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The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.
Methods
Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net (n = 261) and Protect-AD (n = 614).
Results
The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI.
Conclusion
Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.
Patients with severe psychotic disorders exhibit a severely reduced quality of life (QoL) at all stages of the disease. Integrated care often led to an improvement in QoL. However, the specific mediators of QoL change are not yet well understood.
Methods
The ACCESS II study is a prospective, long-term study investigating the effectiveness of an integrated care program for people with severe psychotic disorders (IC-TACT) that includes Therapeutic Assertive Community Treatment within a care network of in- and outpatient services at the University Medical Center Hamburg-Eppendorf, Germany. We examined longitudinal associations between QoL and the hypothesized mediators of change (i.e., negative symptoms, depression, and anxiety), using cross-lagged panel models.
Results
The sample includes 418 severely ill patients treated in IC-TACT for at least 1 year. QoL increased, whereas symptom severity decreased significantly from baseline to 6-month follow-up (p-values ≤ 0.001), and remained stable until 12-month follow-up. QoL and symptom severity demonstrated significant auto-correlated effects and significant cross-lagged effects from QoL at baseline to negative symptoms (6 months, β = −0.20, p < 0.001) to QoL (12 months, β = −0.19, p < 0.01) resulting in a significant indirect, mediated effect. Additionally, negative symptoms after 6 months had a significant effect on the severity of depression after 12 months (β = 0.13, p < 0.05).
Conclusions
Negative symptoms appear to represent an important mechanism of change in IC-TACT indicating that improvement of QoL could potentially be achieved through optimized intervention on negative symptoms. Moreover, this may lead to a reduction in the severity of depression after 12 months.
John D. French's stimulating article, which explores the scope for comparing working-class leaders across time and space, is considered in this contribution by reference to my biography of August Bebel and with a particular focus on the following topics: a) historical actors as shaped by their own particular time and place; b) the importance of personal relationships and networks in making people who they are; c) the importance of psychological elements and the risk in interpreting them in retrospect – recovering them depends upon the sources available; d) how charisma reflects an interdependence between attribution and individual qualities; e) the importance of political milieux for the flourishing of individual working-class leaders; and f) the relationship between political work to both civil society and existing class relations. Using these approaches allows us to write cross-border and cross-temporal “embodied social biographies”, as suggested by French.
Depression risk is associated with a late chronotype pattern often described as an ‘evening chronotype’. Fluctuations in mood over consecutive days have not yet been measured according to chronotype in in-patients with depression. A total of 30 in-patients with depression and 32 healthy controls matched for gender and age completed a chronotype questionnaire and twice-daily ratings on mood for 10 consecutive days (registered in the German Clinical Trials Register: DRKS00010215). The in-patients had Saturdays and Sundays as hospital-leave days. The relationship between chronotype and daily mood was mediated by the weekday–weekend schedule with higher levels of negative affect in the evening-chronotype patient subgroup at weekends. Results are discussed with respect to a probably advantageous standardised clinical setting with early morning routines, especially for patients with evening chronotypes.
Left atrial congestion results from backward failure in dilated cardiomyopathy. We aimed to evaluate feasibility and efficacy of percutaneous atrioseptostomy to create a restrictive atrial septum defect in management of dilated cardiomyopathy.
Methods and results
From June 2009 to December 2016, 27 interventions comprised left atria decompressions in 22 dilated cardiomyopathy patients; 9 females; age: 24 days to 36.9 years; weight: 3–50 kg; NYHA-/Ross class IV (n=16). Mean left ventricular ejection fraction was 21.5±9.7% and brain natriuretic peptide was 2291±1992 pg/ml. Dilated cardiomyopathy was classified as chronic (n=9); acute (n=1) myocarditis; idiopathic (n=5); left ventricular non-compaction (n=4); mitochondriopathy, pacemaker induced, and arrhythmogenic (n=3). Atrioseptostomy was concomitantly performed with myocardial biopsies 6.5 days (±11.7) after admission (n=11). Trans-septal puncture was used in 18 patients; foramen ovale dilatation was done in four patients. Mean balloon size was 11 mm (range 7–14 mm); total procedure time was 133±38 minutes. No procedural complications were observed. Mean left atrial pressure decreased from 15.8±6.8 to 12.2±4.8 mmHg (p=0.005), left/right atrial pressure gradient from 9.6±5.6 to 5±3.5 mmHg; brain natriuretic peptide (n=18) decreased from 1968±1606 to 830±1083 pg/ml (p=0.01). One patient unsuitable for heart transplantation died at home despite additionally performed pulmonary artery banding and three further left atrial decompressions; five patients were bridged to transplantation, two died afterwards. Functional recovery occurred in the remaining 14 patients and in six after additional pulmonary artery banding. No patient required assist device.
Conclusions
Percutaneous left atrial decompression is an age-independent, effective palliation treating patients with dilated cardiomyopathy.
The two high-pressure water-retaining dams at the Ibbenbüren coalmine in Münsterland (Germany) have to perform reliably under the induced tension caused by further exploitation of the current mining area. The load-bearing and the sealing functions of the new barriers were separated and new sealing materials were developed. An innovative multilayer sealing system of bentonite and sandwiched equipotential layers (SANDWICH) supporting homogeneous swelling and sealing, independent of formation water (Nüesch et al., 2002), was applied in this project. A testing program of strain-controlled swelling pressure tests on compacted bentonite specimens and on a bentonite/sand mixture was conducted to ensure an adequate potential for swelling-pressure development.
The measurements under constant volume for dry densities between 1.45 g/cm3 and 1.67 g/cm3 showed an evolving swelling pressure between 1.04 and 1.8 MPa for 100% bentonite samples. Straincontrolled oedometer tests for zero strain and step-wise applied strain up to 2% revealed that a sufficient magnitude of swelling pressure existed at maximum applied strain.
Dilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population.
Method and results
We present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1–26 months). The median follow-up age was 16 months (range 2–80 months). Kaplan–Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3–80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml).
Conclusion
Our data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.
How can a modern concept like Amartya Sen's capability approach be introduced in historical studies? One possibility is to ask how public services were implemented in municipal policy and how these services open up capabilities for the individuals of a city. This article uses Sen's theoretical framework as an analytical tool to explore two Prussian towns, Erfurt and Frankfurt am Main, and their public services (job centres and tramway systems) as examples of social policy at the local level.
Radar sensors are used widely in modern driver assistance systems. Available sensors nowadays often operate in the 77 GHz band and can accurately provide distance, velocity, and angle information about remote objects. Increasing the operation frequency allows improving the angular resolution and accuracy. In this paper, the technical feasibility to move the operation frequency beyond 100 GHz is discussed, by investigating dielectric properties of radome materials, the attenuation of rain and atmosphere, radar cross-section behavior, active circuits technology, and frequency regulation issues. Moreover, a miniaturized antenna at 150 GHz is presented to demonstrate the possibilities of high-resolution radar for cars.
(Bi,Sb)2Te3 + 4 mol%PbTe was quenched in water and on a rotating copper wheel (melt spinning). It was found that PbTe was immiscible in (Bi,Sb)2Te3 when the material is quenched in water and that the thermoelectric figure of merit increases by annealing. Natural nanostructures (nns) were found in melt-spun (Bi,Sb)2Te3, whereas they were hard to detect in (Bi,Sb)2Te3 alloyed with PbTe. There is a correlation between the orientation of the strain field and the nns. Within the grains of melt-spun (Bi,Sb)2Te3 alloyed with PbTe, the chemical composition was homogeneous. An enrichment of Pb was found at the grain boundaries. Quenched (Bi,Sb)2Te3 alloyed with 0.3 wt%PbTe have been spark plasma sintered (SPS). After optimization, the Seebeck coefficients of the melt-spun SPS (MS-SPS) materials were larger than for materials quenched in water and sintered (QW-SPS) materials. In addition, the mobility increases with the carrier concentration in MS-SPS materials, whereas it decreases in QW-SPS materials.
Two photon photopolymerization (2PP) is a new and modern method in solid freeform fabrication. 2PP allows the fabrication of sub-micron structures from a photopolymerizable resin. By the use of near-infrared (NIR) lasers it is possible to produce 3D structures with a spatial feature resolution as good as 200 nm. This technique can be used in polymer-based photonic and micro-electromechanical systems (MEMS), for 3D optical data storage or for the inscription of optical waveguides based on a local refractive index change upon laser exposure. Since the 2PP only takes place inside the focus of the laser beam, complex 3D-structures can be in-scri-bed into a suitable matrix material.
In the presented work, 2PP is used to write optical waveguides into a prefabricated mechanically flexible polydimethylsiloxane matrix. The waveguides were structured by selectively irradiating a polymer network, which was swollen by a monomer mixture. The monomer was polymerized by two photon photopolymerization and the uncured monomer was removed by evaporation at elevated temperatures. This treatment led to a local change in refractive index in the order of Δn = 0.02, which was significantly above the industrial requirement of Δn = 0.003. The measured optical losses were around 2.3dB/cm. Since all unreacted monomers were removed by eva-po-ration, the final waveguide was stable up to temperatures of more than 200°C.
