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Background: In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required. Methods: We describe 3 survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission. Results: All 3 patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest–related heart rate–corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up. When they were subjected to exercise stress testing during follow-up, a delayed diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was made. As a result, these patients were initially managed inappropriately, and their family members were initially not screened for CPVT. Conclusion: In sudden cardiac arrest survivors without an immediately identifiable cause, omission of exercise stress testing or erroneous interpretation of the results can lead to a delayed or missed diagnosis of CPVT, which may have considerable implications for survivors and their family. [ABSTRACT FROM AUTHOR]

Introduction: Ambulatory assessment of the heart rate–corrected QT interval (QTc) can be of diagnostic value, for example in patients on QTc-prolonging medication. Repeating sequential 12-lead electrocardiograms (ECGs) to monitor the QTc is cumbersome, but mobile ECG (mECG) devices can potentially solve this problem. As the accuracy of single-lead mECG devices is reportedly variable, a multilead mECG device may be more accurate. Methods: This prospective dual-centre study included outpatients visiting our cardiology clinics for any indication. Participants underwent an mECG recording using a smartphone-enabled 6‑lead mECG device immediately before or immediately after a conventional 12-lead ECG recording. Multiple QTc values in both recordings were manually measured in leads I and II using the tangent method and subsequently compared. Results: In total, 234 subjects were included (mean ± standard deviation (SD) age: 57 ± 17 years; 58% males), of whom 133 (57%) had cardiac disease. QTc measurement in any lead was impossible due to artefacts in 16 mECGs (7%) and no 12-lead ECGs. Mean (± SD) QTc in lead II on the mECG and 12-lead ECG was 401 ± 30 and 406 ± 31 ms, respectively. Mean (± SD) absolute difference in QTc values between both modalities was 12 ± 9 ms (r = 0.856; p < 0.001). In 55% of the subjects, the absolute difference between QTc values was < 10 ms. Conclusion: A 6-lead mECG allows for QTc assessment with good accuracy and can be used safely in ambulatory QTc monitoring. This may improve patient satisfaction and reduce healthcare costs. [ABSTRACT FROM AUTHOR]

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown. Methods: DPP6 risk haplotype-positive family members (DPP6 cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023. Implantable cardioverter-defibrillator (ICD) indication was divided in primary or secondary prevention. Cumulative survival and event rates were calculated. Results: We included 327 DPP6 cases and 315 DPP6 controls. Median follow-up time was 9 years (interquartile range: 4–12). Of the DPP6 cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at a median age of 45 years (range: 15–97). Median overall survival was 83 years and 87 years for DPP6 cases and DPP6 controls, respectively (p < 0.001). In DPP6 cases, median overall survival was shorter for males (74 years) than females (85 years) (p < 0.001). Of the DPP6 cases, 97 (30%) died, at a median age of 50 years. With a prophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6 cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10 patients experienced a total of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6 cases with a secondary prevention ICD experienced a total of 231 appropriate ICD shocks. Conclusion: Patients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using a risk stratification approach based on risk haplotype, sex and age, a substantial proportion of patients with a primary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy. [ABSTRACT FROM AUTHOR]

Constrained fourth-order latent differential equation (FOLDE) models have been proposed (e.g., Boker et al. 2020) as alternative to second-order latent differential equation (SOLDE) models to estimate second-order linear differential equation systems such as the damped linear oscillator model. When, however, only a relatively small number of measurement occasions T are available (i.e., T = 50 ), the recommendation of which model to use is not clear (Boker et al. 2020). Based on a data set, which consists of T = 56 observations of daily stress for N = 44 individuals, we illustrate that FOLDE can help to choose an embedding dimension, even in the case of a small T. This is of great importance, as parameter estimates depend on the embedding dimension as well as on the latent differential equations model. Consequently, the wavelength as quantity of potential substantive interest may vary considerably. We extend the modeling approaches used in past research by including multiple subjects, by accounting for individual differences in equilibrium, and by including multiple instead of one single observed indicator. [ABSTRACT FROM AUTHOR]

Person-centered methods are useful for studying individual differences in terms of (dis)similarities between response profiles on multivariate outcomes. Multivariate distance matrix regression (MDMR) tests the significance of associations of response profile (dis)similarities and a set of predictors using permutation tests. This paper extends MDMR by deriving and empirically validating the asymptotic null distribution of its test statistic, and by proposing an effect size for individual outcome variables, which is shown to recover true associations. These extensions alleviate the computational burden of permutation tests currently used in MDMR and render more informative results, thus making MDMR accessible to new research domains. [ABSTRACT FROM AUTHOR]

