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Extremophiles and their products have been a major focus of research interest for over 40 years. Through this period, studies of these organisms have contributed hugely to many aspects of the fundamental and applied sciences, and to wider and more philosophical issues such as the origins of life and astrobiology. Our understanding of the cellular adaptations to extreme conditions (such as acid, temperature, pressure and more), of the mechanisms underpinning the stability of macromolecules, and of the subtleties, complexities and limits of fundamental biochemical processes has been informed by research on extremophiles. Extremophiles have also contributed numerous products and processes to the many fields of biotechnology, from diagnostics to bioremediation. Yet, after 40 years of dedicated research, there remains much to be discovered in this field. Fortunately, extremophiles remain an active and vibrant area of research. In the third decade of the twenty-first century, with decreasing global resources and a steadily increasing human population, the world’s attention has turned with increasing urgency to issues of sustainability. These global concerns were encapsulated and formalized by the United Nations with the adoption of the 2030 Agenda for Sustainable Development and the presentation of the seventeen Sustainable Development Goals (SDGs) in 2015. In the run-up to 2030, we consider the contributions that extremophiles have made, and will in the future make, to the SDGs. [ABSTRACT FROM AUTHOR]

Aerosol particles proved to play a key role in airborne transmission of SARS-CoV-2 viruses. Therefore, their size-fractionated collection and analysis is invaluable. However, aerosol sampling in COVID departments is not straightforward, especially in the sub-500-nm size range. In this study, particle number concentrations were measured with high temporal resolution using an optical particle counter, and several 8 h daytime sample sets were collected simultaneously on gelatin filters with cascade impactors in two different hospital wards during both alpha and delta variants of concern periods. Due to the large number (152) of size-fractionated samples, SARS-CoV-2 RNA copies could be statistically analyzed over a wide range of aerosol particle diameters (70–10 µm). Our results revealed that SARS-CoV-2 RNA is most likely to exist in particles with 0.5–4 µm aerodynamic diameter, but also in ultrafine particles. Correlation analysis of particulate matter (PM) and RNA copies highlighted the importance of indoor medical activity. It was found that the daily maximum increment of PM mass concentration correlated the most with the number concentration of SARS-CoV-2 RNA in the corresponding size fractions. Our results suggest that particle resuspension from surrounding surfaces is an important source of SARS-CoV-2 RNA present in the air of hospital rooms. [ABSTRACT FROM AUTHOR]

We give necessary and sufficient conditions on an m-isometry to have an invertible m-isometrical extension. As particular cases, we give a useful characterization for a general m-isometrical unilateral weighted shift and for ℓ -Jordan isometries. In particular, every ℓ -Jordan isometry operator has an invertible (2 ℓ - 1) -isometrical extension. [ABSTRACT FROM AUTHOR]

Background: In dermatology, a medical speciality with a relatively high number of rare diseases, physicians often have to resort to off‐label treatment options. To avoid claims, physicians in Germany can file a cost‐coverage request (off‐label application, OL‐A). Objectives: Our aim was to investigate the extent to which the current regulations affect patient care. Material and methods: Prospective cohort study among tertiary dermatology clinics throughout Germany, consecutively including OL‐As (05/2019–09/2020) and assessing the follow‐up correspondence. We modelled regressions to assess factors associated with cost‐coverage decisions and the time needed by health insurers to process the OL‐As. Results: Thirteen clinics provided data on 121 OL‐As, two of which applied for on‐label treatments. Of the remaining 119 OL‐As, 70 (58.8%) were immediately approved and 44 (37.0%) rejected. Including cases with one or more appeals, 87 of 119 OL‐As (73.1%) were finally approved and 26 (21.9%) rejected. There was an association of the final approval rate with (1) the class of medication/treatment, with approval rates being significantly lower for JAK inhibitors than for biologics (OR 0.16, 95%‐CI: 0.03–0.82); (2) German state, with approval rates being lower in eastern than in western states (OR 0.30, 95%‐CI 0.12–0.76); and (3) cost of the intervention (no linear trend). However, none of these predictors was significant in our multiple logistic regression models. The median health insurer's processing time (first response) was 29 days (IQR 22–38). Our analyses showed no evidence of an association with the predictors we assessed. In cases approved, the median time from the decision to file an OL‐A to the actual initiation of the treatment was 65.5 days (IQR 51–92). Conclusions: Our study points to substantial delays and inequalities in the provision of timely health care for dermatological patients with rare diseases, often involving treatments for which there is no adequate approved therapy. [ABSTRACT FROM AUTHOR]

