Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment

Background: Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intraindividual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. Methods: We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70–90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Results: Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. Conclusions: The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings

What is the Role of Acid-Acid Interactions in Asymmetric Phosphoric Acid Organocatalysis? A Detailed Mechanistic Study using Interlocked and Non-Interlocked Catalysts

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst-catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which react mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and a direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid-acid interactions have a drastic influence on the reaction rate and stereoselectivity of the asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids

Retrieval of surface solar irradiance from satellite imagery using machine learning: pitfalls and perspectives

Knowledge of the spatial and temporal characteristics of solar surface irradiance (SSI) is critical in many domains. While meteorological ground stations can provide accurate measurements of SSI locally, they are sparsely distributed worldwide. SSI estimations derived from satellite imagery are thus crucial to gain a finer understanding of the solar resource. Inferring SSI from satellite images is, however, not straightforward, and it has been the focus of many researchers in the past 30 to 40 years. For long, the emphasis has been on models grounded in physical laws with, in some cases, simple statistical parametrizations. Recently, new satellite SSI retrieval methods have been emerging, which directly infer the SSI from the satellite images using machine learning. Although only a few such works have been published, their practical efficiency has already been questioned. The objective of this paper is to better understand the potential and the pitfalls of this new family of methods. To do so, simple multi-layer-perceptron (MLP) models are constructed with different training datasets of satellite-based radiance measurements from Meteosat Second Generation (MSG) with collocated SSI ground measurements from Météo-France. The performance of the models is evaluated on a test dataset independent from the training set in both space and time and compared to that of a state-of-the-art physical retrieval model from the Copernicus Atmosphere Monitoring Service (CAMS). We found that the data-driven model's performance is very dependent on the training set. Provided the training set is sufficiently large and similar enough to the test set, even a simple MLP has a root mean square error (RMSE) that is 19 % lower than CAMS and outperforms the physical retrieval model at 96 % of the test stations. On the other hand, in certain configurations, the data-driven model can dramatically underperform even in stations located close to the training set: when geographical separation was enforced between the training and test set, the MLP-based model exhibited an RMSE that was 50 % to 100 % higher than that of CAMS in several locations.</p

Technology use, adoption and behaviour in older adults: results from the iStoppFalls Project

Technology use is a common constituent of modern life. However, little is known about older adults’ use of technology. This article presents a subset of data collected via the technology deployed in the iStoppFalls randomized control trial. The primary focus lies on questions about digital device/Internet use, ownership, length, and frequency as well as social networking. Data was collected from participants aged 65 years or older. Seventy-eight participants completed a specifically developed technology survey as part of the baseline assessment. Results showed that the majority of subjects owned a computer with men being its main user. Participants used technological devices on a daily basis for more than 1 year. The main reason for using technology was e-mail communication, search engines, text processing, and online shopping. Only a few participants used social network applications, with Google+ and Facebook being the most popular ones. Future work should consider an in-depth qualitative approach to further increase understanding of technology use in older adults

NMR Spectroscopic Characterization of Charge Assisted Strong Hydrogen Bonds in Brønsted Acid Catalysis

Hydrogen bonding plays a crucial role in Bronsted acid catalysis. However, the hydrogen bond properties responsible for the activation of the substrate are still under debate. Here, we report an in depth study of the properties and geometries of the hydrogen bonds in (R)-TRIP imine complexes (TRIP: 3,3'-Bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diylhydrogen phosphate). From NMR spectroscopic investigations H-1 and N-15 chemical shifts, a Steiner-Limbach correlation, a deuterium isotope effect as well as quantitative values of (1)J(NH), (2h)J(PH) and (3h)J(PN) were used to determine atomic distances (r(OH), r(NH), r(NO)) and geometry information. Calculations at SCS-MP2/CBS//TPSS-D3/def2-SVP-level of theory provided potential surfaces, atomic distances and angles. In addition, scalar coupling constants were computed at TPSS-D3/IGLO-III. The combined experimental and theoretical data reveal mainly ion pair complexes providing strong hydrogen bonds with an asymmetric single well potential. The geometries of the hydrogen bonds are not affected by varying the steric or electronic properties of the aromatic imines. Hence, the strong hydrogen bond reduces the degree of freedom of the substrate and acts as a structural anchor in the (R)-TRIP imine complex

