The Golden Retriever Rule: Alaska’s Identity Privilege for Animal Adoption Agencies and for Adoptive Animal Owners

Sedan 1900-talets mitt har användandet av tegelkonstruktioner i bostadsbyggandet minskat kraftigt; materialet har under modernismen upplevts otidsenligt och byggnadssättet har ansetts ineffektivt. Trots att kanalmurstekniken, som är en byggteknik med bärande tegelkonstruktion och högt isoleringsvärde, togs fram på 1930-talet för att följa hårdare energihushållningskrav, har ändå lätta träregelkonstruktioner dominerat det svenska småhusbyggandet. Kraven på energihushållning har under åren ökat successivt och livscykelanalysen (LCA) har utvecklats. LCA är en metodik som analyserar produkters eller tjänsters klimatbelastning ur livscykelperspektiv. Svårigheter har dock funnits i att omsätta metodiken på större komponenter än enskilda material. Därför har europastandarder tagits fram som enkom tjänar till att systematisera livscykelanalyser av hela byggnader och de kommer att följas i denna studie. Syftet med examensarbetet är att jämföra hur ett typhus med tegel som stommaterial belastar miljön under produktion och drift i en livscykel satt till 100 år, jämfört med ett motsvarande trätyphus. Till tegelhusets nackdel talar den höga energiåtgången vid materialframställningen. Trä å sin sida löper stor risk för förkortad livscykel i och med riskerna för fuktskador. För att undersöka skillnaderna i trä- och tegelkonstruktioner har en typhusritning i kanalmurskonstruktion analyserats mot en motsvarande träkonstruktion, där byggnadstyperna har samma boarea och väggkonstruktionerna samma värmemotstånd. För att få fram husens skillnad energiåtgång under driftskedet har energibehovsberäkningar utförts för byggnaderna. Livscykelanalysen har utförts i programvaran Anavitor utifrån 3D-modeller med byggnadsinformation som matchas mot en materialdatabas med livscykeldata. Ur jämförelsen har resultat kunnat hämtas på vilken av konstruktionerna som belastar miljön minst över livscykeln, med avseende på klimatbelastning räknat i koldioxidekvivalenter. Resultat visar att ett tegelhus belastar miljön dubbelt så mycket som ett trähus i produktionsfasen medan tegelhuset är miljövänligare avseende underhåll och drift. Efter 100 år är skillnaden 7,3 ton koldioxidekvivalenter, till trähusets fördel. Enligt livscykelanalysen har byggnaderna, enligt de antaganden som gjorts, belastat miljön lika efter 168 år. Till tegelhusets fördel talar dess säkerhet gällande livslängd, beständighet, fuktsäkerhet och goda möjlighet till återbruk av stommaterialet.Since the mid-1900s has brick building marginalized; the material has in the modernist era been experienced as dated and the construction method considered inefficient. In the 1930s the canal wall technique were developed to meet the coming stringent energy requirements. Despite opportunities to meet modern building norms have yet lightweight timber structures dominated the Swedish construction sector concerning single-family houses since then. The requirements for energy conservation have increased over the years to an even greater degree, and Life Cycle Assessment (LCA) has been developed; a methodology that analyzes products from a life cycle perspective. There have been difficulties to put the methodology on larger components than individual materials. Therefore, European Standards have been developed that specifically serve to systematize Life Cycle Assessments of entire buildings, which will be followed in this study. The purpose of this study is to compare which impact a standard house with brick structure has a on the environment in a lifecycle set to 100 years, compared with a corresponding timber structure. To the disadvantage for a brick house speaks the high energy consumption in material production. Timber structures at their part are at high risk for shortened life cycle due to risk of moisture damage. To examine the differences in wood and brick structures has a standard house drawing in canal wall technique been analyzed against a corresponding wooden construction. The building types have the same floor area and the wall constructions have the same heat resistance. To receive the differences in energy use during the operational phase between the buildings has energy calculations been made. The life cycle analysis has been performed in the software Anavitor based on 3D models with building information that is matched against a database of materials life cycle data. The results from the comparison are measured in terms of carbon dioxide equivalents, and will show which construction type will make least impact on the environment. Results show that a brick house has doubled environmental impact compared to a wooden house in the production phase. The brick house is a better alternative concerning environmental impact during operational phase and maintenance. After 100 years, the difference is 7,3 tons of carbon dioxide equivalents to the advantage of the wooden house. According to the LCA and the assumptions made, the buildings have charged the environment equally after 168 years. To the advantage of the brick house speaks its longevity, durability, moisture resistance and good opportunity for reuse of the bricks

Lack of Suppressive CD4+CD25+FOXP3+ T Cells in Advanced Stages of Primary Cutaneous T-Cell Lymphoma

Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25− T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25− T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56 +CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) <50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL <50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. Trial Registration: ClinicalTrials.gov NCT00084019

Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-κB Activation

Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-κB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-κB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-κB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis–fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-κB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-κB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS

Dutch Oncology COVID-19 consortium:Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Aim of the study: Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients' characteristics, cancer diagnosis and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results: Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045) and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥65 years). Conclusion: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to severe acute respiratory syndrome coronavirus 2, whereas treatment adjustments and prioritising vaccination, when available, should also be considered

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Cardiac function in a novel dystrophic mouse model

Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disease that primarily affects young males. It causes progressive weakness of the skeletal and cardiac muscles, and is eventually fatal. While there are several existing therapeutic interventions for DMD, currently there is no cure. The purpose of this study was to measure initial cardiac physiological performance in the novel D2 dystrophic mouse model. The genotype of the mouse model utilized in this study contains the same spontaneous dystrophin gene mutation that DMD patients have, while maintaining possession of the utrophin-producing gene. The unique genetic makeup of the D2 mouse is believed to more accurately reflect the physiology and histology experienced by human DMD patients. At four months old and prior to any therapeutic intervention, the D2 mice group (n = 10) and the control group of D2J mice (n = 10) underwent technician-blinded echocardiograms while anesthetized, in order to assess the functionality of their cardiac muscle. Values acquired from these echocardiograms included cardiac output (CO), left ventricular mass (LVmass), percent ejection fraction (%EF), percent fractional shortening (%FS), and stroke volume (SV), to measure cardiac functionality levels. When compared to the D2J mice, D2 mice did not demonstrate statistically significant differences in cardiac physiology. In future research, baseline cardiac measurements of these D2 mice can be compared to cardiac measurements from D2 mice treated in subsequent experiments, in order to evaluate the efficacy of new DMD supplementation and medication