The CXCL13 Index as a Predictive Biomarker for Activity in Clinically Isolated Syndrome.

Multiple sclerosis (MS) is a clinically heterogenous disease. Currently, we cannot identify patients with more active disease who may potentially benefit from earlier interventions. Previous data from our lab identified the CXCL13 index (ICXCL13), a measure of intrathecal production of CXCL13, as a potential biomarker to predict future disease activity in MS patients two years after diagnosis. Patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) underwent a lumbar puncture and blood draw, and the ICXCL13 was determined. They were then followed for at least 5 years for MS activity. Patients with high ICXCL13 were more likely to convert to clinically definite MS (82.4%) compared to those with low ICXCL13 (10.0%). The data presented below demonstrate that this predictive ability holds true in CIS and RIS patients, and for at least five years compared to our initial two-year follow-up study. These data support the concept that ICXCL13 has the potential to be used to guide immunomodulatory therapy in MS.

Distribution and Evolution of Fukushima Dai-ichi derived 137Cs, 90Sr, and 129I in Surface Seawater off the Coast of Japan.

The Fukushima Dai-ichi Nuclear Power Plants (FDNPPs) accident in 2011 led to an unprecedented release of radionuclides into the environment. Particularly important are 90Sr and 137Cs due to their known health detriments and long half-lives (T1/2 ≈ 30 y) relative to ecological systems. These radionuclides can be combined with the longer-lived 129I (T1/2 = 15.7 My) to trace hydrologic, atmospheric, oceanic, and geochemical processes. This study seeks to evaluate 137Cs, 90Sr, and 129I concentrations in seawater off the coast of Japan, reconcile the sources of contaminated waters, and assess the application of 137Cs/90Sr, 129I/137Cs, and 129I/90Sr as oceanic tracers. We present new data from October 2015 and November 2016 off the coast of Japan, with observed concentrations reaching up to 198 ± 4 Bq·m-3 for 137Cs, 9.1 ± 0.7 Bq·m-3 for 90Sr, and (114 ± 2) × 10-5 Bq·m-3 for 129I. The utilization of activity ratios suggests a variety of sources, including sporadic and independent releases of radiocontaminants. Though overall concentrations are decreasing, concentrations are still elevated compared to pre-accident levels. In addition, Japan's Environment Minister has suggested that stored water from the FDNPPs may be released into the environment and thus continued efforts to understand the fate and distribution of these radionuclides is warranted.

Patients with lower extremity dialysis access have poor primary patency and survival.

OBJECTIVE: Lower extremity arteriovenous (AV) access is an alternative when upper extremity access options have been exhausted. Our goal was to assess short- and medium-term outcomes of lower extremity hemodialysis access. METHODS: The Vascular Quality Initiative was reviewed for all lower extremity AV hemodialysis cases. Patient and case details were recorded. Multivariable analysis was used to analyze outcomes. RESULTS: We identified 463 lower extremity AV access cases in the VQI registry. There were 56 AVF (12.1%) and 407 AVG (87.9%). The mean age was 56 ± 15 years, 46.9% were male, and 40.7% were Caucasian. The majority (90%) had a previous upper extremity AV access and 25.4% had a prior lower extremity access. More than one-half (57.9%) had a tunneled line at the time of the procedure. Patients undergoing an AVF vs AVG creation were younger, more often ambulatory, and less often with peripheral arterial disease. For AVF, the superficial femoral artery was more often used for access inflow (76.8% vs 49.4%; P < .001), compared with AVG, and there was no difference in using femoral vein as the main outflow (78.6% vs 82.6%; P = .466). For AVF, compared with AVG, there was no difference in wound infection (12.5% vs 9.6%; P = .571), ischemic steal (5% vs 2.2%; P = .273), or leg swelling (2.5% vs 3.3%; P = .99) at 6 months. Kaplan-Meier analysis of the overall cohort showed that freedom from loss of primary patency at 6 months was 52.9%, freedom from any reintervention at 6 months was 75.3%, and the 1-year survival was 81.9%. Survival at 5 years was 65.5%. Multivariable analysis showed no significant association of access type (AVF vs AVG) with primary patency loss or death (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.36-1.5; P = .4), any reintervention or death (HR, 1.65; 95% CI, 0.82-3.33; P = .163), or mortality (HR, 1.94; 95% CI, 0.71-5.33; P = .197). Factors independently associated with primary patency loss or death included peripheral arterial disease (HR, 1.6; 95% CI, 1.06-2.42; P = .03) and obesity (HR, 1.5; 95% CI, 1.1-2.05; P = .01). Any reintervention or death was associated with obesity (HR, 1.67; 95% CI, 1.09-2.56; P = .015). Mortality was associated with congestive heart failure (HR, 1.82; 95% CI, 1.13-2.94; P = .015) and white race (HR, 1.71; 95% CI, 1.08-2.73; P = .023). CONCLUSIONS: In our contemporary multicenter analysis, patients undergoing lower extremity AV access creation have low primary access patency and almost 20% mortality at 1 year. These results should be considered when suggesting a lower extremity dialysis access, as well as other dialysis alternatives when available.

Preoperative Antiplatelet and Statin Use Does Not Affect Outcomes after Carotid Endarterectomy.

BACKGROUND: The use of statin and antiplatelet medications has been advocated in patients with cerebrovascular disease as primary medical therapy and as an adjunct to carotid endarterectomy (CEA). Our goal was to assess the prevalence of preoperative statin and antiplatelet use and its effect on perioperative outcomes after CEA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program targeted CEA database was queried for patients undergoing CEA between 2011 and 2014. Multivariable analysis was used to assess the effect of preoperative statin and antiplatelet use on CEA. RESULTS: There were 13,521 CEAs identified. The average age was 71 years, and 61.5% were male. More than half of patients (57.9%) were asymptomatic. Preoperative statin use was seen in 80.5% of patients, and antiplatelet use was seen in 89.3% of patients. Statin use was more common in patients with higher body mass index, independent functional status, diabetes, hypertension, bleeding disorders or anticoagulation, nonsmokers, and asymptomatic patients (P < 0.05). On univariate analysis, statin use was not associated with postoperative myocardial infarction (MI) (1.9% vs. 1.4%, P = 0.085), stroke (1.8% vs. 1.9%, P = 0.55), transient ischemic attack (TIA) (0.9% vs. 1.1%), or major adverse cardiovascular events (MACE) (4% vs. 3.6%). On multivariate analysis, preoperative statin use did not independently affect 30-day mortality (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.55-1.6, P = 0.825), perioperative MI (OR 1.1, 95% CI 0.77-1.58, P = 0.573), stroke (OR: 0.891, 95% CI: 0.64-1.2, P = 0.42), or MACE (OR 1.03, 95% CI: 0.81-1.32, P = 0.806). Antiplatelet use was more common with male gender, nonsmoking, diabetes, hypertension, chronic obstructive pulmonary disease, dyspnea, and asymptomatic carotid disease. On univariate analysis, antiplatelet use showed no effect on 30-day mortality (0.7% vs. 1%, P = 0.28), MI (1.9% vs. 1.7%, P = 0.73), stroke (1.8% vs. 1.8%, P = 0.94), TIA (0.9% vs. 1%, P = 0.63), or MACE (3.9% vs. 4%, P = 0.8). On multivariate analysis, preoperative antiplatelet use did not independently affect 30-day mortality (OR: 0.67, 95% CI: 0.37-1.3, P = 0.19), perioperative MI (OR: 0.9, 95% CI: 0.59-1.38, P = 0.637), stroke (OR: 0.92, 95% CI: 0.61-1.4, P = 0.69), or MACE (OR: 0.88, 95% CI: 0.66-1.18, P = 0.39). CONCLUSIONS: Preoperative statin and antiplatelet use in patients undergoing CEA was more often observed in patients with higher rates of comorbidities and asymptomatic disease, and this may represent closer follow-up and engagement with primary care physicians in this patient cohort. Preoperative statin and antiplatelet use did not affect perioperative outcomes suggesting that its short-term use is not essential. In patients who are not on statins or antiplatelet medications, CEA can safely be performed before consideration is given to their initiation.

