Chronically high blood glucose (hyperglycemia) leads to diabetes and fatty liver disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. Here, we show that ...a high-fat diet (HFD) in mice causes early loss of expression of the glycolytic enzyme Hexokinase 2 (HK2) specifically in adipose tissue. Adipose-specific knockout of
reduced glucose disposal and lipogenesis and enhanced fatty acid release in adipose tissue. In a non-cell-autonomous manner,
knockout also promoted glucose production in liver. Furthermore, we observed reduced hexokinase activity in adipose tissue of obese and diabetic patients, and identified a loss-of-function mutation in the
gene of naturally hyperglycemic Mexican cavefish. Mechanistically, HFD in mice led to loss of HK2 by inhibiting translation of
mRNA. Our findings identify adipose HK2 as a critical mediator of local and systemic glucose homeostasis, and suggest that obesity-induced loss of adipose HK2 is an evolutionarily conserved mechanism for the development of selective insulin resistance and thereby hyperglycemia.
Spatial climate data sets that extend back in time over many decades are an important resource for climate monitoring. The long‐term consistency of such data sets is, however, compromised by changes ...in the measurement systems over time. In this paper, we introduce a data set of monthly precipitation on a 5‐km grid over the European Alps that extends back to the late 19th century. In deriving the “long‐term Alpine precipitation reconstruction” (LAPrec), special care is taken of variations in the station network, in order for the data set to satisfy high standards in long‐term consistency. LAPrec builds on a reconstruction method that integrates the available information in two portions: The first is a set of high‐quality homogenized station series, taken from the HISTALP data archive, covering the entire period almost continuously. The second is a high‐resolution gridded precipitation analysis, taken from the “Alpine Precipitation Grid Data Set,” constructed from thousands of rain‐gauges but covering a few decades only. We demonstrate how the reconstruction approach successfully introduces mesoscale structures that are not resolved by the available long‐term station series, more plausibly so than a predecessor data set using conventional interpolation. We also illustrate that LAPrec reveals long‐term precipitation trends that are spatially more consistent and more detailed than the trends in popular climate monitoring data sets. Over the period 1871–2017 a statistically significant increase is found in winter over the northern parts of the Alps (1%–2% per 10 years). LAPrec is available in two versions (back until 1871 and 1901 respectively) from the Copernicus climate data store.
Plain Language Summary
Data sets extending back in time over many decades are an important resource for climate monitoring. In this paper, we introduce a data set on a regular grid of monthly precipitation over the European Alps that extends back to 1871. In deriving the “long‐term Alpine precipitation reconstruction” (LAPrec), special care is taken to keep the station network constant and make use of high‐quality homogenized time series, in order for the data set to be as consistent as possible over time. LAPrec builds on two sources of information: The first is a set of high‐quality station series from the HISTALP data archive, covering the entire period almost continuously. The second is a high‐resolution gridded precipitation analysis, the “Alpine Precipitation Grid Data Set,” constructed from thousands of rain‐gauges but covering a few decades only. We demonstrate how this approach successfully introduces details that are not resolved by the available long‐term station series. We also illustrate that LAPrec reveals long‐term precipitation trends that are spatially more consistent and detailed than the trends in popular climate monitoring data sets. Over the period 1871–2017 a statistically significant increase in winter precipitation is found over the northern parts of the Alps. LAPrec is available from the Copernicus climate data store.
Key Points
Long‐term spatial analyses of precipitation in the European Alps since 1871
For applications such as climate monitoring and trend analysis, the data set meets high standards in long‐term consistency and homogeneity
Long‐term Alpine precipitation reconstruction detects a significant trend in winter precipitation over the northern part of the Alps in the period starting from 1871
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A statistical framework is presented for the assessment of climatological trends in the frequency of rare and extreme weather events. The methodology applies to long-term records of event counts and ...is based on the stochastic concept of binomial distributed counts. It embraces logistic regression for trend estimation and testing, and includes a quantification of the potential/limitation to discriminate a trend from the stochastic fluctuations in a record. This potential is expressed in terms of a detection probability, which is calculated from Monte Carlo–simulated surrogate records, and determined as a function of the record length, the magnitude of the trend and the average return period (i.e., the rarity) of events.