A genome-wide survey of human short-term memory

Recent advances in the development of high-throughput genotyping platforms allow for the unbiased identification of genes and genomic sequences related to heritable traits. In this study, we analyzed human short-term memory, which refers to the ability to remember information over a brief period of time and which has been found disturbed in many neuropsychiatric conditions, including schizophrenia and depression. We performed a genome-wide survey at 909 622 polymorphic loci and report six genetic variations significantly associated with human short-term memory performance after genome-wide correction for multiple comparisons. A polymorphism within SCN1A (encoding the α subunit of the type I voltage-gated sodium channel) was replicated in three independent populations of 1699 individuals. Functional magnetic resonance imaging during an n-back working memory task detected SCN1A allele-dependent activation differences in brain regions typically involved in working memory processes. These results suggest an important role for SCN1A in human short-term memory

Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression

INTRODUCTION: Receptor tyrosine kinases have been extensively studied owing to their frequently abnormal activation in the development and progression of human cancers. Platelet-derived growth factor receptors (PDGFRs) are receptors with intrinsic tyrosine kinase activity that regulate several functions in normal cells and are widely expressed in a variety of malignancies. After the demonstration that gastrointestinal stromal tumours without c-Kit mutations harbour PDGFR-α-activating mutations and that PDGFR-α is also a therapeutic target for imatinib mesylate, the interest for this receptor has increased considerably. Because breast cancer is one of the most frequent neoplasias in women worldwide, and only one study has reported PDGFR-α expression in breast carcinomas, the aim of this work was to investigate the potential significance of PDGFR-α expression in invasive mammary carcinomas. METHODS: We used immunohistochemistry to detect PDGFR-α overexpression on a series of 181 formalin-fixed paraffin-embedded invasive ductal breast carcinomas and in two breast cancer cell lines: MCF-7 and HS578T. We associated its expression with known prognostic factors and we also performed polymerase chain reaction–single-stranded conformational polymorphism and direct sequencing to screen for PDGFR-α mutations. RESULTS: PDGFR-α expression was observed in 39.2% of the breast carcinomas and showed an association with lymph node metastasis (P = 0.0079), HER-2 expression (P = 0.0265) and Bcl2 expression (P = 0.0121). A correlation was also found with the expression of platelet-derived growth factor A (PDGF-A; P = 0.0194). The two cell lines tested did not express PDGFR-α. Screening for mutations revealed alterations in the PDGFR-α gene at the following locations: 2500A→G, 2529T→A and 2472C→T in exon 18 and 1701G→A in exon 12. We also found an intronic insertion IVS17-50insA at exon 18 in all sequenced cases. None of these genetic alterations was correlated with PDGFR-α expression. The cell lines did not reveal any alterations in the PDGFR-α gene sequence. CONCLUSION: PDGFR-α is expressed in invasive breast carcinomas and is associated with biological aggressiveness. The genetic alterations described were not correlated with protein expression, but other mechanisms such as gene amplification or constitutive activation of a signalling pathway inducing this receptor could still sustain PDGFR-α as a potential therapeutic target

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event

Change Patterns in Use: A Critical Evaluation

Process model quality has been an area of considerable research efforts. In this context, the correctness-by-construction principle of change patterns provides promising perspectives. However, using change patterns for model creation imposes a more structured way of modeling. While the process of process modeling (PPM) based on change primitives has been investigated, little is known about this process based on change patterns. To obtain a better understanding of the PPM when using change patterns, the arising challenges, and the subjective perceptions of process designers, we conduct an exploratory study. The results indicate that process designers face little problems as long as control-flow is simple, but have considerable problems with the usage of change patterns when complex, nested models have to be created. Finally, we outline how effective tool support for change patterns should be realized.This research is supported by Austrian Science Fund (FWF): P23699-N23.Weber, B.; Pinggera, J.; Torres Bosch, MV.; Reichert, M. (2013). Change Patterns in Use: A Critical Evaluation. En Enterprise, Business-Process and Information Systems Modeling, BPMDS 2013. Springer Verlag. 261-276. https://doi.org/11007/978-3-642-38484-4_19S26127