Discussion Paper for Regional Consultations on the Implementation of the United Nations Environment Assembly Resolution on Mineral Resource Governance (UNEP/EA.4/Res. 19)

This discussion paper is prepared to support regional consultations held on the implementation of the United Nations Environment Assembly\ua0resolution on Mineral Resource Governance.\ua0The discussion paper summarises global trends in minerals\ua0and sustainable development and presents key findings from recent studies of mineral governance\ua0developed by UNEP and others. Options for the governance of minerals and lessons from best practices are also discussed. Questions are posed for consideration during consultations and future action on the topic. Findings from the regional consultations will feed into the report on the implementation of the resolution, which will be presented to the UNEA at its fifth session in February 2021

Automated detectionof very low surface brightness galaxiesin the Virgo cluster

We report the automatic detection of a new sample of very low surface brightness (LSB) galaxies, likely members of the Virgo cluster. We introduce our new software, {\tt DeepScan}, that has been designed specifically to detect extended LSB features automatically using the DBSCAN algorithm. We demonstrate the technique by applying it over a 5 degree$^2$ portion of the Next-Generation Virgo Survey (NGVS) data to reveal 53 low surface brightness galaxies that are candidate cluster members based on their sizes and colours. 30 of these sources are new detections despite the region being searched specifically for LSB galaxies previously. Our final sample contains galaxies with $26.0\leq\langle \mu_{e}\rangle\leq28.5$ and $19\leq m_{g}\leq21$, making them some of the faintest known in Virgo. The majority of them have colours consistent with the red sequence, and have a mean stellar mass of $10^{6.3\pm0.5} M_{\odot}$ assuming cluster membership. After using {\tt ProFit} to fit S\'ersic profiles to our detections, none of the new sources have effective radii larger than 1.5 Kpc and do not meet the criteria for ultra-diffuse galaxy (UDG) classification, so we classify them as ultra-faint dwarfs.Comment: 16 pages, 14 figures, Accepted for publication in MNRAS 201

Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention

Early-type stars observed in the ESO UVES Paranal Observatory Project - V. Time-variable interstellar absorption

The structure and properties of the diffuse interstellar medium (ISM) on small scales, sub-au to 1 pc, are poorly understood. We compare interstellar absorption-lines, observed towards a selection of O- and B-type stars at two or more epochs, to search for variations over time caused by the transverse motion of each star combined with changes in the structure in the foreground ISM. Two sets of data were used: 83 VLT- UVES spectra with approximately 6 yr between epochs and 21 McDonald observatory 2.7m telescope echelle spectra with 6 - 20 yr between epochs, over a range of scales from 0 - 360 au. The interstellar absorption-lines observed at the two epochs were subtracted and searched for any residuals due to changes in the foreground ISM. Of the 104 sightlines investigated with typically five or more components in Na I D, possible temporal variation was identified in five UVES spectra (six components), in Ca II, Ca I and/or Na I absorption-lines. The variations detected range from 7\% to a factor of 3.6 in column density. No variation was found in any other interstellar species. Most sightlines show no variation, with 3{\sigma} upper limits to changes of the order 0.1 - 0.3 dex in Ca II and Na I. These variations observed imply that fine-scale structure is present in the ISM, but at the resolution available in this study, is not very common at visible wavelengths. A determination of the electron densities and lower limits to the total number density of a sample of the sightlines implies that there is no striking difference between these parameters in sightlines with, and sightlines without, varying components.Comment: 19 pages, 11 figures, accepted for publication in MNRA

A Smartphone-Based Tool for Rapid, Portable, and Automated Wide-Field Retinal Imaging.

Purpose:High-quality, wide-field retinal imaging is a valuable method for screening preventable, vision-threatening diseases of the retina. Smartphone-based retinal cameras hold promise for increasing access to retinal imaging, but variable image quality and restricted field of view can limit their utility. We developed and clinically tested a smartphone-based system that addresses these challenges with automation-assisted imaging. Methods:The system was designed to improve smartphone retinal imaging by combining automated fixation guidance, photomontage, and multicolored illumination with optimized optics, user-tested ergonomics, and touch-screen interface. System performance was evaluated from images of ophthalmic patients taken by nonophthalmic personnel. Two masked ophthalmologists evaluated images for abnormalities and disease severity. Results:The system automatically generated 100° retinal photomontages from five overlapping images in under 1 minute at full resolution (52.3 pixels per retinal degree) fully on-phone, revealing numerous retinal abnormalities. Feasibility of the system for diabetic retinopathy (DR) screening using the retinal photomontages was performed in 71 diabetics by masked graders. DR grade matched perfectly with dilated clinical examination in 55.1% of eyes and within 1 severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity was 93.3% and specificity 56.8%. Conclusions:Automation-assisted imaging produced high-quality, wide-field retinal images that demonstrate the potential of smartphone-based retinal cameras to be used for retinal disease screening. Translational Relevance:Enhancement of smartphone-based retinal imaging through automation and software intelligence holds great promise for increasing the accessibility of retinal screening

Response to Letter to the Editor from Richard Dorin:Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