Calculations of the detection probability for daily events reveal a strong sensitivity upon the rarity of events: in a 100-yr record of seasonal counts, a frequency change by a factor of 1.5 can be detected with a probability of 0.6 for events with an average return period of 30 days; however, this value drops to 0.2 for events with a return period of 100 days. For moderately rare events the detection probability decreases rapidly with shorter record length, but it does not significantly increase with longer record length when very rare events are considered. The results demonstrate the difficulty to determine trends of very rare events, underpin the need for long period data for trend analyses, and point toward a careful interpretation of statistically nonsignificant trend results.
The statistical method is applied to examine seasonal trends of heavy daily precipitation at 113 rain gauge stations in the Alpine region of Switzerland (1901–94). For intense events (return period: 30 days) a statistically significant frequency increase was found in winter and autumn for a high number of stations. For strong precipitation events (return period larger than 100 days), trends are mostly statistically nonsignificant, which does not necessarily imply the absence of a trend.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
14.
Performance of a prototype TORCH time-of-flight detector Bhasin, S.; Blake, T.; Brook, N.H. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2023, Volume:
1050
Journal Article
Peer reviewed
Open access
TORCH is a novel time-of-flight detector, designed to provide charged particle identification of pions, kaons and protons in the momentum range 2–20 GeV/c over a 9.5 m flight path. A detector module, ...comprising a 10 mm thick quartz plate, provides a source of Cherenkov photons which propagate via total internal reflection to one end of the plate. Here, the photons are focused onto an array of custom-designed Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMTs) which measure their positions and arrival times. The target time resolution per photon is 70 ps which, for 30 detected photons per charged particle, results in a 10–15 ps time-of-flight resolution. A 1.25 m length TORCH prototype module employing two MCP-PMTs has been developed, and tested at the CERN PS using a charged hadron beam of 8 GeV/c momentum. The construction of the module, the properties of the MCP-PMTs and the readout electronics are described. Measurements of the collected photon yields and single-photon time resolutions have been performed as a function of particle entry points on the plate and compared to expectations. These studies show that the performance of the TORCH prototype approaches the design goals for the full-scale detector.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Many climate impact assessments require high-resolution precipitation time series that have a spatio-temporal correlation structure consistent with observations, for simulating either current or ...future climate conditions. In this respect, weather generators (WGs) designed and calibrated for multiple sites are an appealing statistical downscaling technique to stochastically simulate multiple realisations of possible future time series consistent with the local precipitation characteristics and their expected future changes. In this study, we present the implementation and validation of a multi-site daily precipitation generator re-built after the methodology described in Wilks (1998). The generator consists of several Richardson-type WGs run with spatially correlated random number streams. This study aims at investigating the capabilities, the added value and the limitations of the precipitation generator for a typical Alpine river catchment in the Swiss Alpine region under current climate. The calibrated multi-site WG is skilful at individual sites in representing the annual cycle of the precipitation statistics, such as mean wet day frequency and intensity as well as monthly precipitation sums. It reproduces realistically the multi-day statistics such as the frequencies of dry and wet spell lengths and precipitation sums over consecutive wet days. Substantial added value is demonstrated in simulating daily areal precipitation sums in comparison to multiple WGs that lack the spatial dependency in the stochastic process. Limitations are seen in reproducing daily and multi-day extreme precipitation sums, observed variability from year to year and in reproducing long dry spell lengths. Given the performance of the presented generator, we conclude that it is a useful tool to generate precipitation series consistent with the mean climatic aspects and likely helpful to be used as a downscaling technique for climate change scenarios.
