1,093 research outputs found

    Saliendo Adelante: Stressors and Coping Strategies Among Immigrant Latino Men Who Have Sex With Men in a Nontraditional Settlement State

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    Immigrant Latino men who have sex with men (MSM) are marginalized along multiple dimensions (e.g., ethnicity, sexual orientation, language use), which can negatively affect their health and well-being. As little is known about how this subgroup experiences the stress of marginalization and how, in turn, they cope with such stress, this study investigated stressors and coping strategies to better understand the factors shaping Latino MSM health. Assisted by a community advisory committee, we conducted in-depth interviews with 15 foreign-born Latino MSM in a nontraditional settlement state. Drawing on grounded theory methods, we analyzed transcripts iteratively to identify processes and characterize themes. Results were confirmed in member check interviews (n = 4) and findings were further contextualized through key informant interviews (n = 3). Participants reported ubiquitous, concurrent stressors due to being an immigrant, being a sexual minority, and being working poor. In particular, homophobia within families and local Latino communities was seen as pervasive. Some participants faced additional stressors due to being undocumented and not being Mexican. Participants drew on four types of coping strategies, with no dominant coping response: passive coping (i.e., not reacting to stressors); attempting to change stressors; seeking social support; and seeking distractions. Family ties, especially with mothers, provided key emotional support but could also generate stress related to participants’ sexuality. This study lays a foundation for future work and is particularly relevant for Latino MSM in nontraditional settlement states. Findings may inform future interventions to reduce stressors and increase resiliency, which can positively affect multiple health outcomes

    Long term Mesenchymal stem cell culture on a defined synthetic substrate with enzyme free passaging

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    Mesenchymal stems cells (MSCs) are currently the focus of numerous therapeutic approaches in tissue engineering/repair because of their wide multi-lineage potential and their ability to modulate the immune system response following transplantation. Culturing these cells, while maintaining their multipotency in vitro, currently relies on biological substrates such as gelatin, collagen and fibronectin. In addition, harvesting cells from these substrates requires enzymatic or chemical treatment, a process that will remove a multitude of cellular surface proteins, clearly an undesirable process if cells are to be used therapeutically. Herein, we applied a high-throughput ‘hydrogel microarray’ screening approach to identify thermo-modulatable substrates which can support hES-MP and ADMSC growth, permit gentle reagent free passaging, whilst maintaining multi-lineage potential. In summary, the hydrogel substrate identified, poly(AEtMA-Cl-co-DEAA) cross-linked with MBA, permitted MSCs to be maintained over 10 passages (each time via thermo-modulation), with the cells retaining expression of MSC associated markers and lineage potency. This chemically defined system allowed the passaging and maintenance of cellular phenotype of this clinically important cell type, in the absence of harsh passaging and the need for biological substrates

    Addition of or switch to insulin therapy in people treated with glucagon-like peptide-1 receptor agonists : a real-world study in 66 583 patients

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    Background Real world outcomes of addition or switch to insulin therapy in type 2 diabetes (T2DM) patients on glucagon-like paptide-1 receptor agonist (GLP-1RA) with inadequately controlled hyperglycaemia, are not known. Materials and methods Patients with T2DM (n = 66 583) with a minimum of 6 months of GLP-1RA treatment and without previous insulin treatment were selected. Those who added insulin (n = 39 599) or switched to insulin after GLP-1RA cessation (n = 4706) were identified. Adjusted changes in glycated haemoglobin (HbA1c), weight, systolic blood pressure (SBP), and LDL cholesterol were estimated over 24 months follow-up. Results Among those who continued with GLP-1RA treatment without adding or switching to insulin, the highest adjusted mean HbA1c change was achieved within 6 months, with no further glycaemic benefits observed during 24 months of follow-up. Addition of insulin within 6 months of GLP-1RA initiation was associated with 18% higher odds of achieving HbA1c <7% at 24 months, compared with adding insulin later. At 24 months, those who added insulin reduced HbA1c significantly by 0.55%, while no glycaemic benefit was observed in those who switched to insulin. Irrespective of intensification with insulin, weight, SBP and LDL cholesterol were significantly reduced by 3 kg, 3 mm Hg, and 0.2 mmol/L, respectively, over 24 months. Conclusions Significant delay in intensification of treatment by addition of insulin is observed in patients with T2DM inadequately controlled with GLP-1RA. Earlier addition of insulin is associated with better glycaemic control, while switching to insulin is not clinically beneficial during 2 years of treatment. Non-responding patients on GLP-1RA would benefit from adding insulin therapy, rather than switching to insulin

    Renal Proliferative and Phenotypic Changes in Rats With Two-Kidney, One-Clip Goldblatt Hypertension

