111 research outputs found
Effect of aspect-ratio on vortex distribution and heat transfer in rotating Rayleigh-B\'enard convection
Numerical and experimental data for the heat transfer as function of the
Rossby number Ro in turbulent rotating Rayleigh-B\'enard convection are
presented for Prandtl number Pr=4.38 and Rayleigh number up
to . The aspect ratio \Gamma = D/L, where L is the height
and D the diameter of the cylindrical sample, is varied between \Gamma=0.5 and
\Gamma=2.0. Without rotation, where the aspect ratio influences the global
large scale circulation, we see a small aspect-ratio dependence in the Nusselt
number for . However, for stronger rotation, i.e. , the heat transport becomes independent of the aspect-ratio. We
interpret this finding as follows: In the rotating regime the heat is mainly
transported by vertically-aligned vortices. Since the vertically-aligned
vortices are local, the aspect ratio has a negligible effect on the heat
transport in the rotating regime. Indeed, a detailed analysis of vortex
statistics shows that the fraction of the horizontal area that is covered by
vortices is independent of the aspect ratio when . In
agreement with the results of Weiss et al. Phys. Rev. Lett., vol 105, 224501
(2010) we find a vortex-depleted area close to the sidewall. Here, we in
addition show that there is also an area with enhanced vortex concentration
next to the vortex-depleted edge region and that the absolute widths of both
regions are independent of the aspect ratio.Comment: 13 pages, 8 figure
Update breast cancer 2020 part 5: moving therapies from advanced to early breast cancer patients
Process evaluation of a stepped-care program to prevent depression in primary care: patients' and practice nurses' experiences
Background: Depression is common in patients with diabetes type 2 (DM2) and/or coronary heart disease (CHD), with high personal and societal burden and may even be preventable. Recently, a cluster randomized trial of stepped care to prevent depression among patients with DM2 and/or CHD and subthreshold depression in Dutch primary care (Step-Dep) versus usual care showed no effectiveness. This paper presents its process evaluation, exploring in-depth experiences from a patient and practice nurse perspective to further understand the results. Methods: A qualitative study was conducted. Using a purposive sampling strategy, data were collected through semi-structured interviews with 24 participants (15 patients and nine practice nurses). All interviews were audiotaped and transcribed verbatim. Atlas.ti 5.7.1 software was used for coding and structuring of themes. A thematic analysis of the data was performed. Results: The process evaluation showed, even through a negative trial, that Step-Dep was perceived as valuable by both patients and practice nurses; perceived effectiveness on improving depressive symptoms varied greatly, but most felt that it had been beneficial for patients' well-being. Facilitators were: increased awareness of mental health problems in chronic disease management and improved accessibility and decreased experienced stigma of receiving mental health care. The Patient Health Questionnaire 9 (PHQ-9), used to determine depression severity, functioned as a useful starting point for the conversation on mental health and patients gained more insight into their mental health by regularly filling out the PHQ-9. However, patients and practice nurses did not widely support its use for monitoring depressive symptoms or making treatment decisions. Monitoring mental health was deemed important in chronically ill patients by both patients and practice nurses and was suggested to start at the time of diagnosis of a chronic disease. Appointed barriers were that patients were primarily motivated to participate in scientific research rather than their intrinsic need to improve depressive symptoms. Additionally, various practice nurses preferred offering individually based therapy over pre-determined interventions in a protocolled sequence and somatic practice nurses expressed a lack of competence to recognise and treat mental health problems. Conclusion: This study demonstrates both the benefits and unique demands of programs such as Step-Dep. The appointed facilitators and barriers could guide the development of future studies aiming to prevent depression in similar patient groups
A Process Algebra for Supervisory Coordination
A supervisory controller controls and coordinates the behavior of different
components of a complex machine by observing their discrete behaviour.
