223 research outputs found

    Chemical signatures of a warped protoplanetary disc

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    Circumstellar discs may become warped or broken into distinct planes if there is a stellar or planetary companion with an orbit that is misaligned with respect to the disc. There is mounting observational evidence for protoplanetary discs with misaligned inner discs and warps that may be caused by such interactions with a previously undetected companion, giving us a tantalising indication of possible planets forming there. Hydrodynamical and radiative transfer models indicate that the temperature varies azimuthally in warped discs due to the variable angle at which the disc surface faces the star and this impacts the disc chemistry. We perform chemical modelling based on a hydrodynamical model of a protoplanetary disc with an embedded planet orbiting at a 12āˆ˜^{\circ} inclination to the disc. Even for this small misalignment, abundances of species including CO and HCO+^+ vary azimuthally and this results in detectable azimuthal variations in submillimetre line emission. Azimuthal variations in line emission may therefore indicate the presence of an unseen embedded companion. Nonaxisymmetric chemical abundances should be considered when interpreting molecular line maps of warped or shadowed protoplanetary discs.Comment: Accepted to MNRAS. 18 pages, 14 figure

    Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans

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    BACKGROUND: Prior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD. MATERIALS/METHODS: This study included Veterans (age ā‰„ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012ā€“2013 to 2015ā€“2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization. RESULTS: Over a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24ā€“0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21ā€“0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13ā€“0.26). A significant part of the effect could be attributed to ā€œhealthy vaccineeā€ bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65ā€“0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60ā€“0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31ā€“0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80ā€“1.18). CONCLUSIONS: Among elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality

    The role of drag and gravity on dust concentration in a gravitationally unstable disc

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    We carry out three-dimensional smoothed particle hydrodynamics simulations to study the role of gravitational and drag forces on the concentration of large dust grains (St > 1) in the spiral arms of gravitationally unstable protoplanetary discs, and the resulting implications for planet formation. We find that both drag and gravity play an important role in the evolution of large dust grains. If we include both, grains that would otherwise be partially decoupled will become well coupled and trace the spirals. For the dust grains most influenced by drag (with Stokes numbers near unity), the dust disc quickly becomes gravitationally unstable and rapidly forms clumps with masses between 0.15ā€“6MāŠ•. A large fraction of clumps are below the threshold where runaway gas accretion can occur. However, if dust self-gravity is neglected, the dust is unable to form clumps, despite still becoming trapped in the gas spirals. When large dust grains are unable to feel either gas gravity or drag, the dust is unable to trace the gas spirals. Hence, full physics is needed to properly simulate dust in gravitationally unstable discs. Dust trapping of large grains in spiral arms of discs stable to gas fragmentation could explain planet formation in very young discs by a population of planetesimals formed due to the combined roles of drag and gravity in the earliest stages of a discā€™s evolution. Furthermore, it highlights that gravitationally unstable discs are not just important for forming gas giants quickly, it can also rapidly form Earth mass bodies

    The Democratic Biopolitics of PrEP

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    PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ā€˜sexual-somatic ethicsā€™ and ā€˜democratic biopoliticsā€™, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ā€˜Biopolitical democratizationā€™ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

    PPARĪ± and PPARĪ³ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective

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    Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARĪ± and PPARĪ³ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARĪ±/Ī³ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARĪ±/Ī³ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARĪ±/Ī³ antagonism alone is not a viable treatment modality for mesothelioma

    Fingolimod: therapeutic mechanisms and ocular adverse effects.

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    Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity

    Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study

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    Recently, peritumoural (lympho)vascular invasion, assessed on haematoxylinā€“eosin (HE)-stained slides, was added to the St Gallen criteria for adjuvant treatment of patients with operable breast cancer (BC). New lymphatic endothelium-specific markers, such as D2-40, make it possible to distinguish between blood (BVI) and lymph vessel invasion (LVI). The aim of this prospective study was to quantify and compare BVI and LVI in a consecutive series of patients with BC. Three consecutive sections of all formalin-fixed paraffin-embedded tissue blocks of 95 BC resection specimens were (immuno)histochemically stained in a fixed order: HE, anti-CD34 (pan-endothelium) and anti-D2-40 (lymphatic endothelium) antibodies. All vessels with vascular invasion were marked and relocated on the corresponding slides. Vascular invasion was assigned LVI (CD34āŠ• or āŠ–/D2-40āŠ•) or BVI (CD34āŠ•/D2-40āŠ–) and intra- (contact with tumour cells or desmoplastic stroma) or peritumoural. The number of vessels with LVI and BVI as well as the number of tumour cells per embolus were counted. Results were correlated with clinico-pathological variables. Sixty-six (69.5%) and 36 (37.9%) patients had, respectively, LVI and BVI. The presence of ā€˜vascular' invasion was missed on HE in 20% (peritumourally) and 65% (intratumourally) of cases. Although LVI and BVI were associated intratumourally (P=0.02), only peritumoural LVI, and not BVI, was associated with the presence of lymph node (LN) metastases (pperi=0.002). In multivariate analysis, peritumoural LVI was the only independent determinant of LN metastases. Furthermore, the number of vessels with LVI was larger than the number of vessels with BVI (P=0.001) and lymphatic emboli were larger than blood vessel emboli (P=0.004). We demonstrate that it is possible to distinguish between BVI and LVI in BC specimens using specific lymphatic endothelium markers. This is important to study the contribution of both processes to BC metastasis. Furthermore, immunohistochemical detection of lymphovascular invasion might be of value in clinical practice

    Factors affecting the use of patient survey data for quality improvement in the Veterans Health Administration

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    <p>Abstract</p> <p>Background</p> <p>Little is known about how to use patient feedback to improve experiences of health care. The Veterans Health Administration (VA) conducts regular patient surveys that have indicated improved care experiences over the past decade. The goal of this study was to assess factors that were barriers to, or promoters of, efforts to improve care experiences in VA facilities.</p> <p>Methods</p> <p>We conducted case studies at two VA facilities, one with stable high scores on inpatient reports of emotional support between 2002 and 2006, and one with stable low scores over the same period. A semi-structured interview was used to gather information from staff who worked with patient survey data at the study facilities. Data were analyzed using a previously developed qualitative framework describing organizational, professional and data-related barriers and promoters to data use.</p> <p>Results</p> <p>Respondents reported more promoters than barriers to using survey data, and particularly support for improvement efforts. Themes included developing patient-centered cultures, quality improvement structures such as regular data review, and training staff in patient-centered behaviors. The influence of incentives, the role of nursing leadership, and triangulating survey data with other data on patients' views also emerged as important. It was easier to collect data on current organization and practice than those in the past and this made it difficult to deduce which factors might influence differing facility performance.</p> <p>Conclusions</p> <p>Interviews with VA staff provided promising examples of how systematic processes for using survey data can be implemented as part of wider quality improvement efforts. However, prospective studies are needed to identify the most effective strategies for using patient feedback to improve specific aspects of patient-centered care.</p
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