Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma

Initial results from a PET/planar small animal imaging system

A pair of stationary, opposed scintillation detectors in time coincidence is being used to create planar projection or tomographic images of small animals injected with positronemitting radiotracers. The detectors are comprised of arrays of individual crystals of bismuth germanate coupled to position-sensitive photomultiplier tubes. The system uses FERA (LeCroy Research Systems) charge-sensitive ADCs and a low cost digital YO board as a E R A bus-to-host bridge. In projection mode, the animal is placed within the 55 mm x 45 mm useful field-of-view of the detectors and images are formed from coincidence lines that fall close to the normals of both detectors. In tomographic mode, the animal is placed on a rotation stage between the detectors and rotated around a vertical axis to acquire all possible lines-of-response. Tomographic images are then reconstructed from those lines falling within a user-specified angle of each detector normal. In mice, the system is capable of high-speed, whole-body dynamic projection imaging, and whole body tomographic imaging of slowly varying tracer distributions. An ECG gating capability is also available for evaluating cardiac function. This system is currently being used to study tracer transport in normal and genetically engineered mice.Publicad

Exploring Halo Substructure with Giant Stars. VI. Extended Distributions of Giant Stars Around the Carina Dwarf Spheroidal Galaxy -- How Reliable Are They?

The question of the existence of active tidal disruption around various dSph galaxies remains controversial. That debate often centers on the nature (bound vs. unbound) of extended populations of stars. However, the more fundamental issue of the very existence of the extended populations is still contentious. We present an evaluation of the debate centering on one particular dSph, Carina, for which claims both for and against the existence of stars beyond the King radius have been made. Our review includes an examination of all previous studies bearing on the Carina radial profile and shows that the survey method which achieves the highest detected dSph signal-to-background in the outer parts of the galaxy is the Washington M, T2 + DDO51 (MTD) filter approach from Paper II in this series. We then address statistical methods used to evaluate the reliability of MTD surveys in the presence of photometric errors and for which a new, a posteriori statistical analysis methodology is provided. Finally, these statistical methods are tested by new spectroscopy of stars in the MTD-selected Carina candidate sample. Of 74 candidate giants with follow-up spectroscopy, the MTD technique identified 61 new Carina members, including 8 stars outside the King radius. From a sample of 29 stars not initially identified as candidate Carina giants but that lie just outside of our selection criteria, 12 have radial velocities consistent with membership, including 5 extratidal stars. Carina is shown to have an extended population of giant stars extending to a major axis radius of 40' (1.44x the nominal King radius).Comment: 56 pages, 10 figures. Submitted to the Astronomical Journal, 2004 Sep 2

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Arsenic pilot plant operation and results : Anthony, New Mexico.

Sandia National Laboratories (SNL) is conducting pilot scale evaluations of the performance and cost of innovative water treatment technologies aimed at meeting the recently revised arsenic maximum contaminant level (MCL) for drinking water. The standard of 10 {micro}g/L (10 ppb) is effective as of January 2006. The pilot tests have been conducted in New Mexico where over 90 sites that exceed the new MCL have been identified by the New Mexico Environment Department. The pilot test described in this report was conducted in Anthony, New Mexico between August 2005 and December 2006 at Desert Sands Mutual Domestic Water Consumers Association (MDWCA) (Desert Sands) Well No.3. The pilot demonstrations are a part of the Arsenic Water Technology Partnership program, a partnership between the American Water Works Association Research Foundation (AwwaRF), SNL and WERC (A Consortium for Environmental Education and Technology Development). The Sandia National Laboratories pilot demonstration at the Desert Sands site obtained arsenic removal performance data for fourteen different adsorptive media under intermittent flow conditions. Well water at Desert Sands has approximately 20 ppb arsenic in the unoxidized (arsenite-As(III)) redox state with moderately high total dissolved solids (TDS), mainly due to high sulfate, chloride, and varying concentrations of iron. The water is slightly alkaline with a pH near 8. The study provides estimates of the capacity (bed volumes until breakthrough at 10 ppb arsenic) of adsorptive media in the same chlorinated water. Adsorptive media were compared side-by-side in ambient pH water with intermittent flow operation. This pilot is broken down into four phases, which occurred sequentially, however the phases overlapped in most cases

Arsenic pilot plant operation and results - Socorro Springs, New Mexico - phase 1.

