Spiral surface growth without desorption

Spiral surface growth is well understood in the limit where the step motion is controlled by the local supersaturation of adatoms near the spiral ridge. In epitaxial thin-film growth, however, spirals can form in a step-flow regime where desorption of adatoms is negligible and the ridge dynamics is governed by the non-local diffusion field of adatoms on the whole surface. We investigate this limit numerically using a phase-field formulation of the Burton-Cabrera-Frank model, as well as analytically. Quantitative predictions, which differ strikingly from those of the local limit, are made for the selected step spacing as a function of the deposition flux, as well as for the dependence of the relaxation time to steady-state growth on the screw dislocation density.Comment: 9 pages, 3 figures, RevTe

Reasons for non-feasibility of therapeutic drug monitoring of oral targeted therapies in oncology - an analysis of the closed cohorts of a multicentre prospective study

BackgroundTherapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.MethodsWe evaluated drug cohorts from the Dutch Pharmacology Oncology Group - TDM study. Based on PK levels taken at pre-specified time points, PK-guided interventions were performed. Feasibility of TDM was evaluated, and based on the success and practicability of TDM, cohorts could be closed.ResultsFor 10 out of 24 cohorts TDM was not feasible and inclusion was closed. A high incidence of adverse events resulted in closing the cabozantinib, dabrafenib/trametinib, everolimus, regorafenib and vismodegib cohort. The enzalutamide and erlotinib cohorts were closed because almost all PK levels were above target. Other, non-pharmacological reasons led to closing the palbociclib, olaparib and tamoxifen cohort.ConclusionsAlthough TDM could help personalising treatment for many drugs, the above-mentioned reasons can influence its feasibility, usefulness and clinical applicability. Therefore, routine TDM is not advised for cabozantinib, dabrafenib/trametinib, enzalutamide, erlotinib, everolimus, regorafenib and vismodegib. Nonetheless, TDM remains valuable for individual clinical decisions

Phase transitions in the antiferromagnetic XY model with a kagome lattice

The ground state of the antiferromagnetic XY model with a kagome lattice is characterized by a well developed accidental degeneracy. As a consequence the phase transition in this system consists in unbinding of pairs of fractional vortices. Addition of the next-to-nearest neighbors (NNN) interaction leads to stabilization of the long-range order in chirality (staggered chirality). We show that the phase transition, related with destruction of this long-range order, can happen as a separate phase transition below the temperature of the fractional vortex pairs unbinding only if the NNN coupling is extremely weak, and find how the temperature of this transition depends on coupling constants. We also demonstarte that the antiferromagnetic ordering of chiralities and, accordingly, the presence of the second phase transition are induced by the free energy of spin wave fluctuations even in absence of the NNN coupling.Comment: 10 pages (Revtex) + 8 figures (in 2 postscript files

Clinical and radiological outcome of conservative vs. surgical treatment of atraumatic degenerative rotator cuff rupture: design of a randomized controlled trial

Background: Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice. Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present. However, degenerative ruptures of the rotator cuff can also be observed in asymptomatic elderly individuals. Treatment of these symptomatic degenerative ruptures may be conservative or surgical. Acceptable results are reported for both treatment modalities. No evidence-based level-1 studies have been conducted so far to compare these treatment modalities. The objective of this study is to determine whether there is a difference in outcome between surgical reconstruction and conservative treatment of a degenerative atraumatic rotator cuff tendon rupture. Methods/Design: A randomized controlled trial will be conducted. Patients aged between 45 and 75 with a symptomatic atraumatic rotator cuff rupture as diagnosed by MRI will be included. Exclusion criteria are traumatic rotator cuff rupture, frozen shoulder and diabetes mellitus. Patients will be randomized into two groups. Conservative treatment includes physical therapy according to a standardized protocol, NSAIDs and, if indicated, subacromial infiltration with a local anesthetic and corticosteroids. Surgical reconstruction is performed under general anesthesia in combination with an interscalenus plexus block. An acromioplasty with reconstruction of the rotator cuff tendon is performed, as described by Rockwood et al. Measurements take place preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. The primary outcome measure is the Constant score. Secondary measures include both disease-specific and generic outcome measures, and an economic evaluation. Additionally, one year after inclusion a second MRI will be taken of all patients in order to determine whether extent and localization of the rupture as well as the amount of fatty degeneration are prognostic factors. Discussion: Both surgical as conservative treatment of a symptomatic atraumatic rotator cuff tendon rupture is used in current practice. There is a lack of level-1 studies comparing surgical vs. conservative treatment. This randomized controlled trial has been designed to determine whether the surgical treatment of a degenerative atraumatic rotator cuff tendon rupture may lead to a better functional and radiological outcome than conservative treatment after one year of follow-up

Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease

Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of future models for integrated PC in Europe. Methods: Cochrane, PubMed, EMBASE, CINAHL, AMED, BNI, Web of Science, NHS Evidence. Five journals and references from included studies were hand-searched. Two reviewers screened the search results. Studies with adult patients with advanced cancer/chronic disease from 1995 to 2013 in Europe, in English, French, German, Dutch, Hungarian or Spanish were included. A narrative synthesis was used. Results: 14 studies were included, 7 models for chronic disease, 4 for integrated care in oncology, 2 for both cancer and chronic disease and 2 for end-of-life pathways. The results show a strong agreement on the benefits of the involvement of a PC multidisciplinary team: better symptom control, less caregiver burden, improvement in continuity and coordination of care, fewer admissions, cost effectiveness and patients dying in their preferred place. Conclusion: Based on our findings, a generic framework for integrated PC in cancer and chronic disease is proposed. This framework fosters integration of PC in the disease trajectory concurrently with treatment and identifies the importance of employing a PC-trained multidisciplinary team with a threefold focus: treatment, consulting and training

Human Osteoblast-Derived Extracellular Matrix with High Homology to Bone Proteome Is Osteopromotive

Efficient osteogenic differentiation of mesenchymal stromal cells (MSCs) is crucial to accelerate bone formation. In this context, the use of extracellular matrix (ECM) as natural 3D framework mimicking in vivo tissue architecture is of interest. The aim of this study was to generate a devitalized human osteogenic MSC-derived ECM and to investigate its impact on MSC osteogenic differentiation to improve MSC properties in bone regeneration. The devitalized ECM significantly enhanced MSC adhesion and proliferation. Osteogenic differentiation and mineralization of MSCs on the ECM were quicker than in standard conditions. The presence of ECM promoted in vivo bone formation by MSCs in a mouse model of ectopic calcification. We analyzed the ECM composition by mass spectrometry, detecting 846 proteins. Of these, 473 proteins were shared with the human bone proteome we previously described, demonstrating high homology to an in vivo microenvironment. Bioinformatic analysis of the 846 proteins showed involvement in adhesion and osteogenic differentiation, confirming the ECM composition as key modulator of MSC behavior. In addition to known ECM components, proteomic analysis revealed novel ECM functions, which could improve culture conditions. In sum

To what degree is palliative care integrated in guidelines and pathways for adult cancer patients in Europe: a systematic literature review

Palliative Care (PC) aims to improve the quality of life for patients with cancer and their families and its benefits have been demonstrated by several studies. The objective of this systematic review is to assess the integration of PC in the content of guidelines/pathways of adult cancer patients in Europe. Methods We included studies of adult patients with cancer published from 01/01/1995 and 31/12/2013 in Europe in six languages. We searched nine electronic databases, hand-searched six journals and also performed citation tracking. Studies were ranked using Emanuel's Integrated Palliative Care (IPC) criteria, a tool containing 11 domains to assess PC content in guidelines. Two reviewers screened the results and narrative synthesis has been employed. Results We identified a total of 28,277 potentially relevant articles from which 637 were eligible for full-text screening. The final review included 60 guidelines and 14 pathways. Eighty percent (80 %) of the guidelines/pathways emphasize a holistic approach and 66 % focus on PC interventions aimed at reducing suffering. Fifty seven percent (57 %) did not discuss referral criteria for PC. Of all studies, five fulfilled at least 10/11 IPC criteria. Differences existed with regard to the referral criteria for bereavement care and the continuous adjustment of goals of care. Conclusion Overall, most of the identified guidelines/pathways highlighted the importance of the holistic approach of IPC. The studies that were found to fulfil at least 10/11 Emanuel's IPC criteria could serve as benchmarks of IPC

Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease:a systematic literature review of European guidelines and pathways

Despite the positive impact of Palliative Care (PC) on the quality of life for patients and their relatives, the implementation of PC in non-cancer health-care delivery in the EU seems scarcely addressed. The aim of this study is to assess guidelines/pathways for integrated PC in patients with advanced Chronic Heart Failure (CHF) and Chronic Obstructive Pulmonary Disease (COPD) in Europe via a systematic literature review. Methods Search results were screened by two reviewers. Eligible studies of adult patients with CHF or COPD published between 01/01/1995 and 31/12/2013 in Europe in 6 languages were included. Nine electronic databases were searched, 6 journals were hand-searched and citation tracking was also performed. For the analysis, a narrative synthesis was employed. Results The search strategy revealed 26,256 studies without duplicates. From these, 19 studies were included in the review; 17 guidelines and 2 pathways. 18 out of 19 focused on suffering reduction interventions, 13/19 on a holistic approach and 15/19 on discussions of illness prognosis and limitations. The involvement of a PC team was mentioned in 13/19 studies, the assessment of the patients’ goals of care in 12/19 and the advance care planning in 11/19. Only 4/19 studies elaborated on aspects such as grief and bereavement care, 7/19 on treatment in the last hours of life and 8/19 on the continuation of goal adjustment. Conclusion The results illustrate that there is a growing awareness for the importance of integrated PC in patients with advanced CHF or COPD. At the same time, however, they signal the need for the development of standardized strategies so that existing barriers are alleviated

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC)

\ua9 2024 The AuthorsBackground: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A

Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.

OBJECTIVES: To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. DESIGN: Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. SETTING: 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. PARTICIPANTS: A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. RESULTS: Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10-68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. CONCLUSIONS: This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk