Abstract Background A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2–related factor 2 (Nrf2) activator, slows progression to end-stage ...renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention. Methods and Results We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min−1 1.73 m−2 ) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl– and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events. Conclusions Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.
Eosinophilic esophagitis (EoE), a food antigen–mediated disease, is effectively treated with the dietary elimination of 6 foods commonly associated with food allergies (milk, wheat, egg, soy, tree ...nuts/peanuts, and fish/shellfish). Because wheat shares homologous proteins (including gluten) with barley and rye and can also be processed with these grains, some clinicians have suggested that barley and rye might also trigger EoE as a result of cross-reaction and/or cross-contamination with wheat. In this article, we discuss the theoretical risks of cross-reactivity and cross-contamination among wheat, barley, and rye proteins (including gluten); assess common practices at EoE treatment centers; and provide recommendations for dietary treatment and future studies of EoE.
The glycemic index (GI) has been included in the Canadian clinical practice guidelines for type 2 diabetes (T2D) management since 2003, and even longer in other parts of the world (e.g., Australia). ...Despite this, dietitians have reported that GI is "too difficult for patients to understand and apply." They have called for diverse GI-utility data and evidence-informed education materials. To address these concerns, we developed and evaluated a GI education workshop and supporting materials, using the Kirkpatrick Model, for a T2D population. Participants (
= 29) with T2D attended a dietitian-facilitated workshop and received education materials. A mixed-form questionnaire (GIQ) and 3-day-diet-record were used to capture patient demographics, satisfaction, knowledge, and application, prior to and immediately after the workshop, 1-week, and 4-weeks post-education. Dietary GI was significantly lower at 1 and 4 weeks post-education (mean ± SEM; both 54 ± 1), compared to pre-education (58 ± 1;
≤ 0.001). Participants (28/29) were satisfied with the intervention. The GI knowledge score was significantly higher post-education at baseline (83.5 ± 3.4%;
≤ 0.001), week one (87.5 ± 2.6%;
= 0.035), and week four (87.6 ± 3.8%;
= 0.011) when compared to pre-education (53.6 ± 5.1%). A significant reduction in dietary GI was achieved by participants living with T2D, after completing the workshop, and they were able to acquire and apply GI knowledge in a relatively short period.
To understand how strong emission-line galaxies (SELGs) contribute to the overall growth of galaxies and star formation history of the universe, we target SELGs from the ZFOURGE imaging survey that ...have blended Hβ+O iii rest-frame equivalent widths of >230 and 2.5 < < 4.0. Using Keck/MOSFIRE, we measure 49 redshifts for galaxies brighter than Ks = 25 mag as part of our Multi-Object Spectroscopic Emission Line (MOSEL) survey. Our spectroscopic success rate is ∼53% and uncertainty is = Δz/(1+z) = 0.0135. We confirm 31 ELGs at , and show that SELGs have spectroscopic rest-frame O iii5007 equivalent widths of 100-500 and tend to be lower-mass systems ∼ 8.2-9.6 compared with more typical star-forming galaxies. The SELGs lie ∼0.9 dex above the star-forming main sequence at z ∼ 3.5 and have high inferred gas fractions of 60%, i.e., the inferred gas masses can easily fuel a starburst to double stellar masses within ∼10-100 Myr. Combined with recent results using ZFOURGE, our analysis indicates that (1) strong O iii5007 emission signals an early episode of intense stellar growth in low-mass galaxies and (2) many, if not most, galaxies at z > 3 go through this starburst phase. If true, low-mass galaxies with strong O iii5007 emission (EWrest > 200 ) may be an increasingly important source of ionizing UV radiation at z > 3.
We measure the evolution of the quiescent fraction and quenching efficiency of satellites around star-forming and quiescent central galaxies with stellar mass ...$\mathrm{log}({M}_{\mathrm{cen}}/{M}_{\odot })\gt 10.5$ at $0.3\lt z\lt 2.5$. We combine imaging from three deep near-infrared-selected surveys (ZFOURGE/CANDELS, Ultra Deep Survey, and UltraVISTA), which allows us to select a stellar-mass complete sample of satellites with $\mathrm{log}({M}_{\mathrm{sat}}/{M}_{\odot })\gt 9.3$. Satellites for both star-forming and quiescent central galaxies ("centrals") have higher quiescent fractions compared to field galaxies matched in stellar mass at all redshifts. We also observe "galactic conformity": satellites around quiescent centrals are more likely to be quenched compared to the satellites around star-forming centrals. Therefore, conformity (and thus satellite quenching) has been present for a significant fraction of the age of the universe. We discuss physical effects that may contribute to galactic conformity, and emphasize that they must allow for continued star formation in the central galaxy even as the satellites are quenched.
The COVID-19 pandemic has put unprecedented pressure on public health resources around the world. From adversity, opportunities have arisen to measure the state and dynamics of human disease at a ...scale not seen before. In the United Kingdom, the evidence that wastewater could be used to monitor the SARS-CoV-2 virus prompted the development of National wastewater surveillance programmes. The scale and pace of this work has proven to be unique in monitoring of virus dynamics at a national level, demonstrating the importance of wastewater-based epidemiology (WBE) for public health protection. Beyond COVID-19, it can provide additional value for monitoring and informing on a range of biological and chemical markers of human health. A discussion of measurement uncertainty associated with surveillance of wastewater, focusing on lessons-learned from the UK programmes monitoring COVID-19 is presented, showing that sources of uncertainty impacting measurement quality and interpretation of data for public health decision-making, are varied and complex. While some factors remain poorly understood, we present approaches taken by the UK programmes to manage and mitigate the more tractable sources of uncertainty. This work provides a platform to integrate uncertainty management into WBE activities as part of global One Health initiatives beyond the pandemic.
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•Wastewater is a relatively unbiased medium transporting multiple markers of human health.•Biological- and chemical-based Wastewater-Based Epidemiology provides flexibility and resilience for public health security.•Measurements of target analytes in wastewater are subject to variability and uncertainty.•Identifying and mitigating uncertainty requires multi-disciplinary collaboration.•UK wastewater monitoring programmes have generated a substantial data resource to derive better understanding of uncertainty.
Precision medicine is projected to become integral to childhood cancer care. As such, it is essential to support families to understand what precision medicine entails.
A total of 182 parents and 23 ...adolescent patients participating in Precision Medicine for Children with Cancer (PRISM), an Australian precision medicine clinical trial for high-risk childhood cancer, completed questionnaires after study enrollment (time 0 T0). Of the parents, 108 completed a questionnaire and 45 completed an interview following return of precision medicine results (time 1 T1). We analyzed the mixed-methods data comprising measures exploring families' perceptions and understanding of PRISM's participant information sheet and consent form (PISCF), and factors associated with understanding.
Most parents were satisfied with the PISCF, rating it as at least "somewhat" clearly presented (n = 160/175; 91%) and informative (n = 158/175; 90%). Many suggested improvements including the use of clearer language and a more visually engaging format. Parents' actual understanding of precision medicine was low on average, but scores improved between T0 and T1 (55.8/100-60.0/100; p = .012). Parents from culturally and/or linguistically diverse backgrounds (n = 42/177; 25%) had lower actual understanding scores than those from a Western/European background whose first language was English (p = .010). There was little correlation between parents' perceived and actual understanding scores (p = .794; Pearson correlation -0.020; 95% CI, -0.169 to 0.116). Most adolescent patients read the PISCF either "briefly" or "not at all" (70%) and had a perceived understanding score of 63.6/100 on average.
Our study revealed gaps in families' understanding of childhood cancer precision medicine. We highlighted areas for potential intervention such as through targeted information resources.
Precision medicine is projected to become part of the standard of care for children with cancer. Precision medicine aims to give the right treatment to the right patient and involves several complex techniques, many of which may be challenging to understand. Our study analyzed questionnaire and interview data from parents and adolescent patients enrolled in an Australian precision medicine trial. Findings revealed gaps in families' understanding of childhood cancer precision medicine. Drawing on parents' suggestions and the literature, we make brief recommendations about improving information provision to families, such as through targeted information resources.
Objective To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. Study design We performed a ...multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. Results One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% IQR 17-88 vs 0% IQR 0-52, P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). Conclusions Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.
We investigate active galactic nuclei (AGN) candidates within the FourStar Galaxy Evolution Survey (ZFOURGE) to determine the impact they have on star formation in their host galaxies. We first ...identify a population of radio, X-ray, and infrared-selected AGN by cross-matching the deep Ks
-band imaging of ZFOURGE with overlapping multiwavelength data. From this, we construct a mass-complete (log(
$M_{{\ast }}/\text{M}_{{\odot }}$
) ≥9.75), AGN luminosity limited sample of 235 AGN hosts over z = 0.2–3.2. We compare the rest-frame U − V versus V − J (UVJ) colours and specific star formation rates (sSFRs) of the AGN hosts to a mass-matched control sample of inactive (non-AGN) galaxies. UVJ diagnostics reveal AGN tend to be hosted in a lower fraction of quiescent galaxies and a higher fraction of dusty galaxies than the control sample. Using 160 μm Herschel PACS data, we find the mean specific star formation rate of AGN hosts to be elevated by 0.34 ± 0.07 dex with respect to the control sample across all redshifts. This offset is primarily driven by infrared-selected AGN, where the mean sSFR is found to be elevated by as much as a factor of ∼5. The remaining population, comprised predominantly of X-ray AGN hosts, is found mostly consistent with inactive galaxies, exhibiting only a marginal elevation. We discuss scenarios that may explain these findings and postulate that AGN are less likely to be a dominant mechanism for moderating galaxy growth via quenching than has previously been suggested.
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