112 research outputs found

    Delays in Claiming Social Security Benefits

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    This paper focuses on Social Security benefit claiming behavior, a take-up decision that has been ignored in the previous literature. Using financial calculations and simulations based on an expected utility maximization model, we show that delaying benefit claim for a period of time after retirement is optimal in a wide variety of cases and that gains from delay may be significant. We find that approximately 10% of men retiring before their 62nd birthday delay claiming for at least one year after eligibility. We estimate hazard and probit models using data from the New Beneficiary Data System to test four cross-sectional predictions. While the data suggest that too few men delay, we find that the pattern of delays by early retirees is generally consistent with the hypotheses generated by our theoretical model.

    Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma

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    PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need. EXPERIMENTAL DESIGN: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a “first in RDEB” phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC

    An Antiproton Decelerator in the CERN PS Complex

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    The present CERN PS low-energy antiproton complex involves 4 machines to collect, cool, decelerate and supply experiments with up to 1010 antiprotons per pulse and per hour of momenta ranging from 0.1 to 2 GeV/c. In view of a possible future physics programme requiring low energy antiprotons, mainly to carry out studies on antihydrogen, a simplified scheme providing at low cost antiprotons at 100 MeV/c has been studied. It requires only one machine, the present Antiproton Collector (AC) converted into a cooler and decelerator (Antiproton Decelerator, AD) and delivering beam to experiments in the hall of the present Antiproton Accumulator Complex (AAC) [1]. This paper describes the feasibility study of such a scheme [2]

    The antiproton decelerator (AD), a simplified antiproton source (feasibility study)

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    In view of a possible future physics programme concerning antihydrogen a simplified scheme for the provision of antiprotons of a few MeV has been studied. It uses the present target area and the modified Antiproton Collector (AC) in its present location. In this report all the systems are reviewed and their modifications discussed

    Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures

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    BACKGROUND: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy

    Dissociable Influences of Auditory Object vs. Spatial Attention on Visual System Oscillatory Activity

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    Given that both auditory and visual systems have anatomically separate object identification (“what”) and spatial (“where”) pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory “what” vs. “where” attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic (“what”) vs. spatial (“where”) aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7–13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400–600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity (“what”) vs. sound location (“where”). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during “what” vs. “where” auditory attention

    The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

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    Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

    A decade of detailed observations (2008-2018) in steep bedrock permafrost at the Matterhorn HĂśrnligrat (Zermatt, CH)

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    The PermaSense project is an ongoing interdisciplinary effort between geo-science and engineering disciplines and started in 2006 with the goals of realizing observations that previously have not been possible. Specifically, the aims are to obtain measurements in unprecedented quantity and quality based on technological advances. This paper describes a unique >10-year data record obtained from in situ measurements in steep bedrock permafrost in an Alpine environment on the Matterhorn HĂśrnligrat, Zermatt, Switzerland, at 3500ma:s:l. Through the utilization of state-of-the-art wireless sensor technology it was possible to obtain more data of higher quality, make these data available in near real time and tightly monitor and control the running experiments. This data set (https://doi.org/10.1594/PANGAEA.897640,Weber et al., 2019a) constitutes the longest, densest and most diverse data record in the history of mountain permafrost research worldwide with 17 different sensor types used at 29 distinct sensor locations consisting of over 114.5 million data points captured over a period of 10 or more years. By documenting and sharing these data in this form we contribute to making our past research reproducible and facilitate future research based on these data, e.g., in the areas of analysis methodology, comparative studies, assessment of change in the environment, natural hazard warning and the development of process models. Finally, the cross-validation of four different data types clearly indicates the dominance of thawing-related kinematics
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