Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Genome-wide detection of copy number variants in European autochthonous and commercial pig breeds by whole-genome sequencing of DNA pools identified breed-characterising copy number states.

In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed-specific DNA pooling approach (30-35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed-specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.

Vaginal atrophy across the menopausal age: results from the ANGEL study.

OBJECTIVES: This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age. METHODS: A multicenter cross-sectional investigation was performed on 747 females, 40-55 years of age, in 30 outpatient public services across the nation. The VA diagnosis was based on the combination of patient sensation of vaginal dryness, an objective sign of VA, and pH >5. RESULTS: VA was diagnosed in 36.8% of women. Prevalence ranged from 19.2% (40-45 year olds) to 53.8% (52-55 year olds). pH >5 (37.5%) was less prevalent than isolated VA symptoms or signs. Vaginal dryness (64.0%) was the most prevalent symptom followed by dyspareunia (54.5%), itching (38.5%) burning (38.3%), and dysuria (28.9%). Prevalence of vaginal signs declined from vaginal dryness (60.3%) to vaginal thinning (54.5%), vaginal pallor (47.4%), presence of petecchiae (15.7%), and mucosa fragility (15.1%). Most signs and symptoms showed an age-related increase in frequency and intensity. VA was independently associated (R2 = 0.139; p < 0.0001) with age (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.03-1.13), being in postmenopause (OR 3.45; 95% CI 2.29-5.19), and presence of vasomotor symptoms (OR 3.10; 95% CI 2.09-4.60). CONCLUSION: VA and its symptoms are common in women across the menopausal age. VA identification may favor early management and treatment.

Transcriptomic changes in Cucurbita pepo fruit after cold storage: differential response between two cultivars contrasting in chilling sensitivity.

BACKGROUND: Zucchini fruit is susceptible to chilling injury (CI), but the response to low storage temperature is cultivar dependent. Previous reports about the response of zucchini fruit to chilling storage have been focused on the physiology and biochemistry of this process, with little information about the molecular mechanisms underlying it. In this work, we present a comprehensive analysis of transcriptomic changes that take place after cold storage in zucchini fruit of two commercial cultivars with contrasting response to chilling stress. RESULTS: RNA-Seq analysis was conducted in exocarp of fruit at harvest and after 14 days of storage at 4 and 20 °C. Differential expressed genes (DEGs) were obtained comparing fruit stored at 4 °C with their control at 20 °C, and then specific and common up and down-regulated DEGs of each cultivar were identified. Functional analysis of these DEGs identified similarities between the response of zucchini fruit to low temperature and other stresses, with an important number of GO terms related to biotic and abiotic stresses overrepresented in both cultivars. This study also revealed several molecular mechanisms that could be related to chilling tolerance, since they were up-regulated in cv. Natura (CI tolerant) or down-regulated in cv. Sinatra (CI sensitive). These mechanisms were mainly those related to carbohydrate and energy metabolism, transcription, signal transduction, and protein transport and degradation. Among DEGs belonging to these pathways, we selected candidate genes that could regulate or promote chilling tolerance in zucchini fruit including the transcription factors MYB76-like, ZAT10-like, DELLA protein GAIP, and AP2/ERF domain-containing protein. CONCLUSIONS: This study provides a broader understanding of the important mechanisms and processes related to coping with low temperature stress in zucchini fruit and allowed the identification of some candidate genes that may be involved in the acquisition of chilling tolerance in this crop. These genes will be the basis of future studies aimed to identify markers involved in cold tolerance and aid in zucchini breeding programs.

Unresolved Gamma-Ray Sky through its Angular Power Spectrum.

The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with ∼3.7σ significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55±0.23 and 1.86±0.15.

Altered miR-193a-5p expression in children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. METHODS: Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. RESULTS: Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. CONCLUSIONS: Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.

Search for Cosmic-Ray Electron and Positron Anisotropies with Seven Years of Fermi Large Area Telescope Data.

The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.

Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope.

We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12} GeV^{-1} for ALP masses 0.5≲m_{a}≲5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the γ-ray opacity of the Universe.

Resolving the Extragalactic γ-Ray Background above 50 GeV with the Fermi Large Area Telescope.

The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN/dS, of extragalactic γ-ray sources at E>50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (∼8×10^{-12} ph cm^{-2} s^{-1}). We employ a one-point photon fluctuation analysis to constrain the behavior of dN/dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, S_{b}, in the range [8×10^{-12},1.5×10^{-11}] ph cm^{-2} s^{-1} and power-law indices below and above the break of α_{2}∈[1.60,1.75] and α_{1}=2.49±0.12, respectively. Integration of dN/dS shows that point sources account for at least 86_{-14}^{+16}% of the total extragalactic γ-ray background. The simple form of the derived source count distribution is consistent with a single population (i.e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.

