Study of effects of space power satellites on life support functions of the earth's magnetosphere

The effects of the Satellite Solar Power System (SSPS) on the life support functions of the earth's magnetosphere were investigated. Topics considered include: (1) thruster effluent effects on the magnetosphere; (2) biological consequences of SSPS reflected light; (3) impact on earth bound astronomy; (4) catastrophic failure and debris; (5) satellite induced processes; and (6) microwave power transmission. Several impacts are identified and recommendations for further studies are provided

Practice Models and Challenges in Teledermatology: A Study of Collective Experiences from Teledermatologists

Despite increasing practice of teledermatology in the U.S., teledermatology practice models and real-world challenges are rarely studied.The primary objective was to examine teledermatology practice models and shared challenges among teledermatologists in California, focusing on practice operations, reimbursement considerations, barriers to sustainability, and incentives. We conducted in-depth interviews with teledermatologists that practiced store-and-forward or live-interactive teledermatology from January 1, 2007 through March 30, 2011 in California.Seventeen teledermatologists from academia, private practice, health maintenance organizations, and county settings participated in the study. Among them, 76% practiced store-and-forward only, 6% practiced live-interactive only, and 18% practiced both modalities. Only 29% received structured training in teledermatology. The average number of years practicing teledermatology was 4.29 years (SD±2.81). Approximately 47% of teledermatologists served at least one Federally Qualified Health Center. Over 75% of patients seen via teledermatology were at or below 200% federal poverty level and usually lived in rural regions without dermatologist access. Practice challenges were identified in the following areas. Teledermatologists faced delays in reimbursements and non-reimbursement of teledermatology services. The primary reason for operational inefficiency was poor image quality and/or inadequate history. Costly and inefficient software platforms and lack of communication with referring providers also presented barriers.Teledermatology enables underserved populations to access specialty care. Improvements in reimbursement mechanisms, efficient technology platforms, communication with referring providers, and teledermatology training are necessary to support sustainable practices

The length dependence of the series elasticity of pig bladder smooth muscle

Strips of urinary bladder smooth muscle were subjected to a series of quick release measurements. Each measurement consisted of several releases and resets to the original length, made during one contraction. The complete length-force characteristic of series elasticity was quantified by estimating H, the amplitude of quick release necessary to reduce the active force to exactly zero, and Db, a measure for the deviation of the characteristic from a straight line. By measuring a series of contractions at increasing stretched strip lengths, the length dependence of these parameters was studied. It was found that H depends linearly on stretched strip length. On average H/length amounted to 0.04. Db decreased when strips were stretched, i.e. a straight line was more closely approximated. Both parameter dependencies support the concept of two separate elastic mechanisms, a linear true passive elasticity in series with a non-linear elasticity in the cross-bridges. For the latter, H amounts to 3.8% of the initial strip length

Deformation and Grain Growth of Low-Temperature-Sintered High-Purity Alumina

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66091/1/j.1151-2916.1990.tb06489.x.pd

The impact of nature of onset of pain and posttraumatic stress on adjustment to chronic pain and treatment outcome

Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Impact of Splenectomy on Thrombocytopenia, Chemotherapy, and Survival in Patients with Unresectable Pancreatic Cancer

Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p < 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6–27). The patients with PDAC had a median survival of 20 months (range 4–67) from the time of diagnosis and 10.6 months (range 0.6–39.8) from the time of splenectomy. Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls

Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials.</p> <p>Methods</p> <p>The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For <it>in vivo </it>studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired <it>t </it>test using GraphPad prism software.</p> <p>Results</p> <p>Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. <it>In vivo </it>testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine.</p> <p>Conclusion</p> <p>These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.</p