The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite ...regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.
To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.
Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.
These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.
NCT00750438.
Though there has been a significant amount of work investigating the early stages of low-mass star formation in recent years, the evolution of the mass assembly rate onto the central protostar ...remains largely unconstrained. Examining in depth the variation in this rate is critical to understanding the physics of star formation. Instabilities in the outer and inner circumstellar disk can lead to episodic outbursts. Observing these brightness variations at infrared or submillimeter wavelengths constrains the current accretion models. The JCMT Transient Survey is a three-year project dedicated to studying the continuum variability of deeply embedded protostars in eight nearby star-forming regions at a one-month cadence. We use the SCUBA-2 instrument to simultaneously observe these regions at wavelengths of 450 and 850 m. In this paper, we present the data reduction techniques, image alignment procedures, and relative flux calibration methods for 850 m data. We compare the properties and locations of bright, compact emission sources fitted with Gaussians over time. Doing so, we achieve a spatial alignment of better than 1″ between the repeated observations and an uncertainty of 2%-3% in the relative peak brightness of significant, localized emission. This combination of imaging performance is unprecedented in ground-based, single-dish submillimeter observations. Finally, we identify a few sources that show possible and confirmed brightness variations. These sources will be closely monitored and presented in further detail in additional studies throughout the duration of the survey.
Understanding the influence of peripheral functionality on optoelectronic properties of conjugated materials is an important task for the continued development of chromophores for myriad ...applications. Here, π-extended 1,4-dihydropyrrolo3,2-bpyrrole (DHPP) chromophores with varying electron-donating or electron-withdrawing capabilities were synthesized via Suzuki cross-coupling reactions, and the influence of functionality on optoelectronic properties was elucidated. First, chromophores display distinct differences in the UV–vis absorbance spectra measured via UV–vis absorbance spectroscopy in addition to changes in the onset of oxidation measured with cyclic voltammetry and differential pulse voltammetry. Solution oxidation studies found that variations in the electron-donating and -withdrawing capabilities result in different absorbance profiles of the radical cations that correspond to quantifiably different colors. In addition to fundamental insights into the molecular design of DHPP chromophores and their optoelectronic properties, two chromophores display high-contrast electrochromism, which makes them potentially compelling in electronic devices. Overall, this study represents the ability to fine-tune the optoelectronic properties of DHPP chromophores in their neutral and oxidized states and expands the understanding of structure–property relationships that will guide the continued development of DHPP-based materials.
Abstract The James Clerk Maxwell Telescope (JCMT) Transient Survey has been monitoring eight Gould Belt low-mass star-forming regions since 2015 December and six somewhat more distant ...intermediate-mass star-forming regions since 2020 February with the Submillimeter Common User Bolometer Array 2 on board JCMT at 450 and 850 μ m and with an approximately monthly cadence. We introduce our pipeline v2 relative calibration procedures for image alignment and flux calibration across epochs, improving on our previous pipeline v1 by decreasing measurement uncertainties and providing additional robustness. These new techniques work at both 850 and 450 μ m, where version 1 only allowed investigation of the 850 μ m data. Pipeline v2 achieves better than 0.″5 relative image alignment, less than a tenth of the submillimeter beam widths. The version 2 relative flux calibration is found to be 1% at 850 μ m and <5% at 450 μ m. The improvement in the calibration is demonstrated by comparing the two pipelines over the first 4 yr of the survey and recovering additional robust variables with version 2. Using the full 6 yr of the Gould Belt survey, the number of robust variables increases by 50%, and at 450 μ m we identify four robust variables, all of which are also robust at 850 μ m. The multiwavelength light curves for these sources are investigated and found to be consistent with the variability being due to dust heating within the envelope in response to accretion luminosity changes from the central source.
•Quantification of HPV viral load in oropharyngeal cancer is possible with droplet PCR.•A high viral load is indicative of improved clinical outcome.•Viral load may further risk-stratify HPV positive ...oropharyngeal cancer.
Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available.
In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as “medium/high” if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage.
L1 VL ranged from 0.0014–304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012–356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes.
HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients
Investigating variability at the earliest stages of low-mass star formation is fundamental in understanding how a protostar assembles mass. While many simulations of protostellar disks predict ...non-steady accretion onto protostars, deeper investigation requires robust observational constraints on the frequency and amplitude of variability events characterized across the observable SED. In this study, we develop methods to robustly analyze repeated observations of an area of the sky for submillimeter variability in order to determine constraints on the magnitude and frequency of deeply embedded protostars. We compare 850 m JCMT Transient Survey data with archival JCMT Gould Belt Survey data to investigate variability over 2-4 year timescales. Out of 175 bright, independent emission sources identified in the overlapping fields, we find seven variable candidates, five of which we classify as Strong, and the remaining two we classify as Extended to indicate that the latter are associated with larger-scale structure. For the Strong variable candidates, we find an average fractional peak brightness change per year of 4.0 % yr − 1 , with a standard deviation of 2.7 % yr − 1 . In total, 7% of the protostars associated with 850 m emission in our sample show signs of variability. Four of the five Strong sources are associated with a known protostar. The remaining source is a good follow-up target for an object that is anticipated to contain an enshrouded, deeply embedded protostar. In addition, we estimate the 850 m periodicity of the submillimeter variable source, EC 53, to be 567 32 days, based on the archival Gould Belt Survey data.