Introduction: Rejection-sensitivity is a prevalent yet understudied emotional symptom often associated with adult ADHD. While ADHD research typically focuses on behavioral and cognitive facets, emerging evidence highlights the significance of emotional symptoms. Emotional dysregulation in ADHD impacts psychological well-being and mental health. Our study examines how ADHD symptoms relate to rejection sensitivity, considering factors like resiliency, self-regulation, and overall well-being. Objectives: Our study seeks to establish a direct connection between ADHD scores and rejection sensitivity among college students. We also investigate the mediating role of well-being, creative executive efficiency, self-regulation, and resilience, while exploring the moderating role of savoring capacity. Methods: Between February and May of 2023, we conducted a cross-sectional study using an online questionnaire, gathering data from 304 Hungarian higher education students aged 18 to 35. The majority, 78.0%, were female, and 71.4% were full-time students. Most participants were pursuing a bachelor's degree (56.6%), followed by undivided master's (21.7%), doctoral studies (13.8%), and traditional master's degrees (6.9%). We administered the Adult ADHD Self-Report Scale (ASRS-v.1.1), The Mental Health Test (MHT), and the Rejection Sensitivity Questionnaire (A-RSQ) for our research. Results: First, the ADHD scores were significantly associated with each mediator (well-being: β = -.343, p <.001; creative and executive efficiency: β = -.183, p <.01; self-regulation (β = -.230, p <.001; and resilience: β = -.321, p <.001). There was a direct effect of ADHD scores on rejection sensitivity scores (β =.466, p <.001). Finally, we also detected the indirect effects of ADHD scores on rejection sensitivity scores through the four mediators (β =.227, p <.001). Savoring capacity significantly moderated the relationship between ADHD and rejection sensitivity scores (β = -.244, p <.001). Conclusions: ADHD scores in our study population significantly correlate with well-being, creative and executive efficiency, self-regulation, and resilience. Furthermore, these scores directly influence rejection sensitivity, suggesting a heightened vulnerability to perceived rejection among those with higher ADHD scores. The indirect effects emphasize that the relationship between ADHD and rejection sensitivity is mediated by the aforementioned positive psychological constructs. This underscores the need for holistic interventions in ADHD populations, addressing not just core ADHD symptoms but also enhancing well-being, cognitive efficiency, self-regulation, and resilience to potentially mitigate rejection sensitivity. Disclosure of Interest: V. Müller Grant / Research support from: This project received funding from the New National Excellence Program under the Ministry for Culture and Innovation, sourced from the National Research, Development, and Innovation Fund, reference #ÚNKP-23-3-SZTE-66., B. Pikó: None Declared [ABSTRACT FROM AUTHOR]

We show that the set of all possible constant diagonals of a bounded Hilbert space operator is always convex. This, in particular, answers an open question of Bourin (2003). Moreover, we show that the joint numerical range of a commuting operator tuple is, in general, not convex, which fills a gap in the literature. We also prove that the Asplund–Ptak numerical range (which is convex for pairs of operators) is, in general, not convex for tuples of operators. [ABSTRACT FROM AUTHOR]

