A systematic correlation between two-dimensional flow topology and the abstract statistics of turbulence

Velocity differences in the direct enstrophy cascade of two-dimensional turbulence are correlated with the underlying flow topology. The statistics of the transverse and longitudinal velocity differences are found to be governed by different structures. The wings of the transverse distribution are dominated by strong vortex centers, whereas, the tails of the longitudinal differences are dominated by saddles. Viewed in the framework of earlier theoretical work this result suggests that the transfer of enstrophy to smaller scales is accomplished in regions of the flow dominated by saddles.Comment: 4 pages, 4 figure

Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies.

Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical resection of the tumour followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light of 652 nm from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The light delivery to the thoracic cavity was monitored by in situ isotropic light detectors. The position of the light delivery fibre was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and haematopericardium). The operation time was increased by a maximum of 1 h to illuminate the total hemithoracic surface with 10 J cm(-2) (incident and scattered light). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 h after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with PMN cells and oedema of the striated muscles cells. Of the five patients treated, four are alive with no signs of recurrent tumour with a follow-up of 9-11 months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (< 1 h). In situ dosimetry ensures optimal light distribution and allows total doses (incident plus scattered light) to be monitored at different positions within the cavity. This combination of light delivery and dosimetry is well suited for adjuvant treatment with PDT in malignant pleural tumours

Are Steadily Moving Crystals Unstable?

We study the dynamics of small fluctuations about the uniform state of a crystal moving through a dissipative medium, e.g. a sedimenting colloidal crystal or a moving flux lattice, using a set of continuum equations for the displacement fields, and a one-dimensional driven lattice-gas model for the coupled concentration and tilt fields. For the colloidal crystal we predict a continuous nonequilibrium phase transition to a clumped state above a critical Peclet number.Comment: 4 pages, revtex, 2 .eps figures, uses epsf.sty; To be published in Phys. Rev. Lett. This version is substantially rewritten but the essential content is the same as befor

Implications of the new MRI-based rectum definition according to the sigmoid take-off:multicentre cohort study

Background: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. Methods: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). Results: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P &lt; 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P &lt; 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P &lt; 0.001). Three-year oncological outcomes were comparable. Conclusion: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.</p

Implications of the new MRI-based rectum definition according to the sigmoid take-off:multicentre cohort study

Background: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. Methods: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). Results: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P &lt; 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P &lt; 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P &lt; 0.001). Three-year oncological outcomes were comparable. Conclusion: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.</p

Bioavailability and toxicity after oral administration of m-iodobenzylguanidine (MIBG)

meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for diagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocytoma and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v., is used in several clinical studies. These include palliation of the carcinoid syndrome, in which MIBG proved to be effective in 60% of the patients. Oral MIBG administration might be convenient to maintain palliation and possibly improve the percentage of responders. We have, therefore, investigated the feasibility of oral administration of MIBG in an animal model. Orally administered MIBG demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg−1. The first and only toxicity encountered was a decrease in renal function, measured by a reduced clearance of [51Cr]EDTA and accompanied by histological tubular damage. Repeated MIBG administration of 40 mg kg−1for 5 sequential days or of 20 mg kg−1for two courses of 5 sequential days with a 2-day interval did not affect renal clearance and was not accompanied by histological abnormalities in kidney, stomach, intestines, liver, heart, lungs, thymus, salivary glands and testes. Because of a sufficient bioavailability in absence of gastrointestinal toxicity, MIBG is considered suitable for further clinical investigation of repeated oral administration in patients. 1999 Cancer Research Campaig

Turbulence and passive scalar transport in a free-slip surface

We consider the two-dimensional (2D) flow in a flat free-slip surface that bounds a three-dimensional (3D) volume in which the flow is turbulent. The equations of motion for the two-dimensional flow in the surface are neither compressible nor incompressible but strongly influenced by the 3D flow underneath the surface. The velocity correlation functions in the 2D surface and in the 3D volume scale with the same exponents. In the viscous subrange the amplitudes are the same, but in the inertial subrange the 2D one is reduced to 2/3 of the 3D amplitude. The surface flow is more strongly intermittent than the 3D volume flow. Geometric scaling theory is used to derive a relation between the scaling of the velocity field and the density fluctuations of a passive scalar advected on the surface.Comment: 11 pages, 10 Postscript figure

Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with Granulomatosis with polyangiitis

OBJECTIVES: Granulomatosis with polyangiitis (GPA) is a chronic relapsing systemic autoimmune vasculitis. Current treatment of GPA is unsatisfactory as it relies on strong immunosuppressive regimens, with either cyclophosphamide or rituximab, that reduce the immunogenicity of several vaccines and are risk factors of severe form of COVID-19. This emphasizes the need to identify new drug target and to develop treatment strategies with less harmful side effects. Since CD4+ effector memory T cells (TEM) play a key role in the pathogenesis of GPA, we aimed in this study to modulate CD4+TEM cell activity via Kv1.3 blockade using the specific peptide inhibiter, ShK-186.METHODS: Peripheral blood of 27 GPA-patients in remission and 16 age- and sex-matched healthy controls (HCs) were pre-incubated in vitro in the presence or absence of ShK-186, followed by stimulation with PMA, calcium ionophore and brefeldin-A. The effect of ShK-186 on the cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+TH cells were assessed using flow cytometry.RESULTS: ShK-186 reduced the expression level of IFNγ, TNFα, IL-4, IL-17, and IL-21 in CD4+TH cells from GPA-patients in vitro. Further analysis performed on sorted CD4+T cell subsets, revealed that ShK-186 predominantly inhibited the cytokine production of CD4+TEM cells. ShK-186 treatment reduced the production of the pro-inflammatory cytokines to the level seen in CD4+ TH cells from HCs.CONCLUSIONS: Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.</p