The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33.

Long γ-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae. They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium. Here we report observations of the unusual GRB 101225A. Its γ-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy.

Comparative quality of life in patients following abdominoperineal excision and low anterior resection for low rectal cancer.

BACKGROUND: It is widely believed that quality of life is worse after abdominoperineal excision then after low anterior resection. However, this view is not supported unequivocally. OBJECTIVE: The aim of this study was to compare quality of life in patients 1 year following low anterior resection and abdominoperineal excision for low rectal cancer. DESIGN: Data were collected prospectively on 62 patients undergoing low anterior resection (32) and abdominoperineal excision (30) for low rectal adenocarcinoma within 6 cm of the anal verge. Patients with metastatic disease were excluded. Quality of life was assessed by the use of the European Organization for Research and Treatment of Cancer's QLQ-C30 and QLQ-CR38 modules and Coloplast stoma quality-of-life questionnaire. Bowel function was assessed by using the St Mark's bowel function questionnaire. Quality of life in patients who had low anterior resection was compared with those who had abdominoperineal excision both preoperatively and 1 year after surgery. SETTINGS: This study was conducted at 3 centers in the United Kingdom and 1 center in Europe. PATIENTS: Included were consecutive patients with rectal cancer within 6 cm of the anal verge, all of whom provided written consent for participation. MAIN OUTCOME MEASURES: Mann-Whitney U test comparisons of QLQ-C30 and QLQ-CR38 module scores for patients undergoing low anterior resection and abdominoperineal excision were the main outcomes measured. RESULTS: Patients undergoing low anterior resection were younger (median age, 59.5 vs 67, p = 0.03) with higher tumors (4 vs 3, p < 0.001) and less likely to receive neoadjuvant therapy (p = 0.02). At 1 year postoperatively, global quality-of-life ratings were comparable, but patients undergoing abdominoperineal excision reported better cognitive (100 vs 83, p = 0.018) and social (100 vs 67, p = 0.012) function, and less symptomatology with respect to pain (0 vs 17, p = 0.027), sleep disturbance (0 vs 33, p = 0.013), diarrhea (0 vs 33, p = 0.017), and constipation (p = 0.021). Patients undergoing low anterior resection reported better sexual function (33 vs 0, p = 0.006), but 72% experienced a degree of fecal incontinence. LIMITATIONS: This study was limited by its relatively small sample size. CONCLUSION: Abdominoperineal excision should not be regarded as an operation that is inferior to low anterior resection in the management of low rectal cancer on the basis of quality of life alone.

Transfusion service disaster planning.

The Mayo Clinic, in Rochester, Minnesota, recently set forth a directive to develop a Mayo Emergency Incident Command System (MEICS) plan to respond to major disasters. The MEICS plan that was developed interfaces with national response plans to ensure effective communication and coordination between our institution and local, state, and federal agencies to establish a common language and communication structure. The MEICS plan addresses multiple aspects of dealing with resource needs during a crisis, including the need for blood and transfusion medicine services. The MEICS plan was developed to supplement our current local emergency preparedness procedures and provide a mechanism for responding to the escalating severity of an emergency to deal with situations of a magnitude that is outside the normal experience. A plan was developed to interface the existing Transfusion Medicine disaster plan standard operating procedures (SOP) with the institutional and Department of Laboratory Medicine (DLMP) MEICS plans. The first step in developing this interface was defining MEICS. Other major steps were defining the chain of command, developing a method for visually indicating who is "in charge," planning communication, defining the actions to be taken, assessing resource needs, developing flowcharts and updating SOPs, and developing a blood rationing team to deal with anticipated blood shortages. Several key features of the interface and updated disaster plan that were developed are calling trees for response personnel, plans for relocating leadership to alternative command centers, and action sheets to assist with resource assessment. The action sheets also provide documentation of key actions by response personnel.

The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in multiple myeloma (MM); however, factors affecting ALC-15 in MM remain unknown. We hypothesized that the dose of infused peripheral blood autograft lymphocytes (autograft absolute lymphocyte count: A-ALC) impacts ALC-15 recovery. Between 1989 and 2001, 267 consecutive MM patients underwent APHSCT. We set out to determine the correlation between A-ALC and ALC-15 and the utility of A-ALC as a marker for ALC-15 recovery. A-ALC was found to be both a strong predictor for area under curve (AUC=0.93; P=0.0001) and strongly correlated with (r(s)=0.83; P=0.0001) ALC-15 recovery. Higher infused A-ALC was significantly correlated with an ALC-15>/=500/microl. In addition, median post-transplant overall survival (OS) and time to progression (TTP) were longer in patients who received an A-ALC>/=0.5 x 10(9) lymphocytes/kg versus A-ALC <0.5 x 10(9) lymphocytes/kg (58 vs 30 months, P=0.00022; 22 vs 15 months, P<0.00012, respectively). Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM.

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

Examination of in vivo influences on bioluminescent microbial assessment of corrosion product toxicity.

The composition of ionically dissolved and precipitated corrosion products from both free corrosion of ASTM F75 Co-Cr-Mo and galvanostatic polarization of Co-Cr-Mo and F138 316L stainless steel was determined using differential pulse polarography and inductively coupled plasma atomic emission spectroscopy. A bacterial bioluminescence assay, Microtox, was used to assess the toxicity of the solid and dissolved corrosion products produced by galvanostatic polarization and the individual ions within them. The role of in vivo salinity, temperature, and protein content as modulators of corrosion product toxicity assessment was investigated empirically and mechanistically. Co-Cr-Mo products were found to be more toxic than those of 316L, and the most toxic ions were Cr6+, Ni2+, and Co2+. Ringer's solution potentiated the toxicity of the more toxic metal ions and reduced the toxicity of the less toxic ions. Using theoretical analysis in conjunction with experimental measurements, the ions in both alloys were found to interact in an antagonistic fashion. The presence of albumin was found to decrease metal toxicity, presumably by chelation.

Use of a.c. impedance methods to study the corrosion behaviour of implant alloys.

The a.c. impedance method is a very useful technique for studying the corrosion behaviour of surgical implant alloys. In this article information is presented on how to efficiently and reliably acquire and analyse experimental data through the use of Nyquist, Bode and Rre versus omega Rim plots. Also, experiments were conducted in which 316L stainless steel specimens were subjected to polarization conditions which caused pitting corrosion. The increased surface area caused by the pitting, inferred from a.c. impedance measurements of specimen capacitance, was found to be well correlated with ASTM standard methods for assessment of pitting.

Stress-enhanced ion release--the effect of static loading.

Static stresses affect the corrosion behaviour of 316L stainless steel, Ti-6AI-4V, and a Co-Cr-Mo alloy. Several corrosion parameters are modified by stress, although the changes most relevant to the clinical situation are lowering of breakdown potentials and increases in corrosion currents. AC impedance techniques to measure capacitance allowed the latter effect to be partitioned into components of true current density and true area changes. Although loading past the yield point can definitely cause stress-enhanced ion release (SEIR), it is not required. SEIR can also be caused by elastic loading. The basic mechanism for this phenomenon appears to be passive film disruption followed by slow repassivation kinetics. Polished, grit-blasted, and porous-coated surfaces were examined. The porous-coated materials seemed to be most susceptible to SEIR. If effects similar to those observed here apply to in vivo conditions, then tests on unstressed alloys in vitro could grossly underestimate ion release rates of stressed implant devices in vivo.

pH shifts and precipitation associated with metal ions in tissue culture.

Recently there has been interest in tests to assess the physiological response to surgical implant corrosion products. Both cell culturing in metal-bearing solutions and intramuscular injection of such solutions have been carried out. This paper examines the effects of the constraints of multicomponent equilibrium conditions on the characteristics of the solutions used in these biocompatibility tests. It is demonstrated that, unbuffered, they will have pH values shifted from neutral and that, in the buffered state, these solutions may contain both dissolved metal ions and insoluble hydroxides. The implications of these characteristics for the interpretation of the results of biocompatibility tests are discussed.

Evaluation of metallic and polymeric biomaterial surface energy and surface roughness characteristics for directed cell adhesion.

Directed cell adhesion remains an important goal of implant and tissue engineering technology. In this study, surface energy and surface roughness were investigated to ascertain which of these properties show more overall influence on biomaterial-cell adhesion and colonization. Jet impingement was used to quantify cellular adhesion strength. Cellular proliferation and extracellular matrix secretion were used to characterize colonization of 3T3MC fibroblasts on: HS25 (a cobalt based implant alloy, ASTM F75), 316L stainless steel, Ti-6Al4V (a titanium implant alloy), commercially pure tantalum (Ta), polytetrafluoroethylene (PTFE), silicone rubber (SR), and high-density polyethylene (HDPE). The metals exhibited a nearly five-fold greater adhesion strength than the polymeric materials tested. Generally, surface energy was proportional to cellular adhesion strength. Only polymeric materials demonstrated significant increased adhesion strength associated with increased surface roughness. Cellular adhesion on metals demonstrated a linear correlation with surface energy. Less than half as much cellular proliferation was detected on polymeric materials compared to the metals. However the polymers tested demonstrated greater than twice the amount of secreted extracellular matrix (ECM) proteins on a per cell basis than the metallic materials. Thus, surface energy may be a more important determinant of cell adhesion and proliferation, and may be more useful than surface roughness for directing cell adhesion and cell colonization onto engineered tissue scaffoldings.

Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma.

The purpose of this study was to determine the effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. We performed a retrospective review of 67 patients newly diagnosed with multiple myeloma at Mayo Clinic and treated with a single regimen prior to stem cell transplantation between January of 2000 and September of 2001. Stem cells were collected from 24 patients who received thalidomide, 200 mg/day, with dexamethasone as initial therapy before stem cell collection. These patients were compared with 43 control patients seen during the same period who had received only one previous regimen before stem cell collection and transplantation. The cumulative thalidomide dose before stem cell collection was 17 000 mg over a median of four cycles (range, 2-7 cycles). The thalidomide and control groups were not significantly different in their baseline characteristics, number of stem cells collected, time to collection, or time to engraftment of neutrophils or platelet count of 50 000/microl. Time to platelet count of 20 000/microl was delayed by a median of 4 days (P=0.008), but platelet transfusion requirements did not differ (P=0.95). We concluded that thalidomide does not substantially affect peripheral cell mobilization or engraftment.

Infused peripheral blood autograft absolute lymphocyte count correlates with day 15 absolute lymphocyte count and clinical outcome after autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in non-Hodgkin's lymphoma (NHL). Factors affecting ALC-15 remain unknown. We hypothesized that dose of infused autograft lymphocytes (A-ALC) directly impacts upon ALC-15. A total of 190 consecutive NHL patients received A-ALC between 1993 and 2001. The primary end point was correlation between A-ALC and ALC-15. A strong correlation was identified (r=0.71). A higher A-ALC was infused into patients achieving an ALC-15 > or =500/microl vs ALC-15 <500/microl (median of 0.68 x 10(9)/kg (0.04-2.21 x 10(9)/kg), vs 0.34 x 10(9)/kg (0.04-1.42 x 10(9)/kg), P<0.0001). The median follow-up for all patients was 36 months (maximum of 109 months). The A-ALC threshold was determined at 0.5 x 10(9)/kg. The median overall survival (OS) and progression-free survival (PFS) times were longer in patients who received an A-ALC >/=0.5 x 10(9)/kg vs A-ALC <0.5 x 10(9)/kg (76 vs 17 months, P<0.0001; 49 vs 10 months, P<0.0001, respectively). Multivariate analysis demonstrated A-ALC to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that ALC-15 and survival are dependent upon the dose of infused A-ALC in NHL.

Unilateral posterior arch fractures of the atlas.

Unilateral posterior arch fractures of the atlas are discussed with two clinical examples and an experimental study of their mechanism. Laboratory fracturing of posterior arches of atlas specimens with a specially adapted universal testing machine produced nonsimultaneous fractures of the two sides in four of six specimens. In three of these specimens, a complete fracture on one side was temporarily displaced because the orientation of the leverage acting on the other side changed from sagittal to oblique. The consequent increase in the effective length of the lever arm reduced the angular deformation and strain on the second side. The second fracture occurred only after additional deflection of the posterior tubercle by up to 3 mm reproduced on the second side about the same angle of deformation that had caused the first fracture. A posterior arch fracture occurring by this mechanism will remain unilateral if the deflection is arrested before failure of the second side.

Corrosion and other electrochemical aspects of biomaterials.