Although modern cochlear implants (CIs) are approved for magnetic resonance imaging (MRIs) adverse events still occur with unacceptable frequency. Methods: In this retrospective study, magnet displacement due to MRIs was analysed. Relevant factors e.g. symptoms during MRI, diagnostics, surgical intervention following the diagnosis and possible subsequent damage were assessed. 16 patients were enclosed. All patients complained about pain while the scan was conducted. Computed tomography (CT) scans of the temporal bone or X-rays of the skull were performed to confirm diagnosis. Artefacts on CT scans delayed immediate diagnosis in some cases. Despite various studies demonstrating the range of adverse events related to CIs following MRI, little information is available on diagnosis and radiologic recognition of magnet dislocation. In patients complaining about pain following an MRI scan an X-ray of the head should be performed immediately. Most adverse events occur in radiological centres without expertise in cochlear implants. Comprehensive training of patients, surgeons and radiologists is the most efficient tool to prevent damage to the CI and the patient. X-ray of the skull is suggested to be used as the method of choice in imaging. [ABSTRACT FROM AUTHOR]

If T is a Kreiss bounded operator on a Banach space, then ‖ T n ‖ = O (n) . Forty years ago Shields conjectured that in Hilbert spaces, ‖ T n ‖ = O (n) . A negative answer to this conjecture was given by Spijker, Tracogna and Welfert in 2003. We improve their result and show that this conjecture is not true even for uniformly Kreiss bounded operators. More precisely, for every ε > 0 there exists a uniformly Kreiss bounded operator T on a Hilbert space such that ‖ T n ‖ ∼ (n + 1) 1 - ε for all n ∈ N . On the other hand, any Kreiss bounded operator on Hilbert spaces satisfies ‖ T n ‖ = O (n log n ) . We also prove that the residual spectrum of a Kreiss bounded operator on a reflexive Banach space is contained in the open unit disc, extending known results for power bounded operators. As a consequence we obtain examples of mean ergodic Hilbert space operators which are not Kreiss bounded. [ABSTRACT FROM AUTHOR]

Introduction: Hematological diseases represent a diverse disease group ranging from benign to life-threatening conditions, with hematological malignancies being a major cause of mortality in the population worldwide. Although most hematological diseases require ongoing medical care making these conditions even more difficult for patients to endure. Since these diseases can pose many challenges by causing symptoms and limitations in various aspects of daily life, health-related quality of life (HRQoL) is a crucial aspect of their healthcare. Different dimensions of health-related quality of life are influenced by several psychological factors, including illness perception, stigmatization, and optimism: a more positive illness perception, along with optimism and reduced stigmatization, can contribute to a better HRQoL among hematology patients. Objectives: Since hematological diseases often cause serious life changes, the current study aimed to explore the direct and indirect effects of illness perception on health-related quality of life among hematology patients in Hungary, including stigmatization and optimism as possible contributors. Methods: In this cross-sectional study, 96 hematology patients (mean age = 56.45 years; SD = 15.55 years; 43.8% female) completed a self-administered survey including the following instruments: EORTC Quality of Life Scale, Brief Illness Perception Questionnaire, Stigma Scale for Chronic Illness, Revised Life Orientation Test. Results: By creating two pathway models, illness perception had significant indirect effects on physical functioning (β = -.205, p < .05) through role and cognitive functioning while emotional functioning had significant indirect effects on social functioning (β =.369, p <.01) through illness perception and stigmatization, both effects moderated by optimism. After controlling for other factors, both illness perception and emotional functioning directly influenced physical and social functioning, respectively. Conclusions: Our study supports previous research on the direct and indirect effects of illness perception on HRQoL. Based on our data, more optimistic illness perceptions and greater emotional functioning improve hematology patients' health-related quality of life by facilitating an unbiased understanding of the disease. Optimism serves as a potential moderating mechanism by positively altering indirect effects. Healthcare professionals need to optimize patients' illness perception to improve physical and social functioning. Disclosure of Interest: H. Kiss Grant / Research support from: This work was supported by the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund, #ÚNKP-22-4-SZTE-301., V. Müller: None Declared, K. Dani: None Declared, B. Pikó: None Declared [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the modeling of dynamic ferroelectric hysteresis loops in purified rubidium[sub2] zinc chlorine[sub4] crystals. Experimental setup; Results; Discussion.