Reassessment of (90)Sr, (137)Cs, and (134)Cs in the Coast off Japan Derived from the Fukushima Dai-ichi Nuclear Accident.

The years following the Fukushima Dai-ichi nuclear power plant (FDNPP) accident, the distribution of (90)Sr in seawater in the coast off Japan has received limited attention. However, (90)Sr is a major contaminant in waters accumulated within the nuclear facility and in the storage tanks. Seawater samples collected off the FDNPP in September 2013 showed radioactive levels significantly higher than pre-Fukushima levels within 6 km off the FDNPP. These samples, with up to 8.9 ± 0.4 Bq·m(-3) for (90)Sr, 124 ± 3 Bq·m(-3) for (137)Cs, and 54 ± 1 Bq·m(-3) for (134)Cs, appear to be influenced by ongoing releases from the FDNPP, with a characteristic (137)Cs/(90)Sr activity ratio of 3.5 ± 0.2. Beach surface water and groundwater collected in Sendai Bay had (137)Cs concentrations of up to 43 ± 1 Bq·m(-3), while (90)Sr was close to pre-Fukushima levels (1-2 Bq·m(-3)). These samples appear to be influenced by freshwater inputs carrying a (137)Cs/(90)Sr activity ratio closer to that of the FDNPP fallout deposited on land in the spring of 2011. Ongoing inputs of (90)Sr from FDNPP releases would be on the order of 2.3-8.5 GBq·d(-1) in September 2013, likely exceeding river inputs by 2-3 orders of magnitude. These results strongly suggest that a continuous surveillance of artificial radionuclides in the Pacific Ocean is still required.

In vitro effects of tamoxifen on adipose-derived stem cells.

In breast reconstructive procedures, adipose-derived stem cells (ASCs) that are present in clinical fat grafting isolates are considered to play the main role in improving wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. However, it is unclear if tamoxifen (TAM) as the most widely used hormonal therapeutic agent for breast cancer treatment, affects the ASCs and ultimately wound healing. This study evaluated whether TAM exposure to in vitro human ASCs modulate cellular functions. Human ASCs were isolated and treated with TAM at various concentrations. The effects of TAM on cell cycle, cell viability and proliferation rates of ASCs were examined by growth curves, MTT assay and BrdU incorporation, respectively. Annexin V and JC-1 Mitochondrial Membrane Potential assays were used to analyze ASC apoptosis rates. ASCs were cultured in derivative-specific differentiation media with or without TAM (5 uM) for 3 weeks. Adipogenic and osteogenic differentiation levels were measured by quantitative RT-PCR and histological staining. TAM has cytotoxic effects on human ASCs through apoptosis and inhibition of proliferation in dose- and time-dependent manners. TAM treatment significantly down-regulates the capacity of ASCs for adipogenic and osteogenic differentiation (p<0.05 vs. control), and inhibit the ability of the ASCs to subsequently formed cords in Matrigel. This study is the first findings to our knowledge that demonstrated that TAM inhibited ASC proliferation and multi-lineage ASC differentiation rates. These results may provide insight into the role of TAM with associated poor soft tissue wound healing and decreased fat graft survival in cancer patients receiving TAM.

Tracking the Fate of Particle Associated Fukushima Daiichi Cesium in the Ocean off Japan.