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    Angiotensin II (All) is a vasoconstrictive peptide with hypertrophic and mitogenic effects on many cell types. Previous studies have shown that in vivo administration of All in rats results in proliferation of, and phenotypic changes in, many renal cell populations, but in doses also causing hypertension. Thus, it was not possible to differentiate nonhemodynamic from hypertensive effects of All. Therefore, we studied rats with renin-dependent, All-mediated hypertension (the two-kidney, oneclip Goldblatt model; mean systolic blood pressure 238 ± 48 ν 140 ± 6 mm Hg in sham-operated controls). The undipped kidneys, which were exposed to high blood pressure, developed significant glomerular and tubulointerstitial injury, tubulointerstitial cell proliferation, dense focal interstitial monocyte-macrophage influx, increased deposition of types I and IV collagen, as well as increased cellular expression of desmin and actin, in tubulointerstitial areas when examined at 11 weeks. In contrast, clipped kidneys, protected from hypertension but with high local renin expression, had minimal abnormalities. These studies suggest that in this model increased renin, and presumably All, does not mediate significant proliferative or phenotypic changes in the kidney in the absence of hypertension at 11 weeks. Am J Hypertens 1994;7:177-18

    A study of interaction effects due to bored tunnels in clay

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    Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2006.Includes bibliographical references (leaf 59).As more and more tunnels are being bored in urban environments it is essential to understand the effects that this will have on adjacent structures, for example, the state of Singapore, which has been expanding its underground transit system extensively. The effects of tunneling twin tunnels in Singapore marine clay are outlined, analyzed and discussed. Three different configurations are taken into account, side-by-side tunnels, piggyback tunnels and angular-offset tunnels, located at a typical depth for Singapore. Empirical correlations, derived from extensive field data, are used to calculate ground movements caused by twin bored tunnel constructions using superposition. Non-linear finite element analysis is used for the same situations, as well as for analyzing the stresses in the tunnel lining. The use of superposition was tested using the non-linear analysis to check whether or not its use with empirical methods is appropriate. Although the numerical solutions suggest that superposition is a good approximation for twin tunnel bores, there is a clear discrepancy in the magnitude and distribution of ground movements calculated by empirical and numerical solutions.by Paul Sweeney.M.Eng

    Identifying and modeling unwanted traffic on the Internet

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    Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, February 2006.Includes bibliographical references (p. 61-62).Accurate models of Internet traffic are important for successful testing of devices that provide network security. However, with the growth of the Internet. it has become increasingly difficult to develop and maintain accurate traffic models. While much internet traffic is legitimate, productive communications between users and services, a significant portion of Internet traffic is the result of unwanted messages sent to IP addresses without regard as to whether there is an active host at that address. In an effort to analyze unwanted traffic, tools were developed that generate statistics and plots on captured unwanted traffic to unused IP addresses. These tools were used on a four-day period of traffic received on an inactive IPv4 class A network address space. Each class B subnet in this address space received an average of 7 million packets corresponding to 21 packets per second. Analyses were performed on a range of class B and C subnets with the intent of discovering the types of variability that are characteristic of unwanted traffic. Traffic volume over time, number of scans, destinations ports, and traffic sources varied substantially across class B and C subnets.(cont.) The results of the analyses, along with tools to replay traffic. allow security tools to be analyzed on the LARIAT network testbed. LARIAT is a real-time adaptable network testbed developed at Lincoln Laboratory that provides an Internet-like environment in which to test network hardware and software.by Paul Soto.M.Eng

    Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

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    BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

    Estimating the Public Health Impact of Rabies

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    Rabies is a fatal, preventable zoonosis, but it is not effectively controlled throughout much of the developing world. The impetus for control is hampered by a lack of awareness of its true impact. We estimate a disability-adjusted life year (DALY) score for rabies to quantify the disease impact relative to other diseases to set priorities for public health interventions

    Instability of retroviral vectors with HIV-1-specific RT aptamers due to cryptic splice sites in the U6 promoter

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    <p>Abstract</p> <p>Background</p> <p>Internal polymerase III promoters in retroviral vectors have been used extensively to express short RNA sequences, such as ribozymes, RNA aptamers or short interfering RNA inhibitors, in various positions and orientations. However, the stability of these promoters in the reverse orientation has not been rigorously evaluated.</p> <p>Results</p> <p>A series of retroviral vectors was generated carrying the U6+1 promoter with 3 different HIV-1 RT-specific RNA aptamers and one control aptamer, all in the reverse orientation. After shuttle packaging, the CD4<sup>+ </sup>cell line CEMx174 was transduced with each vector, selected for expression of GFP, and challenged with HIV-1. We did not observe inhibition of HIV-1 replication in these transduced populations. PCR amplification of the U6+1 promoter-RNA aptamer inhibitor cassette from transduced CEMx174 cells and RT-PCR amplification from transfected Phoenix (amphotropic) packaging cells showed two distinct products: a full-length product of the expected size as well as a truncated product. The sequence of the full-length PCR product was identical to the predicted amplicon sequence. However, sequencing of the truncated product revealed a 139 bp deletion in the U6 promoter. This deletion decreased transcriptional activity of the U6 promoter. Analysis of the deleted sequences from the U6 promoter in the antisense direction indicated consensus splice donor, splice acceptor and branch point sequences.</p> <p>Conclusion</p> <p>The existence of a cryptic splice site in the U6 promoter when expressed in a retroviral vector in the reverse orientation generates deletions during packaging and may limit the utility of this promoter for expression of small RNA inhibitors.</p
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