Targeted Albumin Therapy Does Not Improve Short-Term Outcome in Hyponatremic Patients Hospitalized With Complications of Cirrhosis: Data From the ATTIRE Trial

INTRODUCTION: Patients with decompensated cirrhosis and hyponatremia have a poor prognosis. We investigated Albumin to Prevent Infection in Chronic Liver Failure trial data to determine whether targeted albumin infusions improved outcome in patients with hyponatremia at baseline. METHODS: We examined the interaction between targeted albumin and standard care for the composite primary end point, stratifying by baseline sodium ≥ and <130 mmol/L. RESULTS: Randomization to albumin was associated with a significant increase in sodium; however, there was no interaction between sodium category and treatment for the trial primary end point. DISCUSSION: Targeted intravenous albumin infusions increased serum sodium level in hospitalized hyponatremic patients with cirrhosis, but this did not improve outcome

Use of non-selective B-blockers is safe in hospitalised decompensated cirrhosis patients and exerts a potential anti-inflammatory effect: Data from the ATTIRE trial

Background: Nonselective B-blockers (NSBBs) are believed to have pleiotropic effects beyond reducing portal pressure. However, studies also report potential harm in patients hospitalized with cirrhosis and ascites. We therefore investigated whether NSBB use at ATTIRE trial entry (Albumin to prevent infection in chronic liver failure, 2016-19) was associated with increased renal or cardiovascular dysfunction, compared the incidence of infection and plasma markers of systemic inflammation, and examined mortality at 28-days, 3 and 6-months. Methods: In ATTIRE patients grouped by NSBB use at trial entry, we studied infection at baseline, hospital acquired infection and organ dysfunction during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. Findings: There were no differences in renal or cardiovascular dysfunction between patients treated with NSBBs or not, during days 3–15 of hospitalization, despite elevated serum creatinine in NSBB patients at hospitalisation. Use of NSBBs was associated with a significant reduction in infection at hospitalization (p = 0.006), lower white cell counts throughout hospital stay (p < 0.001) and reduced plasma procalcitonin (p = 0.009) and interlukin-8 levels (p = 0.04) at baseline, but markers of bacterial translocation and systemic inflammation were the same in treatment groups. There was no reduction in hospital acquired infections in patients taking NSBBs and no beneficial impact on mortality at 28-days, 3 and 6-months. Interpretations: Our real-world data from a completed randomised trial show that use of NSBBs in decompensated cirrhosis patients is safe during hospitalisation. We also show a potential anti-inflammatory role for NSBBs which may be mediated by a downregulation of IL-8 induced leucocytosis, that was associated with reduced infection at baseline but not a survival benefit. Funding: Wellcome Trust and Department of Health and Social Care

Gas-phase CO2 emission toward Cepheus A East: the result of shock activity?

We report the first detection of gas-phase CO2 emission in the star-forming region Cepheus A East, obtained by spectral line mapping of the v2 bending mode at 14.98 micron with the Infrared Spectrograph (IRS) instrument onboard the Spitzer Space Telescope. The gaseous CO2 emission covers a region about 35'' x 25'' in extent, and results from radiative pumping by 15 micron continuum photons emanating predominantly from the HW2 protostellar region. The gaseous CO2 exhibits a temperature distribution ranging from 50 K to 200 K. A correlation between the gas-phase CO2 distribution and that of H2 S(2), a tracer of shock activity, indicates that the CO2 molecules originate in a cool post-shock gas component associated with the outflow powered by HW2. The presence of CO2 ice absorption features at 15.20 micron toward this region and the lack of correlation between the IR continuum emission and the CO2 gas emission distribution further suggest that the gaseous CO2 molecules are mainly sputtered off grain mantles -- by the passage of slow non-dissociative shocks with velocities of 15-30 km/s -- rather than sublimated through grain heating.Comment: 11 pages, 6 figures, accepted for publication in ApJ

Investigating potential confounding by indication when considering the association between proton pump inhibitor use, infection, hepatic encephalopathy and mortality in hospitalised decompensated cirrhosis: a post-hoc analysis of the ATTIRE trial