Intensive longitudinal data provide rich information, which is best captured when specialized models are used in the analysis. One of these models is the multilevel autoregressive model, which psychologists have applied successfully to study affect regulation as well as alcohol use. A limitation of this model is that the autoregressive parameter is treated as a fixed, trait-like property of a person. We argue that the autoregressive parameter may be state-dependent, for example, if the strength of affect regulation depends on the intensity of affect experienced. To allow such intra-individual variation, we propose a multilevel threshold autoregressive model. Using simulations, we show that this model can be used to detect state-dependent regulation with adequate power and Type I error. The potential of the new modeling approach is illustrated with two empirical applications that extend the basic model to address additional substantive research questions. [ABSTRACT FROM AUTHOR]

Vectors designed for protein production in Escherichia coli and by wheat germ cell-free translation were tested using 21 well-characterized eukaryotic proteins chosen to serve as controls within the context of a structural genomics pipeline. The controls were carried through cloning, small-scale expression trials, large-scale growth or synthesis, and purification. Successfully purified proteins were also subjected to either crystallization trials or H-N HSQC NMR analyses. Experiments evaluated: (1) the relative efficacy of restriction/ligation and recombinational cloning systems; (2) the value of maltose-binding protein (MBP) as a solubility enhancement tag; (3) the consequences of in vivo proteolysis of the MBP fusion as an alternative to post-purification proteolysis; (4) the effect of the level of LacI repressor on the yields of protein obtained from E. coli using autoinduction; (5) the consequences of removing the His tag from proteins produced by the cell-free system; and (6) the comparative performance of E. coli cells or wheat germ cell-free translation. Optimal promoter/repressor and fusion tag configurations for each expression system are discussed. [ABSTRACT FROM AUTHOR]

One possible way to produce ultra-cold, high-phase-space-density quantum gases of molecules in the rovibronic ground state is given by molecule association from quantum-degenerate atomic gases on a Feshbach resonance and subsequent coherent optical multi-photon transfer into the rovibronic ground state. In ultra-cold samples of Cs2 molecules, we observe two-photon dark resonances that connect the intermediate rovibrational level | v=73, J=2〉 with the rovibrational ground state | v=0, J=0〉 of the singlet X1 Σ ground-state potential. For precise dark resonance spectroscopy we exploit the fact that it is possible to efficiently populate the level | v=73, J=2〉 by two-photon transfer from the dissociation threshold with the stimulated Raman adiabatic passage (STIRAP) technique. We find that at least one of the two-photon resonances is sufficiently strong to allow future implementation of coherent STIRAP transfer of a molecular quantum gas to the rovibrational ground state | v=0, J=0〉. [ABSTRACT FROM AUTHOR]

A simple approach that allows cost-effective automated purification of recombinant proteins in levels sufficient for functional characterization or structural studies is described. Studies with four human stem cell proteins, an engineered version of green fluorescent protein, and other proteins are included. The method combines an expression vector (pVP62K) that provides in vivo cleavage of an initial fusion protein, a factorial designed auto-induction medium that improves the performance of small-scale production, and rapid, automated metal affinity purification of His8-tagged proteins. For initial small-scale production screening, single colony transformants were grown overnight in 0.4 ml of auto-induction medium, produced proteins were purified using the Promega Maxwell 16, and purification results were analyzed by Caliper LC90 capillary electrophoresis. The yield of purified [ U-15N]-His8-Tcl-1 was 7.5 μg/ml of culture medium, of purified [ U-15N]-His8-GFP was 68 μg/ml, and of purified selenomethione-labeled AIA–GFP (His8 removed by treatment with TEV protease) was 172 μg/ml. The yield information obtained from a successful automated purification from 0.4 ml was used to inform the decision to scale-up for a second meso-scale (10–50 ml) cell growth and automated purification. 1H–15N NMR HSQC spectra of His8-Tcl-1 and of His8-GFP prepared from 50 ml cultures showed excellent chemical shift dispersion, consistent with well folded states in solution suitable for structure determination. Moreover, AIA–GFP obtained by proteolytic removal of the His8 tag was subjected to crystallization screening, and yielded crystals under several conditions. Single crystals were subsequently produced and optimized by the hanging drop method. The structure was solved by molecular replacement at a resolution of 1.7 Å. This approach provides an efficient way to carry out several key target screening steps that are essential for successful operation of proteomics pipelines with eukaryotic proteins: examination of total expression, determination of proteolysis of fusion tags, quantification of the yield of purified protein, and suitability for structure determination. [ABSTRACT FROM AUTHOR]