A three year time-series of particle fluxes is presented from sediment traps deployed at 500 and 1000 m at a site 115 km southeast of Fukushima Daiichi Nuclear Power Plant (FDNPP). Results show a high fraction of lithogenic material and mass flux peaks that do not align between the trap depths, suggesting a lateral source of sediments. Fukushima cesium-137 and cesium-134 were enhanced in flux peaks that, given variations in trap (137)Cs/(210)Pbex ratios, are characteristic of material derived from shelf and slope sediments found from <120 to >500 m. These lateral flux peaks are possibly triggered by passing typhoons. The Cs fluxes are an order of magnitude higher than were previously reported for the trap located 100 km due east of FDNPP. We attribute this large difference to the position of our trap under the southeasterly currents that carry contaminated waters and resuspended sediments away from FDNPP and into the Pacific. These higher Cs sedimentary fluxes offshore are still small relative to the inventory of Cs currently buried nearshore. Consequently, we do not expect them to effect any rapid decrease in Cs levels for the coastal sediments near FDNPP that have been linked to enhanced Cs in demersal fish.

Fukushima-derived radionuclides in the ocean and biota off Japan.

The Tohoku earthquake and tsunami of March 11, 2011, resulted in unprecedented radioactivity releases from the Fukushima Dai-ichi nuclear power plants to the Northwest Pacific Ocean. Results are presented here from an international study of radionuclide contaminants in surface and subsurface waters, as well as in zooplankton and fish, off Japan in June 2011. A major finding is detection of Fukushima-derived (134)Cs and (137)Cs throughout waters 30-600 km offshore, with the highest activities associated with near-shore eddies and the Kuroshio Current acting as a southern boundary for transport. Fukushima-derived Cs isotopes were also detected in zooplankton and mesopelagic fish, and unique to this study we also find (110 m)Ag in zooplankton. Vertical profiles are used to calculate a total inventory of ~2 PBq (137)Cs in an ocean area of 150,000 km(2). Our results can only be understood in the context of our drifter data and an oceanographic model that shows rapid advection of contaminants further out in the Pacific. Importantly, our data are consistent with higher estimates of the magnitude of Fukushima fallout and direct releases [Stohl et al. (2011) Atmos Chem Phys Discuss 11:28319-28394; Bailly du Bois et al. (2011) J Environ Radioact, 10.1016/j.jenvrad.2011.11.015]. We address risks to public health and marine biota by showing that though Cs isotopes are elevated 10-1,000× over prior levels in waters off Japan, radiation risks due to these radionuclides are below those generally considered harmful to marine animals and human consumers, and even below those from naturally occurring radionuclides.

Immunological shifts during early-stage Parkinson's disease identified with DNA methylation data on longitudinally collected blood samples.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the United States. Decades before motor symptoms manifest, non-motor symptoms such as hyposmia and rapid eye movement (REM) sleep behavior disorder are highly predictive of PD. Previous immune profiling studies have identified alterations to the proportions of immune cells in the blood of clinically defined PD patients. However, it remains unclear if these phenotypes manifest before the clinical diagnosis of PD. We utilized longitudinal DNA methylation (DNAm) microarray data from the Parkinson's Progression Marker's Initiative (PPMI) to perform immune profiling in clinically defined PD and prodromal PD patients (Prod). We identified previously reported changes in neutrophil, monocyte, and T cell numbers in PD patients. Additionally, we noted previously unrecognized decreases in the naive B cell compartment in the defined PD and Prod patient group. Over time, we observed the proportion of innate immune cells in PD blood increased, but the proportion of adaptive immune cells decreased. We identified decreases in T and B cell subsets associated with REM sleep disturbances and early cognitive decline. Lastly, we identified increases in B memory cells associated with both genetic (LRRK2 genotype) and infectious (cytomegalovirus seropositivity) risk factors of PD. Our analysis shows that the peripheral immune system is dynamic as the disease progresses. The study provides a platform to understand how and when peripheral immune alterations occur in PD and whether intervention at particular stages may be therapeutically advantageous.

CXCL10/IgG1 Axis in Multiple Sclerosis as a Potential Predictive Biomarker of Disease Activity.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a heterogeneous disease, and its course is difficult to predict. Prediction models can be established by measuring intrathecally synthesized proteins involved in inflammation, glial activation, and CNS injury. METHODS: To determine how these intrathecal proteins relate to the short-term, i.e., 12 months, disease activity in relapsing-remitting MS (RRMS), we measured the intrathecal synthesis of 46 inflammatory mediators and 14 CNS injury or glial activation markers in matched serum and CSF samples from 47 patients with MS (pwMS), i.e., 23 RRMS and 24 clinically isolated syndrome (CIS), undergoing diagnostic lumbar puncture. Subsequently, all pwMS were followed for ≥12 months in a retrospective follow-up study and ultimately classified into "active", i.e., developing clinical and/or radiologic disease activity, n = 18) or "nonactive", i.e., not having disease activity, n = 29. Disease activity in patients with CIS corresponded to conversion to RRMS. Thus, patients with CIS were subclassified as "converters" or "nonconverters" based on their conversion status at the end of a 12-month follow-up. Twenty-seven patients with noninflammatory neurologic diseases were included as negative controls. Data were subjected to differential expression analysis and modeling techniques to define the connectivity arrangement (network) between neuroinflammation and CNS injury relevant to short-term disease activity in RRMS. RESULTS: Lower age and/or higher CXCL13 levels positively distinguished active/converting vs nonactive/nonconverting patients. Network analysis significantly improved the prediction of short-term disease activity because active/converting patients featured a stronger positive connection between IgG1 and CXCL10. Accordingly, analysis of disease activity-free survival demonstrated that pwMS, both RRMS and CIS, with a lower or negative IgG1-CXCL10 correlation, have a higher probability of activity-free survival than the patients with a significant correlation (p < 0.0001, HR ≥ 2.87). DISCUSSION: Findings indicate that a significant IgG1-CXCL10 positive correlation predicts the risk of short-term disease activity in patients with RRMS and CIS. Thus, the present results can be used to develop a predictive model for MS activity and conversion to RRMS.

Hierarchical deconvolution for extensive cell type resolution in the human brain using DNA methylation.

Introduction: The human brain comprises heterogeneous cell types whose composition can be altered with physiological and pathological conditions. New approaches to discern the diversity and distribution of brain cells associated with neurological conditions would significantly advance the study of brain-related pathophysiology and neuroscience. Unlike single-nuclei approaches, DNA methylation-based deconvolution does not require special sample handling or processing, is cost-effective, and easily scales to large study designs. Existing DNA methylation-based methods for brain cell deconvolution are limited in the number of cell types deconvolved. Methods: Using DNA methylation profiles of the top cell-type-specific differentially methylated CpGs, we employed a hierarchical modeling approach to deconvolve GABAergic neurons, glutamatergic neurons, astrocytes, microglial cells, oligodendrocytes, endothelial cells, and stromal cells. Results: We demonstrate the utility of our method by applying it to data on normal tissues from various brain regions and in aging and diseased tissues, including Alzheimer's disease, autism, Huntington's disease, epilepsy, and schizophrenia. Discussion: We expect that the ability to determine the cellular composition in the brain using only DNA from bulk samples will accelerate understanding brain cell type composition and cell-type-specific epigenetic states in normal and diseased brain tissues.

Theiler's virus-induced demyelinating disease as an infectious model of progressive multiple sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease of unknown etiology. However, several studies suggest that infectious agents, e.g., Human Herpes Viruses (HHV), may be involved in triggering the disease. Molecular mimicry, bystander effect, and epitope spreading are three mechanisms that can initiate immunoreactivity leading to CNS autoimmunity in MS. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a pre-clinical model of MS in which intracerebral inoculation of TMEV results in a CNS autoimmune disease that causes demyelination, neuroaxonal damage, and progressive clinical disability. Given the spectra of different murine models used to study MS, this review highlights why TMEV-IDD represents a valuable tool for testing the viral hypotheses of MS. We initially describe how the main mechanisms of CNS autoimmunity have been identified across both MS and TMEV-IDD etiology. Next, we discuss how adaptive, innate, and CNS resident immune cells contribute to TMEV-IDD immunopathology and how this relates to MS. Lastly, we highlight the sexual dimorphism observed in TMEV-IDD and MS and how this may be tied to sexually dimorphic responses to viral infections. In summary, TMEV-IDD is an underutilized murine model that recapitulates many unique aspects of MS; as we learn more about the nature of viral infections in MS, TMEV-IDD will be critical in testing the future therapeutics that aim to intervene with disease onset and progression.