Sandia National Laboratories (SNL) is conducting pilot scale evaluations of the performance and cost of innovative water treatment technologies aimed at meeting the recently revised arsenic maximum contaminant level (MCL) for drinking water. The standard of 10 {micro}g/L (10 ppb) is effective as of January 2006. The first pilot tests have been conducted in New Mexico where over 90 sites that exceed the new MCL have been identified by the New Mexico Environment Department. The pilot test described in this report was conducted in Socorro New Mexico between January 2005 and July 2005. The pilot demonstration is a project of the Arsenic Water Technology Partnership program, a partnership between the American Water Works Association Research Foundation (AwwaRF), SNL and WERC (A Consortium for Environmental Education and Technology Development). The Sandia National Laboratories pilot demonstration at the Socorro Springs site obtained arsenic removal performance data for five different adsorptive media under constant ambient flow conditions. Well water at Socorro Springs has approximately 42 ppb arsenic in the oxidized (arsenate-As(V)) redox state with moderate amounts of silica, low concentrations of iron and manganese and a slightly alkaline pH (8). The study provides estimates of the capacity (bed volumes until breakthrough at 10 ppb arsenic) of adsorptive media in the same chlorinated water. Near the end of the test the feedwater pH was lowered to assess the affect on bed capacity and as a prelude to a controlled pH study (Socorro Springs Phase 2)

Focal adhesion kinase contributes to proliferative potential of ErbB2 mammary tumour cells but is dispensable for ErbB2 mammary tumour induction in vivo

INTRODUCTION: Activation of focal adhesion kinase (FAK) is hypothesized to play an important role in the pathogenesis of human breast cancer. METHODS: To directly evaluate the role of FAK in mammary tumour progression, we have used a conditional FAK mouse model and mouse mammary tumour virus (MMTV)-driven Cre recombinase strain to inactivate FAK in the mammary epithelium of a transgenic mouse model of ErbB2 breast cancer. RESULTS: Although mammary epithelial disruption of FAK in this model resulted in both a delay in onset and a decrease in the number of neoplastic lesions, mammary tumours occurred in 100% of virgin female mice. All of the tumours and derived metastases that developed were proficient for FAK due to the absence of Cre recombinase expression. The hyperplastic epithelia where Cre-mediated recombination of FAK could be detected exhibited a profound proliferative defect. Consistent with these observations, disruption of FAK in established tumour cells resulted in reduced tumour growth that was associated with impaired proliferation. To avoid the selection for FAK-proficient ErbB2 tumour epithelia through escape of Cre-mediated recombination, we next intercrossed the FAK conditional mice with a separate MMTV-driven ErbB2 strain that co-expressed ErbB2 and Cre recombinase on the same transcriptional unit. CONCLUSIONS: While a delay in tumour induction was noted, FAK-deficient tumours arose in 100% of female animals indicating that FAK is dispensable for ErbB2 tumour initiation. In addition, the FAK-null ErbB2 tumours retained their metastatic potential. We further demonstrated that the FAK-related Pyk2 kinase is still expressed in these tumours and is associated with its downstream regulator p130Cas. These observations indicate that Pyk2 can functionally substitute for FAK in ErbB2 mammary tumour progression

Communications Biophysics

Contains research objectives and summary of research on nine research projects split into four sections.National Institutes of Health (Grant 5 ROI NS11000-03)National Institutes of Health (Grant 1 P01 NS13126-01)National Institutes of Health (Grant 1 RO1 NS11153-01)National Institutes of Health (Grant 2 R01 NS10916-02)Harvard-M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare (Grant 23-P-55854)National Institutes of Health (Grant 1 ROl NS11680-01)National Institutes of Health (Grant 5 ROI NS11080-03)M.I.T. Health Sciences Fund (Grant 76-07)National Institutes of Health (Grant 5 T32 GM07301-02)National Institutes of Health (Grant 5 TO1 GM01555-10