Edge state in pipe flow experiments

Recent numerical studies suggest that in pipe and related shear flows, the region of phase space separating laminar from turbulent motion is organized by a chaotic attractor, called an edge state, which mediates the transition process. We here confirm the existence of the edge state in laboratory experiments. We observe that it governs the dynamics during the decay of turbulence underlining its potential relevance for turbulence control. In addition we unveil two unstable traveling wave solutions underlying the experimental flow fields. This observation corroborates earlier suggestions that unstable solutions organize turbulence and its stability border.Postprint (published version

Poor results of drilling in early stages of juxta-articular osteonecrosis in 12 joints affected by Gaucher disease

Background and purpose Gaucher disease is heterogeneous. One of the most devastating complications is bone involvement, ranging from mild osteopenia to osteonecrosis, but no markers have been discovered to predict onset and/or progression. We describe our experience in a large referral center using drilling for juxta-articular osteonecrosis in young patients with Gaucher disease

Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study

OBJECTIVE: To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce clinical tolerance, defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. METHODS: Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group in whom a complete response was achieved at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/day). RESULTS: There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. A complete response was achieved in 33% of the subjects in the treatment group and in 31% of the subjects in the control group at week 24. Fifty percent of the subjects in the treatment group who met complete response criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their complete response status through week 52. CONCLUSION: The addition of abatacept to a regimen of CYC followed by AZA did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered

Dental profile of patients with Gaucher disease

BACKGROUND: This study was conducted to determine whether patients with Gaucher disease had significant dental pathology because of abnormal bone structure, pancytopenia, and coagulation abnormalities. METHODS: Each patient received a complete oral and periodontal examination in addition to a routine hematological evaluation. RESULTS: Gaucher patients had significantly fewer carious lesions than otherwise healthy carriers. Despite prevalence of anemia, there was no increase in gingival disease; despite the high incidence of thrombocytopenia, gingival bleeding was not noted; and despite radiological evidence of bone involvement, there was no greater incidence loss of teeth or clinical tooth mobility. CONCLUSIONS: These data represent the first survey of the oral health of a large cohort of patients with Gaucher disease. It is a pilot study of a unique population and the results of the investigation are indications for further research. Based on our findings, we recommend regular oral examinations with appropriate dental treatment for patients with Gaucher disease as for other individuals. Consultation between the dentist and physician, preferably one with experience with Gaucher disease, should be considered when surgical procedures are planned

Discipline-Specific Compared to Generic Training of Teachers in Higher Education

A recurrent theme arising in the higher education sector is the suitability and effectiveness of generic versus discipline-specific training of university teachers, who are often recruited based on their disciplinary specialties to become teachers in higher education. We compared two groups of participants who had undergone training using a generic post-graduate certificate in higher education (PGCertGeneric) versus a discipline-specific course in veterinary education (PGCertVetEd). The study was conducted using a survey that allowed comparison of participants who completed PGCertGeneric (n=21) with PGCertVetEd (n=22). Results indicated that participants from both PGCertGeneric and PGCertVetEd considered teaching to be satisfying and important to their careers, valued the teaching observation component of the course, and identified similar training needs. However, the participants of the PGCertVetEd felt that the course made them better teachers, valued the relevance of the components taught, understood course design better, were encouraged to do further courses/reading in teaching and learning, changed their teaching as a result of the course, and were less stressed about teaching as compared to the PGCertGeneric participants (p<.05). It is likely that the PGCertVetEd, which was designed and developed by veterinarians with a wider understanding of the veterinary sector, helped the participants perceive the training course as suited to their needs

Acute Kidney Injury in Patients with Systemic Sclerosis Participating in Hematopoietic Cell Transplantation Trials in the United States

Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc

Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease

Background: Gaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1. Methods: We used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain of GBA2-deficient mice and mRNA and protein expression of GBA2 in GBA1-deficient murine fibroblasts were analyzed. Furthermore we crossed GBA2-deficient mice with conditional Gba1 knockout mice in order to quantify the interaction between GBA1 and GBA2. Finally, a genetic approach was used to test whether genetic variation in GBA2 is associated with GD and/or acts as a modifier in Gaucher patients. We tested 22 SNPs in the GBA2 and GBA1 genes in 98 type 1 and 60 type 2/3 Gaucher patients for single-and multi-marker association with GD. Results: We found a significant accumulation of GlcCer compared to wild-type controls in all three organs studied. In addition, a significant increase of Gba2-protein and Gba2-mRNA levels in GBA1-deficient murine fibroblasts was observed. GlcCer levels in the spleen from Gba1/Gba2 knockout mice were much higher than the sum of the single knockouts, indicating a cross-talk between the two glucosylceramidases and suggesting a partially compensation of the loss of one enzyme by the other. In the genetic approach, no significant association with severity of GD was found for SNPs at the GBA2 locus. However, in the multi-marker analyses a significant result was detected for p.L444P (GBA1) and rs4878628 (GBA2), using a model that does not take marginal effects into account. Conclusions: All together our observations make GBA2 a likely candidate to be involved in GD etiology. Furthermore, they point to GBA2 as a plausible modifier for GBA1 in patients with GD

The diagnostic role of gut feelings in general practice A focus group study of the concept and its determinants

Contains fulltext : 81297.pdf (publisher's version ) (Open Access)BACKGROUND: General practitioners sometimes base clinical decisions on gut feelings alone, even though there is little evidence of their diagnostic and prognostic value in daily practice. Research into these aspects and the use of the concept in medical education require a practical and valid description of gut feelings. The goal of our study was therefore to describe the concept of gut feelings in general practice and to identify their main determinants METHODS: Qualitative research including 4 focus group discussions. A heterogeneous sample of 28 GPs. Text analysis of the focus group discussions, using a grounded theory approach. RESULTS: Gut feelings are familiar to most GPs in the Netherlands and play a substantial role in their everyday routine. The participants distinguished two types of gut feelings, a sense of reassurance and a sense of alarm. In the former case, a GP is sure about prognosis and therapy, although they may not always have a clear diagnosis in mind. A sense of alarm means that a GP has the feeling that something is wrong even though objective arguments are lacking. GPs in the focus groups experienced gut feelings as a compass in situations of uncertainty and the majority of GPs trusted this guide. We identified the main determinants of gut feelings: fitting, alerting and interfering factors, sensation, contextual knowledge, medical education, experience and personality. CONCLUSION: The role of gut feelings in general practice has become much clearer, but we need more research into the contributions of individual determinants and into the test properties of gut feelings to make the concept suitable for medical education