Implications for workability and survivability in populations exposed to extreme heat under climate change: A modelling study

Background: Changes in temperature and humidity due to climate change affect living and working conditions. An understanding of the effects of different global temperature changes on population health is needed to inform the continued implementation of the Paris Climate Agreement and to increase global ambitions for greater cuts in emissions. By use of historical and projected climate conditions, we aimed to investigate the effects of climate change on workability (ie, the ability to work) and survivability (the ability to survive). Methods: In this modelling study, we estimated the changes in populations exposed to excessive heat stress between the recent past (ie, 1986–2005) and 2100. We used climate data from four models to calculate the wet-bulb globe temperature, an established heat exposure index that can be used to assess the effects of temperature, humidity, and other environmental factors on humans. We defined and applied thresholds for risks to workability (where the monthly mean of daily maximum wet-bulb globe temperature exceeds 34°C) and survivability (where the maximum daily wet-bulb globe temperature exceeds 40°C for 3 consecutive days), and we used population projections to quantify changes in risk associated with different changes to the global temperature. Findings: The risks to workability increase substantially with global mean surface temperature in all four climate models, with approximately 1 billion people affected globally after an increase in the global temperature of about 2·5°C above pre-industrial levels. There is greater variability between climate models for exposures above the threshold for risks to survivability than for risks to workability. The number of people who are likely to be exposed to heat stress exceeding the survivability threshold increases with global temperature change, to reach around 20 million people globally after an increase of about 2·5°C, estimated from the median of the models, but with a large model uncertainty. More people are likely to be exposed to heat stress in urban than in rural areas. Population exposure can fluctuate over time and change substantially within one decade. Interpretation: Exposure to excessive heat stress is projected to be widespread in tropical or subtropical low-income and middle-income countries, highlighting the need to build on the Paris Agreement regarding global temperature targets, to protect populations who have contributed little to greenhouse gas emissions. The non-linear dependency of heat exposure risk on temperature highlights the importance of understanding thresholds in coupled human-climate systems

Prostate Diffusion Weighted-Magnetic Resonance Image analysis using Multivariate Curve Resolution methods

[EN] Multivariate Curve Resolution (MCR) has been applied on prostate Diffusion Weighted-Magnetic Resonance Images (DW-MRI). Different physiological-based modeling approaches of the diffusion process have been submitted to validation by sequentially incorporating prior knowledge on the MCR constraints. Results validate the biexponential diffusion modeling approach and show the capability of the MCR models to find, characterize and locate the behaviors related to the presence of an early prostate tumor.The authors want to thank prof. Anna de Juan for her comments and help in using the software for this study. This research work was partially supported by the Spanish Ministry of Economy and Competitiveness under the project DPI 2011-28112-004-02.Aguado Sarrió, E.; Prats-Montalbán, JM.; Sanz Requena, R.; Marti Bonmati, L.; Alberich Bayarri, Á.; Ferrer Riquelme, AJ. (2015). Prostate Diffusion Weighted-Magnetic Resonance Image analysis using Multivariate Curve Resolution methods. Chemometrics and Intelligent Laboratory Systems. 140:43-48. https://doi.org/10.1016/j.chemolab.2014.11.002S434814

65 Cybele in the thermal infrared: Multiple observations and thermophysical analysis

We investigated the physical and thermal properties of 65 Cybele}, one of the largest main-belt asteroids. Based on published and recently obtained thermal infrared observations, including ISO measurements, we derived through thermophysical modelling (TPM) a size of 302x290x232 km (+/- 4 %) and an geometric visible albedo of 0.050+/-0.005. Our model of a regolith covered surface with low thermal inertia and "default" roughness describes the wavelengths and phase angle dependent thermal aspects very well. Before/after opposition effect and beaming behaviour can be explained in that way. We found a constant emissivity of 0.9 at wavelengths up to about 100 micron and lower values towards the submillimetre range, indicating a grain size distribution dominated by 200 micron particle sizes. The spectroscopic analysis revealed an emissivity increase between 8.0 and 9.5 micron. We compared this emissivity behaviour with the Christiansen features of carbonaceous chondrite meteorites, but a conclusive identification was not possible. A comparison between the Standard Thermal Model (STM) and the applied TPM clearly demonstrates the limitations and problems of the STM for the analysis of multi-epoch and -wavelengths observations. While the TPM produced a unique diameter/albedo solution, the calculated STM values varied by +/-30 % and showed clear trends with wavelength and phase angle. Cybele can be considered as a nice textbook case for the thermophysical analysis of combined optical and thermal infrared observations.Comment: 11 pages, 8 figures, accepted for publication by A&

De Novo Missense Variants in SLC32A1 Cause a Developmental and Epileptic Encephalopathy Due to Impaired GABAergic Neurotransmission

Objective:Rare inherited missense variants inSLC32A1, the gene that encodes the vesicular gamma-aminobutyric acid(GABA) transporter, have recently been shown to cause genetic epilepsy with febrile seizures plus. We aimed to clarifyif de novo missense variants inSLC32A1can also cause epilepsy with impaired neurodevelopment.Methods:Using exome sequencing, we identified four individuals with a developmental and epileptic encephalopathyand de novo missense variants inSLC32A1. To assess causality, we performed functional evaluation of the identifiedvariants in a murine neuronal cell culture model.Results:The main phenotype comprises moderate-to-severe intellectual disability, infantile-onset epilepsy within thefirst 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder. In silico modeling and functionalanalyses reveal that three of these variants, which are located in helices that line the putative GABA transport pathway,result in reduced quantal size, consistent with impairedfilling of synaptic vesicles with GABA. The fourth variant,located in the vesicular gamma-aminobutyric acid N-terminus, does not affect quantal size, but increases presynapticrelease probability, leading to more severe synaptic depression during high-frequency stimulation. Thus, variants invesicular gamma-aminobutyric acid can impair GABAergic neurotransmission through at least two mechanisms, byaffecting synaptic vesiclefilling and by altering synaptic short-term plasticity.Interpretation:This work establishes de novo missense variants inSLC32A1as a novel cause of a developmental andepileptic encephalopathy

In cis TP53 and RAD51C pathogenic variants may predispose to sebaceous gland carcinomas

Pathogenic variants in TP53 have been classically thought to cause Li-Fraumeni syndrome (LFS), a cancer predisposition with high risks for various childhood- and adult-onset malignancies. However, increased genetic testing has lately revealed, that pathogenic variant carriers exhibit a broader range of phenotypes and that penetrance may be dependent both on variant type and modifiers. Using next generation sequencing and short tandem repeat analysis, we identified germline pathogenic variants in TP53 and RAD51C located in cis on chromosome 17 in a 43-year-old male, who has developed a rare sebaceous gland carcinoma (SGC) but so far no tumors of the LFS spectrum. This course mirrors a Trp53-Rad51c-double-mutant cis mouse-model, which similarly develops SGC, while the characteristic Trp53-associated tumor spectrum occurs with significantly lower frequency. Therefore, we propose that co-occurent pathogenic variants in RAD51C and TP53 may predispose to SGC, reminiscent of Muir-Torre syndrome. Further, this report supports the diversity of clinical presentations associated with germline TP53 alterations, and thus, the proposed expansion of LFS to heritable TP53-related cancer syndrome

ISM Properties in Low-Metallicity Environments II. The Dust Spectral Energy Distribution of NGC 1569

We present new 450 and 850 microns SCUBA data of the dwarf galaxy NGC 1569. We construct the mid-infrared to millimeter SED of NGC 1569, using ISOCAM, ISOPHOT, IRAS, KAO, SCUBA and MAMBO data, and model the SED in order to explore the nature of the dust in low metallicity environments. The detailed modeling is performed in a self-consistent way, synthesizing the global ISRF of the galaxy using an evolutionary synthesis model with further constraints provided by the observed MIR ionic lines and a photoionisation model. Our results show that the dust properties are different in this low metallicity galaxy compared to other more metal rich galaxies. The results indicate a paucity of PAHs probably due to the destructive effects of the ISRF penetrating a clumpy environment and a size-segregation of grains where the emission is dominated by small grains of size ~3 nm, consistent with the idea of shocks having a dramatic effect on the dust properties in NGC 1569. A significant millimetre excess is present in the dust SED which can be explained by the presence of ubiquitous very cold dust (T = 5-7 K). This dust component accounts for 40 to 70 % of the total dust mass in the galaxy (1.6 - 3.4 10^5 Msol) and could be distributed in small clumps (size a few pc) throughout the galaxy. We find a gas-to-dust mass ratio of 740 - 1600, larger than that of the Galaxy and a dust-to-metals ratio of 1/4 to 1/7. We generate an extinction curve for NGC 1569, consistent with the modeled dust size distribution. This extinction curve has relatively steep FUV rise and smaller 2175 Angstroms bump, resembling the observed extinction curve of some regions in the Large Magellanic Cloud.Comment: 20 pages, 20 figures, accepted by A&

Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion

The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive. We analyzed gene expression using blood from three individuals with 15q13.3 microdeletion and brain cortex tissue from ten mice Df[h15q13]/+. We assessed differentially expressed genes (DEGs), protein–protein interaction (PPI) functional modules, and gene expression in brain developmental stages. The deleted genes’ haploinsufficiency was not transcriptionally compensated, suggesting a dosage effect may contribute to the pathomechanism. DEGs shared between tested individuals and a corresponding mouse model show a significant overlap including genes involved in monogenic neurodevelopmental disorders. Yet, network-wide dysregulatory effects suggest the phenotype is not caused by a single critical gene. A significant proportion of blood DEGs, silenced in adult brain, have maximum expression during the prenatal brain development. Based on DEGs and their PPI partners we identified altered functional modules related to developmental processes, including nervous system development. We show that the 15q13.3 microdeletion has a ubiquitous impact on the transcriptome pattern, especially dysregulation of genes involved in brain development. The high phenotypic variability seen in 15q13.3 microdeletion could stem from an increased vulnerability during brain development, instead of a specific pathomechanism

Laser locking to the 199Hg clock transition with 5.4x10^(-15)/sqrt(tau) fractional frequency instability

With Hg atoms confined in an optical lattice trap in the Lamb-Dicke regime, we obtain a spectral line at 265.6 nm in which the full-width at half-maximum is <15Hz. Here we lock an ultrastable laser to this ultranarrow clock transition and achieve a fractional frequency stability of 5.4x10^(-15)/sqrt(tau) for tau<=400s. The highly stable laser light used for the atom probing is derived from a 1062.6 nm fiber laser locked to an ultrastable optical cavity that exhibits a mean drift rate of -6.0x10^(-17) s^(-1) (or -16.9 mHz.s^(-1) at 282 THz) over a five month period. A comparison between two such lasers locked to independent optical cavities shows a flicker noise limited fractional frequency instability of 4x10^(-16) per cavity

ISO spectroscopy of disks around Herbig Ae/Be stars

We have investigated the infrared spectra of all 46 Herbig Ae/Be stars for which spectroscopic data is available in the ISO data archive. Our quantitative analysis of these spectra focusses on the emission bands linked to polycyclic aromatic hydrocarbons (PAHs), the amorphous 10 micron silicate band and the crystalline silicate band at 11.3 micron. We have detected PAH emission in 57% of the Herbig stars in our sample. Clear examples of differences in the PAH spectra are present within our sample, indicating differences in PAH size, chemistry and/or ionization. Amorphous silicate emission was detected in the spectra of 52% of the sample stars, amorphous silicate absorption in 13%. We have detected crystalline silicate emission in 11 stars (24% of our sample), of which four (9%) also display strong PAH emission. We have classified the sample sources according to the strength of their mid-IR energy distribution. The systems with stronger mid-infared (20-100 um) excesses relative to their near-infrared (1-5 um) excess display significantly more PAH emission than those with weaker mid-infrared excesses. This provides strong observational support for the disk models by Dullemond (2002), in which systems with a flaring disk geometry display a strong mid-infrared excess, whereas those with disks that are strongly shadowed by the puffed-up inner rim of the disk only display modest amounts of mid-infrared emission. The PAH emission is expected to be produced mainly in the part of the disk atmosphere that is directly exposed to radiation from the central star. In this model, self-shadowed disks should display weaker PAH emission than flared disks, consistent with our observations.Comment: 27 pages, 26 figures, A&A accepted (22/06/2004