The Vehicle, Fall 1983

Vol. 25, No. 1 Table of Contents Amish BoyDevon Flesorpage 3 SyllogismJ. Maura Davispage 3 Ten SecondsD.L. Lewispage 4 The Cedar ChestBridget M. Howepage 4 A Christmas With CarolSteve Longpage 5 TeethMichelle Mitchellpage 7 An I-Love-You PoemD.L. Lewispage 8 The Dragon SlayerSusan Gradypage 8 A DefinitionAmy J. Eadespage 9 FingernailsSuzanne Hornpage 10 The Liar\u27s TableBrook Wilsonpage 10 Fifi\u27s Last PartySteve Longpage 12 Absence/PresenceSuzanne Hornpage 13 From the Rantings of a Mad Astronomy StudentAmy J. Eadespage 13 In the Name of the Father, the Son, and MachiavelliF. Link Rapierpage 15 Errant LoverBecky Lawsonpage 16 DaddyKevin Lylespage 16 GhostsGary Ervinpage 17 TangoF. Link Rapierpage 17 Grandma\u27s SlippersBecky Lawsonpage 18 EdgesAmy J. Eadespage 19 Having ChildrenDevon Flesorpage 20 Young Black GirlKevin Lylespage 21 CatSuzanne Hornpage 22 Breakfast for OneMichelle Mitchellpage 22 A Modest ProposalBrooke Sanfordpage 23 Post MortemF. Link Rapierpage 26 Who Said I Forgot?Lynne Krausepage 27 The Corner Booth at StuckeysMaggie Kennedypage 28 The First DayDavis Brydenpage 29 DownLynne Krausepage 30 Fairie RingDevon Flesorpage 31 The LaundrymatKathy Fordpage 32 Sunday in OctoberBridget M. Howepage 32 The Kitchen WindowMaggie Kennedypage 33 UntitledChristina Maire Vitekpage 34 8th Grade Field Trip to SpringfieldMichelle Mitchellpage 34 Children of the FortiesF. Link Rapierpage 35 one winter and i was eightGary Ervinpage 35 Don\u27t we all know?Thomas B. Waltrippage 36 The TravelerMaggie Kennedypage 36 The VisitKathy Fordpage 40 CubismMaggie Kennedypage 40https://thekeep.eiu.edu/vehicle/1042/thumbnail.jp

The Vehicle, Fall 1983

Vol. 25, No. 1 Table of Contents Amish BoyDevon Flesorpage 3 SyllogismJ. Maura Davispage 3 Ten SecondsD.L. Lewispage 4 The Cedar ChestBridget M. Howepage 4 A Christmas With CarolSteve Longpage 5 TeethMichelle Mitchellpage 7 An I-Love-You PoemD.L. Lewispage 8 The Dragon SlayerSusan Gradypage 8 A DefinitionAmy J. Eadespage 9 FingernailsSuzanne Hornpage 10 The Liar\u27s TableBrook Wilsonpage 10 Fifi\u27s Last PartySteve Longpage 12 Absence/PresenceSuzanne Hornpage 13 From the Rantings of a Mad Astronomy StudentAmy J. Eadespage 13 In the Name of the Father, the Son, and MachiavelliF. Link Rapierpage 15 Errant LoverBecky Lawsonpage 16 DaddyKevin Lylespage 16 GhostsGary Ervinpage 17 TangoF. Link Rapierpage 17 Grandma\u27s SlippersBecky Lawsonpage 18 EdgesAmy J. Eadespage 19 Having ChildrenDevon Flesorpage 20 Young Black GirlKevin Lylespage 21 CatSuzanne Hornpage 22 Breakfast for OneMichelle Mitchellpage 22 A Modest ProposalBrooke Sanfordpage 23 Post MortemF. Link Rapierpage 26 Who Said I Forgot?Lynne Krausepage 27 The Corner Booth at StuckeysMaggie Kennedypage 28 The First DayDavis Brydenpage 29 DownLynne Krausepage 30 Fairie RingDevon Flesorpage 31 The LaundrymatKathy Fordpage 32 Sunday in OctoberBridget M. Howepage 32 The Kitchen WindowMaggie Kennedypage 33 UntitledChristina Maire Vitekpage 34 8th Grade Field Trip to SpringfieldMichelle Mitchellpage 34 Children of the FortiesF. Link Rapierpage 35 one winter and i was eightGary Ervinpage 35 Don\u27t we all know?Thomas B. Waltrippage 36 The TravelerMaggie Kennedypage 36 The VisitKathy Fordpage 40 CubismMaggie Kennedypage 40https://thekeep.eiu.edu/vehicle/1042/thumbnail.jp

Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia

PURPOSE A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure

Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults: The Jackson Heart Study Cohort

Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

The human brainome: network analysis identifies \u3ci\u3eHSPA2\u3c/i\u3e as a novel Alzheimer’s disease target

Our hypothesis is that changes in gene and protein expression are crucial to the development of late-onset Alzheimer’s disease. Previously we examined how DNA alleles control downstream expression of RNA transcripts and how those relationships are changed in late-onset Alzheimer’s disease. We have now examined how proteins are incorporated into networks in two separate series and evaluated our outputs in two different cell lines. Our pipeline included the following steps: (i) predicting expression quantitative trait loci; (ii) determining differential expression; (iii) analysing networks of transcript and peptide relationships; and (iv) validating effects in two separate cell lines. We performed all our analysis in two separate brain series to validate effects. Our two series included 345 samples in the first set (177 controls, 168 cases; age range 65–105; 58% female; KRONOSII cohort) and 409 samples in the replicate set (153 controls, 141 cases, 115 mild cognitive impairment; age range 66–107; 63% female; RUSH cohort). Our top target is heat shock protein family A member 2 (HSPA2), which was identified as a key driver in our two datasets. HSPA2 was validated in two cell lines, with overexpression driving further elevation of amyloid-B40 and amyloid-B42 levels in APP mutant cells, as well as significant elevation of microtubule associated protein tau and phosphorylated-tau in a modified neuroglioma line. This work further demonstrates that studying changes in gene and protein expression is crucial to understanding late onset disease and further nominates HSPA2 as a specific key regulator of late-onset Alzheimer’s disease processes

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.</p> <p>Objective</p> <p>To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).</p> <p>A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.</p> <p>Methods</p> <p>A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.</p> <p>Results</p> <p>There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).</p> <p>Conclusion</p> <p>The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.</p