We analyze results from the first 18 months of monthly submillimeter monitoring of eight star-forming regions in the JCMT Transient Survey. In our search for stochastic variability in 1643 bright ...peaks, only the previously identified source, EC 53, shows behavior well above the expected measurement uncertainty. Another four sources-two disks and two protostars-show moderately enhanced standard deviations in brightness, as expected for stochastic variables. For the two protostars, this apparent variability is the result of single epochs that are much brighter than the mean. In our search for secular brightness variations that are linear in time, we measure the fractional brightness change per year for 150 bright peaks, 50 of which are protostellar. The ensemble distribution of slopes is well fit by a normal distribution with ∼ 0.023. Most sources are not rapidly brightening or fading at submillimeter wavelengths. Comparison against time-randomized realizations shows that the width of the distribution is dominated by the uncertainty in the individual brightness measurements of the sources. A toy model for secular variability reveals that an underlying Gaussian distribution of linear fractional brightness change = 0.005 would be unobservable in the present sample, whereas an underlying distribution with = 0.02 is ruled out. Five protostellar sources, 10% of the protostellar sample, are found to have robust secular measures deviating from a constant flux. The sensitivity to secular brightness variations will improve significantly with a sample over a longer time duration, with an improvement by factor of two expected by the conclusion of our 36 month survey.
Abstract
The Submillimetre Common User Bolometer Array 2 (SCUBA-2) is the James Clerk Maxwell Telescope’s continuum imager, operating simultaneously at 450 and 850
μ
m. SCUBA-2 was commissioned in ...2009–2011, and since that time, regular observations of point-like standard sources have been performed whenever the instrument is in use. Expanding the calibrator observation sample by an order of magnitude compared to previous work, in this paper we derive updated opacity relations at each wavelength for a new atmospheric extinction correction, analyze the Flux Conversion Factors used to convert instrumental units to physical flux units as a function of date and observation time, present information on the beam profiles for each wavelength, and update secondary calibrator source fluxes. Between 07:00 and 17:00 UTC, the portion of the night that is most stable to temperature gradients that cause dish deformation, the total flux uncertainty and the peak flux uncertainty measured at 450
μ
m are found to be 14% and 17%, respectively. Measured at 850
μ
m, the total flux and peak flux uncertainties are 6% and 7%, respectively. The analysis presented in this work is applicable to all SCUBA-2 projects observed since 2011.
The binary T Tauri system JW 566 in the Orion Molecular Cloud underwent an energetic, short-lived flare observed at submillimeter wavelengths by the SCUBA-2 instrument on 2016 November 26 (UT). The ...emission faded by nearly 50% during the 31 minute integration. The simultaneous source fluxes averaged over the observation are at 450 m and at 850 m. The 850 m flux corresponds to a radio luminosity of , approximately one order of magnitude brighter (in terms of ) than that of a flare of the young star GMR-A, detected in Orion in 2003 at 3mm. The event may be the most luminous known flare associated with a young stellar object and is also the first coronal flare discovered at submillimeter wavelengths. The spectral index between 450 and 850 m of = 0.11 is broadly consistent with nonthermal emission. The brightness temperature was in excess of . We interpret this event to be a magnetic reconnection that energized charged particles to emit gyrosynchrotron/synchrotron radiation.
Background
Elevated lipoprotein(a) (Lpa) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease ...(CAD) in patients admitted to the coronary care unit (CCU) remain to be defined.
Hypothesis
Elevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk.
Methods
Plasma Lp(a) concentrations were measured in consecutive patients admitted to the CCU with an acute coronary syndrome (ACS) or prior history of CAD for 6.5 months. Elevated Lp(a) was defined as concentrations ≥0.5 g/L. Patients with LDL‐C ≥ 5 mmol/L exhibited phenotypic FH. Premature CAD was diagnosed in those age < 60 years, and the relationship between this and elevated Lp(a) and FH was determined by logistic regression.
Results
316 patients were screened; 163 (51.6%) had premature CAD. Overall, elevated Lp(a) and FH were identified in 27.0% and 11.6% of patients, respectively. Both disorders were detected in 4.4% of individuals. Elevated Lp(a) (32.0% vs 22.2%; P = 0.019) and FH phenotype (15.5% vs 8.0%; P = 0.052) were more common with premature vs nonpremature CAD. Elevated Lp(a) alone conferred a 1.9‐fold, FH alone a 3.2‐fold, and the combination a 5.3‐fold increased risk of premature CAD (P = 0.005).
Conclusions
Elevated Lp(a) and phenotypic FH were commonly encountered and more frequent with premature CAD. The combination of both disorders is especially associated with increased CAD risk. Patients admitted to the CCU with ACS or previously documented CAD should be routinely screened for elevated Lp(a) and FH.
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