In a second approach highly porous sol-gel materials (based on tetramethoxysilane (TMOS) as precursor and the surfactant cetylpyridinium chloride monohydrate as structural temp-late) were utilized as matrix materials. The precursor was organically modified with poly(ethylene glycol) spacers in order to increase the toughness and thus facilitate the fabrication of transparent porous monoliths and flexible films. The pores of the sol-gel-derived matrix were filled with acrylate-based monomers of high refractive index and after selective irradiation using 2PP waveguides (Δn = 0.015) could be written into the material.
The development of new optimized photoinitiators for the two-photon induced photopolymerization (TPIP) is essential in order to obtain high resolutions in this solid freeform fabrication process. Herein, we present the syntheses and characterizations of a series of efficient photoinitiators, comprising of a cross conjugated D-π-A-π-D system. The different donor- and acceptor functionalities of the investigated photoinitiators as well as the synthesis of targeted derivatives containing double and triple bonds in the conjugated backbone allowed the evaluation of structure-activity relationships. The basic photophysical properties as well as the activity and ideal processing window under TPIP conditions were investigated for each initiator and compared with typical commercially available one-photon initiator and with two highly potential initiators well known from literature. These tests figured out that the new chromophores are highly potential even at concentrations down to 0.05 wt%.
The melt spinning technique (MST) combined with post annealing processes is evaluated for the development of thermoelectric nanocomposites. The evaluated ones are based on two components almost immiscible in solid state but with crystallographic correlation. One is taken from the V-VI-components system and the other one from the IV-VI-components system. This concept was applied to p-(Bi0,2Sb0,8)2Te3 and to p-[(Bi0,2Sb0,8)2Te3]1-xPbTex composites. MST samples of all types were characterised for some structural and thermoelectric properties. All V-VI materials are clearly textured after MST and show no deterioration concerning the thermoelectric properties even after subsequent annealing processes. Structural analysis of p-[(Bi0,2Sb0,8)2Te3]1-xPbTex composites gave significant hints for oriented precipitates of a IV-VI-rich phase incorporated into the V-VI-rich matrix. The thermoelectric figure of merit of the evaluated composites could be enhanced by suitable annealing procedures of both the quenched bulk materials and the melt spin material.
We report here a procedure for the functioalization of SiO2-coated, SiONx waveguides for biological assays. Surface functionalization occurs by self-assembly of an amine-terminated silane monolayer on the waveguide, followed by partial chemical modification with functionalized polyethylene glycol (PEG) groups. Functionalized surfaces were characterized by atomic force microscopy and contact angle measurements. When combined with a BSA blocking step, these functional PEG surfaces significantly reduced non-specific binding and allowed for specific binding to occur. An antibody sandwich assay for detection of Bacillus anthracis protective antigen was used to validate these surfaces for sensing applications.
The suitability of two commercial dry diets for rearing Coregonus lavaretus larvae was tested in a 58-day experiment. A diet of live zooplankton was used for comparison. The trials were conducted at water temperature of 12 °C in 800 l tanks, with a stocking density of 10 000-25 000 larvae per tank. Diets were evaluated by means of growth and liver histological analysis. Best growth was obtained with zooplankton, but one of the two dry diets (TetraWerke Az 20) also resulted in satisfactory gowth. Examination of liver structure using light and electron microscopy revealed no nutritional pathology for larvae fed with dry diet Az 20. Histological diagnosis presented evidence for a close association between hepatic protein synthesis and larval growth. From the data of the present study it can be concluded that a large-scale rearing of larvae of Coregonus lavaretus exclusively on dry food, is feasible.
The main result of this paper is the theorem in the title. Only special cases of it seem to be known so far. As an application, we obtain a result on the unique extension of Galois connexions. As a matter of fact, it is only by the use of Galois connexions that we obtain the main result, in its present generality.
Słomiński (9), as well as the author (8), gave a descriptive, i.e., noncategory-theoretic, definition of the direct sum of partial algebras, i.e., the co-product in the category of partial algebras (A,ƒ), where ƒ = (ƒi)i∈I, ƒi: dom ƒi ⟶ A, dom ƒi ⊂ AKi, of fixed type A = (Ki)i∈I.
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