153 research outputs found
Information-Geometric Optimization Algorithms: A Unifying Picture via Invariance Principles
We present a canonical way to turn any smooth parametric family of
probability distributions on an arbitrary search space into a
continuous-time black-box optimization method on , the
\emph{information-geometric optimization} (IGO) method. Invariance as a design
principle minimizes the number of arbitrary choices. The resulting \emph{IGO
flow} conducts the natural gradient ascent of an adaptive, time-dependent,
quantile-based transformation of the objective function. It makes no
assumptions on the objective function to be optimized.
The IGO method produces explicit IGO algorithms through time discretization.
It naturally recovers versions of known algorithms and offers a systematic way
to derive new ones. The cross-entropy method is recovered in a particular case,
and can be extended into a smoothed, parametrization-independent maximum
likelihood update (IGO-ML). For Gaussian distributions on , IGO
is related to natural evolution strategies (NES) and recovers a version of the
CMA-ES algorithm. For Bernoulli distributions on , we recover the
PBIL algorithm. From restricted Boltzmann machines, we obtain a novel algorithm
for optimization on . All these algorithms are unified under a
single information-geometric optimization framework.
Thanks to its intrinsic formulation, the IGO method achieves invariance under
reparametrization of the search space , under a change of parameters of the
probability distributions, and under increasing transformations of the
objective function.
Theory strongly suggests that IGO algorithms have minimal loss in diversity
during optimization, provided the initial diversity is high. First experiments
using restricted Boltzmann machines confirm this insight. Thus IGO seems to
provide, from information theory, an elegant way to spontaneously explore
several valleys of a fitness landscape in a single run.Comment: Final published versio
Risiken der Fissions-Kernenergienutzung unter Berücksichtigung der verfügbaren Nuklearbrennstoffressourcen
nicht angegebe
Clinical Impact of Physical Activity and Cough on Disease Progression in Fibrotic Interstitial Lung Disease
Physical activity limitations and cough are common in patients with interstitial lung disease (ILD), potentially leading to reduced health-related quality of life. We aimed to compare physical activity and cough between patients with subjective, progressive idiopathic pulmonary fibrosis (IPF) and fibrotic non-IPF ILD. In this prospective observational study, wrist accelerometers were worn for seven consecutive days to track steps per day (SPD). Cough was evaluated using a visual analog scale (VAScough) at baseline and weekly for six months. We included 35 patients (IPF: n = 13; non-IPF: n = 22; mean ± SD age 61.8 ± 10.8 years; FVC 65.3 ± 21.7% predicted). Baseline mean ± SD SPD was 5008 ± 4234, with no differences between IPF and non-IPF ILD. At baseline, cough was reported by 94.3% patients (mean ± SD VAScough 3.3 ± 2.6). Compared to non-IPF ILD, patients with IPF had significantly higher burden of cough (p = 0.020), and experienced a greater increase in cough over six months (p = 0.009). Patients who died or underwent lung transplantation (n = 5), had significantly lower SPD (p = 0.007) and higher VAScough (p = 0.047). Long-term follow up identified VAScough (HR: 1.387; 95%-CI 1.081–1.781; p = 0.010) and SPD (per 1000 SPD: HR 0.606; 95%-CI: 0.412–0.892; p = 0.011) as significant predictors for transplant-free survival. In conclusion, although activity didn’t differ between IPF and non-IPF ILD, cough burden was significantly greater in IPF. SPD and VAScough differed significantly in patients who subsequently experienced disease progression and were associated with long-term transplant-free survival, calling for better acknowledgement of both parameters in disease management
Variability of forced vital capacity in progressive interstitial lung disease: a prospective observational study
BACKGROUND Fibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD.
METHODS In this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6~months. Hospital based spirometry was performed after three and 6~months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline \textgreater 10% relative was assessed in the cohort. RESULTS From May 2017 until August 2018, we included 47 patients (IPF n = 20; non-IPF n = 27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n = 17; non-IPF n = 23), who had a mean ± SD age of 60.7 ± 11.3 years and FVC 64.7 ± 21.7% predicted (2.4 ± 0.8 L), 12 patients experienced disease progression (death: n =~2; lung transplantation: n = 3; acute exacerbation: n = 1; FVC decline \textgreater 10%: n = 6). Within the first 28 days, a group of patients had high daily variability in FVC, with 60.0% having a variation \geq5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p = 0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050-1.378; p = 0.0076).
CONCLUSIONS Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression
Verfügbarkeit von Uran
Die Verfügbarkeit von Uran ist ein Schlüsselfaktor für den zukünftigen Ausbau sowie den mittel- bis langfristigen potenziellen Beitrag der Kernenergie zur Stromerzeugung. Im vorliegenden Diskussionspapier wird der aktuelle Wissensstand zu Uranressourcen und zur Uranproduktion beschrieben und auf dieser Grundlage Abschätzungen zur zukünftigen Versorgungssituation entwickelt
Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation : a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation
No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.7 months (95% confidence interval: 4.1-5.3) and the 2-year survival rate was 17.7% (95% confidence interval: 14.8-21.2%). Shorter remission after transplantation (PPeer reviewe
Mucus detachment by host metalloprotease meprin \beta requires shedding of its inactive pro-form, which is abrogated by the pathogenic protease RgpB
The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin β activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin β into its active form, impairing meprin β shedding and its function as a mucus-detaching protease
A national evaluation analysis and expert interview study of real-world data sources for research and healthcare decision-making
Real-world data (RWD) can provide intel (real-world evidence, RWE) for research and development, as well as policy and regulatory decision-making along the full spectrum of health care. Despite calls from global regulators for international collaborations to integrate RWE into regulatory decision-making and to bridge knowledge gaps, some challenges remain. In this work, we performed an evaluation of Austrian RWD sources using a multilateral query approach, crosschecked against previously published RWD criteria and conducted direct interviews with representative RWD source samples. This article provides an overview of 73 out of 104 RWD sources in a national legislative setting with favourable RWD incentives, which can be used to extrapolate to other EU data regions under the General Data Protection Regulation (GDPR) and upcoming legislation such as the European Health Data Space Act (EHDS). We were able to detect omnipresent challenges associated with data silos, variable standardisation efforts and governance issues. Our findings suggest a strong need for a national health data strategy and governance framework, which should inform researchers, as well as policy- and decision-makers to improve RWD-based research in the healthcare sector to ultimately support actual regulatory decision-making and provide strategic information for governmental health data policies
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