Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer: Treatment outcome outside clinical trials

Background: Phase II trials of neoadjuvant treatment in UICC-TNM stageII and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity. Patients and methods: Retrospective evaluation of 34 patients treated from 2005-2008 outside clinical trials (CTR) with neoadjuvant irradiation (45-50.4Gy) and simultaneous capecitabine 825mg/m2 b.i.d. on days 1-14 and 22-35 and oxaliplatin 50mg/m2 on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000mg/m2 b.i.d. on days 1-14 and oxaliplatin 130mg/m2 on day 1 (XELOX) prior to simultaneous chemoradiotherapy. Results: UICC-TNM stage regression was observed in 60% (n = 20). Dworak's regression grades 3 and 4 were achieved in 18.2% (n = 6) and 15.1% (n = 5) of the patients. Sphincter-preserving surgery was performed in 53% (n = 8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1patient had progressive disease and 5patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n = 6) and perianal pain 9% (n = 3). Nevertheless, severe cardiac events (n = 2), severe electrolyte disturbances (n = 2), and syncopes (n = 2) were observed as well. Conclusion: Treatment efficacy and common toxicity are similar to the reports of phaseI/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CT

Phenytoin crystal growth rates in the presence of phosphate and chloride ions

Phenytoin crystal growth kinetics have been measured as a function of supersaturation in pH 2.2 phosphoric acid and pH 2.2 hydrochloric acid solutions. Two different methods were used for the kinetic analysis. The first involved a zone-sensing device which provided an analysis of the distribution of crystals in a batch crystallizer. Crystal growth rates were calculated from the increase in the size of the distribution with time. In the second method, growth rates were evaluated from the change in size with time of individual crystals observed under an inverted microscope. The results from each method compare favorably. The use of both techniques provides an excellent opportunity to exploit the strengths of each: an average growth rate from a population of crystals from batch crystallization and insight into the effect of growth on the morphology of the crystals from the individual crystal measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29867/1/0000215.pd

The mechanism of phenytoin crystal growth

Phenytoin crystal growth kinetics have been measured as a function of pH, supersaturation and temperature in phosphate buffer. Incorporation of growth units into the crystal lattice was not influenced by diffusion from the bulk to the solid surface. Thus, the rate limiting step for phenytoin growth is surface integration. Phenytoin crystal growth is via a screw-dislocation mechanism; this mechanism explains the observed dependence of growth rate on supersaturation and the increase in growth rate with pH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30628/1/0000269.pd

Assessing Change in Student Critical Thinking for Introduction to Sociology Classes

Although there is widespread agreement among academics that critical thinking is an important component to the college classroom, there is little empirical evidence to verify that it is being taught in courses. Using four sections of introductory sociology, we developed an experimental design using pretests and posttests to assess students’ critical thinking skills. Controlling for grade point average, cumulative credit hours completed, gender, race/ethnicity, socioeconomic status, instructor, and initial levels of critical thinking, being in the experimental group had a statistically significant impact on critical thinking at the end of the semester. Thus, inclusion of writing assignments and classroom discussion designed to enhance creative thought processes for the experimental group helped students improve from one-dimensional thinking toward more multistructural analysis

A possible mechanism for cold denaturation of proteins at high pressure

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.Comment: 4 pages for double column and single space. 3 figures Added references Changed conten

Interrater reliability of the mind map assessment rubric in a cohort of medical students

<p>Abstract</p> <p>Background</p> <p>Learning strategies are thinking tools that students can use to actively acquire information. Examples of learning strategies include mnemonics, charts, and maps. One strategy that may help students master the tsunami of information presented in medical school is the mind map learning strategy. Currently, there is no valid and reliable rubric to grade mind maps and this may contribute to their underutilization in medicine. Because concept maps and mind maps engage learners similarly at a metacognitive level, a valid and reliable concept map assessment scoring system was adapted to form the mind map assessment rubric (MMAR). The MMAR can assess mind map depth based upon concept-links, cross-links, hierarchies, examples, pictures, and colors. The purpose of this study was to examine interrater reliability of the MMAR.</p> <p>Methods</p> <p>This exploratory study was conducted at a US medical school as part of a larger investigation on learning strategies. Sixty-six (<it>N </it>= 66) first-year medical students were given a 394-word text passage followed by a 30-minute presentation on mind mapping. After the presentation, subjects were again given the text passage and instructed to create mind maps based upon the passage. The mind maps were collected and independently scored using the MMAR by 3 examiners. Interrater reliability was measured using the intraclass correlation coefficient (<it>ICC</it>) statistic. Statistics were calculated using SPSS version 12.0 (Chicago, IL).</p> <p>Results</p> <p>Analysis of the mind maps revealed the following: concept-links <it>ICC </it>= .05 (95% CI, -.42 to .38), cross-links <it>ICC </it>= .58 (95% CI, .37 to .73), hierarchies <it>ICC </it>= .23 (95% CI, -.15 to .50), examples <it>ICC </it>= .53 (95% CI, .29 to .69), pictures <it>ICC </it>= .86 (95% CI, .79 to .91), colors <it>ICC </it>= .73 (95% CI, .59 to .82), and total score <it>ICC </it>= .86 (95% CI, .79 to .91).</p> <p>Conclusion</p> <p>The high <it>ICC </it>value for total mind map score indicates strong MMAR interrater reliability. Pictures and colors demonstrated moderate to strong interrater reliability. We conclude that the MMAR may be a valid and reliable tool to assess mind maps in medicine. However, further research on the validity and reliability of the MMAR is necessary.</p

Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis

BACKGROUND:Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS:Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-beta) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months -2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-beta comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-beta comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-beta comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-beta comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE:Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-beta, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION:ClinicalTrials.gov NCT00616187

Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS

Background Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods MOG35-55 induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results EAE disease course was slightly attenuated in male apoE-deficient (apoE −/− ) mice compared to wildtype mice (cumulative median score: apoE −/−  = 2 [IQR 0.0–4.5]; wildtype = 4 [IQR 1.0–5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE −/− mice compared to wildtype mice (cumulative median score: apoE −/−  = 3 [IQR 2.0–4.5]; wildtype = 3 [IQR 0.0–4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease