1 Construction of a 12 ” Cyclotron

Our chapter proposes to design and construct a 12 ” cyclotron. The design and construction process will be split over multiple semesters to offset costs and allow more students the opportunity to participate. The final product will be a fixture of our physics department for future undergraduate research, education, and outreach. 3 Statement of the Activity: Background and Relation to the Clemson SPS Chapter Objectives: The cyclotron was one of the major workhorses of atomic physics in the mid-twentieth century and is still used in medicine due to its high ion energy relative to its size. Because of the spherical path it accelerates ions along, a 9 ” cyclotron can obtain maximum ion energies of 184 keV or more and a 12 ” can reach 800 keV [1]. Furthermore, a very barebones 6 ” cyclotron was able to be built from scratch for under $1000 using hand-made or second-hand components [2], showing that such an undertaking is possible on a limited budget. The Clemson University physics department has a strong departmental background in atmospheric physics, astrophysics, and quantum physics but fewer opportunities in particle or accelerator physics. As such, the Clemson University chapter of the Society of Physics Student

What to do with diabetes therapies when HbA1c lowering is inadequate:add, switch, or continue? A MASTERMIND study

This is the author accepted manuscript. The final version is available from BioMed Central via the DOI in this record.Background: It is unclear what to do when people with type 2 diabetes have had no or a limited glycemic response to a recently introduced medication. Intra-individual HbA1c variability can obscure true response. Some guidelines suggest stopping apparently ineffective therapy, but no studies have addressed this issue. Methods: In a retrospective cohort analysis using the UK Clinical Practice Research Datalink (CPRD), we assessed the outcome of 55,530 patients with type 2 diabetes starting their second or third non-insulin glucose lowering medication, with a baseline HbA1c >58mmol/mol (7.5%). For those with no HbA1c improvement or a limited response at 6 months (HbA1c fall <5.5mmol/mol [0.5%]) we compared HbA1c 12 months later in those who continued their treatment unchanged, switched to new treatment, or added new treatment. Results: An increase or a limited reduction in HbA1c was common, occurring in 21.9% (12,168/55,230), who had a mean HbA1c increase of 2.5mmol/mol (0.2%). After this limited response, continuing therapy was more frequent (n=9,308; 74%) than switching (n=1,177; 9%) or adding (n=2,163; 17%). Twelve months later, in those who switched medication HbA1c fell (-6.8mmol/mol [-0.6%], 95%CI -7.7, -6.0) only slightly more than those who continued unchanged (-5.1 mmol/mol [-0.5%], 95%CI -5.5, -4.8). Adding another new therapy was associated with a substantially better reduction (-12.4mmol/mol [-1.1%], 95%CI -13.1, -11.7). Propensity score matched subgroups demonstrated similar results. Conclusions: Where glucose lowering therapy does not appear effective on initial HbA1c testing, changing agents does not improve glycemic control. The initial agent should be continued with another therapy added.Medical Research Council (MRC)National Institute for Health Research (NIHR

Adherence to oral glucose-lowering therapies and associations with 1-year HbA_1c:A retrospective cohort analysis in a large primary care database

JOURNAL ARTICLEOBJECTIVE: The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS: Data were extracted for patients treated between 2004 and 2014 who were newly-prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase-4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS: In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4mmmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS: Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.A.J.F. and R.R.H. are National Institute for Health Research (NIHR) Senior Investigators and receive additional support from the Oxford NIHR Biomedical Research Centre. M.N.W. was supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). E.R.P. holds a Wellcome Trust New Investigator award. The MASTERMIND consortium is funded by the U.K. Medical Research Council MR-K005707-1. The funder of the trial had no role in study design, data collection, data analysis, data interpretation, or writing of the report

Maximal aerobic and anaerobic power generation in large crocodiles versus mammals: implications for dinosaur gigantothermy

Inertial homeothermy, the maintenance of a relatively constant body temperature that occurs simply because of large size, is often applied to large dinosaurs. Moreover, biophysical modelling and actual measurements show that large crocodiles can behaviourally achieve body temperatures above 30°C. Therefore it is possible that some dinosaurs could achieve high and stable body temperatures without the high energy cost of typical endotherms. However it is not known whether an ectothermic dinosaur could produce the equivalent amount of muscular power as an endothermic one. To address this question, this study analyses maximal power output from measured aerobic and anaerobic metabolism in burst exercising estuarine crocodiles, Crocodylus porosus, weighing up to 200 kg. These results are compared with similar data from endothermic mammals. A 1 kg crocodile at 30°C produces about 16 watts from aerobic and anaerobic energy sources during the first 10% of exhaustive activity, which is 57% of that expected for a similarly sized mammal. A 200 kg crocodile produces about 400 watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy source, used only in the first seconds of exercise and of similar concentrations in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power for exercise, but also the endurance, that are evident in endothermic mammals. Despite the ability to achieve high and fairly constant body temperatures, therefore, large, ectothermic, crocodile-like dinosaurs would have been competitively inferior to endothermic, mammal-like dinosaurs with high aerobic power. Endothermy in dinosaurs is likely to explain their dominance over mammals in terrestrial ecosystems throughout the Mesozoic.Roger S. Seymou

FISH as an effective diagnostic tool for the management of challenging melanocytic lesions

<p>Abstract</p> <p>Background</p> <p>The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions.</p> <p>Methods</p> <p>A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens.</p> <p>Results</p> <p>Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively.</p> <p>Conclusions</p> <p>Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.</p

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Spectral morphometric characterization of breast carcinoma cells

The spectral morphometric characteristics of standard haematoxylin and eosin breast carcinoma specimens were evaluated by light microscopy combined with a spectral imaging system. Light intensity at each wavelength in the range of 450–800 nm was recorded for 104 pixels from each field and represented as transmitted light spectra. A library of six characteristic spectra served to scan the cells and reconstruct new images depicting the nuclear area occupied by each spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular carcinoma were examined; nine of the infiltrating ductal carcinoma and three of the lobular carcinoma showed an in situ component. The spectral morphometric analysis revealed a correlation between specific patterns of spectra and different groups of breast carcinoma cells. The most consistent result was that lobular carcinoma cells of in situ and infiltrating components from all patients showed a similar spectral pattern, whereas ductal carcinoma cells displayed spectral variety. Comparison of the in situ and the infiltrating ductal solid, cribriform and comedo carcinoma cells from the same patient revealed a strong similarity of the spectral elements and their relative distribution in the nucleus. The spectrum designated as number 5 in the library incorporated more than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in 13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2 appeared in all infiltrating ductal cells examined and in none of the lobular cells. These results indicate that spectrum number 5 is related to infiltrating lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating ductal carcinoma cells. Spectral similarity mapping of central necrotic regions of comedo type in situ carcinoma revealed nuclear fragmentation into defined segments composed of highly condensed chromatin. We conclude that the spectral morphometric features found for lobular and ductal cell populations may serve future automated histological diagnostics. © 1999 Cancer Research Campaig

Is there a role of statins in the prevention of aortic biological prostheses degeneration

It has been recently observed that statins might slow the progression of aortic stenosis or sclerosis. Preliminary reports suggested a similar positive effect in reducing the degeneration of aortic valve bioprostheses even though this hypothesis should be further proven and supported by new data. In this review the present evidences of the possible effects of statins in this field are discussed

Osteological and Soft-Tissue Evidence for Pneumatization in the Cervical Column of the Ostrich (Struthio camelus) and Observations on the Vertebral Columns of Non-Volant, Semi-Volant and Semi-Aquatic Birds

© 2015 Apostolaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article