Future time perspectives and career commitment. Does age influence this? A quantitative examination of a New Zealand working population.

The inability to commit to a career can have long-term negative consequences on the quality of life of individuals. Those who have obtained career success have been found to possess high levels of future time perspective, the capacity to not only place a high value on future goals but to also identify what actions are required to achieve future goals. To date, there has been no research conducted examining the relationship between future time perspective and career commitment in a working New Zealand population; nor has any research investigated if there are any differences between different age cohorts of New Zealanders. This study examined this relationship by conducting correlation, regression, analysis of variance, and moderation analyses on data taken from 96 employed New Zealand citizens/residents who participated in an online survey. The correlational analysis suggests that connectedness and valence are positively associated with commitment-making and identification, and negatively associated with self-doubt, and flexibility. Regression analysis suggests that connectedness influences flexibility, and valence influences commitment-making, identification, and flexibility. ANOVA analysis shows that there is a difference between individual’s aged 16 – 44, and 45 – 75+ concerning commitment-making, self-doubt, and flexibility. Moderation analysis results suggest that age has a buffering effect on the relationship between connectedness and self-doubt in those aged 16 – 44 years old, and an enhancing effect in those aged 45 – 74+. Method of participant recruitment, categorisation of age cohorts, and the constraint of this study examining a single time period contribute to this studies limitations. Future research and practical implications of the current study are discussed

Direct Observation of Broadband Coating Thermal Noise in a Suspended Interferometer

We have directly observed broadband thermal noise in silica/tantala coatings in a high-sensitivity Fabry-Perot interferometer. Our result agrees well with the prediction based on indirect, ring-down measurements of coating mechanical loss, validating that method as a tool for the development of advanced interferometric gravitational-wave detectors.Comment: Final version synchronized with publication in Phys. Lett.

Titania-doped tantala/silica coatings for gravitational-wave detection

Reducing thermal noise from optical coatings is crucial to reaching the required sensitivity in next generation interferometric gravitational-wave detectors. Here we show that adding TiO2 to Ta2O5 in Ta2O5/SiO2 coatings reduces the internal friction and in addition present data confirming it reduces thermal noise. We also show that TiO2-doped Ta2O5/SiO2 coatings are close to satisfying the optical absorption requirements of second generation gravitational-wave detectors

Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids

Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3^+TCR-αβ^+ single-positive CD8^+ or CD4^+ cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs. ATO-derived T cells exhibited mature naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function. ATOs initiated with TCR-engineered HSPCs produced T cells with antigen-specific cytotoxicity and near-complete lack of endogenous TCR Vβ expression, consistent with allelic exclusion of Vβ-encoding loci. ATOs provide a robust tool for studying human T cell differentiation and for the future development of stem-cell-based engineered T cell therapies

Ambient Fine Particulate Matter Exposure and Myocardial Ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) Study

BackgroundAmbient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated.MethodsWe studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999–2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 μm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec.ResultsOverall, 6% of the remaining 55,529 women (52–90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from −14 to 349 μV). PM2.5 (mean ± SD) averaged over lag0–2 was 14 ± 7 μg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-μg/m3 increase in lag0–2 PM2.5 was associated with a 4% [95% confidence interval (CI), −3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of −2 μV (95% CI, −5 to 0 μV) in lead V3.ConclusionsShort-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST–T abnormalities and decreases in T amplitude

The Vehicle, 1962, Vol. 4

Vol. 4 Table of Contents The SearchLarry Pricepage 7 If We Should MeetPauline B. Smithpage 16 Sonnet No. 1Linda Campbellpage 17 SnowflakesPauline B. Smithpage 17 Encounter in the VoidEric Crookspage 18 symbolBen Polkpage 24 The Sound of SilenceJames Wilhelmpage 24 ColoursJean Ellen Danenbargerpage 26 vegetableBen Polkpage 27 The GiftJan Holstlawpage 29 The Tiled OvenRichard Glassonpage 30 This Lover Ever WeepsBen Polkpage 31 El DoradoPauline B. Smithpage 32 I\u27m SorryMary Jean Pitratpage 32 The WalkDavid Schwarzpage 33 The Twenty-Third ChannelBen Polkpage 34 After the PicnicLinda Campbellpage 35 SoliloquyJanice Brookspage 35 JulieMyra Edmanpage 36 Poems (1) (2)Gale Crousepage 40 Boardwalk at NightSheran Broadwaypage 41 SunsetPauline B. Smithpage 42 SummerC.E.M.page 42 It\u27s Spring AgainJanice Brookspage 43 Chinese SymbolsJean Ellen Danenbargerpage 43 Why Do You Wait?Gale Crousepage 44 seekerBen Polkpage 46 Poems (3) (4) (5)Gale Crousepage 47 Opposite AttractionsC.E.M.page 48 Illustrations for the winning short story and poemDouglas Koertgehttps://thekeep.eiu.edu/vehicle/1010/thumbnail.jp

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

The Vehicle, 1963, Vol. 5

Vol. 5 Table of Contents Milepostspage 3 Rhyme Conceived At DawnDaun Alan Leggpage 4 NightRoss Kokospage 4 UncrownedOra Blanche T. Kingpage 4 SunfishingL.J.G.page 5 The Man Who Went To New YorkEric Crookspage 7 The DreamPauline B. Smithpage 18 Open WindowsDavid Helmpage 19 SalvationChristine McCollpage 19 The Chess GamePierre Hooverpage 20 CataclysmRaymond Kapraunpage 20 A Microscopic ViewKenneth L. Vadovskypage 21 See How Love ComesLiz Puckettpage 21 A Can Of Beer For AndyKenneth L. Vadovskypage 22 A MonsterDixie Lee Motleypage 28 InconstancyJanice Brookspage 29 DreamerDaun Alan Leggpage 29 The Third WishGlenda Vursellpage 30 The MiracleJanice Brookspage 32 What Lives Where Love Once Dwelt?Vernell Vyvialpage 33 The Most Unforgettable Person I Have Ever KnownJames Flingpage 34 Winter ThoughtsPauline B. Smithpage 35 A Winter NightPeggy Lambertpage 35 The Silver WhaleL.J.G.page 36 RaindropsDixie Lee Motleypage 40 Conflict Of Soul IJean Konzelmanpage 40 JudyChristine McCollpage 41 Sadness No. 3 (Vergessen)Sherry Sue Frypage 41 Lost GoldLarry Pricepage 42 EchoesCharles Cooleypage 48 TruthDaun Alan Leggpage 48 SunsetCarol Bennettpage 48 Cover designTom Windsor Illustration for winning storyJoel E. Hendrickshttps://thekeep.eiu.edu/vehicle/1011/thumbnail.jp

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis