Vitamin D Levels in Patients with Colorectal Cancer and Matched Household Members.

BackgroundVitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients.MethodsThirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/- 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise.ResultsMedian serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P>0.05). Household members were more likely than CRC patients to be overweight and to exercise more.ConclusionsVitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.

BackgroundCTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.MethodsWe used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.ResultsWhile melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p<0.001 vs r=-0.59, p=0.02).Trial registration numbersNCT00064129; NCT01363206

Pengaruhmodel Pembelajaran Vak (Visual, Auditori, Kinestetik) Terhadap Kemampuan Menulis Puisi Oleh Siswa Kelas VIII SMP N. 2 Porsea Tahun Pembelajaran 2012/2013

This study aimed to clarify the effect of the learning model VAK (Visual, Auditory,Kinesthetic) the ability to write poetry by the students of class VIII SMP N.2 PorseaLearning Year 2012/2013. The population of this research is all eighth grade studentsas junior N.2 Porsea 266 people. Samples were taken at random as many as 30people.The method used in this study is an experimental method. The instrument usedis the argument essay writing test. The average value of post-test is 75.50, while forthe pre-test is is 67.1. Thus, it can be said that the average value of students\u27 ability towrite poetry after treatment (post-test) higher than before treatment (pre-test).Hypothesis testing is done by using the test "t". Test hypotheses derived from thecalculation of t = 2.95, then consulted with the table t at 5% significance level = 2.04.Since t = 2.95> t = 2.04 nil then the hypothesis (H) is rejected. It is proved that thelearning model VAK (Visual, Auditory, Kinesthetic) affects the ability to writepoetry class VIII SMP Porsea N.2

Enhancing Grant-Writing Expertise in BUILD Institutions: Building Infrastructure Leading to Diversity

Background The lack of race/ethnic and gender diversity in grants funded by the National Institutes of Health (NIH) is a persistent challenge related to career advancement and the quality and relevance of health research. We describe pilot programs at nine institutions supported by the NIH-sponsored Building Infrastructure Leading to Diversity (BUILD) program aimed at increasing diversity in biomedical research. Methods We collected data from the 2016–2017 Higher Education Research Institute survey of faculty and NIH progress reports for the first four years of the program (2015–2018). We then conducted descriptive analyses of data from the nine BUILD institutions that had collected data and evaluated which activities were associated with research productivity. We used Poisson regression and rate ratios of the numbers of BUILD pilots funded, students included, abstracts, presentations, publications, and submitted and funded grant proposals. Results Teaching workshops were associated with more abstracts (RR 4.04, 95% CI 2.21–8.09). Workshops on grant writing were associated with more publications (RR 2.64, 95% CI 1.64–4.34) and marginally with marginally more presentations. Incentives to develop courses were associated with more abstracts published (RR 4.33, 95% CI 2.56–7.75). Workshops on research skills and other incentives were not associated with any positive effects. Conclusions Pilot interventions show promise in supporting diversity in NIH-level research. Longitudinal modeling that considers time lags in career development in moving from project development to grants submissions can provide more direction for future diversity pilot interventions

Kata Ganti Orang Dalam Bahasa Inggris Dan Bahasa Selaru (Suatu Analisis Kontrastif)

This research attempts to identify and classify personal pronouns in English and Selaru language. The data are taken from interviewing some informants (native speakers) who was born in Selaru and understand the language and can interact effectively. The identified data are analyzed according to the concept of Bloomfield and then contrast them by using Lado\u27s concept. In analyzing the data, the writer uses descriptive method. The problems of this research ore focused on what are the personal pronouns in terms of form and function in English and Selaru language and what are the similarities and differences of personal pronouns in terms of form and function in English and Selaru language. The aims of the research are to identify and classify personal pronouns in English and Selaru language and to find out the similarities as well as dissimilarities of personal pronouns in both languages in terms of form and function. The results of this research shows that English and Selaru language has similarities and dissimilarities. Similarities in English and Selaru language which has the form of the first person, second, third, both singular and plural and dissimilarities in English and Selaru language namely: in English has object, possessive pronoun and third person singular neutral,whereas in selaru language not found

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies

Background CTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.Methods We used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman’s rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.Results While melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=−0.81, p<0.001 vs r=−0.59, p=0.02).Trial registration numbers NCT00064129; NCT01363206

Longitudinal Comparison of Patient-Level Outcomes and Costs Across Prostate Cancer Treatments With Urinary Problems.

Prostate cancer (PCa) is the leading cancer in men in the United States. This study evaluated direct costs of treating urinary problems after PCa treatments and determined predictors of long-term costs for urinary problems. Data from the Cancer of Prostate Strategic Urologic Research Endeavor registry was analyzed for this study. Annual treatment costs for urinary problems for up to 14 years were compared among different primary PCa treatments, which included radical prostatectomy, external beam radiation therapy, brachytherapy, and watchful waiting. A multivariate generalized estimating equation (GEE) model with bootstrapping was estimated to identify the predictors associated with treatment costs for urinary problems. A total of 3,062 eligible patients were identified with a mean age of 65 years at diagnosis. Mean annual treatment cost for urinary problems across all patients with PCa was $118/patient. Those greater than 74 years old had the highest cost ($238/patient). Mean annual cost for urinary problems among only those with urinary problems was $432. Multivariate regression showed patients undergoing radical prostatectomy had significantly lower (-63%, p = .01) costs for urinary problems than those treated with watchful waiting. This study helps to understand the importance of treating urinary problems associated with different PCa treatments and highlights their medical care costs. The pattern of treatment costs for urinary problems across all PCa treatments suggests that clinicians need to offer treatment for urinary problems to all PCa patients over longer time periods, even to those choosing watchful waiting