Medical and patient attitude towards vaginal atrophy: the AGATA study.

OBJECTIVES: To provide data on current management of vaginal atrophy (VA) in a nationwide setting. METHODS: A cross-sectional, multicenter study was made in 913 postmenopausal women consulting 22 gynecological outpatient services. VA was diagnosed with a combination of subjective symptoms and objective evaluations. Women with a previous diagnosis and those with a new diagnosis of VA filled additional questionnaires regarding modalities of VA management and reasons for missing diagnosis, respectively. RESULTS: 730/913 (80%) women had ever had a diagnosis of VA. In 274 (37.5%), the diagnosis was made prior to, and in 456 (62.5%) during the investigation. Of women with a new VA diagnosis, 81.1% had never discussed their symptoms with the health-care practitioner (HCP), and 78.7% (n = 359) had never been questioned by an HCP. Of women with a previous VA diagnosis, 90.2% had been treated with systemic (10.1%), local hormonal (49.4%) or local non-hormonal (30.5%) therapy. At the time of investigation, 61.9% of these women had stopped treatment, with only 3.3% having been successfully cured. CONCLUSIONS: VA is highly prevalent in postmenopausal women. Its current management and treatment seem to be highly unsatisfactory and can be improved by medical sensitization and patient education.

Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data.

The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ≲100 GeV annihilating via quark and τ-lepton channels.

New upper limit on strange quark matter abundance in cosmic rays with the PAMELA space experiment.

In this work we present results of a direct search for strange quark matter (SQM) in cosmic rays with the PAMELA space spectrometer. If this state of matter exists it may be present in cosmic rays as particles, called strangelets, having a high density and an anomalously high mass-to-charge (A/Z) ratio. A direct search in space is complementary to those from ground-based spectrometers. Furthermore, it has the advantage of being potentially capable of directly identifying these particles, without any assumption on their interaction model with Earth's atmosphere and the long-term stability in terrestrial and lunar rocks. In the rigidity range from 1.0 to ∼1.0×10^{3} GV, no such particles were found in the data collected by PAMELA between 2006 and 2009. An upper limit on the strangelet flux in cosmic rays was therefore set for particles with charge 1≤Z≤8 and mass 4≤A≤1.2×10^{5}. This limit as a function of mass and as a function of magnetic rigidity allows us to constrain models of SQM production and propagation in the Galaxy.

Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes.

AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.

A limit on the variation of the speed of light arising from quantum gravity effects.

A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximately 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximately 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves. Here we report the detection of emission up to approximately 31 GeV from the distant and short GRB 090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space-time on a very small scale linearly alters the speed of light.

Relation between oxidative stress and climacteric symptoms in early postmenopausal women.

OBJECTIVES: To evaluate the relation between climacteric symptoms or other risk factors for cardiovascular disease and oxidative status of postmenopausal women. METHODS: Cross-sectional investigation performed at the outpatient service for the menopause at the University Hospital, on 50 apparently healthy women in physiological postmenopause. The whole-blood free oxygen radical test (FORT), free oxygen radical defence (FORD), age, months since menopause, weight, body mass index, waist circumference, waist-to-hip ratio, estradiol, lipids, glucose, insulin, insulin resistance (glucose/insulin and HOMA-IR), and fibrinogen were evaluated. The Greene Climacteric Scale with its subscales was used to evaluate climacteric symptoms. The pulsatility index, an index of downstream blood flow resistance, was determined for both the internal carotid artery and the brachial artery. RESULTS: The waist-to-hip ratio (r = 0.540; p = 0.0001), estradiol (r = 0.548; p = 0.0004) and waist circumference (r = 0.345; p = 0.02) were independently related to blood FORT. The score in the Greene vasomotor subscale was the only parameter independently related to blood FORD (r = 0.554; p = 0.0001). FORT was not related to the artery pulsatility index, while FORD was negatively related to the pulsatility index of both the internal carotid (r = 0.549; p = 0.0001) and the brachial (r = 0.484; p = 0.0001) arteries. DISCUSSION: In postmenopausal women, abdominal adiposity and hypoestrogenism increase oxidative stress. Climacteric symptoms, particularly vasomotor symptoms, markedly reduce antioxidant defences. Lower antioxidant defences are associated with higher resistance to blood flow in the great arteries. In women early after the menopause, visceral fat, hypoestrogenism and climacteric symptoms may increase the risk for cardiovascular disease.