Purpose: To improve the outcome of fetuses with gastrochisis several studies evaluated prenatal predictors. But there are different guidelines established and therefore the prenatal care is not standardized. With our study we wanted to evaluate the outcome of fetuses with gastroschisis after modification of prenatal management strategies at the Department of Obstetrics and Gynecology of the University Hospital Münster.Methods: In this explorative retrospective study of 39 fetuses with gastroschisis, we compare the clinical outcome between two management groups. In the first group (group 1, n = 14) prenatal indication for delivery was confirmed by a subjective evaluation of the small bowel diameter and the wall thickness without established cut-off values for these parameters. In the second group (group 2, n = 25) certain limits for the small bowel diameter (25 mm) and the wall thickness (2.5 mm) were used for fetal surveillance.Results: Noticeable differences between the two groups regarding birth weight, weight centile, arterial pH, small bowel diameter, wall thickness, adverse bowel condition and re-operations could not be observed. In group 2, delivery was earlier (p = 0.011), and a lower rate of prenatal complications was observed (p = 0.016).Conclusion: To avoid adverse prenatal complications we recommend the observation of fetuses with gastroschisis by sonographic monitoring of the small bowel diameter and the wall thickness. [ABSTRACT FROM AUTHOR]

Copyright of Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the advent of wide-field cosmological surveys, we are approaching samples of hundreds of thousands of galaxy clusters. While such large numbers will help reduce statistical uncertainties, the control of systematics in cluster masses is crucial. Here we examine the effects of an important source of systematic uncertainty in galaxy-based cluster mass estimation techniques: the presence of significant dynamical substructure. Dynamical substructure manifests as dynamically distinct subgroups in phase-space, indicating an 'unrelaxed' state. This issue affects around a quarter of clusters in a generally selected sample. We employ a set of mock clusters whose masses have been measured homogeneously with commonly used galaxy-based mass estimation techniques (kinematic, richness, caustic, radial methods). We use these to study how the relation between observationally estimated and true cluster mass depends on the presence of substructure, as identified by various popular diagnostics.We find that the scatter for an ensemble of clusters does not increase dramatically for clusters with dynamical substructure. However, we find a systematic bias for all methods, such that clusters with significant substructure have higher measured masses than their relaxed counterparts. This bias depends on cluster mass: the most massive clusters are largely unaffected by the presence of significant substructure, but masses are significantly overestimated for lower mass clusters, by ~10 per cent at 1014 and ≳20 per cent for ≲1013.5. The use of cluster samples with different levels of substructure can therefore bias certain cosmological parameters up to a level comparable to the typical uncertainties in current cosmological studies. [ABSTRACT FROM AUTHOR]

Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLEpulm, than in patients without pulmonary manifestations. CCL21 correlated negatively with DLCO (r=-0.73; p<0.01) and KLCO (r=-0.62; p<0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p<0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p<0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DLCO/KLCO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients. [ABSTRACT FROM AUTHOR]

We prove a van der Corput-type lemma for power bounded Hilbert space operators. As a corollary we show that $$N^{-1}\sum _{n=1}^N T^{p(n)}$$ converges in the strong operator topology for all power bounded Hilbert space operators T and all polynomials p satisfying $$p(\mathbb {N}_0)\subset \mathbb {N}_0$$ . This generalizes known results for Hilbert space contractions. Similar results are true also for bounded strongly continuous semigroups of operators. [ABSTRACT FROM AUTHOR]