MethylMasteR: A Comparison and Customization of Methylation-Based Copy Number Variation Calling Software in Cancers Harboring Large Scale Chromosomal Deletions.

DNA methylation-based copy number variation (CNV) calling software offers the advantages of providing both genetic (copy-number) and epigenetic (methylation) state information from a single genomic library. This method is advantageous when looking at large-scale chromosomal rearrangements such as the loss of the short arm of chromosome 3 (3p) in renal cell carcinoma and the codeletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q) commonly seen in histologically defined oligodendrogliomas. Herein, we present MethylMasteR: a software framework that facilitates the standardization and customization of methylation-based CNV calling algorithms in a single R package deployed using the Docker software framework. This framework allows for the easy comparison of the performance and the large-scale CNV event identification capability of four common methylation-based CNV callers. Additionally, we incorporated our custom routine, which was among the best performing routines. We employed the Affymetrix 6.0 SNP Chip results as a gold standard against which to compare large-scale event recall. As there are disparities within the software calling algorithms themselves, no single software is likely to perform best for all samples and all combinations of parameters. The employment of a standardized software framework via creating a Docker image and its subsequent deployment as a Docker container allows researchers to efficiently compare algorithms and lends itself to the development of modified workflows such as the custom workflow we have developed. Researchers can now use the MethylMasteR software for their methylation-based CNV calling needs and follow our software deployment framework. We will continue to refine our methodology in the future with a specific focus on identifying large-scale chromosomal rearrangements in cancer methylation data.

Review of the analysis of 234Th in small volume (2-4 L) seawater samples: improvements and recommendations.

The short-lived radionuclide 234Th is widely used to study particle scavenging and transport from the upper ocean to deeper waters. This manuscript optimizes, reviews and validates the collection, processing and analyses of total 234Th in seawater and suggests areas of further improvements. The standard 234Th protocol method consists of scavenging 234Th from seawater via a MnO2 precipitate, beta counting, and using chemical recoveries determined by adding 230Th. The revised protocol decreases sample volumes to 2 L, shortens wait times between steps, and simplifies the chemical recovery process, expanding the ability to more rapidly and safely apply the 234Th method.

Importance of conserved cysteine residues in the coronavirus envelope protein.

Coronavirus envelope (E) proteins play an important, not fully understood role(s) in the virus life cycle. All E proteins have conserved cysteine residues located on the carboxy side of the long hydrophobic domain, suggesting functional significance. In this study, we confirmed that mouse hepatitis coronavirus A59 E protein is palmitoylated. To understand the role of the conserved residues and the necessity of palmitoylation, three cysteines at positions 40, 44, and 47 were changed singly and in various combinations to alanine. Double- and triple-mutant E proteins resulted in decreased virus-like particle output when coexpressed with the membrane (M) protein. Mutant E proteins were also studied in the context of a full-length infectious clone. Single-substitution viruses exhibited growth characteristics virtually identical to those of the wild-type virus, while the double-substitution mutations gave rise to viruses with less robust growth phenotypes indicated by smaller plaques and decreased virus yields. In contrast, replacement of all three cysteines resulted in crippled virus with significantly reduced yields. Triple-mutant viruses did not exhibit impairment in entry. Mutant E proteins localized properly in infected cells. A comparison of intracellular and extracellular virus yields suggested that release is only slightly impaired. E protein lacking all three cysteines exhibited an increased rate of degradation compared to that of the wild-type protein, suggesting that palmitoylation is important for the stability of the protein. Altogether, the results indicate that the conserved cysteines and presumably palmitoylation are functionally important for virus production.

Measure what matters: institutional outcome data are superior to the use of surrogate markers to define "center of excellence" for abdominal aortic aneurysm repair.