Metallic materials are used extensively as orthopedic implants, dental materials, sensing elements of bioelectrodes, and other applications. The electrochemical behavior of these biomaterials is of interest for a variety of reasons. The corrosion resistance of an implant material influences its functional performance and durability and is a primary factor governing biocompatibility. Among the aspects affecting biocompatibility are the amounts and forms of released corrosion products and their disposition in the body after release. Electrochemical principles are very useful for understanding the factors affecting corrosion resistance and also form the foundation for many biosensors that measure the concentration of various chemical entities (including released corrosion products and naturally occurring substances). Many electrochemical measurement techniques have been used to study biomaterials for years (e.g., polarization curve measurement), while others (such as polarography and AC impedance methods) have been applied more recently. This work focuses on four main topics. The first is the nature of the body's environment as it affects in vivo electrochemical phenomena, that is, the chemical, mechanical, biological, and bioelectrical phenomena that affect the behavior and performance of biomaterials. The second deals with methodology--the techniques used for corrosion measurement and concentration determination, the appropriate environment (laboratory, cell culture, in vivo, etc.), and experimental problems encountered. The third topic treated is the knowledge accumulated regarding the performance of implant alloys in various applications, for example, the forms of corrosion to which they are susceptible, etc. Finally, improvements that may come about in the future regarding both materials and testing methodology are considered.

Correlation of field-measured toxicity with chemical concentration and pollutant availability.

Direct field toxicity tests were performed in two Louisiana waterways, Bayous Trepagnier and St. John, on sediments containing organic/heavy metal mixtures. Our approach involved bioluminescent bacterial toxicity assays (using DeltaTox, which qualitatively identifies polluted areas, and Microtox, which quantifies toxicity). Samples were more completely analyzed in our laboratory using inductively coupled plasma atomic emission spectroscopy (ICP-AES) and gas chromatography/mass spectrometry (GC/MS). Results indicate that lead is the primary toxic metal at the sites examined, though concentrations of metals fluctuate due to spatial variation and the dynamic nature of the waterways. Polycyclic aromatic hydrocarbons (PAHs) are the most abundant group of organics measured and appear to contribute to the overall toxic response. DeltaTox located toxic hotspots where there was an average light loss of 53-100%. Toxicity results from both assays agree but are well correlated with concentration measurements only for certain sediment fractions. Overall, the DeltaTox/Microtox approach appears to be rapid and cost effective for on-site hotspot identification, and may increase understanding of hazards associated with heavy metal and organic contaminants in these waterways.

Bioaccumulation of lead in Xenopus laevis tadpoles from water and sediment.

The overall objective of this research was to monitor the uptake kinetics of lead in an amphibian model and correlate metal content with embryo development. Based upon the concentration of lead found in the water and sediment of a Louisiana swamp adjacent to a Superfund site, a controlled laboratory experiment exploring lead uptake from water and sediment by Xenopus laevis tadpoles was conducted. For 5 weeks, tadpoles were exposed to water and a simulated sediment, kaolin, spiked with 1, 5, or 10 times the concentration of lead found in field water and sediment samples. Additionally, organisms were exposed to the 5 x condition for 3 and 6 weeks. The experimental controls consisted of unexposed tadpoles and ones exposed to lead originating from water or sediment exclusively. At the end of the exposure periods, developmental data, i.e., body weight and developmental stage, were recorded, and the tadpoles were analyzed for whole body lead concentration. Lead extraction was accomplished by dry ashing, and its amount was quantified polarographically. Results showed that lead inhibited the normal development of these amphibians, in a manner that generally was more severe as exposure level increased. The hindrance of tadpole development also coincided with an increase in whole body lead concentration at higher exposures. Temporally, at the 5 x exposure concentration, the mean lead level increased with time, but this difference was not statistically significant (P<.05). Additionally, control animals exposed to lead (either in water or in sediment) showed no statistical difference with regard to weight and lead uptake, indicating that lead originating from both water and sediment is incorporated into the tadpole. The controlled laboratory experimental protocol used here is thus capable of investigating the uptake of a single metal (Pb in this case) and determining its effect on the development of tadpoles while differentiating the significance of multiple sources of exposure.

A mathematical algorithm to identify toxicity and prioritize pollutants in field sediments.

