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

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

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

The link between rejection sensitivity and borderline personality disorder:A systematic review and meta-analysis

OBJECTIVE: People with Borderline Personality Disorder (BPD) may experience heightened rejection sensitivity (RS), a disposition developing from repeated childhood rejecting experiences. It is not known whether the full RS model accounts for the cognitive-affective experiences common in BPD. This systematic review extends upon previous reviews, firstly by assessing the link between childhood rejecting experiences and adult RS, and secondly by considering the link between BPD and RS in both non-clinical and clinical samples.METHOD: Two research questions were devised, and searches based on predetermined criteria were conducted using PsycNET, PubMed, SCOPUS, and Web of Science. Data were extracted by one researcher and 20% was inter-rated, with high levels of agreement. Forty-three papers were systematically reviewed, and 31 included in meta-analysis and meta-regression.RESULTS: Studies assessing the link between childhood rejection and RS are limited; however, emotional abuse and neglect appears linked with RS. Pooled effect sizes suggest RS is linked with BPD (r = .326), with strong effect sizes when comparing clinical and control samples (r = .655). Qualitative synthesis suggests this may be mediated by executive control, although further research is required. The small number of studies considering the full RS model with regard to BPD suggests the interaction between emotional abuse and neglect affects rejection sensitivity; however, outcomes are inconsistent.CONCLUSIONS: Childhood rejection, particularly emotional abuse and neglect, appears to be linked to rejection sensitivity, and rejection sensitivity is linked to BPD. However, this may not be linear. Implications for clinical practice and research are discussed.PRACTITIONER POINTS: Rejection sensitivity is consistently linked with BPD, in clinical and non-clinical samples. Supporting mentalization or improved theory of mind may offer a therapeutic target for this disposition. Considering the causes and effects of rejection sensitivity may offer a non-blaming explanation of interpersonal difficulties in BPD and could be utilized as part of formulation and the therapeutic relationship. However, the possible interaction between emotional abuse and neglect and rejection sensitivity suggests rejection sensitivity is not always apparent for people with BPD. Idiosyncratic formulation should consider this. The literature included in the review is limited to Western populations with a high proportion of females, which may limit generalizability. Measures of rejection sensitivity included in the review were restricted to self-report, which may be subject to bias. Furthermore, measures of childhood rejection were retrospective in nature due to the exclusion of child samples. Further research should consider longitudinal and observational study designs.</p

On Correctness of Data Structures under Reads-Write Concurrency

Abstract. We study the correctness of shared data structures under reads-write concurrency. A popular approach to ensuring correctness of read-only operations in the presence of concurrent update, is read-set validation, which checks that all read variables have not changed since they were first read. In practice, this approach is often too conserva-tive, which adversely affects performance. In this paper, we introduce a new framework for reasoning about correctness of data structures under reads-write concurrency, which replaces validation of the entire read-set with more general criteria. Namely, instead of verifying that all read conditions over the shared variables, which we call base conditions. We show that reading values that satisfy some base condition at every point in time implies correctness of read-only operations executing in parallel with updates. Somewhat surprisingly, the resulting correctness guarantee is not equivalent to linearizability, and is instead captured through two new conditions: validity and regularity. Roughly speaking, the former re-quires that a read-only operation never reaches a state unreachable in a sequential execution; the latter generalizes Lamport’s notion of regular-ity for arbitrary data structures, and is weaker than linearizability. We further extend our framework to capture also linearizability. We illus-trate how our framework can be applied for reasoning about correctness of a variety of implementations of data structures such as linked lists.

Genetic variants and blood pressure in a population-based cohort: the cardiovascular risk in young Finns study

Clinical relevance of a genetic predisposition to elevated blood pressure was quantified during the transition from childhood to adulthood in a population-based Finnish cohort (N=2,357). Blood pressure was measured at baseline in 1980 (age 3–18 years) and in follow-ups in 1983, 1986, 2001 and 2007. Thirteen single nucleotide polymorphisms associated with blood pressure were genotyped and three genetic risk scores associated with systolic and diastolic blood pressure and their combination were derived for all participants. Effects of the genetic risk score were 0.47 mmHg for systolic and 0.53 mmHg for diastolic blood pressure (both p<0.01). The combination genetic risk score was associated with diastolic blood pressure from age 9 onwards (β=0.68 mmHg, p=0.015). Replications in 1194 participants of the Bogalusa Heart Study showed essentially similar results. The participants in the highest quintile of the combination genetic risk score had a 1.82-fold risk of hypertension in adulthood (p<0.0001) compared with the lowest quintile, independent of a family history of premature hypertension. These findings show that genetic variants are associated with preclinical blood pressure traits in childhood, individuals with several susceptibility alleles have on average a 0.5 mmHg higher blood pressure and this trajectory continues from childhood to adulthood

Infant Vaccination Education Preferences among Low-Income Pregnant Women

Childhood vaccination is an important public health intervention, yet many children remain under-vaccinated. The objective of this study was to examine infant vaccination education preferences in a population of low-income pregnant women by ethnicity, nativity, and language. Pregnant women 14–44 y old (n = 335) attending a participating low-income reproductive health clinic in southeast Texas from May 26-July 21, 2017, and who completed a paper survey offered in English and Spanish were included. Participants were asked to complete questions about their demographic characteristics and preferences about infant vaccination education. To examine differences in vaccine education preferences by participant demographic characteristics, chi-squared tests, or Fisher’s exact tests and one-way analysis of variance (ANOVA) were conducted using Stata SE Version 15.1 with α = 0.05. Nearly half (47.5%) of participants considered pregnancy the best time to get information about infant vaccination and were most likely (40.6%) to indicate the nurse who gives vaccines during pregnancy as the health-care worker with whom they would like to discuss infant vaccination. There were no demographic differences in preferred timing of vaccine education delivery or provider who delivers vaccine education. Prenatal, nurse-delivered vaccine educational programs would be well accepted in this low-income population

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P&lt;0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P&lt;0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition

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