Diabetes mellitus: pathophysiological changes and therap

Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

Context: Patients with critical illness are thought to be at risk of adrenal insufficiency. There are no models of dynamic hypothalamic-pituitary-adrenal (HPA) axis function in this group of patients and thus current methods of diagnosis are based on aggregated, static models.Objective: To characterize the secretory dynamics of the HPA axis in the critically ill (CI) after cardiac surgery.Design: Mathematical modeling of cohorts.Setting: Cardiac critical care unit.Patients: 20 male patients CI at least 48 hours after cardiac surgery and 19 healthy (H) male volunteers. Interventions: None.Main Outcome Measures: Measures of hormone secretory dynamics were generated from serum adrenocorticotrophic hormone (ACTH) sampled every hour and total cortisol every 10 min for 24 h.Results: All CI patients had pulsatile ACTH and cortisol profiles. CI patients had similar ACTH secretion (1036.4 [737.6] pg/mL/24 h) compared to the H volunteers (1502.3 [1152.2] pg/mL/24 h; P=.20), but increased cortisol secretion (CI: 14 447.0 [5709.3] vs H: 5915.5 [1686.7)] nmol/L/24 h; P<.0001). This increase in cortisol was due to nonpulsatile (CI: 9253.4 [3348.8] vs H: 960 [589.0] nmol/L/24 h, P<.0001), rather than pulsatile cortisol secretion (CI: 5193.1 [3018.5] vs H: 4955.1 [1753.6] nmol/L/24 h; P=.43). Seven (35%) of the 20 CI patients had cortisol pulse nadirs below the current international guideline threshold for critical illness-related corticosteroid insufficiency, but an overall secretion that would not be considered deficient.Conclusions: This study supports the premise that current tests of HPA axis function are unhelpful in the diagnosis of adrenal insufficiency in the CI. The reduced ACTH and increase in nonpulsatile cortisol secretion imply that the secretion of cortisol is driven by factors outside the HPA axis in critical illness.Diabetes mellitus: pathophysiological changes and therap

Non-resonant Coherent Amplitude Transfer in Attosecond Four-Wave Mixing Spectroscopy

Attosecond four-wave mixing spectroscopy using an XUV pulse and two noncollinear near-infrared pulses is employed to measure Rydberg wavepacket dynamics resulting from extreme ultraviolet excitation of a 3s electron in atomic argon into a series of autoionizing 3s-1np Rydberg states around 29 eV. The emitted signals from individual Rydberg states exhibit oscillatory structure and persist well beyond the expected lifetimes of the emitting Rydberg states. These results reflect substantial contributions of longer-lived Rydberg states to the four wave mixing emission signals of each individually detected state. A wavepacket decomposition analysis reveals that coherent amplitude transfer occurs predominantly from photoexcited 3s-1(n+1)p states to the observed 3s-1np Rydberg states. The experimental observations are reproduced by time-dependent Schr\"odinger equation simulations using electronic structure and transition moment calculations. The theory highlights that coherent amplitude transfer is driven non-resonantly to the 3s-1np states by the near-infrared light through 3s-1(n+1)s and 3s-1(n-1)d dark states during the four-wave mixing process

Detecting Regulatory Mechanisms in Endocrine Time Series Measurements

The regulatory mechanisms underlying pulsatile secretion are complex, especially as it is partly controlled by other hormones and the combined action of multiple agents. Regulatory relations between hormones are not directly observable but may be deduced from time series measurements of plasma hormone concentrations. Variation in plasma hormone levels are the resultant of secretion and clearance from the circulation. A strategy is proposed to extract inhibition, activation, thresholds and circadian synchronicity from concentration data, using particular association methods. Time delayed associations between hormone concentrations and/or extracted secretion pulse profiles reveal the information on regulatory mechanisms. The above mentioned regulatory mechanisms are illustrated with simulated data. Additionally, data from a lean cohort of healthy control subjects is used to illustrate activation (ACTH and cortisol) and circadian synchronicity (ACTH and TSH) in real data. The simulation and the real data both consist of 145 equidistant samples per individual, matching a 24-hr time span with 10 minute intervals. The results of the simulation and the real data are in concordance

Heaviness, health and happiness: a cross-sectional study of 163 066 UK Biobank participants

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Obesity is known to increase the risk of many diseases and reduce overall quality of life. This study examines the relationship with self-reported health (SRH) and happiness.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; &lt;p&gt;&lt;/p&gt;We conducted a cross-sectional study of the 163 066 UK Biobank participants who completed the happiness rating. The association between adiposity and SRH and happiness was examined using logistic regression. SRH was defined as good (excellent, good), or poor (fair, poor). Self-reported happiness was defined as happy (extremely, very, moderately) or unhappy (moderately, very, extremely). &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; &lt;p&gt;&lt;/p&gt;Poor health was reported by 44 457 (27.3%) participants. The adjusted ORs for poor health were 3.86, 2.92, 2.60 and 6.41 for the highest, compared with lowest, deciles of Body Mass Index, waist circumference, waist to hip ratio and body fat percent, respectively. The associations were stronger in men (p&lt;0.001). Overall, 7511 (4.6%) participants felt unhappy, and only class III obese participants were more likely to feel unhappy (adjusted OR 1.33, 95% CI 1.15 to 1.53, p&lt;0.001) but the associations differed by sex (p&lt;0.001). Among women, there was a significant association between unhappiness and all levels of obesity. By contrast, only class III obese men had significantly increased risk and overweight and class I obese men were less likely to be unhappy. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt;Obesity impacts adversely on happiness as well as health, but the association with unhappiness disappeared after adjustment for self-reported health, indicating this may be mediated by health. Compared with obese men, obese women are less likely to report poor health, but more likely to feel unhappy. &lt;p&gt;&lt;/p&gt