Showing papers by "Utrecht University published in 2008"

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Abstract: BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)

Membrane lipids: where they are and how they behave.

Abstract: Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

Towards a model of work engagement

Abstract: Purpose - This paper aims to provide an overview of the recently introduced concept of work engagement. Design/methodology/approach - Qualitative and quantitative studies on work engagement are reviewed to uncover the manifestation of engagement, and reveal its antecedents and consequences. Findings - Work engagement can be defined as a state including vigor, dedication, and absorption. Job and personal resources are the main predictors of engagement; these resources gain their salience in the context of high job demands. Engaged workers are more creative, more productive, and more willing to go the extra mile. Originality/value - The findings of previous studies are integrated in an overall model that can be used to develop work engagement and advance career development in today's workplace.

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Cross-National Prevalence and Risk Factors for Suicidal Ideation, Plans, and Attempts

Abstract: Background Suicide is a leading cause of death worldwide; however, the prevalence and risk factors for the immediate precursors to suicide – suicidal ideation, plans and attempts – are not wellknown, especially in low- and middle-income countries. Aims To report on the prevalence and risk factors for suicidal behaviours across 17 countries. Method A total of 84 850 adults were interviewed regarding suicidal behaviours and socio-demographic and psychiatric risk factors. Results The cross-national lifetime prevalence of suicidal ideation, plans, and attempts is 9.2% (s.e.=0.1), 3.1% (s.e.=0.1), and 2.7% (s.e.=0.1). Across all countries, 60% of transitions from ideation to plan and attempt occur within the first year after ideation onset. Consistent cross-national risk factors included being female, younger, less educated, unmarried and having a mental disorder. Interestingly, the strongest diagnostic risk factors were mood disorders in high-income countries but impulse control disorders in low- and middle-income countries. Conclusion There is cross-national variability in the prevalence of suicidal behaviours, but strong consistency in the characteristics and risk factors for these behaviours. These findings have significant implications for the prediction and prevention of suicidal behaviours.

Intersectionality as buzzword A sociology of science perspective on what makes a feminist theory successful

Abstract: Since its inception, the concept of `intersectionality' — the interaction of multiple identities and experiences of exclusion and subordination — has been heralded as one of the most important cont...

General and abdominal adiposity and risk of death in Europe.

Abstract: Background Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. Methods We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. Results During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumfer...

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds

Abstract: Existing methods for reprogramming somatic cells to 'induced pluripotent stem cells' are inefficient, with only a small fraction of the starting cell population becoming pluripotent. Working with mouse embryonic fibroblasts, Hunagfu et al. increase reprogramming efficiency by treatment with DNA methyltransferase and histone deacetylase inhibitors. Reprogramming of mouse and human somatic cells can be achieved by ectopic expression of transcription factors, but with low efficiencies. We report that DNA methyltransferase and histone deacetylase (HDAC) inhibitors improve reprogramming efficiency. In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter. VPA also enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.

Work engagement: An emerging concept in occupational health psychology

Abstract: This position paper introduces the emerging concept of work engagement: a positive, fulfilling, affective-motivational state of work-related well-being that is characterized by vigour, dedication, and absorption. Although there are different views of work engagement, most scholars agree that engaged employees have high levels of energy and identify strongly with their work. The most often used instrument to measure engagement is the Utrecht Work Engagement Scale, a self-report instrument that has been validated in many countries across the world. Research on engagement has investigated how engagement differs from related concepts (e.g., workaholism, organizational commitment), and has focused on the most important predictors of work engagement. These studies have revealed that engagement is a unique concept that is best predicted by job resources (e.g., autonomy, supervisory coaching, performance feedback) and personal resources (e.g., optimism, self-efficacy, self-esteem). Moreover, the first studies have shown that work engagement is predictive of job performance and client satisfaction. The paper closes with an account of what we do not know about work engagement, and offers a brief research agenda for future work.

Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2.

Abstract: Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.

