Pathways from physical frailty to activity limitation in older people: identifying moderators and mediators in the English longitudinal study of ageing

Physical frailty increases the risk of future activity limitation, which in turn, compromises independent living of older people and limits their healthspan. Thus, we seek to identify moderators and mediators of the effect of physical frailty on activity limitation change in older people, including gender- and age-specific effects. In a longitudinal study using data from waves 2, 4, and 6 of the English Longitudinal Study of Ageing, unique physical frailty factor scores of 4,638 respondents aged 65 to 89 years are obtained from confirmatory factor analysis of physical frailty, which is specified by three indicators, namely slowness, weakness, and exhaustion. Using a series of autoregressive cross-lagged models, we estimate the effect of physical frailty factor score on activity limitation change, including its moderation by social conditions, and indirect effects through physical and psychological conditions. We find that the effect of physical frailty on activity limitation change is significantly stronger with older age, while it has significant indirect effects through low physical activity, depressive symptoms, and cognitive impairment. In turn, indirect effects of physical frailty through low physical activity and cognitive impairment are stronger with older age. Sensitivity analyses suggest that these effects vary in their robustness to unmeasured confounding. We conclude that low physical activity, depressive symptoms, and cognitive impairment are potentially modifiable mediators on pathways from physical frailty to activity limitation in older people, including those who are very old. This evidence offers support for population-level interventions that target these conditions, to mitigate the effect of physical frailty on activity limitation, and thereby enhance healthspan

Effect of worksheet scaffolds on student learning in problem-based learning

The purpose of this study was to investigate the effect of worksheets as a scaffolding tool on students’ learning achievement in a problem-based learning (PBL) environment. Seventeen PBL classes (N = 241) were randomly assigned to two experimental groups—one with a worksheet provided and the other without. Students’ learning of the topic at hand was evaluated by comparing results from pre- and post-lesson concept recall tests. We also obtained information about students’ perceptions of factors impacting their learning using a Learning Impact Questionnaire. The data was analyzed by means of analyses of variance. Results of the study indicated that there was no statistically significant difference between the levels of understanding for both groups of students. In addition, survey results revealed that the strongest factor perceived by students to impact their learning in a PBL context is the tutor followed by team and class dynamics, while the influence of the worksheet was rated lowest. These findings suggest that scaffolds such as worksheets may not play a significant role in enhancing students’ learning within the social constructivist framework of problem-based learning. On the other hand, the importance of the role of tutor and collaborative small group learning which are key features of PBL is reinforced

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study

Background Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. Objectives We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. Methods This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. Results One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. Conclusion Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation

Rotational Symmetry Breaking in a Trigonal Superconductor Nb-Doped Bi₂Se₃

The search for unconventional superconductivity has been focused on materials with strong spin-orbit coupling and unique crystal lattices. Doped bismuth selenide (Bi2Se3) is a strong candidate, given the topological insulator nature of the parent compound and its triangular lattice. The coupling between the physical properties in the superconducting state and its underlying crystal symmetry is a crucial test for unconventional superconductivity. In this paper, we report direct evidence that the superconducting magnetic response couples strongly to the underlying trigonal crystal symmetry in the recently discovered superconductor with trigonal crystal structure, niobium (Nb)-doped Bi2Se3. As a result, the in-plane magnetic torque signal vanishes every 60°. More importantly, the superconducting hysteresis loop amplitude is enhanced along one preferred direction, spontaneously breaking the rotational symmetry. This observation indicates the presence of nematic order in the superconducting ground state of Nb-doped Bi2Se3

Higher-order nonlinear modes and bifurcation phenomena due to degenerate parametric four-wave mixing

We demonstrate that weak parametric interaction of a fundamental beam with its third harmonic field in Kerr media gives rise to a rich variety of families of non-fundamental (multi-humped) solitary waves. Making a comprehensive comparison between bifurcation phenomena for these families in bulk media and planar waveguides, we discover two novel types of soliton bifurcations and other interesting findings. The later includes (i) multi-humped solitary waves without even or odd symmetry and (ii) multi-humped solitary waves with large separation between their humps which, however, may not be viewed as bound states of several distinct one-humped solitons.Comment: 9 pages, 17 figures, submitted to Phys. Rev.

