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The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection.

Background and aimsFatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media.MethodsThree healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4–12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima.ResultsHigh lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima.ConclusionThe arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection. [ABSTRACT FROM AUTHOR]

Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV). HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order

Two experiments investigated why preschool children sometimes produce multiple words for a referent (i.e. polynomy), but other times seem to allow only one word. In Experiment 1, 40 three- and four-year-olds completed a modification of Deák & Maratsos' (1998) naming task. Although social demands to produce multiple words were reduced, children produced, on average, more than two words per object. Number of words produced was predicted by receptive vocabulary. Lexical insight (i.e. knowing that a word refers to function or appearance) and metalexical beliefs (i.e. that a hypothetical referent has one label, or more than one) were not preconditions of polynomy. Polynomy was independent of bias to map novel words to unfamiliar referents. In Experiment 2, 40 three- and four-year-olds learned new words for nameable objects. Children showed a correction effect, yet produced more than two words per object. Children do not have a generalized one-word-per-object bias, even during word learning. Other explanations (e.g. contextual restriction of lexical access) are discussed.

Qingwen Xie,1 Tian Zhou,2 Lawrence Yen,2 Mina Shariff,3 Tuong Nguyen,3 Kenneth Kami,3 Pingping Gu,3 Liang Liang,2 Jianyu Rao,2 Rong Shi1 1Department of Preventive Medicine, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 3Department of Research, DRM Resources, Costa Mesa, CA, USA Background: Osteoarthritis is a common chronic disease affecting aged populations. Conventional therapies tend to result in side effects when used long-term. Arthro-7® (Robinson Pharma, Orange County, CA, USA) has been used by osteoarthritis patients for more than 10 years in the USA and has showed promising effects at relieving osteoarthritis-related symptoms. A previous small, double-blind study has shown some positive effects of Arthro-7 in relieving symptoms of osteoarthritis. The current study was performed specifically in osteoarthritis patients with mild to moderate arthralgia. Methods: A total of 100 subjects over the age of 50 years old who were diagnosed with osteoarthritis and had at least one of the related symptoms were recruited to the study. After primary evaluation, 64 eligible males and females with mild or moderate degrees of arthralgia were randomly assigned 12-week treatment with either Arthro-7 or placebo. The primary outcome measurement was changes in the scores of the related symptoms before and after treatment, using the modified Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 questionnaire. Prior to and at the end of the study, evaluations of symptom scores were recorded. Additionally, self-reported overall changes were recorded at the end of 2, 4, and 8 weeks of treatment and at the end of the study (12 weeks). Results: Arthro-7 improved most symptoms significantly compared with placebo, as indicated by significant reductions in symptom scores. In the Arthro-7 group, 74.5% of the participants reported symptom improvement over the study period versus only 16.3% in the placebo group. Conclusion: In this study, Arthro-7 has shown potent effects in improving and relieving osteoarthritis-related symptoms, particularly joint pain, anchylosis, and difficulty going down stairs. Keywords: joint pain, anchylosis, arthroncus, WOMAC 3.1

Because of their racial ambiguity in the United States, Asian Americans have been constructed historically to be both like and unlike Black and White people, and Asian American men have been both hypermasculinized and feminized, just as Asian American women have been both masculinized and hyperfeminized. (SLD)