Workaholism, Burnout, and Work Engagement: Three of a Kind or Three Different Kinds of Employee Well‐being?

Abstract: The present study investigated in a sample of 587 telecom managers whether workaholism, burnout, and work engagement—the supposed antipode of burnout—can be distinguished empirically. These three concepts were measured with existing, validated multi-dimensional questionnaires. Structural equation modeling revealed that a slightly modified version of the hypothesised model that assumed three distinct yet correlated constructs—burnout, engagement, and workaholism—fitted the data best. Multiple regression analyses revealed that these three concepts retained unique hypothesised patterns of relationships with variables from five clusters representing (1) long working hours, (2) job characteristics, (3) work outcomes, (4) quality of social relationships, and (5) perceived health, respectively. In sum, our analyses provided converging evidence that workaholism, burnout, and engagement are three different kinds of employee well-being rather than three of a kind. La presente etude examine aupres d’un echantillon de 587 cadres des telecommunications la question de savoir si l’addiction au travail, le burnout et l’engagement au travail—suppose l’inverse du burnout—peuvent etre distingues empiriquement. Ces trois concepts sont mesures a partir de questionnaires multi-dimensionnels existants et valides. La modelisation d’equation structurale indique qu’une version legerement modifiee du modele teste selon lequel le burnout, l’engagement au travail et l’addiction au travail sont trois formes distinctes bien que correlees du bien-etre, rend mieux compte des resultats. Des analyses de regression multiples montrent que ces trois concepts renvoient

Synchronizing Rock Clocks of Earth History

Abstract: Calibration of the geological time scale is achieved by independent radioisotopic and astronomical dating, but these techniques yield discrepancies of ∼1.0% or more, limiting our ability to reconstruct Earth history. To overcome this fundamental setback, we compared astronomical and 40 Ar/ 39 Ar ages of tephras in marine deposits in Morocco to calibrate the age of Fish Canyon sanidine, the most widely used standard in 40 Ar/ 39 Ar geochronology. This calibration results in a more precise older age of 28.201 ± 0.046 million years ago (Ma) and reduces the 40 Ar/ 39 Ar method9s absolute uncertainty from ∼2.5 to 0.25%. In addition, this calibration provides tight constraints for the astronomical tuning of pre-Neogene successions, resulting in a mutually consistent age of ∼65.95 Ma for the Cretaceous/Tertiary boundary.

Adipose tissue dysfunction in obesity, diabetes, and vascular diseases

Abstract: The classical perception of adipose tissue as a storage place of fatty acids has been replaced over the last years by the notion that adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e.g. tumour necrosis factor-α, interleukin-6, adiponectin, leptin, and plasminogen activator inhibitor-1. The increased prevalence of excessive visceral obesity and obesity-related cardiovascular risk factors is closely associated with the rising incidence of cardiovascular diseases and type 2 diabetes mellitus. This clustering of vascular risk factors in (visceral) obesity is often referred to as metabolic syndrome. The close relationship between an increased quantity of visceral fat, metabolic disturbances, including low-grade inflammation, and cardiovascular diseases and the unique anatomical relation to the hepatic portal circulation has led to an intense endeavour to unravel the specific endocrine functions of this visceral fat depot. The objective of this paper is to describe adipose tissue dysfunction, delineate the relation between adipose tissue dysfunction and obesity and to describe how adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases. First, normal physiology of adipocytes and adipose tissue will be described.

The ALICE experiment at the CERN LHC

Abstract: ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.

The Job Demands-Resources model: A three-year cross-lagged study of burnout, depression, commitment, and work engagement

Abstract: By using a full panel design in a representative sample of Finnish dentists (N=2555), the present study aimed to test longitudinally the motivational and health impairment processes as proposed in the Job Demands-Resources (JD-R) model. The second aim was to investigate whether home resources and home demands have an additional influence on both processes over time. The hypotheses were tested with cross-lagged analyses based on two waves over a three-year period. The results supported both the motivational process and the health impairment process. Job resources influenced future work engagement, which, in turn, predicted organizational commitment, whereas job demands predicted burnout over time, which, in turn, predicted future depression. In addition, job resources had a weak negative impact on burnout. Home demands and home resources did not influence the motivational or health impairment process over time. The results support the central role of work characteristics for health and well-being....

Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment

Abstract: Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Eleven studies of aerobic physical activity programmes for healthy people over the age of 55 years have been included in this review. Eight of these 11 studies reported that aerobic exercise interventions resulted in increased fitness of the trained group and an improvement in at least one aspect of cognitive function. The largest effects were on cognitive speed, auditory and visual attention. However, the cognitive functions which improved were not the same in each study and the majority of comparisons yielded no significant results. The data are insufficient to show that the improvements in cognitive function which can be attributed to physical exercise are due to improvements in cardiovascular fitness.

Positive organizational behavior: Engaged employees in flourishing organizations

Abstract: Summary ThiseditorialintroducesaspecialissueoftheJournalof OrganizationalBehavioronpositive organizationalbehavior(POB). POB emphasizes the need for more focused theory building, research, and effective application of positive traits, states, and behaviors of employees in organizations. We argue that in order to make a substantive contribution to organizational science, POB will need to show the added value of the positive over and above the negative. In addition, the emerging concept of employee engagement is briefly introduced. The papers in the special issue describe exciting positive organizational behavior studies that each tap into an interesting direction in which POB research might go. Copyright# 2008 John Wiley & Sons, Ltd.

Recent Antarctic ice mass loss from radar interferometry and regional climate modelling

Abstract: Observed estimates of ice losses in Antarctica combined with regional modelling of ice accumulation in the interior suggest that East Antarctica is close to a balanced mass budget, but large losses of ice occur in the narrow outlet channels of West Antarctic glaciers and at the northern tip of the Antarctic peninsula.

Core level spectroscopy of solids

Abstract: INTRODUCTION FUNDAMENTAL ASPECTS OF CORE LEVEL SPECTROSCOPIES Core holes Overview of core level spectroscopies Interaction of x-rays with matter Optical transition operators and x-ray absorption spectrum The interaction of electrons with matter X-ray sources Electron sources MANY-BODY CHARGE-TRANSFER EFFECTS IN XPS AND XAS Introduction Many-body charge-transfer effects in XPS General expressions of many-body effects General effects in XPS spectra Typical examples of XPS spectra Many-body charge-transfer effects in XAS Comparison of XPS and XAS CHARGE TRANSFER MULTIPLET THEORY Atomic multiplet theory Ligand field multiplet theory The charge transfer multiplet theory X-RAY PHOTOEMISSION SPECTROSCOPY Introduction Experimental aspects XPS of TM compounds XPS of RE compounds Resonant photoemission spectroscopy Hard XPS Resonant inverse photoemission spectroscopy Nonlocal screening effect in XPS Auger photoemission coincidence spectroscopy Spin polarization and magnetic dichroism in XPS X-RAY ABSORPTION SPECTROSCOPY Basics of XAS Experimental aspects The L2, 3 edges of 3d TM systems Other x-ray absorption spectra of the 3d TM systems X-ray absorption spectra of the 4d and 5d TM systems X-ray absorption spectra of the 4f RE and 5f actinide systems X-RAY MAGNETIC CIRCULAR DICHROISM Introduction XMCD effects in the L2, 3 edges of TM ions and compounds Sum rules XMCD effects in the K edges of transition metals XMCD effects in the M edges of rare earths XMCD effects in the L edges of rare earth systems Applications of XMCD RESONANT X-RAY EMISSION SPECTROSCOPY Introduction Rare earth compounds High Tc Cuprates and related materials Nickel and Cobalt compounds Iron and Manganese compounds Early transition metal compounds Electron spin states detected by RXES and NXES MCD in RXES of ferromagnetic systems APPENDICES Precise derivation of XPS formula Derivation of Eq. (88) in Chapter 3 Fundamental tensor theory Derivation of the orbital moment sum rule Theoretical test of the spin sum rule Calculations of XAS spectra with single electron excitation models REFERENCES INDEX