Multiple Fermi Surfaces in Superconducting Nb-Doped Bi₂Se₃

Topological insulator Bi2Se3 has shown a number of interesting physical properties. Doping Bi2Se3 with copper or strontium has been demonstrated to make the material superconducting and potentially even a topological superconductor. The recent discovery of superconducting niobium-doped Bi2Se3 reveals an exciting new physical phenomenon, the coexistence of superconductivity and magnetic ordering, as well as signatures of an odd-parity p-wave superconducting order. To understand this new phenomenon, a detailed knowledge of the electronic structure is needed. We present an observation of quantum oscillations in the magnetization (the de Haas-van Alphen effect) of Nb-doped Bi2Se3. In the fully superconducting crystal, two distinct orbits are observed, in sharp contrast to Bi2Se3, Cu-doped Bi2Se3, and Sr-doped Bi2Se3. The multiple frequencies observed in our quantum oscillations, combined with our electrical transport studies, indicate the multi-orbit nature of the electronic state of Nb-doped Bi2Se3

Eradication of large solid tumors by gene therapy with a T cell receptor targeting a single cancer-specific point mutation

PURPOSE: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic non-synonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T cell receptor (TCR) that is specific for a single AAS. EXPERIMENTAL DESIGN: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. RESULTS: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intra-tumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. CONCLUSIONS: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape

Improving signal-to-noise ratio of structured light microscopy based on photon reassignment

In this paper, we report a method for 3D visualization of a biological specimen utilizing a structured light wide-field microscopic imaging system. This method improves on existing structured light imaging modalities by reassigning fluorescence photons generated from off-focal plane excitation, improving in-focus signal strength. Utilizing a maximum likelihood approach, we identify the most likely fluorophore distribution in 3D that will produce the observed image stacks under structured and uniform illumination using an iterative maximization algorithm. Our results show the optical sectioning capability of tissue specimens while mostly preserving image stack photon count, which is usually not achievable with other existing structured light imaging methods

Band alignment and enhanced breakdown field of simultaneously oxidized and nitrided Zr film on Si

The band alignment of ZrO2/interfacial layer/Si structure fabricated by simultaneous oxidation and nitridation of sputtered Zr on Si in N2O at 700°C for different durations has been established by using X-ray photoelectron spectroscopy. Valence band offset of ZrO2/Si was found to be 4.75 eV, while the highest corresponding conduction offset of ZrO2/interfacial layer was found to be 3.40 eV; owing to the combination of relatively larger bandgaps, it enhanced electrical breakdown field to 13.6 MV/cm at 10-6 A/cm2

Unsupervised Learning of Category-Specific Symmetric 3D Keypoints from Point Sets

Automatic discovery of category-specific 3D keypoints from a collection of objects of a category is a challenging problem. The difficulty is added when objects are represented by 3D point clouds, with variations in shape and semantic parts and unknown coordinate frames. We define keypoints to be category-specific, if they meaningfully represent objects’ shape and their correspondences can be simply established order-wise across all objects. This paper aims at learning such 3D keypoints, in an unsupervised manner, using a collection of misaligned 3D point clouds of objects from an unknown category. In order to do so, we model shapes defined by the keypoints, within a category, using the symmetric linear basis shapes without assuming the plane of symmetry to be known. The usage of symmetry prior leads us to learn stable keypoints suitable for higher misalignments. To the best of our knowledge, this is the first work on learning such keypoints directly from 3D point clouds for a general category. Using objects from four benchmark datasets, we demonstrate the quality of our learned keypoints by quantitative and qualitative evaluations. Our experiments also show that the keypoints discovered by our method are geometrically and semantically consistent