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jedc.2010.01.001 Byline: PA[yen]l Boug (a), a'dne Cappelen (a), Anders Rygh Swensen (a)(b) Abstract: Several authors have questioned the evidence claimed by and that a hybrid version of the new Keynesian Phillips curve approximates European and US inflation dynamics quite well. We re-examine the evidence using the vector autoregressive framework and likelihood based methods, paying particular attention to the stationary and nonstationary, and possibly cointegrated, nature of variables involved. Our results show that the exact as well as the inexact form of the hybrid NKPC are clearly at odds with the European data. On the other hand, finding that the inexact hybrid NKPC is a 'good first approximation' to the US inflation dynamics seems less at odds with the data. However, the assumption of the model that the stochastic term forms a sequence of innovations may be problematic as we find indication of autocorrelation in the estimated residuals. The exact form of the hybrid NKPC is firmly rejected by the US data. Author Affiliation: (a) Statistics Norway, Research Department, P.O.B. 8131 Dep., 0033 Oslo, Norway (b) University of Oslo, Department of Mathematics, P.O.B. 1053 Blindern, 0316 Oslo, Norway Article History: Received 8 November 2008; Revised 6 October 2009; Accepted 19 November 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.religion.2009.01.001 Byline: PA[yen]l Repstad Abstract: This is a report from an on-going project. Based mainly at the University of Agder, Norway, this research project involves over 20 full- and part-time researchers in studying religious change in the SA[cedilla]rlandet or Agder region in Norway. This article, written by the project director, aims mainly to summarize some of the main empirical results. In sum, the empirical studies show that in the last few decades the strict Christian movements in the region have moved in a more liberal direction, especially concerning life-style issues. Towards the end the article also presents some reflections on the dynamics of change in religious organizations with a conservative self-understanding, as well as on the interplay between such a project and the regional discourse on religion. Author Affiliation: University of Agder, Norway Article Note: (footnote) [star] English text revised by Catherine Humes.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.comnet.2008.06.003 Byline: Knut-Helge Vik, PA[yen]l Halvorsen, Carsten Griwodz Keywords: Distributed interactive applications; Overlay multicast; Steiner-tree heuristics; Tree-diameter Abstract: Latency reduction in distributed interactive applications has been studied intensively. Such applications may have stringent latency requirements and dynamic user groups. We focus on application-layer multicast with a centralized approach to the group management. The groups are organized in overlay networks that are created using graph algorithms that create a tree structure for the group. A tree has no cycles and uses a small routing table, as opposed to a connected overlay mesh. We investigated a group of spanning tree problems that are referred to as Steiner-tree problems, and we have a particular focus on reducing the diameter of a tree, which is the maximum pairwise latency in a tree. In addition, we focus on reducing the time it takes to execute membership changes. In that context, we use core-selection heuristics to find well-placed client nodes, and edge-pruning algorithms to reduce the number of edges in an otherwise fully meshed overlay. Our edge-pruning algorithms strongly connect well-placed client nodes to the remaining group members, to create new and pruned group graphs. Consequently, when a tree algorithm is applied to a pruned group graph, it is manipulated into creating trees with a smaller diameter. We devised new Steiner-tree heuristics that reduced the diameter, and also proposed new edge-pruning algorithms to make the tree construction faster. These heuristics and algorithms were implemented and analyzed experimentally along with several spanning-tree and core-selection heuristics found in the literature. We found that a full-mesh of shortest paths makes it difficult for Steiner-tree heuristics to find better trees than spanning tree algorithms. The network seen from the application layer is in fact a full mesh of shortest paths. In addition, we found that faster Steiner-tree heuristics that do not explicitly optimize the diameter are able to compete with slower heuristics that do optimize it. Author Affiliation: Simula Research Laboratory, University of Oslo, Oslo, Norway

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.dsr.2006.09.008 Byline: PA[yen]l Erik Isachsen (a), Cecilie Mauritzen (b), Harald Svendsen (c)(d) Abstract: The relationship between the surface water mass transformation over the Nordic Seas and the large-scale diapycnal overturning flow through the same region was examined. The surface transformation was estimated from climatological and reanalyzed surface hydrography and air-sea buoyancy fluxes. Ocean currents and transports were assembled from climatological wind stresses and modern hydrographic data with reference level velocities for thermal wind calculations gathered from independent studies and adjusted in a linear inverse model. The data reveal a close match between the surface transformation and the magnitude of the large-scale diapycnal overturning. This result confirms an existing hypothesis that turbulent fluxes of buoyancy and nonlinearities in the equation of state are of secondary importance in high-latitude dense water production regions. Fields from a coupled numerical ocean-ice model also suggest that the seasonal cycle of freezing and melting within the Nordic Seas has a small net effect on the surface transformation, particularly at high densities ( Author Affiliation: (a) Norwegian Institute of Water Research, Oslo, Norway (b) Norwegian Meteorological Institute, Oslo, Norway (c) Geophysical Institute, University of Bergen, Bergen, Norway (d) Norwegian Polar Institute, TromsA[cedilla], Norway Article History: Received 26 May 2005; Revised 14 September 2006; Accepted 19 September 2006