentation of a clinical trial. Due to its generic design, CSMD-plots can be applied to other medical documentation processes such as order-entry processes.Conclusions: Monitoring of completeness and speed of medical documentation is feasible and can provide quantitative information on these processes. [ABSTRACT FROM AUTHOR]

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Background:Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort.Methods:PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response.Results:PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1β, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002).Conclusions:In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC. [ABSTRACT FROM AUTHOR]

Background:Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC.Methods:One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC.Results:Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml−1) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047).Conclusions:Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease. [ABSTRACT FROM AUTHOR]

Precursor T-cell acute lymphoblastic leukemia (T-ALL) remains an important challenge in pediatric oncology. Because of the particularly poor prognosis of relapses, it is vital to identify molecular risk factors allowing early and effective treatment stratification. Activating NOTCH1 mutations signify a favorable prognosis in patients treated on ALL-BFM protocols. We have now tested if NOTCH pathway activation at different steps has similar clinical effects and if multiple mutations in this pathway function synergistically. Analysis of a validation set of 151 T-ALL patients and of the total cohort of 301 patients confirms the low relapse rate generally and the overall favorable effect of activating NOTCH1 mutations. Subgroup analysis shows that the NOTCH1 effect in ALL-BFM is restricted to patients with rapid early treatment response. Inactivation of the ubiquitin ligase FBXW7 is associated with rapid early treatment response and synergizes with NOTCH1 receptor activation. However, the effect of FBXW7 inactivation is separable from NOTCH1 activation by not synergizing with NOTCH1 mutations in predicting favorable long-term outcome, which can probably be explained by the interaction of FBXW7 with other clients. Finally, the comparison with other European protocols suggests that the NOTCH effect is treatment dependent generally and may depend on the intensity of central nervous system-directed therapy specifically. [ABSTRACT FROM AUTHOR]

Background:Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC).Methods:Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of 10 mg l–1 or modified Glasgow prognostic score (mGPS) of 1), and nutritional status were assessed in newly diagnosed OGC patients (n=293). Healthy volunteers (n=35) served as controls.Results:MIC-1 was elevated in patients (median=1371 pg ml–1; range 141–39 053) when compared with controls (median=377 pg ml–1; range 141–3786; P<0.001). Patients with gastric tumours (median=1592 pg ml–1; range 141–12 643) showed higher MIC-1 concentrations than patients with junctional (median=1337 pg ml–1; range 383–39 053) and oesophageal tumours (median=1180 pg ml–1; range 258–31 184; P=0.015). Patients showed a median weight loss of 6.4% (range 0.0–33.4%), and 42% of patients had an mGPS of 1 or plasma CRP of 10 mg l–1 (median=9 mg l–1; range 1–200). MIC-1 correlated positively with disease stage (r2=0.217; P<0.001), age (r2=0.332; P<0.001), CRP (r2=0.314; P<0.001), and mGPS (r2=0.336; P<0.001), and negatively with Karnofsky Performance Score (r2=−0.269; P<0.001). However, although MIC-1 correlated weakly with dietary intake (r2=0.157; P=0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median=204 days; 95% CI 157–251) when compared with patients with MIC-1 levels in the lower three quartiles (median=316 days; 95% CI 259–373; P=0.036), but MIC-1 was not an independent prognostic indicator.Conclusions:There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC. [ABSTRACT FROM AUTHOR]

The shape of and proportions between the surface areas of the medial coronoid process (MCP) and the fovea of the radial head were determined in 88 juvenile dogs and 146 adult dogs grouped as giant, large, mid-sized, chondrodystrophic, or small dogs. Thereby, the longitudinal (length) and transverse (width) extension of the MCP and fovea of the radial head have been measured. Original values were used to describe changes of the parameters attributed to growth. Normalized values (i.e. values expected in case of a width of the fovea of the radial head of 20 mm) were used to determine potential differences between constitutional types. All original values increased during growth ( P < 0.05) except for the width and length of the MCP in chondrodystrophic and small breeds. Normalized values revealed a proportional decrease in width and length of the MCP during growth ( P < 0.05) compared with the radial head. In adults, the normalized MCP was widest in giant dogs followed by large, mid-sized, small, and chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in large and chondrodystrophic dogs with those of large dogs being significantly ( P < 0.05) shorter than those in giant, mid-sized and small dogs. Present results suggest that a deficiency in length-growth of the MCP – which has been present especially in large dogs – results in smaller humeral contact areas and decreased weight-bearing capacity of the MCP. Because loading forces acting on the MCP increase with body weight, the condition noted in large dogs might increase the risk of fragmentation of the MCP in these. [ABSTRACT FROM AUTHOR]

Twenty Parkinson’s disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [11C]d-threo-methylphenidate ([11C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [11C]dMP binding potential (BPdMP) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 ± 8.9 yrs; disease duration 5.2 ± 3.3 yrs; UPDRS motor score 24.2 ± 9.8; Hoehn & Yahr 2.1 ± 0.8; mean ± SD) BPdMP was reduced to 30% (range: 11–55%) in the putamen and 52% (range: 14–96%) in the caudate nucleus. BPdMP in the putamen closely correlated with the UPDRS motor score ( r = −0.79, p < 0.001), and disease duration ( r = −0.76, p < 0.001) but not with age at onset. The correlation with the UPDRS score depended on akinesia and rigidity, while the tremor scores were related neither to putamen nor caudate BPdMP. Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BPdMP in the contralateral putamen (exponential fit: 34% at onset) than the other PD patients (41% at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical “true” disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37% contra- and 62% ipsilateral, corresponding with an observed mean BPdMP of 51% (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BPdMP were observed between patients with essential tremor and healthy controls. [11C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity. [ABSTRACT FROM AUTHOR]

