Establishing Research Competitiveness in Biophysical Sciences in Maine

The Maine EPSCoR Research Infrastructure Improvement award is designed to enhance Maine\u27s competitiveness in molecular biophysical sciences through a partnership between the University of Maine and Maine\u27s non-profit research organizations. The proposed Biophysical Sciences Institute brings together University of Maine faculty in physics, chemistry, biology, mathematics, and spatial engineering, with biomedical researchers at the Jackson Laboratory and Maine Medical Center Research Institute. Maine EPSCoR proposes to hire additional tenure-track faculty in the fields of biophysics and advanced optics, biochemistry, structural biology, applied mathematics, computer science, image analysis and visualization, and material science. The new and existing investigators will form research teams to develop new measurement techniques, new sensors, and innovative approaches to data processing and interpretation in intracellular structures and dynamics, functional materials as a means to manipulate cellular reactions, and biocomputing. In addition to establishing the institute, Maine EPSCoR will integrate research and education through improvements to graduate training

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Statements of Agreement From the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting Held in Pittsburgh, October 15-16, 2015

Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment

Genetic characterization of large parathyroid adenomas

In this study, we genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated in our institution during 2005–2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (P<0.001). Further analysis of 21 LPTAs revealed low MIB1 proliferation index (0.1–1.5%), MEN1 mutations in five cases, and one HRPT2 (CDC73) mutation. Total or partial loss of parafibromin expression was observed in ten tumors, two of which also showed loss of APC expression. Using array CGH, we demonstrated recurrent copy number alterations most frequently involving loss in 1p (29%), gain in 5 (38%), and loss in 11q (33%). Totally, 21 minimal overlapping regions were defined for losses in 1p, 7q, 9p, 11, and 15q and gains in 3q, 5, 7p, 8p, 16q, 17p, and 19q. In addition, 12 tumors showed gross alterations of entire or almost entire chromosomes most frequently gain of 5 and loss of chromosome 11. While gain of 5 was the most frequent alteration observed in LPTAs, it was only detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A significant positive correlation was observed between parathyroid hormone level and total copy number gain (r=0.48, P=0.031). These results support that LPTAs represent a group of patients with pronounced parathyroid hyperfunction and associated with specific genomic features

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Electrochemical synthesis of electroactive polymers for drugrelease for bio scaffolds.

Stem cell based therapy has the potential to treat several severe diseases; Parkinson’s disease is one well- known example. Transplantation of stem cell derived cells into animal models is unfortunately often associated with tumour formation or- uncontrolled growth of the transplanted cells. One strategy to suppress this tumour formation might be to induce differentiation of these cells, which in turn would prevent them from dividing.   Neuroblastoma tumors are known to demonstrate the complete transition from an undifferentiated state to a completely harmful, differentiated appearance and derived cells can be used as a model for cell differentiation and tumor suppression.   In this Master Thesis’s the conducting polymers PEDOT and PPy, that upon formation can be doped with biologically active compounds which in- turn can be released in a controlled manner through electrical stimulation, were formed together with various drugs (e.g. Methotrexate and Mycophenolic Acid), here shown to have effect on Neuroblastoma cells. Neuroblastoma- derived cell line SH- SY5Y was used as a model system for neuronal differentiation and tumour inhibition. Release profiles of neuroblastoma active drugs following electrical stimulation were evaluated and the effects from electrochemical processes on simultaneously growing SH- SY5Y cells were investigated.   The methods to deposit and release the drugs were based on electropolymerization and electrochemically controlled release, respectively. Controlled release of various drugs and compounds was monitored using Vis- and UV- spectroscopy and on some occasions using HPLC.   The electrochemically controlled release of a biologically inactive compound that can be used as a negative control for electrochemical release in future experiments was shown and that resulting electrochemical processes have negative effects on neuroblastoma cell growth

Developing an Initial Set of Quality Indicators for Chiropractic Care: A Scoping Review

The objective of this project is to perform a scoping review of clinical guidelines, best practice publications, quality standards, and other related literature to develop a preliminary set of quality indicators for chiropractic care, to identify gaps, and to inform future research

Modeling of free fatty acid dynamics : insulin and nicotinic acid resistance under acute and chronic treatments

Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc-FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework. We also developed a new turnover model that describes the adaptation seen in plasma FFA concentrations in lean Sprague-Dawley and obese Zucker rats following acute and chronic NiAc exposure. The adaptive mechanisms within the system were described using integral control systems and dynamic efficacies in the traditional [Formula: see text] model. Insulin was incorporated in parallel with NiAc as the main endogenous co-variate of FFA dynamics. The model captured profound insulin resistance and complete drug resistance in obese rats. The efficacy of NiAc as an inhibitor of FFA release went from 1 to approximately 0 during sustained exposure in obese rats. The potency of NiAc as an inhibitor of insulin and of FFA release was estimated to be 0.338 and 0.436 [Formula: see text], respectively, in obese rats. A range of dosing regimens was analyzed and predictions made for optimizing NiAc delivery to minimize FFA exposure. Given the exposure levels of the experiments, the importance of washout periods in-between NiAc infusions was illustrated. The washout periods should be [Formula: see text]2 h longer than the infusions in order to optimize 24 h lowering of FFA in rats. However, the predicted concentration-response relationships suggests that higher AUC reductions might be attained at lower NiAc exposures