Cross Talk in Defense Signaling

Abstract: Plants are equipped with an array of defense mechanisms to protect themselves against attack by herbivorous insects and microbial pathogens. Some of these defense mechanisms are preexisting, whereas others are only activated upon insect or pathogen invasion. Induced defense responses entail fitness

metan: fixed- and random-effects meta-analysis

Abstract: This article describes updates of the meta-analysis command metan and options that have been added since the command's original publication (Bradburn, Deeks, and Altman, metan – an alternative meta...

A survey of content based 3D shape retrieval methods

Abstract: Recent developments in techniques for modeling, digitizing and visualizing 3D shapes has led to an explosion in the number of available 3D models on the Internet and in domain-specific databases. This has led to the development of 3D shape retrieval systems that, given a query object, retrieve similar 3D objects. For visualization, 3D shapes are often represented as a surface, in particular polygonal meshes, for example in VRML format. Often these models contain holes, intersecting polygons, are not manifold, and do not enclose a volume unambiguously. On the contrary, 3D volume models, such as solid models produced by CAD systems, or voxels models, enclose a volume properly. This paper surveys the literature on methods for content based 3D retrieval, taking into account the applicability to surface models as well as to volume models. The methods are evaluated with respect to several requirements of content based 3D shape retrieval, such as: (1) shape representation requirements, (2) properties of dissimilarity measures, (3) efficiency, (4) discrimination abilities, (5) ability to perform partial matching, (6) robustness, and (7) necessity of pose normalization. Finally, the advantages and limitations of the several approaches in content based 3D shape retrieval are discussed.

Molecular networks regulating Arabidopsis seed maturation, after-ripening, dormancy and germination

Abstract: The transition between dormancy and germination represents a critical stage in the life cycle of higher plants and is an important ecological and commercial trait. In this review we present current knowledge of the molecular control of this trait in Arabidopsis thaliana, focussing on important components functioning during the developmental phases of seed maturation, after-ripening and imbibition. Establishment of dormancy during seed maturation is regulated by networks of transcription factors with overlapping and discrete functions. Following desiccation, after-ripening determines germination potential and, surprisingly, recent observations suggest that transcriptional and post-transcriptional processes occur in the dry seed. The single-cell endosperm layer that surrounds the embryo plays a crucial role in the maintenance of dormancy, and transcriptomics approaches are beginning to uncover endosperm-specific genes and processes. Molecular genetic approaches have provided many new components of hormone signalling pathways, but also indicate the importance of hormone-independent pathways and of natural variation in key regulatory loci. The influence of environmental signals (particularly light) following after-ripening, and the effect of moist chilling (stratification) are increasingly being understood at the molecular level. Combined postgenomics, physiology and molecular genetics approaches are beginning to provide an unparalleled understanding of the molecular processes underlying dormancy and germination.

Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Abstract: Aims To critically review the available transcatheter aortic valve implantation techniques and their results, as well as propose recommendations for their use and development. Methods and results A committee of experts including European Association of Cardio-Thoracic Surgery and European Society of Cardiology representatives met to reach a consensus based on the analysis of the available data obtained with transcatheter aortic valve implantation and their own experience. The evidence suggests that this technique is feasible and provides haemodynamic and clinical improvement for up to 2 years in patients with severe symptomatic aortic stenosis at high risk or with contraindications for surgery. Questions remain mainly concerning safety and long-term durability, which have to be assessed. Surgeons and cardiologists working as a team should select candidates, perform the procedure, and assess the results. Today, the use of this technique should be restricted to high-risk patients or those with contraindications for surgery. However, this may be extended to lower risk patients if the initial promise holds to be true after careful evaluation. Conclusion Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aortic stenosis. Today, careful evaluation is needed to avoid the risk of uncontrolled diffusion.