Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion. METHODS: We recognized 13 patients who underwent intrathecal narcotic pump (ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation (TP + ICT) for chronic pancreatitis (CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control (using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up. RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5 (on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus (DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT. CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes

Avalanches on a conical bead pile: scaling with tuning parameters

Uniform spherical beads were used to explore the behavior of a granular system near its critical angle of repose on a conical bead pile. We found two tuning parameters that could take the system to a critical point where a simple power-law described the avalanche size distribution as predicted by self-organized criticality, which proposed that complex dynamical systems self-organize to a critical point without need for tuning. Our distributions were well described by a simple power-law with the power {\tau} = 1.5 when dropping beads slowly onto the apex of a bead pile from a small height. However, we could also move the system from the critical point using either of two tuning parameters: the height from which the beads fell onto the top of the pile or the region over which the beads struck the pile. As the drop height increased, the system did not reach the critical point yet the resulting distributions were independent of the bead mass, coefficient of friction, or coefficient of restitution. All our apex-dropping distributions for any type of bead (glass, stainless steel, zirconium) showed universality by scaling onto a common curve with {\tau} = 1.5 and {\sigma} = 1.0, where 1/{\sigma} is the power of the tuning parameter. From independent calculations using the moments of the distribution, we find values for {\tau} = 1.6 \pm 0.1 and {\sigma} = 0.91 \pm 0.15. When beads were dropped across the surface of the pile instead of solely on the apex, then the system also moved from the critical point and again the avalanche size distributions fell on a common curve when scaled similarly using the same values of {\tau} and {\sigma}. We also observed that an hcp structure on the base of the pile caused an emergent structure in the pile that had six faces with some fcc or hcp structure.Comment: 8 pages, 6 figures; submitted to Granular Matter; Reformatted into LaTeX from Word; Fixed typo in uncertainty of tau; Rearranged two paragraphs to improve flo

The Development of FVIII Inhibitor in Hispanic American Patients with Hemophilia A Critically Impacts Coagulation Potential

Background: Hemophilia A (HA) is caused by deficiencies in plasma-FVIII and heterogeneous factor-VIII-gene mutations that impair intrinsic coagulation amplification. In severe hemophilia A patients (HAPs), FVIII infusions are begun at toddlerhood to prevent hemarthrosis induced crippling. However, approximately 30% of these patients develop FVIII inhibitors. Gain-of-function mutations in the common pathway of coagulation increases coagulation potential and decreases bleeding and FVIII-utilization in HAPs which should decrease FVIII-inhibitor-risk. We identified loss-of-function mutations in this pathway which decrease coagulation-potential as they increase FVIII-inhibitor risk in HAPs. Methods: We screened Mexican-American-pedigrees of the South-Texas-Family-Study (STFS) for protein-altering-variants. Subjects were genotyped using Illumina-exome-24-chip. Protein-altering-variants were analyzed for associations with FII:C, PT, and aPTT. Linear-mixed-model-analyses was performed to estimate trait-heritability and examine single-nucleotide-variations (SNVs) for gene association. Significant associations’ p-values fell below Bonferroni-adjusted significance level. Results: Heritability-estimates for FII:C, aPTT, and PT were highly-significant with p-values of 0.49, 0.49, and 0.54 (for all, pT in the FII-gene (F2)—which encodes 543R\u3eL and has a large effect-size on each trait (for all, pT have lower FII:C levels but correspondingly prolonged aPTT and PT times. Conclusion: We hypothesize that FII-543R\u3eL (Prothrombin-RGV) likely contributes to the high-incidence of FVIII-inhibitor-development in HA-patients of Mexican-ancestry, resulting in higher risk of developing anti-tFVIII-antibodies than patients without the variant. Patients with the RGV variant are likely to bleed more which can require surgery, further increasing the development of FVIII inhibitor development

The use of sleep aids among Emergency Medicine residents: a web based survey

BACKGROUND: Sleepiness is a significant problem among residents due to chronic sleep deprivation. Recent studies have highlighted medical errors due to resident sleep deprivation. We hypothesized residents routinely use pharmacologic sleep aids to manage their sleep deprivation and reduce sleepiness. METHODS: A web-based survey of US allopathic Emergency Medicine (EM) residents was conducted during September 2004. All EM residency program directors were asked to invite their residents to participate. E-mail with reminders was used to solicit participation. Direct questions about use of alcohol and medications to facilitate sleep, and questions requesting details of sleep aids were included. RESULTS: Of 3,971 EM residents, 602 (16%) replied to the survey. Respondents were 71% male, 78% white, and mean (SD) age was 30 (4) years, which is similar to the entire EM resident population reported by the ACGME. There were 32% 1st year, 32% 2nd year, 28% 3rd year, and 8% 4th year residents. The Epworth Sleepiness Scale (ESS) showed 38% of residents were excessively sleepy (ESS 11–16) and 7% were severely sleepy (ESS>16). 46% (95 CI 42%–50%) regularly used alcohol, antihistamines, sleep adjuncts, benzodiazepines, or muscle relaxants to help them fall or stay asleep. Study limitations include low response and self-report. CONCLUSION: Even with a low response rate, sleep aid use among EM residents may be common. How this affects performance, well-being, and health remains unknown

KELT-24b: A 5MJ Planet on a 5.6day Well-aligned Orbit around the Young V = 8.3 F-star HD 93148

We present the discovery of KELT-24 b, a massive hot Jupiter orbiting a bright (V = 8.3 mag, K = 7.2 mag) young F-star with a period of 5.6 days. The host star, KELT-24 (HD 93148), has a Teff = 6509-+4950 K, a mass of M* = 1.460-+0.0590.055 Me, a radius of R* = 1.506 ± 0.022 Re, and an age of 0.78-+0.420.61 Gyr. Its planetary companion (KELT-24 b) has a radius of RP = 1.272 ± 0.021 RJ and a mass of MP = 5.18-+0.220.21 MJ, and from Doppler tomographic observations, we find that the planet’s orbit is well-aligned to its host star’s projected spin axis (l = 2.6-+3.65.1). The young age estimated for KELT-24 suggests that it only recently started to evolve from the zero-age main sequence. KELT-24 is the brightest star known to host a transiting giant planet with a period between 5 and 10 days. Although the circularization timescale is much longer than the age of the system, we do not detect a large eccentricity or significant misalignment that is expected from dynamical migration. The brightness of its host star and its moderate surface gravity make KELT-24b an intriguing target for detailed atmospheric characterization through spectroscopic emission measurements since it would bridge the current literature results that have primarily focused on lower mass hot Jupiters and a few brown dwarfs

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin