University Scholars Day

This paper discusses dissolved lithium concentrations and the spatial distribution of suicide mortality rates in Texas counties from 1980 to 1998

Bioactive growth hormone in older men and women: Its relationship to immune markers and healthspan

Objective: The consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. Design: Forty-one men and women of advanced age (men: N=16, age, 80.5±6.5years; height, 173.1±6.9cm; body mass, 81.8±13.0kg) and (women: N=25, age, 80.7±7.2years; height, 157.7±6.0cm; body mass, 68.8±17kg), were recruited for a cross-sectional study. Participants filled out PROMIS (Patient-Reported Outcomes Measurement Information System, U. S. Department of Health and Human Services) scales, undertook physical performance tests and had fasted blood samples obtained at rest for measurement of hormonal and immunology biomarkers. Results: When measured by the well-established rat tibial line GH bioassay, one half of the plasma samples (n=20) contained bioassayable GH (bGH), but the other half (n=21) failed to mount increases in tibial plate width above saline injected controls. This difference did not correlate with the age, sex or physical functionality of the plasma donor. It also did not correlate with hGH concentrations measured by immunoassay. In those cases in which bGH was detected, various hierarchical regression models predicted that GHRH, c-peptide, VEGF, NPY, IL-4 and T-regulatory lymphocytes were associated with the difference and predicted bGH. Conclusion: Results from this study suggest that the actions of bGH at the cellular level may be modified by other factors and that this may explain the lack of correlations observed in this study

The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress

The effect of GINST15, an enzyme fermented ginseng supplement, on hormonal and inflammatory responses to physical stress in humans is unknown. The purpose of this investigation was to examine the constitutive and stress-induced effects of GINST15 supplement on hypo-pituitary-adrenal (HPA) and antioxidant activity in addition to muscle damage. Ten women (age: 38.7 ± 7.8 years; height: 163.81 ± 4.4 cm; body mass 76.0 ± 11.6 kg) and nine men (age: 41.2. ± 9.7 years; height: 177.4 ± 5.3 cm; body mass: 88.5 ± 5.0 kg) participated in a double-blinded, placebo-controlled, counterbalanced within-group study. Participants completed three 14-day treatment cycles with different doses (high: 960 mg; low: 160 mg; placebo: 0 mg) separated by a 1-week washout period. At the end of treatment, physical stress was imposed with intense resistance exercise work stress. Participants provided blood at rest and various time points after exercise (immediately [IP], 30 min [30], 60 min [60], 24 h [+24HR]). Cortisol (CORT), superoxide dismutase (SOD), total glutathione, nonspecific antioxidant activity, total antioxidant power (TAP), and creatine kinase were measured. GINST15 supplementation produced stress-inducible dose-dependent reductions in circulating cortisol and increased enzymatic and nonspecific antioxidant activity. Twenty-four hours after intense exercise, a high dose GINST15, a bioactive ginsenoside metabolite, significantly reduces muscle damage and HPA responses to physical stress in humans; these effects may result from increased antioxidant expression

Nurses\u27 Alumnae Association Bulletin - Volume 17 Number 1

Alumnae Notes Committee Reports Digest of Alumnae Association Meetings Greetings from Miss Childs Greetings from the Educational Director Greetings from the President Graduation Awards - 1951 Jefferson\u27s New Hospital Addition Marriages Necrology Neurosurgery Department New Arrivals New Drugs Notes on the Cause of Leukemia Nursing Staff Saul Among the Prophets Staff Activities, 1951-1952 Students\u27 Corner The Hospital Pharmacy The Student Nurse Association of Pennsylvania White Haven and Barton Memorial Division

Formation of a rotating hole from a close limit head-on collision

Realistic black hole collisions result in a rapidly rotating Kerr hole, but simulations to date have focused on nonrotating final holes. Using a new solution of the Einstein initial value equations we present here waveforms and radiation for an axisymmetric Kerr-hole-forming collision starting from small initial separation (the ``close limit'' approximation) of two identical rotating holes. Several new features are present in the results: (i) In the limit of small separation, the waveform is linear (not quadratic) in the separation. (ii) The waveforms show damped oscillations mixing quasinormal ringing of different multipoles.Comment: 4 pages, 4 figures, submitted to PR

Validation of population-based disease simulation models: a review of concepts and methods

Abstract Background Computer simulation models are used increasingly to support public health research and policy, but questions about their quality persist. The purpose of this article is to review the principles and methods for validation of population-based disease simulation models. Methods We developed a comprehensive framework for validating population-based chronic disease simulation models and used this framework in a review of published model validation guidelines. Based on the review, we formulated a set of recommendations for gathering evidence of model credibility. Results Evidence of model credibility derives from examining: 1) the process of model development, 2) the performance of a model, and 3) the quality of decisions based on the model. Many important issues in model validation are insufficiently addressed by current guidelines. These issues include a detailed evaluation of different data sources, graphical representation of models, computer programming, model calibration, between-model comparisons, sensitivity analysis, and predictive validity. The role of external data in model validation depends on the purpose of the model (e.g., decision analysis versus prediction). More research is needed on the methods of comparing the quality of decisions based on different models. Conclusion As the role of simulation modeling in population health is increasing and models are becoming more complex, there is a need for further improvements in model validation methodology and common standards for evaluating model credibility

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS

Relationships of Physical Performance Tests to Military-relevant Tasks in Women

Purpose: This investigation sought to determine the most predictive measures of performance on a repetitive box lifting task (RBLT) and load bearing task (LBT) among 123 women (aged 23±4 years, height 165±7 cm, body mass 64±10 kg). Methods: To determine the relationship of various predictors to performance on the RBLT and LBT, multiple regression analysis was conducted on body mass, height, leg cross-sectional area, upper and lower body muscular strength, lower body explosive power, upper and lower body local muscular endurance, and aerobic capacity. Results: The mean±SD (range) number of repetitions for the RBLT was 86±23 (20-159). The mean±SD (range) time to complete the LBT was 2,054±340 seconds (1,307-3,447). The following equations were generated: RBLT (number of repetitions)=57.4 + 0.2(peak jump power) + 0.4(number of pushups in 2 minutes) + 0.15(number of repetitions during the squat endurance test) + 1.39(one repetition maximal strength boxlift (kg)) – 0.04(2-mile run time (2MR) in seconds), R=0.81; standard error of the estimate (SEE)=14; LBT (in seconds)=1,831 – 4.28(number of repetitions during the squat endurance test) + 0.95(2MR in seconds) – 13.4(body mass), R=0.73; SEE=232. Conclusions: We found that the 2MR and squat endurance test were signifi cant predictive factors for performance on both load carriage tasks. These data also imply that women’s performance in combat-related tasks can be improved with training that targets muscular strength, power, and local muscular endurance in addition to aerobic capacity

Sarcoma and the 100,000 Genomes Project: our experience and changes to practice

The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5 years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4 °C for up to 96 h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design