In order to evaluate sediment toxicity, a mathematical algorithm was developed to compute the toxicity of multiple component mixtures acting in an additive manner. A statistical approach was devised to determine the presence of potential interactive effects among mixture components. The algorithm uses three kinds of data to obtain an integrative approach to sediment toxicity assessment: Microtox toxicity data (EC50 values), sediment pollutant concentration measurements, and sequential extraction (SEQ) data to investigate metal partitioning. To simplify the analysis of complex mixtures using a prioritization scheme based on intrinsic toxicity and relative abundance, a toxicity index (TI) was employed as an indicator of adverse ecological impact. In general, the ranking of contaminants using the TI approach was found to be most efficient in reducing computational time, and concentrations using bioavailability data from SEQ was found to be the best theoretical predictor of the experimental mixture toxicity value. Only a few pollutants that were present at the greatest abundance were needed to provide a good approximation of the calculated EC50 found when all components were included. Not only does this substantially reduce the computational time needed to determine the EC50, it could in some cases dramatically reduce the pollutant monitoring effort required to track toxicity effectively. This approach would have substantial implications for both risk assessment and for remediation strategies, making them more efficient by focusing on the priority pollutants identified.

Titanium metal release after posterior cervical spine plate placement in a canine model.

The local tissue concentration of released titanium from Ti-6Al-4V posterior cervical spine plates in canines was determined using inductively coupled plasma atomic emission spectroscopy. The plates were also evaluated for percentage of surface area damage. The highest titanium levels (> 100 ppm dry weight) and most severe surface damage were associated with screw-plate interfaces. A model to explain the metal release mechanisms was proposed, consisting of a combination of fretting wear, diffusion through the passive oxide layer, and dissolution of this layer.

Cell adhesion to biomaterials: correlations between surface charge, surface roughness, adsorbed protein, and cell morphology.

Adhesion of cells to a biomaterial surface can be a major factor mediating its biocompatibility. In this investigation, jet impingement techniques were used to quantify strength of cellular adhesion to various material surfaces. The metals tested: HS25 (a cobalt-based alloy similar to F75), 316L stainless steel, Ti-6Al-4V, and commercially pure tantalum, exhibited nearly a fivefold increase in adhesion strength above that characteristic of the polymeric materials tested (PTFE, silicone rubber, and HDPE). The present study examines physical and biological factors that might influence fibroblast adhesion to the biomaterial surface. The relation between surface charge and cellular adhesion was investigated in a controlled manner by measuring adhesion strength over a range of charge densities. The cells showed charge and electrical potential-dependent adhesion maxima, suggesting that surface alloying for optimum adherence may be possible. In a preliminary series of experiments adsorbed serum protein layers on a series of materials of differing adherence were investigated using gel electrophoresis to assess protein composition. Analysis of adsorbed proteins revealed little difference in relative abundance or total adsorption quantity. SEM micrographs of cells on Ti-6Al-4V and silicone rubber (high and low adhesion materials, respectively) demonstrated differences in cell morphology and cell density.

Social skills training for young adolescents: symbolic and behavioral components.

The assertiveness program developed by Wise, Bundy, Bundy, and Wise (1991), which focused on the unique problems and peer interactions of young adolescents, was expanded to a 12-week program and presented to a group of 28 sixth graders. Cognitive acquisition and retention of the symbolic information was measured with a pretest, posttest, and follow-up administration of the multiple-choice tests that were designed and used in the prior study. Verbal content of assertive behavior was measured in a pretest and posttest role-play situation. When trained students were compared to a control group on the symbolic measures, a significant effect for treatment (p < or = .000); a significant effect for measures (p < or = .000); and a significant Treatment x Measure interaction (p < or = .000) were found. A comparison of means showed a significant difference between pretest vs. posttest and follow-up (p < or = .000). However, no difference between posttest and follow-up was found (p < .351). Unlike the earlier study, in which girls benefited more from training than did boys, no treatment by gender interaction was found for the cognitive measure (p < .691). Boys and girls benefited similarly in terms of the cognitive acquisition of assertiveness information from this program. However, the results did not show that these students were able to demonstrate assertiveness on the behavioral level. Results are discussed in terms of the difference between simply having stored symbolic information regarding assertive responses and recognizing contexts in which accessing the information would be appropriate. Suggestions for designing programs aimed at bringing about changes in adolescents' assertive behavior that will generalize to their lives beyond the training context are also offered.