Learning to Sew: A Student Pharmacist’s Service-Learning Experience

Karolina Grzesiak is a fourth-year professional student in the College of Pharmacy at Purdue University and will earn her Doctor of Pharmacy degree in May 2017. She was raised in Poland but has called La Porte, Indiana home for the past eight years. Craig Vargo is a 2012 pharmacy graduate working as a clinical specialist pharmacist at the James Cancer Hospital at The Ohio State University Wexner Medical Center in Columbus, Ohio

Amphoteric dissolution of two-dimensional polytriazine imide carbon nitrides in water

Crystalline two-dimensional carbon nitrides with polytriazine imide (PTI) structure are shown to act amphoterically, buffering both HCl and NaOH aqueous solutions, resulting in charged PTI layers that dissolve spontaneously in their aqueous media, particularly for the alkaline solutions. This provides a low energy, green route to their scalable solution processing. Protonation in acid is shown to occur at pyridinic nitrogens, stabilized by adjacent triazines, whereas deprotonation in base occurs primarily at basal plane NH bridges, although NH 2 edge deprotonation is competitive. We conclude that mildly acidic or basic pHs are necessary to provide sufficient net charge on the nanosheets to promote dissolution, while avoiding high ion concentrations which screen the repulsion of like-charged PTI sheets in solution. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'

Rigorous 3D change determination in Antarctic Peninsula glaciers from stereo WorldView-2 and archival aerial imagery

This paper presents detailed elevation and volume analysis of 16 individual glaciers, grouped at four locations, spread across the Antarctic Peninsula (AP). The study makes use of newly available WorldView-2 satellite stereo imagery to exploit the previously untapped value of archival stereo aerial photography. High resolution photogrammetric digital elevation models (DEMs) are derived to determine three-dimensional glacier change over an unprecedented time span of six decades with an unparalleled mean areal coverage of 82% per glacier. The use of an in-house robust surface matching algorithm ensured rigorous alignment of the DEMs to overcome inherent problems associated with processing archival photography, most notably the identification and correction of scale error in some datasets. The analysis provides insight into one of the most challenging and data-scarce areas on the planet by expanding the spatial extent north of the AP to include previously un-studied glaciers located in the South Shetland Islands. 81% of glaciers studied showed considerable loss of volume over the period of record. The mean annual mass loss for all glaciers yielded 0.24 ± 0.08 m.w.e. per year, with a maximum mass loss of up to 62 m.w.e. and frontal retreat exceeding 2.2 km for Stadium Glacier, located furthest north on Elephant Island. Observed volumetric loss was broadly, though not always, correlated with frontal retreat. The combined mass balance of all 16 glaciers yielded − 1.862 ± 0.006 Gt, which corresponds to − 0.005 mm sea level equivalent (SLE) over the 57 year observation period

Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože

Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI

Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD

Sex in basic research – Concepts in the cardiovascular field

Women and men, female and male animals and cells are biologically different, and acknowledgement of this fact is critical to advancing medicine. However, incorporating concepts of sex-specific analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug development.Research funding agencies recently approached these issues but implementation of policy changes in the scientific community is still limited probably due to deficits in concepts, knowledge and proper methodology. This expert review is based on the EUGenMed project (www.eugenmed.eu) developing a roadmap for implementing sex and gender in biomedical and health research. For sake of clarity and conciseness, examples are mainly taken from the cardiovascular field that may serve as a paradigm for others, since a significant amount of knowledge how sex and estrogen determine the manifestation of many cardiovascular diseases (CVD) has been accumulated. As main concepts for implementation of sex in basic research, the study of primary cell and animals of both sexes, the study of the influence of genetic versus hormonal factors and the analysis of sex chromosomes and sex specific statistics in genome wide association studies (GWAS) are discussed. The review also discusses methodological issues, and analyses strength, weaknesses, opportunities and threats in implementing sex-sensitive aspects into basic research

Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p&lt;0.005) and correlated with age (rho=0.39, p&lt;0.0005), CACS (rho=0.19, p&lt;0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p&lt;0.0005), 6-min walking distance (rho=−0.17, p&lt;0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p&lt;0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p&lt;0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p&lt;0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9Gs

Validation of Canopy Height Profile methodology for small-footprint full-waveform airborne LiDAR data in a discontinuous canopy environment

A Canopy Height Profile (CHP) procedure presented in Harding et al. (2001) for large footprint LiDAR data was tested in a closed canopy environment as a way of extracting vertical foliage profiles from LiDAR raw-waveform. In this study, an adaptation of this method to small-footprint data has been shown, tested and validated in an Australian sparse canopy forest at plot- and site-level. Further, the methodology itself has been enhanced by implementing a dataset-adjusted reflectance ratio calculation according to Armston et al. (2013) in the processing chain, and tested against a fixed ratio of 0.5 estimated for the laser wavelength of 1550nm. As a by-product of the methodology, effective leaf area index (LAIe) estimates were derived and compared to hemispherical photography-derived values. To assess the influence of LiDAR aggregation area size on the estimates in a sparse canopy environment, LiDAR CHPs and LAIes were generated by aggregating waveforms to plot- and site-level footprints (plot/site-aggregated) as well as in 5m grids (grid-processed). LiDAR profiles were then compared to leaf biomass field profiles generated based on field tree measurements. The correlation between field and LiDAR profiles was very high, with a mean R2 of 0.75 at plot-level and 0.86 at site-level for 55 plots and the corresponding 11 sites. Gridding had almost no impact on the correlation between LiDAR and field profiles (only marginally improvement), nor did the dataset-adjusted reflectance ratio. However, gridding and the dataset-adjusted reflectance ratio were found to improve the correlation between raw-waveform LiDAR and hemispherical photography LAIe estimates, yielding the highest correlations of 0.61 at plot-level and of 0.83 at site-level. This proved the validity of the approach and superiority of dataset-adjusted reflectance ratio of Armston et al. (2013) over a fixed ratio of 0.5 for LAIe estimation, as well as showed the adequacy of small-footprint LiDAR data for LAIe estimation in discontinuous canopy forests

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score

Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Methods and findings Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer’s Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10−5 ). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer’s Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer’s Disease Center [NIA ADC], and Alzheimer’s Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62–4.24, p = 1.0 × 10−22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10−26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran–Armitage trend test, p = 1.5 × 10−10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10−6 , and Consortium to Establish a Registry for Alzheimer’s Disease score for neuritic plaques, p = 6.8 × 10−6 ) and in vivo markers of AD neurodegeneration (ADNI, volume loss within the entorhinal cortex, p = 6.3 × 10−6 , and hippocampus, p = 7.9 × 10−5 ). Additional prospective validation of these results in non-US, non-white, and prospective community-based cohorts is necessary before clinical use. Conclusions We have developed a PHS for quantifying individual differences in age-specific genetic risk for AD. Within the cohorts studied here, polygenic architecture plays an important role in modifying AD risk beyond APOE. With thorough validation, quantification of inherited genetic variation may prove useful for stratifying AD risk and as an enrichment strategy in therapeutic trials