Outcome analysis is increasingly being used to develop health-care policy and direct patient referral. For example, the Leapfrog Group health-care quality initiative has proposed "evidence-based hospital" referral criteria for specific procedures including elective abdominal aortic aneurysm repair (AAA-R). These criteria include an annual hospital AAA operative volume exceeding 50 cases and provision of intensive care unit (ICU) care by board-certified intensivists. Outcomes after AAA-R are reportedly influenced by presentation (intact vs. ruptured), operative approach (endovascular vs. open, transperitoneal vs. retroperitoneal), surgeon subspecialty, case volume (hospital and surgeon), and provision of postoperative care by an intensivist. The purpose of this study was to compare our single-center results with those of high-volume centers to assess the validity of the concept that surrogate markers, such as case volume or intensivist involvement, can be used to estimate procedural outcome. A retrospective review was performed of AAA-Rs at one low-volume academic medical center from January 1994 to March 2005. Demographic data, aneurysm diameter and location, operative indications, and repair approach were documented. Postoperative complications, mortality rates, and hospital and ICU length of stay (LOS) were noted and compared to established benchmarks. During the study period, 270 patients underwent AAA-R (annual mean = 27 hospital cases and 13.4 cases/attending vascular surgeon). ICU care was provided by a dedicated vascular surgery service without routine intensivist involvement. Open, elective, infrarenal AAA-R was performed in 161 patients (60%), with a 2.5% hospital mortality rate (30-day, 3.1%). Thirty-three (12%) patients underwent elective endovascular aneurysm repair (EVAR), with no mortality. Both ICU (3.7 vs. 1.4 days, p = 0.03) and hospital (9.2 vs. 2.8 days, p = 0.002) LOS were significantly reduced after EVAR compared to open repair. Hospital LOS was significantly lower after open retroperitoneal repair compared to transperitoneal repair (6.1 vs. 10.3 days, p = 0.001). Thirty-five patients (13%) underwent ruptured AAA-R, with only 34.3% mortality (in-hospital and 30-day). Forty-one patients (15%) underwent repair of complex aortic aneurysms, with 14.1% mortality. There are increasing societal and economic pressures to direct patient referrals to "centers of excellence" for specific surgical procedures. Although our institution meets neither of the Leapfrog Group's proposed criteria, our mortality and LOS for both intact and ruptured infrarenal AAA-R are equivalent or superior to published benchmarks for high-volume hospitals. Individual institutional outcome results such as these suggest that patient referral and care should be based upon actual, carefully verified outcome data rather than utilization of surrogate markers such as case volume and subspecialist involvement in postoperative care.

Lingering radioactivity at the Bikini and Enewetak Atolls.

We made an assessment of the levels of radionuclides in the ocean waters, seafloor and groundwater at Bikini and Enewetak Atolls where the US conducted nuclear weapons tests in the 1940's and 50's. This included the first estimates of submarine groundwater discharge (SGD) derived from radium isotopes that can be used here to calculate radionuclide fluxes in to the lagoon waters. While there is significant variability between sites and sample types, levels of plutonium (239,240Pu) remain several orders of magnitude higher in lagoon seawater and sediments than what is found in rest of the world's oceans. In contrast, levels of cesium-137 (137Cs) while relatively elevated in brackish groundwater are only slightly higher in the lagoon water relative to North Pacific surface waters. Of special interest was the Runit dome, a nuclear waste repository created in the 1970's within the Enewetak Atoll. Low seawater ratios of 240Pu/239Pu suggest that this area is the source of about half of the Pu in the Enewetak lagoon water column, yet radium isotopes suggest that SGD from below the dome is not a significant Pu source. SGD fluxes of Pu and Cs at Bikini were also relatively low. Thus radioactivity associated with seafloor sediments remains the largest source and long term repository for radioactive contamination. Overall, Bikini and Enewetak Atolls are an ongoing source of Pu and Cs to the North Pacific, but at annual rates that are orders of magnitude smaller than delivered via close-in fallout to the same area.

Application of cross-flow ultrafiltration for the determination of colloidal abundances in suboxic ferrous-rich ground waters.