Background: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer.Methods: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk).Results: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P<0.001, and OAS, P=0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P<0.001 and P=0.075 for cohort B and P=0.043 and P<0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P=0.0065, OAS, not significant; cohort C: DFS, P=0.026, OAS, P<0.001.Conclusion: Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called 'high-risk' breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Extracellular-regulated kinases (ERK1, ERK2) play important roles in the malignant behaviour of breast cancer cells in vitro. In our present study, 148 clinical breast cancer samples (120 cases with follow-up data) were studied for the expression of ERK1, ERK2 and their phosphorylated forms p-ERK1 and p-ERK2 by immunoblotting, and p-ERK1/2 expression in corresponding paraffin sections was analysed by immunohistochemistry. The results were correlated with established clinical and histological prognostic parameters, follow-up data and expression of seven cell-cycle regulatory proteins as well as MMP1, MMP9, PAI-1 and AP-1 transcription factors, which had been analysed before. High p-ERK1 expression as determined by immunoblots correlated significantly with a low frequency of recurrences and infrequent fatal outcome (P = 0.007 and 0.008) and was an independent indicator of long relapse-free and overall survival in multivariate analysis. By immunohistochemistry, strong p-ERK staining in tumour cells was associated with early stages (P = 0.020), negative nodal status (P = 0.003) and long recurrence-free survival (P = 0.017). In contrast, expression of the unphosphorylated kinases ERK1 and ERK2 was not associated with clinical and histological prognostic parameters, except a positive correlation with oestrogen receptor status. Comparison with the expression of formerly analysed cell-cycle- and invasion-associated proteins corroborates our conclusion that activation of ERK1 and ERK2 is not associated with enhanced proliferation and invasion of mammary carcinomas. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability-based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array-based comparative genomic hybridization. Analyzing clinical blood samples from metastatic ( n = 20) and nonmetastatic ( n = 6) cancer patients in parallel with CellSearch® system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM-negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as 'liquid biopsies.' [ABSTRACT FROM AUTHOR]

Purpose: The transcription factor Fos-related antigen-1 (Fra-1) has been described to affect the morphology, motility and invasive potential of breast cancer cells. Since tumor cell adhesion plays an essential role in the metastatic process, especially for extravasation from blood vessels, we investigated the influence of Fra-1 on breast cancer cell interactions with the endothelium. Methods: Using Fra-1-overexpressing MCF7 [weakly invasive, estrogen receptor (ER)-positive] and MDA MB231 (strongly invasive, ER-negative) cells, we performed dynamic cell flow adhesion assays on surfaces coated with E-selectin or with human pulmonary microvascular endothelial cells. Results: We found a significant increased adhesion of Fra-1-overexpressing MCF7 cells to E-selectin but also to activate endothelial cells, whereas the MDA MB231 cell line showed moderate enhanced cell rolling and tethering on both coated surfaces. These different adhesion behaviors corresponded to an up-regulation of various adhesion-related proteins such as CD44 and integrin α5 in Fra-1-overexpressing MCF7 cells measured by microarray analysis and flow cytometry in comparison with no deregulation of key adhesion molecules observed in Fra-1-overexpressing MDA MB231 cells. In line with these results and based on cDNA microarray data of breast cancer patients ( n = 197), high Fra-1 expression significantly correlates with shorter overall survival and higher rate of lung metastasis in ER-positive breast cancer patients ( n = 130), but has no impact on the prognosis of patients with ER-negative tumors. Conclusion: Thus, in addition to its pro-invasive and pro-migratory effect, Fra-1 might influence the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells under flow conditions. [ABSTRACT FROM AUTHOR]

Objectives: In 2010, the American College of Rheumatology (ACR) proposed new criteria for the diagnosis of fibromyalgia (FM) in the context of objections to components of the criteria of 1990. The new criteria consider the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS). This study evaluated the implications of the new diagnostic criteria for FM across other functional pain syndromes.Method: A cohort of 300 consecutive in-patients with functional pain syndromes underwent a diagnostic screen according to the ACR 2010 criteria. Additionally, systematic pain assessment including algometric and psychometric data was carried out.Results: Twenty-five patients (8.3%) had been diagnosed with FM according to the ACR 1990 criteria. Twenty-one of them (84%) also met the new ACR 2010 criteria. In total, 130 patients (43%) fulfilled the new ACR 2010 criteria. A comparison of new vs. old cases showed a high degree of conformity in most of the pain characteristics. The new FM cases, however, revealed a pronounced heterogeneity in the anatomical pain locations, including several types of localized pain syndromes. Furthermore, patients fulfilling the ACR 2010 FM criteria differed from those with other functional pain syndromes; they had increased pain sensitivity scores and increased psychometric values for depression, anxiety, and psychological distress (p<0.01).Conclusions: FM according to the ACR 2010 criteria describes the 'severe half' of the spectrum of functional pain syndromes. By dropping the requirement of 'generalized pain', these criteria result in a blurring of the distinction between FM and more localized functional pain syndromes. [ABSTRACT FROM AUTHOR]