Modelling spatial covariance is an essential part of all geostatistical methods. Traditionally, parametric semivariogram models are fit from available data. More recently, it has been suggested to ...use nonparametric correlograms obtained from spatially complete data fields. Here, both estimation techniques are compared. Nonparametric correlograms are shown to have a substantial negative bias. Nonetheless, when combined with the sample variance of the spatial field under consideration, they yield an estimate of the semivariogram that is unbiased for small lag distances. This justifies the use of this estimation technique in geostatistical applications. Various formulations of geostatistical combination (Kriging) methods are used here for the construction of hourly precipitation grids for Switzerland based on data from a sparse realtime network of raingauges and from a spatially complete radar composite. Two variants of Ordinary Kriging (OK) are used to interpolate the sparse gauge observations. In both OK variants, the radar data are only used to determine the semivariogram model. One variant relies on a traditional parametric semivariogram estimate, whereas the other variant uses the nonparametric correlogram. The variants are tested for three cases and the impact of the semivariogram model on the Kriging prediction is illustrated. For the three test cases, the method using nonparametric correlograms performs equally well or better than the traditional method, and at the same time offers great practical advantages. Furthermore, two variants of Kriging with external drift (KED) are tested, both of which use the radar data to estimate nonparametric correlograms, and as the external drift variable. The first KED variant has been used previously for geostatistical radar-raingauge merging in Catalonia (Spain). The second variant is newly proposed here and is an extension of the first. Both variants are evaluated for the three test cases as well as an extended evaluation period. It is found that both methods yield merged fields of better quality than the original radar field or fields obtained by OK of gauge data. The newly suggested KED formulation is shown to be beneficial, in particular in mountainous regions where the quality of the Swiss radar composite is comparatively low. An analysis of the Kriging variances shows that none of the methods tested here provides a satisfactory uncertainty estimate. A suitable variable transformation is expected to improve this.
The TORCH time-of-flight detector Harnew, N.; Gao, R.; Hadavizadeh, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2023, Volume:
1048
Journal Article
Peer reviewed
Open access
TORCH is a large-area time-of-flight (ToF) detector, proposed for the Upgrade-II of the LHCb experiment. It will provide charged hadron identification over a 2–20 GeV/c momentum range, given a 9.5m ...flight distance from the LHC interaction point. To achieve this level of performance, a 15ps timing resolution per track is required. A TORCH prototype module having a 1250×660×10mm3 fused-silica radiator plate and equipped with two MCP-PMTs has been tested in a 8GeV/c CERN test-beam. Single-photon time resolutions of between 70–100ps have been achieved, dependent on the beam position in the radiator. The measured photon yields agree with expectations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Currently, limited studies have quantified the risk of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) for MRSA-colonized patients on discharge from ...hospital. Our retrospective, case-control study identified independent risk factors for the development of MRSA SSTIs among such patients detected by active MRSA nasal screening in an acute care hospital by PCR on admission, and bacteriological cultures on discharge. Cases were MRSA-colonized patients aged ⩾18 years who developed a MRSA SSTI post-discharge and controls were those who did not develop a MRSA SSTI post-discharge. Controls were matched to cases by length of follow-up (±10 days) for up to 18 months. Potential demographic and clinical risk factors for MRSA infection were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests and variables with P values ⩽0·05 in bivariable analysis were entered into a logistic regression model. Multivariable analysis demonstrated prior hospital admission within 12 months (P = 0·02), prior MRSA infection (P = 0·05), and previous myocardial infarction (P = 0·01) were independently predictive of a MRSA SSTI post-discharge. Identification of MRSA colonization upon admission and recognition of risk factors could help identify a high-risk population that could benefit from MRSA SSTI prevention strategies.
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Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and ...inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance HOMA-IR) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.
The TORCH detector R&D: Status and perspectives Gys, T.; Brook, N.; García, L. Castillo ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2017, Volume:
876
Journal Article
Peer reviewed
Open access
TORCH (Timing Of internally Reflected CHerenkov photons) is a time-of-flight detector for particle identification at low momentum. It has been originally proposed for the LHCb experiment upgrade. ...TORCH is using plates of quartz radiator in a modular design. A fraction of the Cherenkov photons produced by charged particles passing through this radiator propagate by total internal reflection, they emerge at the edges and are subsequently focused onto fast, position-sensitive single-photon detectors. The recorded position and arrival time of the photons are used to precisely reconstruct their trajectory and propagation time in the quartz. The on-going R&D programme aims at demonstrating the TORCH basic concept through the realization of a full detector module and has been organized on the following main development lines: micro-channel plate photon detectors featuring the required granularity and lifetime, dedicated fast front-end electronics preserving the picosecond timing information provided by single photons, and high-quality quartz radiator and focussing optics minimizing photon losses. The present paper reports on the TORCH results successfully achieved in the laboratory and in charged particle beam tests. It will also introduce the latest developments towards a final full-scale module prototype.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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