A suboxic groundwater from a sandy coastal aquifer was sampled using a new air free, large volume sampling method. Subsequent processing for size fractionation was completed with a modified cross-flow ultrafiltration (CFF) system equipped with a 1 kDa CFF membrane. By purging the CFF system with nitrogen, no oxygen was able to reach the sample. With this optimization, the sample was processed with higher than 90% recovery in terms of both iron and phosphate. Only about 4% of iron and 20% of phosphate in the filtered (0.2 microm) groundwater sample was found to be in colloidal form in the groundwater. In contrast, if no care was taken to maintain the suboxic environment of the original sample, iron was rapidly and completely oxidized and subsequently adsorbed to the CFF membrane. Other elements, such as phosphorus, were also lost to the CFF membrane to a substantial degree, and the mechanism is most likely coprecipitation with iron oxides. This study thus strongly supports the importance of maintaining ambient redox conditions during sampling and fractionation, especially for the determinations of colloid abundances in groundwater.

Infrainguinal open reconstruction: a review of surgical considerations and expected outcomes.

Infrainguinal arterial occlusive disease can lead to potentially disabling and limb-threatening conditions. Revascularization may be indicated for claudication, rest pain, or tissue loss. Although endovascular interventions are becoming more prevalent, open surgeries such as endarterectomy and bypass are still needed and performed regularly. Open reconstruction has been associated with postoperative morbidity, both at the local and at the systemic levels. Local complications include surgical site infections (SSIs 0-5.3%), graft failure (12-60%), and amputation (5.7-27%), and more systemic issues include cardiac (2.6-18.4%), respiratory (2.5%), renal (4%), neurovascular (1.5%), and thromboembolic (0.2-1%) complications. While such outcomes present an additional challenge to the postoperative management of surgical patients, it may be possible to minimize their occurrence through careful risk stratification and preoperative assessment. Therefore, individualized selection of candidates for open repair requires weighing the need for intervention against the likelihood of adverse outcomes based on preoperative risk factors. This review provides an overview of open reconstruction, focusing on identifying the clinical indications for surgery and perioperative morbidity and mortality.

Plutonium in groundwater at the 100K-Area of the U.S. DOE Hanford Site.

We examined the concentration, size distribution, redox state and isotopic composition of plutonium (Pu) in groundwater at the 100K-Area at the U.S. Department of Energy's (DOE) Hanford Site. Total concentrations of Pu isotopes were extremely low (10(-4) to 10(-6) pCi/kg, approximately 10(4) to 10(6) atoms/kg) but measurable for the first time in the 100K-Area wells using mass spectrometric analyses that are much more sensitive than alpha spectroscopy methods used previously. Size fractionation data from two wells suggest that 7-29% of the Pu is associated with colloids, operationally defined here as particles between 1 kDa-0.2 microm in size. These colloids were collected using a 1 kDa cross-flow ultrafiltration (CFF) system developed specifically for groundwater actinide studies to include careful controls both in the field and during processing to ensure in situ geochemical conditions are maintained and size separations can be well characterized. Pu in this colloidal fraction was exclusively in the more reduced Pu(III/IV) form, consistent with the higher affinity of Pu in the lower oxidation states for particle surfaces. While the overall concentrations of Pu were low, the Pu isotopic composition suggests at least two local sources of groundwater Pu, namely, local Hanford reactor operations at the 100K-Area and spent nuclear fuel from the N-reactor, which was stored in concrete pools at this site. Differences between this site and the Savannah River Site (SRS) are noted, since groundwater Pu at the F-Area seepage basin at SRS has been found using these same methods, to be characterized by lower colloidal abundances and higher oxidation states. This difference is not directly attributable to groundwater redox potential or geochemical conditions, but rather the physical-chemical difference in Pu sources, which at SRS appear to be dominated downstream from the seepage basins by decay of 244Cm, resulting in more oxidized forms of 240Pu. There is no clear evidence for colloid facilitated transport of Pu in groundwater at the Hanford Site, since downstream wells have both an order of magnitude lower concentrations of Pu and a lower fractional colloidal distribution.