We obtain new characterizations of Li–Yorke chaos for linear operators on Banach and Fréchet spaces. We also offer conditions under which an operator admits a dense set or linear manifold of irregular vectors. Some of our general results are applied to composition operators and adjoint multipliers on spaces of holomorphic functions. [ABSTRACT FROM PUBLISHER]

The causes of weight loss in Huntington's disease (HD) are not entirely clear. The aim was to identify risk factors that are associated with a loss of metabolically active tissues, i.e. fat-free mass. A consecutive cohort of non-diabetic HD participants (manifest HD, n = 43; CAG: mean 43.6.0 ± 3.6; preHD, n = 10; CAG: mean 41.4 ± 1.4) and 36 healthy controls was recruited. Twenty-five HD participants were early-stage HD (UHDRS Total Functional Capacity [TFC] stages I and II), 12 mid-stage HD (TFC stage III), and 6 participants were in late-stage HD (TFC stages IV and V). Food intake, basic metabolic rate and glucose homeostasis were assessed. In addition, fat-free mass was determined using bioelectric impedance analysis, and leptin, insulin and ghrelin as key metabolic regulators. Sex ratio and age were similar in HD participants (71 % women; age 50.6 ± 10.9) and controls (66 % women; age 46.4 ± 14.5). Body mass index (BMI) was lower in HD participants than controls (median 24.1 vs. 25.9, p = 0.04). However, fat-free mass and basic metabolic rate were not statistically different between groups and showed no association with disease burden. In controls and HD participants, leptin was the most important predictor of fat-free mass. While BMI was lower in HD participants, fat-free mass was similar to controls with leptin as its most important predictor. Leptin levels and fat-free mass measurements using bioelectric impedance analysis may be good screening tools to identify HD patients at risk for weight loss. [ABSTRACT FROM AUTHOR]

This paper is the second in a series in which we perform an extensive comparison of various galaxy-based cluster mass estimation techniques that utilize the positions, velocities and colours of galaxies. Our aim is to quantify the scatter, systematic bias and completeness of cluster masses derived from a diverse set of 25 galaxy-based methods using two contrasting mock galaxy catalogues based on a sophisticated halo occupation model and a semi-analytic model. Analysing 968 clusters, we find a wide range in the rms errors in log M200c delivered by the different methods (0.18-1.08 dex, i.e. a factor of ~1.5-12), with abundance-matching and richness methods providing the best results, irrespective of the input model assumptions. In addition, certain methods produce a significant number of catastrophic cases where the mass is under- or overestimated by a factor greater than 10. Given the steeply falling high-mass end of the cluster mass function, we recommend that richness- or abundance-matching-based methods are used in conjunction with these methods as a sanity check for studies selecting high-mass clusters. We see a stronger correlation of the recovered to input number of galaxies for both catalogues in comparison with the group/cluster mass, however, this does not guarantee that the correct member galaxies are being selected. We do not observe significantly higher scatter for either mock galaxy catalogues. Our results have implications for cosmological analyses that utilize the masses, richnesses, or abundances of clusters, which have different uncertainties when different methods are used. [ABSTRACT FROM AUTHOR]

Background:Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer.Methods:We examined PLS3 expression in breast cancer cell lines with epithelial and mesenchymal traits and in circulating tumour cells (CTCs) obtained from the peripheral blood of breast cancer patients. We investigated PLS3 expression in the peripheral blood of 594 patients with breast cancer to evaluate the clinical significance of PLS3 expression.Results:Robust PLS3 expression was observed in different breast cancer cell lines (Hs578t, MCF-7, MDA-MB-468, and MDA-MB-231) as well as in a bone marrow derived cancer cell line (BC-M1). In both the training (n=298) and validation (n=296) sets, PLS3 expression was observed in CTCs of patients with breast cancer. PLS3-positive patients showed significantly poorer overall and disease-free survival than PLS3-negative patients (P=0.0001 and 0.003, respectively). Subset analysis revealed that this prognostic biomarker was relevant in patients with stage I-III cancer, particularly in patients with luminal-type and triple-negative-type tumours.Conclusions:These data demonstrated that PLS3 was expressed in CTCs undergoing the epithelial-mesenchymal transition in patients with breast cancer. Furthermore, PLS3 may be an excellent biomarker for identifying groups at risk of recurrence or with a poor prognosis. [ABSTRACT FROM AUTHOR]

Background:Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive human malignancies with an overall 5-year survival rate of <5%. Despite significant advances in treatment of the disease during the past decade, the median survival rate (∼6 months) has hardly improved, warranting the need to identify novel targets for therapeutic approaches.Methods:Quantitative real time PCR, western blot analyses and immunohistochemical staining of tissue microarrays were used to analyse the expression of TTK gene in primary PDAC tissues and cell lines. To inhibit TTK kinase expression in a variety of pancreatic cancer cell lines, RNA interference was used. Functional roles of this kinase in the context of PDAC were studied using cell proliferation, viability and anchorage-independent growth assays. Western blotting, fluorescence-activated cell sorting analyses and fluorescence microscopy were used to gain mechanistic insight into the functional effects.Conclusions:We show that the dual specificity kinase TTK (also known as Mps1), is strongly overexpressed in human PDAC. Functionally, cell proliferation was significantly attenuated following TTK knockdown, whereas apoptosis and necrosis rates were significantly increased. In addition, anchorage-independent growth, a hallmark of malignant transformation and metastatic potential, was strongly impaired in the absence of TTK gene function. Interestingly, immortalised normal pancreatic hTERT-HPNE cells were not affected by loss of TTK function. Mechanistically, these effects in cancer cells were associated with increased formation of micronuclei, suggesting that loss of TTK function in pancreatic cancer cells results in chromosomal instability and mitotic catastrophe. Taken together, our data show that TTK function is critical for growth and proliferation of pancreatic cancer cells, thus establishing this kinase as an interesting new target for novel therapeutic approaches in combating this malignancy. [ABSTRACT FROM AUTHOR]

Background: MAGE-A (melanoma-associated antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS.Methods: To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years.Results: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1.Conclusions: Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis. [ABSTRACT FROM AUTHOR]

Background:MAGE-A (melanoma-associated antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS.Methods:To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years.Results:The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1.Conclusions:Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis. [ABSTRACT FROM AUTHOR]

Most available knowledge on fungal arginine metabolism is derived from studies on S accharomyces cerevisiae, in which arginine catabolism is initiated by releasing urea via the arginase reaction. Orthologues of the S . cerevisiae genes encoding the first three enzymes in the arginase pathway were cloned from K luyveromyces lactis and shown to functionally complement the corresponding deletion in S . cerevisiae. Surprisingly, deletion of the single K . lactis arginase gene KlCAR1 did not completely abolish growth on arginine as nitrogen source. Growth rate of the deletion mutant strongly increased during serial transfer in shake-flask cultures. A combination of RNAseq-based transcriptome analysis and 13 C-15 N-based flux analysis was used to elucidate the arginase-independent pathway. Isotopic 13 C15 N-enrichment in γ-aminobutyrate revealed succinate as the entry point in the TCA cycle of the alternative pathway. Transcript analysis combined with enzyme activity measurements indicated increased expression in the Klcar1Δ mutant of a guanidinobutyrase ( EC.3.5.3.7), a key enzyme in a new pathway for arginine degradation. Expression of the K . lactis KLLA0 F27995g (renamed KlGBU1) encoding guanidinobutyrase enabled S . cerevisiae to use guanidinobutyrate as sole nitrogen source and its deletion in K . lactis almost completely abolish growth on this nitrogen source. Phylogenetic analysis suggests that this enzyme activity is widespread in fungi. [ABSTRACT FROM AUTHOR]