Fludarabine is commonly used in combination with busulfan as part of conditioning regimens before allogeneic stem cell transplantation. So far, no data are available on busulfan–fludarabine drug interactions in transplant recipients. The pharmacokinetic (PK) properties of F-ara-A (9-β-D-arabinosyl-2-fluoradenine) before and after application of busulfan were prospectively investigated in 16 patients with hematological malignancies. The conditioning regimen consisted of intravenous fludarabine 30 mg/m2 over 30 min from day −6 to day −3, and oral busulfan given at 1 mg/kg every 6 h from day −5 to day −2. PK parameters of F-ara-A, derived from plasma and urine on day −6, −5, −4 and −3, were determined using high-performance liquid chromatography (HPLC). AUC, Cmax, t1/2, Cltotal and VSS were 21.9 μMh, 3.5 μM, 13.0 h, 4.3 l/h/m2, 60.0 l/m2 on day −6 and 22.4 μMh, 3.5 μM, 14.0 h, 4.7 l/h/m2, 69.0 l/m2 on day −5 to (−2), respectively. Clrenal and the urine-recovery were 4.8 l/h, 43.7% of the fludarabine dose on day −6 and 3.9 l/h, 44.2% of the fludarabine dose on day −5 to (−2), respectively. There were no changes in PK parameters of fludarabine given before and after intake of busulfan. This implies that a clinically relevant busulfan–fludarabine drug interaction is unlikely.Bone Marrow Transplantation (2007) 39, 201–206. doi:10.1038/sj.bmt.1705565; published online 8 January 2007 [ABSTRACT FROM AUTHOR]

Recently, we have reported photoassociation of laser-cooled Rb and Cs atoms, decay of the RbCs photoassociation resonances to high levels of thestate, and reexcitation to vibronic levels of thestate [Kerman et al. , Phys. Rev. Lett.92, 033004; 153001 (2004)]. Considering the reexcitation spectrum, we report here a preliminary analysis of perturbations in thecstate by high levels of theand low levels of thestate. Mixing with theBstate provides the singlet character needed to stimulate decay tov= 0 of theground state. We conclude that an experimental procedure that involves photoassociation of laser-cooled atoms, radiative decay, and stimulated Raman transfer to the ground electronic state is a feasible method for producing translationally, rotationally, vibrationally and electronically cold RbCs molecules. [ABSTRACT FROM AUTHOR]

As it has become more widely recognized that increasing numbers of people are living to progressively older ages, it is important to understand the nature of individual traits that promote resilience and well-being in later life, to describe how these traits develop, to identify the factors that threaten and undermine their maintenance, and to elucidate the mechanisms that support and promote their growth. To have a knowledge base upon which to build intervention programs to improve and maintain well-being in later life, it is necessary to build understanding of what the multiple pathways are that lead to resilience, how these pathways may change, and what can be done to stop or forestall maladjustment and decline. Progress on these issues requires a greater understanding of process. In this article, we highlight theoretical areas of research on resilience and well-being that have received relatively little attention in previous work with older adults. We also identify unresolved methodological challenges associated with the measurement and analysis of within-person phenomena and elaborate on the implications of these challenges for process research in aging populations. Finally, we discuss future intervention directions to advance knowledge of resilience and positive health in later adulthood. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine reserve capacity in minority elderly and to identify the protective factors that promoted more optimal outcomes even in the face of a life filled with adversity. These notions were examined using life stories or personal accounts of the important events and experiences that shape an individual's development. Life story interviews were conducted with 10 African American elders (aged 58–88). Tape-recorded interviews were examined for thematic content. One of the themes that emerged as being important to participants' reserve potential comprised spirituality and religiosity. As described by the respondents, spirituality and religiosity were used as a reserve resource from which they were able to draw in times of stress, thus allowing them to grow as a result of their hardships. Overall, this research has important implications. For example, the methodology provided the opportunity to assess the process by which spirituality and religiosity contribute to well-being, either indirectly as a coping mechanism or as means of garnering social support, or more directly, via enhancing a sense of self. Descriptive accounts of this type can help to elucidate how protective factors promote more optimal outcomes and ultimately inform intervention strategies. [ABSTRACT FROM AUTHOR]