Supervisory control theory studies automated synthesis of controller models,
known as supervisors, based on formal models of the machine components and a
formalization of the requirements. Subsequently, code generation can be used to
implement this supervisor in software, on a PLC, or embedded microprocessor. In
this article, we take a closer look at the control loop that couples the
supervisory controller and the machine. We model both event-based and
state-based observations using process algebra and bisimulation-based
semantics. The main application area of supervisory control that we consider is
coordination, referred to as supervisory coordination, and we give an academic
and an industrial example, discussing the process-theoretic concepts employed.Comment: In Proceedings PACO 2011, arXiv:1108.145
Everolimus in Metastatic Renal Cell Carcinoma after Failure of Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFr-TKI) Therapy: Results of an Interim Analysis of a Non-Interventional Study
Background: Everolimus is approved for treatment of anti-vascularendothelial growth factor (VEGF)-refractory patients with metastaticrenal cell carcinoma (mRCC). Clinical trials rarely mirror treatmentreality. Thus, a broader evaluation of everolimus is valuable forroutine use. Patients and Methods: A German multicenternon-interventional study documented mRCC patients starting everolimusafter failure of initial VEGF-targeted therapy. Primary endpoint waseffectiveness, defined as time to progression (TIP) according toinvestigator assessment (time from first dose to progression). Results:Of 382 documented patients, 196 were included in this interim analysis
Perturbation of the yeast mitochondrial lipidome and associated membrane proteins following heterologous expression of Artemia-ANT
Heterologous expression is a landmark technique for studying a protein itself or its effect on the expression host, in which membrane-embedded proteins are a common choice. Yet, the impact of inserting a foreign protein to the lipid environment of host membranes, has never been addressed. Here we demonstrated that heterologous expression of the Artemia franciscana adenine nucleotide translocase (ANT) in yeasts altered lipidomic composition of their inner mitochondrial membranes. Along with this, activities of complex II, IV and ATP synthase, all membrane-embedded components, were significantly decreased while their expression levels remained unaffected. Although the results represent an individual case of expressing a crustacean protein in yeast inner mitochondrial membranes, it cannot be excluded that host lipidome alterations is a more widespread epiphenomenon, potentially biasing heterologous expression experiments. Finally, our results raise the possibility that not only lipids modulate protein function, but also membrane-embedded proteins modulate lipid composition, thus revealing a reciprocal mode of regulation for these two biomolecular entities
Triose Phosphate Isomerase Deficiency Is Caused by Altered Dimerization–Not Catalytic Inactivity–of the Mutant Enzymes
Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell extracts of affected individuals. These observations allowed concluding that the different mutations in the TPI alleles result in catalytically inactive enzymes. However, despite a high occurrence of TPI null alleles within several human populations, the frequency of this disorder is exceptionally rare. In order to address this apparent discrepancy, we generated a yeast model allowing us to perform comparative in vivo analyses of the enzymatic and functional properties of the different enzyme variants. We discovered that the majority of these variants exhibit no reduced catalytic activity per se. Instead, we observed, the dimerization behavior of TPI is influenced by the particular mutations investigated, and by the use of a potential alternative translation initiation site in the TPI gene. Additionally, we demonstrated that the overexpression of the most frequent TPI variant, Glu104Asp, which displays altered dimerization features, results in diminished endogenous TPI levels in mammalian cells. Thus, our results reveal that enzyme deregulation attributable to aberrant dimerization of TPI, rather than direct catalytic inactivation of the enzyme, underlies the pathogenesis of TPI deficiency. Finally, we discovered that yeast cells expressing a TPI variant exhibiting reduced catalytic activity are more resistant against oxidative stress caused by the thiol-oxidizing reagent diamide. This observed advantage might serve to explain the high allelic frequency of TPI null alleles detected among human populations
Benefits of early and prolonged fulvestrant treatment in 848 postmenopausal advanced breast cancer patients
Patients’ and practice nurses’ perceptions of depression in patients with type 2 diabetes and/or coronary heart disease screened for subthreshold depression
Background
Comorbid depression is common in patients with type 2 diabetes (DM2) and/or coronary heart disease (CHD) and is associated with poor quality of life and adverse health outcomes. However, little is known about patients’ and practice nurses’ (PNs) perceptions of depression. Tailoring care to these perceptions may affect depression detection and patient engagement with treatment and prevention programs. This study aimed to explore patients’ and PNs’ perceptions of depression in patients with DM2/CHD screened for subthreshold depression.
Methods
A qualitative study was conducted as part of a Dutch stepped-care prevention project. Using a purposive sampling strategy, data were collected through semi-structured interviews with 15 patients and 9 PNs. After consent, all interviews were recorded, transcribed verbatim and analyzed independently by two researchers with Atlas.ti.5.7.1 software. The patient and PN datasets were inspected for commonalities using a constant comparative method, from which a final thematic framework was generated.
Results
Main themes were: illness perception, need for care and causes of depression. Patients generally considered themselves at least mildly depressed, but perceived severity levels were not always congruent with Patient Health Questionnaire 9 scores at inclusion. Initially recognizing or naming their mental state as a (subthreshold) depression was difficult for some. Having trouble sleeping was frequently experienced as the most burdensome symptom. Most experienced a need for care; psycho-educational advice and talking therapy were preferred. Perceived symptom severity corresponded with perceived need for care, but did not necessarily match help-seeking behaviour. Main named barriers to help-seeking were experienced stigma and lack of awareness of depression and mental health care possibilities. PNs frequently perceived patients as not depressed and with minimal need for specific care except for attention. Participants pointed to a mix of causes of depression, most related to negative life events and circumstances and perceived indirect links with DM2/CHD.
Conclusion
Data of the interviewed patients and PNs suggest that they have different perceptions about (subthreshold) depressive illness and the need for care, although views on its causes seem to overlap more
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