Although existential needs are highly prevalent in patients with cancer, specific sources of meaning have been little explored. We investigated whether specific sources of meaning predict global meaning and psychological distress. N = 258 patients with breast (45%), lung (39%) and gynaecological cancer (16%) completed a battery of validated questionnaires at T1. Six months later (T2), n = 183 (78%) patients participated again. The primary outcomes -- sources of meaning, global meaning and psychosocial distress -- were measured with the Sources of Meaning Profile-Revised (SOMP-R), Life Attitude Profile-Revised (LAP-R) and modules for depression and anxiety of the Patient Health Questionnaire (PHQ-9, GAD-7). Most important sources of meaning were 'engaging in personal relationships', 'preserving human values and ideals' and 'feeling financially secure'. Stepwise multivariate regression analyses controlling for demographic and medical factors revealed that 'engaging in personal relationships', 'preservation of culture and tradition' and 'interest in social and/or political causes' predicted lower depression. 'Leaving a legacy for the next generation' and 'feeling financially secure' predicted both higher depression and anxiety. The findings highlight the relevance of sources of meaning for the psychological well-being of cancer patients and point towards specific sources of meaning that should be focused in psychosocial interventions. [ABSTRACT FROM AUTHOR]

Background The measurement of safety culture in healthcare is generally regarded as a first step towards improvement. Based on a self-assessment of safety culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare teams to improve safety culture in their organisations. In this study we assessed the effects of FraTrix on safety culture in general practice. Methods We conducted an open randomised controlled trial in 60 general practices. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practices. At baseline and after 12 months, scores were allocated for safety culture as expressed in practice structure and processes (indicators), in safety climate and in patient safety incident reporting. The primary outcome was the indicator error management. Results During the team sessions, practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it. After 12 months, no significant differences were found between intervention and control groups in terms of error management (competing probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety culture indicators and safety climate scales. Intervention practices showed better reporting of patient safety incidents, reflected in a higher number of incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than control practices. Conclusions Applied as a team-based instrument to assess safety culture, FraTrix did not lead to measurable improvements in error management. Comparable studies with more positive results had less robust study designs. In future research, validated combined methods to measure safety culture will be required. In addition, more attention should be paid to evaluation of process parameters. Implemented actions and incident reporting may be more appropriate target endpoints. Trial registration German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145 [ABSTRACT FROM AUTHOR]

We have investigated the distribution and evolution of ~3100 intergalactic neutral hydrogen (HI) absorbers with H i column densities log  NHI = [12.75,17.0] at 1.9 < z < 3.2, using 18 high resolution, high signal-to-noise quasar spectra obtained from the ESO VLT/UVES archive. We used two sets of Voigt profile fitting analysis, one including all the available high-order Lyman lines to obtain reliable HI column densities of saturated lines, and another using only the Lyα transition. There is no significant difference between the Lyα-only fit and the high-order Lyman fit results. Combining our Lyα-only fit results at 1.7 < z < 3.6 with high-quality literature data, the mean number density at 0 < z < 4 is not well described by a single power law and strongly suggests that its evolution slows down at z ≤ 1.5 at the high and low column density ranges. We also divided our entire HI absorbers at 1.9 < z < 3.2 into two samples, the unenriched forest and the CIV-enriched forest, depending on whether HI lines are associated with CIV at log NCIV ≥ 12.2 within a given velocity range. The entire HI column density distribution function (CDDF) can be described as the combination of these two well-characterised populations which overlap at log NHI ~ 15. At log NHI ≤ 15, the unenriched forest dominates, showing a similar power-law distribution to the entire forest. The CIV-enriched forest dominates at log NHI ≥ 15, with its distribution function as ∝NHI~-1.45. However, it starts to flatten out at lower NHI, since the enriched forest fraction decreases with decreasing NHI. The deviation from the power law at log NHI = [14,17] shown in the CDDF for the entire HI sample is a result of combining two different HI populations with a different CDDF shape. The total HI mass density relative to the critical density is ΩHI ~ 1.6 × 10-6 h-1, where the enriched forest accounts for ~40% of ΩHI. [ABSTRACT FROM AUTHOR]