Citations

Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Objectives Helicopter air ambulance (HAA) of pediatric trauma patients is a life-saving intervention. Triage remains a challenge for both scene transport and interhospital transfer of injured children. We aimed to understand whether overtriage or undertriage was a feature of scene or interhospital transfer and how in or out of state transfers affected these rates. Methods Children (<18 years) who underwent trauma activation at a level I trauma center between 2011 and 2013 were identified and reviewed. Patients transported by HAA were compared with those transported by ground ambulance (GA). Results Of 399 pediatric patients (median age, 10.4 years; range, 0.1–17 years; 264 male [66%]), 71 (18%) were transported by HAA. Seventy-two percent of HAA patients went to the intensive care unit or the operating room from the trauma bay or suffered in-hospital mortality (vs 42% GA, P < 0.001). More patients were overtriaged (HAA with injury severity score [ISS] of <15) from interhospital transfers than from the scene (25% vs 3%, P = 0.002). Undertriage (GA with ISS >15) was acceptable at 5% from the scene and 14% from interhospital transfers (P = 0.08). Overtriage of patients with ISS less than 15 to HAA was significantly lower from in-state hospitals (22%) than out-of-state hospitals (45%) (P = 0.02). Undertriage of patients with ISS greater than 15 to GA was also lower from in-state hospitals (20%) versus out-of-state hospitals (38%) (P = 0.03). Conclusions Triage of pediatric trauma patients to HAA remains difficult. There remains potential for improvement, particularly as regards interhospital HAA overtriage, but well developed transfer protocols (such in-state protocols) may help.

Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery.

Abstract Yoga is increasing in popularity in the United States and across the globe. However, most yoga programs are provided outside the worksite; although many companies offer worksite wellness programs, at present there is limited documentation regarding the potential benefits of participating in a worksite yoga program. Therefore, the purpose of this project was to examine the potential effect of a worksite yoga program on self-acceptance, quality of life, and perceived stress. A prospective cohort pilot study that examined a structured worksite yoga program was designed and tailored to individuals new to yoga. The 8-week Yoga Foundations program was conducted at an academic medical center's worksite wellness center with 86 subjects. Outcome measures were the 36-item Self-Acceptance Scale; a six-item quality-of-life measure that assesses overall, social, mental, physical, emotional, and spiritual well-being; and the ten-item Perceived Stress Scale. Participants demonstrated significant improvement in their overall self-acceptance (p &lt; 0.001), quality of life (p &lt; 0.001), and perceived stress (p &lt; 0.001) levels. They also highly rated the yoga instructors and the weekly format of the program. Participation in a Yoga Foundations program was associated with improvements in self-acceptance, quality of life and stress levels in worksite wellness center members. Future studies should use randomized designs and examine other wellness domains to learn more about the potential benefits of worksite yoga programs.

Abstract Background Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered. Methods We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [ 13 C]‐octanoic acid and off axis‐ integrated cavity output spectroscopy ( OA ‐ ICOS ). Stretched gamma variate and 2‐component stretched gamma variate models fit measured breath excretion data. Key Results These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin‐induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two‐phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two‐phase gastric emptying curves. A greater proportion of two‐phase gastric emptying was induced in Balb/c mice with the administration of PYY (8‐80 nmol) 60 min following meal ingestion. Conclusions and Inferences Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two‐phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.

Objectives To (1) test whether patient attitudes toward intake forms at three Midwestern outpatient clinics are significantly more negative among those who are asked to complete SOGI questions versus those who are not; and (2) gain an in‐depth understanding of patient concerns about SOGI questions. Study Setting Data were collected between 6/29/2015 and 2/29/2016 from new patients ( N = 491) who presented at three outpatient clinics in a large academic medical center. This study was originally a quality improvement project, and later, institutional review board approval was obtained for secondary data analysis. Study Design Two‐stage mixed‐methods study. (1) Experimental: New patients at three sites were randomly assigned to complete either routine intake forms (control) or routine intake forms with SOGI questions (experimental); and (2) qualitative: interviews with patients who responded negatively to SOGI questions. Principal Findings There were no significant differences in patient attitudes between experimental and control groups ( p > .05). Of those who received SOGI questions, only 3 percent reported being distressed, upset, or offended by the SOGI questions. Conclusions Collection of SOGI data as a part of the routine clinical patient intake process is not distressing to 97 percent of patients who are heterosexual, cisgender, and older than 50 years.

Abstract BACKGROUND The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE To examine these uncertainties. METHODS NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method. RESULTS A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings ( P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire ( P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [ P = .048], Trail Making Test Part A [ P = .035], and Controlled Oral Word Association [ P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.