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed to prevent and treat upper gastrointestinal ulceration and bleeding. Studies have identified increased incidence of spontaneous bacterial peritonitis and hepatic encephalopathy (HE) in cirrhosis patients taking PPIs. However, results are conflicting, and as PPIs are prescribed for variceal bleeding, a major risk factor for infection and HE, it is challenging to discern whether these associations are causal. METHODS: In this post-hoc analysis of the ATTIRE trial, we pooled all patient data to investigate the effects of PPI use on clinical outcomes. ATTIRE was a multicentre, open-label, randomised trial of targeted 20% human albumin solution (HAS) daily infusions versus standard care involving 777 adults with decompensated cirrhosis hospitalised with acute complications and albumin <30 g/L. Study recruitment was between Jan 25, 2016, and June 28, 2019, at 35 hospitals across England, Scotland, and Wales. Key exclusion criteria were advanced hepatocellular carcinoma with life expectancy <8 weeks and patients receiving palliative care. In ATTIRE, patients were grouped by PPI use at trial entry. We studied infection and HE at baseline and incidence of hospital acquired infection, new onset HE, renal dysfunction and mortality. We attempted with propensity score matching to account for differences in disease severity. FINDINGS: Overall PPI use at baseline was not associated with increased incidence of infection, renal dysfunction or mortality, but was associated with significantly increased incidence of grade III/IV HE during hospital stay (P = 0.011). This was only significant for those taking intravenous PPIs and these patients had >10 times the incidence of variceal bleeding and near double the 28-day mortality compared to non-PPI patients. However, propensity score matching was not possible as there was such a strong selection of patients for PPI use, that we could not find sufficient non-PPI patients to match to. We found no impact of PPI use on plasma markers of bacterial translocation, infection or systemic inflammation. INTERPRETATIONS: Our real-world data from a completed randomised trial show that PPIs are widely prescribed in the UK and judicious use appears safe in patients hospitalised with decompensated cirrhosis. However, patients prescribed PPIs had fundamentally different phenotypes to those not prescribed PPIs, a form of confounding by indication, which should be strongly considered when interpreting studies and making recommendations about their use. FUNDING: Wellcome Trust and Department of Health and Social Care

Fully Sampled Maps of Ices and Silicates in Front of Cepheus A East with Spitzer

We report the first fully sampled maps of the distribution of interstellar CO2 ices, H2O ices and total hydrogen nuclei, as inferred from the 9.7 micron silicate feature, toward the star-forming region Cepheus A East with the IRS instrument onboard the Spitzer Space Telescope. We find that the column density distributions for these solid state features all peak at, and are distributed around, the location of HW2, the protostar believed to power one of the outflows observed in this star-forming region. A correlation between the column density distributions of CO2 and water ice with that of total hydrogen indicates that the solid state features we mapped mostly arise from the same molecular clumps along the probed sight lines. We therefore derive average CO2 ice and water ice abundances with respect to the total hydrogen column density of X(CO2)_ice~1.9x10^-5 and X(H2O)_ice~7.5x10^-5. Within errors, the abundances for both ices are relatively constant over the mapped region exhibiting both ice absorptions. The fraction of CO2 ice with respect to H2O ice is also relatively constant at a value of 22% over that mapped region. A clear triple-peaked structure is seen in the CO2 ice profiles. Fits to those profiles using current laboratory ice analogs suggest the presence of both a low-temperature polar ice mixture and a high-temperature methanol-rich ice mixture along the probed sightlines. Our results further indicate that thermal processing of these ices occurred throughout the sampled region.Comment: 26 pages, 8 figures, accepted for publication in Ap

The IRAC Shallow Survey

The IRAC shallow survey covers 8.5 square degrees in the NOAO Deep Wide-Field Survey in Bootes with 3 or more 30 second exposures per position. An overview of the survey design, reduction, calibration, star-galaxy separation, and initial results is provided. The survey includes approximately 370,000, 280,000, 38,000, and 34,000 sources brighter than the 5 sigma limits of 6.4, 8.8, 51, and 50 microJy at 3.6, 4.5, 5.8, and 8 microns respectively, including some with unusual spectral energy distributions.Comment: To appear in ApJS, Spitzer special issue. For full resolution see http://cfa-www.harvard.edu/irac/publication

Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis

Currently there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, first, that family networks hold strong potential for cascading genetic information, making the adoption of a family centred approach an efficient strategy for this community. However, this is dependent on provision of high quality and timely information from health care providers. Secondly, families’ experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals’ views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information

Politics, Governance, and Leadership: What Can We Learn From the Academy of Management’s Response to EO13769?

Organization design seeks to balance potentially conflicting objectives while achieving a broader mission. EO13769 created a challenge for the president of the Academy of Management in leading through these conflicts, as President Anita McGahan describes: how to be true to her own moral values while leading an organization with well-established design constraints, and members with diverse opinions. This article shares the perspectives of 12 scholars on the lessons we can learn from Professor McGahan’s leadership of a constraining organization through a challenging time

The difference that tenure makes

This paper argues that housing tenures cannot be reduced to either production relations or consumption relations. Instead, they need to be understood as modes of housing distribution, and as having complex and dynamic relations with social classes. Building on a critique of both the productionist and the consumptionist literature, as well as of formalist accounts of the relations between tenure and class, the paper attempts to lay the foundations for a new theory of housing tenure. In order to do this, a new theory of class is articulated, which is then used to throw new light on the nature of class-tenure relations