The subchondral split line patterns of the canine medial coronoid process (MCP) were compared with fragmentation line patterns of the MCP in case of elbow dysplasia. Split line patterns were determined in paired ulnae from the killed 26 large-breed dogs ranging in age between 0.8 and 15 years and in two ulnae affected by fragmentation of the MCP. The macerated ulnae were degreased with methylene chloride and decalcified in 5% nitric acid. The subchondral bony layer was pierced at right angles in regular intervals using a round needle that was dipped in black liquid acrylic colour. Three main types of split line patterns could be differentiated (i.e. a sagittal type, a transverse type and an intermediate type). In the sagittal type, split lines were aligned in parallel to the lateral border and at right angles to the rim of the tip and medial border of the MCP. In the transverse type, split lines were orientated in a transverse line to both collateral borders. The intermediate type was characterized as a transition type between sagittal and transverse type as the split lines were aligned obliquely to the longitudinal axis of the MCP. These three types corresponded well with the fissure and fragmentation line patterns of the MCP. The present findings strongly suggest an association between split line pattern and type of fragmentation of the MCP. [ABSTRACT FROM AUTHOR]

Vertebral and inter-vertebral parameters obtained in large breeds ( n = 74), small breeds ( n = 35), and Dachshunds ( n = 30) were compared to reveal potential differences in the range of motion of the cervical spine between these three groups of breeds. Body size normalized dimensions of vertebral and inter-vertebral parameters and correlations between these indicate large canine breeds to have a tendency towards higher range of motion in sagittal rotation and lateral bending compared with Dachshunds and small breeds. Higher mobility in large breeds is based on significantly ( P < 0.05) lower vertebral endplate heights and widths, shorter vertebral bodies and longer inter-vertebral discs, wider but shorter cranial and caudal articular surfaces, larger differences in width between caudal and cranial joining facets (compared with Dachshunds from C3/4 to C6/7, compared with small breeds from C4/5 to C5/6), and larger differences in length between caudal and cranial joining facets. Large differences in width between caudal and cranial joining facets were associated with small distances between the most medial (C3/4 to C6/7) and lateral (C3/4 to C5/6) aspects of the articular surfaces as well as with small differences in length between caudal and cranial joining facets (C3/4 to C5/6). This suggests that from C3/4 to C5/6 a higher range of motion in lateral bending is coupled to a lower range of motion in sagittal rotation. The present findings contribute also to explain the higher incidence of degenerative lesions of the cervical spine in large dogs. [ABSTRACT FROM AUTHOR]

Summary A total of 17 parameters (nine lengths, four heights, four widths) was used to characterize the shape of the skull in a sample of 69 pure bred cats. Results of the discriminant analysis confirmed three phenotypically different skull formations, i.e. the round-shaped, the triangular and the cuneiform. Further statistical analyses revealed that the appearance of the skull was especially variable in the case of a round shape and that the lengths had been especially affected by these characteristics. The round shape of the brachycephalic skull was attributed to a reduction in length of the face and braincase as well. In many cases, this condition was associated with disproportional increase in height and width of the braincase and an increase in convexity of the calvaria. The decrease in length of the face was more pronounced at the dorsal surface of the nose than at the palate. Therefore, the inclination of the bony nasal aperture became flatter and the inclination of the maxilloturbinate became steeper. As a result, the ventral nasal meatus changed its direction twice. This condition might predispose to dyspnoea by restricting the air passageways within the nasal cavity. Round-shaped skulls were also associated with a decrease in facial width. Morphological variants that were frequently seen in round-shaped skulls include almost rectangular inclination of the nasal bone and more distant extension of the foramen magnum between the occipital condyles. [ABSTRACT FROM AUTHOR]

Summary Casts of the nasolacrimal duct system were obtained from 50 euthanised cats including brachy-, meso- and dolichocephalic breeds. The course of the nasolacrimal duct, which was assessed radiographically and gross-anatomically, was strongly related to the shape of the skull. In meso- and dolichocephalic cats the nasolacrimal duct formed a dorsally opened arch with the descending part being directed rostroventrally. The main part of the duct passed the nasal cavity in a rather horizontal course parallel to the hard palate and was located ventrally to the lacrimal foramen. However, foreshortening of the face was associated with a right-angled or even acute-angled alignment of the duct. In higher degrees of brachycephaly the main part of the duct ascended beyond the level of the lacrimal foramen and passed the nasal cavity dorsal to the level of the lacrimal foramen. This specific course of the nasolacrimal duct in brachycephalic cats was consistent with a steeper alignment and attachment of the maxilloturbinate. Accessory orifices of the nasolacrimal duct opening into the nasal cavity had never been observed. The present results strongly suggest that the specific course of the nasolacrimal duct in brachycephalic cats might hinder the drainage of the lacrimal fluid irrespective of the diameter of the lumen of the nasolacrimal duct system. [ABSTRACT FROM AUTHOR]