Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Sampling-based Algorithms for Optimal Motion Planning

During the last decade, sampling-based path planning algorithms, such as Probabilistic RoadMaps (PRM) and Rapidly-exploring Random Trees (RRT), have been shown to work well in practice and possess theoretical guarantees such as probabilistic completeness. However, little effort has been devoted to the formal analysis of the quality of the solution returned by such algorithms, e.g., as a function of the number of samples. The purpose of this paper is to fill this gap, by rigorously analyzing the asymptotic behavior of the cost of the solution returned by stochastic sampling-based algorithms as the number of samples increases. A number of negative results are provided, characterizing existing algorithms, e.g., showing that, under mild technical conditions, the cost of the solution returned by broadly used sampling-based algorithms converges almost surely to a non-optimal value. The main contribution of the paper is the introduction of new algorithms, namely, PRM* and RRT*, which are provably asymptotically optimal, i.e., such that the cost of the returned solution converges almost surely to the optimum. Moreover, it is shown that the computational complexity of the new algorithms is within a constant factor of that of their probabilistically complete (but not asymptotically optimal) counterparts. The analysis in this paper hinges on novel connections between stochastic sampling-based path planning algorithms and the theory of random geometric graphs.Comment: 76 pages, 26 figures, to appear in International Journal of Robotics Researc

Improving the scalability of cloud-based resilient database servers

Many rely now on public cloud infrastructure-as-a-service for database servers, mainly, by pushing the limits of existing pooling and replication software to operate large shared-nothing virtual server clusters. Yet, it is unclear whether this is still the best architectural choice, namely, when cloud infrastructure provides seamless virtual shared storage and bills clients on actual disk usage. This paper addresses this challenge with Resilient Asynchronous Commit (RAsC), an improvement to awell-known shared-nothing design based on the assumption that a much larger number of servers is required for scale than for resilience. Then we compare this proposal to other database server architectures using an analytical model focused on peak throughput and conclude that it provides the best performance/cost trade-off while at the same time addressing a wide range of fault scenarios

Frequent demonstration of human herpesvirus 8 (HHV-8) in bone marrow biopsy samples from Turkish patients with multiple myeloma (MM)

In order to investigate the frequency of HHV-8 in MM patients from another geographic location, we obtained fresh bone marrow (BM) biopsies from Turkish patients with MM (n = 21), monoclonal gammopathy of undetermined significance (MGUS) (n = 2), plasmacytoma (n = 1) with BM plasma cell infiltration, various hematological disorders (n = 6), and five healthy Turkish controls. The frequency of HHV-8 was analyzed by polymerase chain reaction (PCR) in two independent laboratories in the USA and in Turkey. Using fresh BM biopsies, 17/21 MM patients were positive for HHV-8 whereas all five healthy controls, and six patients with other hematological disorders were negative. Two patients with MGUS, and one patient with a solitary plasmacytoma were also negative. The data from the two laboratories were completely concordant. Also using primer pairs for v IRF and v IL-8R confirmed the results observed with the KS330233 primers. Furthermore, sequence analysis demonstrated a C3 strain pattern in the ORF26 region which was also found in MM patients from the US. Thus, HHV-8 is present in the majority of Turkish MM patients, and the absence of the virus in healthy controls further supports its role in the pathogenesis of MM

Analysis of protein glycation in human fingernail clippings with near-infrared (NIR) spectroscopy as an alternative technique for the diagnosis of diabetes mellitus

BACKGROUND: Glycated keratin allows the monitoring of average tissue glucose exposure over previous weeks. In the present study, we wanted to explore if near-infrared (NIR) spectroscopy could be used as a non-invasive diagnostic tool for assessing glycation in diabetes mellitus. METHODS: A total of 52 patients with diabetes mellitus and 107 healthy subjects were enrolled in this study. A limited number (n=21) of nails of healthy subjects were glycated in vitro with 0.278 mol/L, 0.556 mol/L and 0.833 mol/L glucose solution to study the effect of glucose on the nail spectrum. Consequently, the nail clippings of the patients were analyzed using a Thermo Fisher Antaris II Near-IR Analyzer Spectrometer and near infrared (NIR) chemical imaging. Spectral classification (patients with diabetes mellitus vs. healthy subjects) was performed using partial least square discriminant analysis (PLS-DA). RESULTS: In vitro glycation resulted in peak sharpening between 4300 and 4400 cm-1 and spectral variations at 5270 cm-1 and between 6600 and 7500 cm-1. Similar regions encountered spectral deviations during analysis of the patients' nails. Optimization of the spectral collection parameters was necessary in order to distinguish a large dataset. Spectra had to be collected at 16 cm-1, 128 scans, region 4000-7500 cm-1. Using standard normal variate, Savitsky-Golay smoothing (7 points) and first derivative preprocessing allowed for the prediction of the test set with 100% correct assignments utilizing a PLS-DA model. CONCLUSIONS: Analysis of protein glycation in human fingernail clippings with NIR spectroscopy could be an alternative affordable technique for the diagnosis of diabetes mellitus

Three-year tracking of fatty acid composition of plasma phospholipids in healthy children

Objectives: The fatty acid composition of plasma phospholipids reflects the dietary fatty acid intake as well as endogenous turnover. We aimed at investigating the potential tracking of plasma phospholipid fatty acid composition in children that participated in a prospective cohort study. Methods: 26 healthy children participated in a longitudinal study on health risks and had been enrolled after birth. All children were born at term with birth weights appropriate for gestational age. Follow-up took place at ages 24, 36 and 60 months. At each time point a 24-hour dietary recall was obtained, anthropometric parameters were measured and a blood sample for phospholipid fatty acid analysis was taken. Results: Dietary intake of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids at the three time points were not correlated. We found lower values for plasma MUFA and the MUFA/SFA ratio at 60 months compared to 24 months. In contrast, total PUFA, total n-6 and n-6 long-chain polyunsaturated fatty acids (LC-PUFA) were higher at 60 months. Significant averaged correlation coefficients (average of Pearson's R for 24 versus 36 months and 36 versus 60 months) were found for n-6 LC-PUFA (r = 0.67), n-6/n-3 LC-PUFA ratio (r = 0.59) and arachidonic acid/linoleic acid ratio (r = 0.64). Partial tracking was found for the docosahexaenoic acid/alpha-linolenic acid ratio (r = 0.33). Body mass index and sum of skinfolds Z-scores were similar in the three evaluations. Conclusions: A significant tracking of n-6 LC-PUFA, n-6 LC-PUFA/n-3 LC-PUFA ratio, arachidonic acid/ linoleic acid ratio and docosahexaenoic acid/alpha-linolenic acid ratio may reflect an influence of individual endogenous fatty acid metabolism on plasma concentrations of some, but not all, fatty acids. Copyright (c) 2007 S. Karger AG, Basel

End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study

<p>Abstract</p> <p>Background</p> <p>Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.</p> <p>Methods</p> <p>The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.</p> <p>Results</p> <p>Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m²among ESRD cases and 18.6 kg/m²and 18.9 kg/m²among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.</p> <p>Conclusion</p> <p>These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.</p

A Qualitative Study of an Integrated Maternity, Drugs and Social Care Service for Drug-using Women

Background: The care of drug-using pregnant women is a growing health and social care concern in many countries. A specialist clinic was established offering multidisciplinary care and advice to pregnant drug users in and around Aberdeen (UK) in 1997. The majority of women stabilise and reduce their drug use. By determining the needs and views of the women more appropriate services and prevention strategies may be developed. There has been little research conducted in this area and none in Scotland. Methods: This is a qualitative study that aimed to gain an understanding of the experiences of women drug users, seeking and receiving prenatal care and drug services from a specialist clinic. Twelve women participated in semi-structured one-to-one interviews. Results: The women preferred the multidisciplinary clinic (one-stop shop) to traditional prenatal care centred within General Practice. The relationships of the clients to the range of Clinic professionals and in hospital were explored as well as attitudes to Clinic care. The study participants attributed success in reducing their drug use to the combination of different aspects of care of the multi-agency clinic, especially the high level prenatal support. It is this arrangement of all aspects of care together that seem to produce better outcomes for mother and child than single care elements delivered separately. Some women reported that their pregnancy encouraged them to rapidly detoxify due to the guilt experienced. The most important aspects of the Clinic care were found to be non-judgemental attitude of staff, consistent staff, high level of support, reliable information and multi-agency integrated care. Conclusion: There is an impetus for women drug users to change lifestyle during pregnancy. The study highlighted a need for women to have access to reliable information on the effects of drugs on the baby. Further research is required to determine whether positive outcomes related to clinic attendance in the prenatal period are sustained in the postnatal period. Early referral to a specialist clinic is of benefit to the women, as they reported to receive more appropriate care, especially in relation to their drug use. A greater awareness of needs of the pregnant drug user could help the design of more effective prevention strategies