Inferred cosmic-ray spectrum from Fermi large area telescope γ-ray observations of Earth's limb.

Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range ∼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above ∼200 GeV, respectively.

Metabolic responses in root nodules of Phaseolus vulgaris and Vicia sativa exposed to the imazamox herbicide.

Alterations on growth, amino acids metabolism and some antioxidant enzyme activities as result of imazamox treatment were examined in determinate and indeterminate nodules, formed by Phaseolus vulgaris and Vicia sativa, respectively. Young seedlings of both legumes were inoculated with their respective microsymbionts and grown under controlled conditions. At vegetative growth, plants were treated with imazamox (250µM) in the nutrient solution and harvested 7days after. Imazamox was mainly accumulated in V. sativa where concentrations were more than six fold higher than those detected in P. vulgaris. Nodule dry weight and total nitrogen content were reduced by the herbicide treatment: the highest decrease of nodule biomass (50%) and nitrogen content (40%) were registered in V. sativa and P. vulgaris, respectively. The concentration of branched-chain amino acids (BCAA) did not change in neither determinate nor indeterminate nodules even though the acetohydroxyacid synthase activity decreased in root and nodules of both symbioses with the herbicide application. Based on this last result and taking into account that total free amino acids increased in roots but not in nodules of common vetch, a possible BCAA translocation from root to nodule could occur. Our results suggest that the maintenance of BCAA balance in nodule become a priority for the plant in such conditions. The involvement of activities glutathione-S-transferase, guaiacol peroxidase and superoxide dismutase in the response of the symbioses to imazamox are also discussed.

Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes.

Pre-clinical trials have demonstrated the neuroprotective effects of transplanted human neural stem cells (hNSCs) during the post-ischemic phase. However, the exact neuroprotective mechanism remains unclear. Tunneling nanotubes (TNTs) are long plasma membrane bridges that physically connect distant cells, enabling the intercellular transfer of mitochondria and contributing to post-ischemic repair processes. Whether hNSCs communicate through TNTs and their role in post-ischemic neuroprotection remains unknown. In this study, non-immortalized hNSC lines derived from fetal human brain tissues were examined to explore these possibilities and assess the post-ischemic neuroprotection potential of these hNSCs. Using Tau-STED super-resolution confocal microscopy, live cell time-lapse fluorescence microscopy, electron microscopy, and direct or non-contact homotypic co-cultures, we demonstrated that hNSCs generate nestin-positive TNTs in both 3D neurospheres and 2D cultures, through which they transfer functional mitochondria. Co-culturing hNSCs with differentiated SH-SY5Y (dSH-SY5Y) revealed heterotypic TNTs allowing mitochondrial transfer from hNSCs to dSH-SY5Y. To investigate the role of heterotypic TNTs in post-ischemic neuroprotection, dSH-SY5Y were subjected to oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) with or without hNSCs in direct or non-contact co-cultures. Compared to normoxia, OGD/R dSH-SY5Y became apoptotic with impaired electrical activity. When OGD/R dSH-SY5Y were co-cultured in direct contact with hNSCs, heterotypic TNTs enabled the transfer of functional mitochondria from hNSCs to OGD/R dSH-SY5Y, rescuing them from apoptosis and restoring the bioelectrical profile toward normoxic dSH-SY5Y. This complete neuroprotection did not occur in the non-contact co-culture. In summary, our data reveal the presence of a functional TNTs network containing nestin within hNSCs, demonstrate the involvement of TNTs in post-ischemic neuroprotection mediated by hNSCs, and highlight the strong efficacy of our hNSC lines in post-ischemic neuroprotection. Human neural stem cells (hNSCs) communicate with each other and rescue ischemic neurons through nestin-positive tunneling nanotubes (TNTs). A Functional mitochondria are exchanged via TNTs between hNSCs. B hNSCs transfer functional mitochondria to ischemic neurons through TNTs, rescuing neurons from ischemia/reperfusion ROS-dependent apoptosis.

Implantation of a novel insertable cardiac monitor: preliminary multicenter experience in Europe.

BACKGROUND: The LUX-Dx™ is a novel insertable cardiac monitor (ICM) introduced into the European market since October 2022. PURPOSE: The aim of this investigation was to provide a comprehensive description of the ICM implantation experience in Europe during its initial year of commercial use. METHODS: The system comprises an incision tool and a single-piece insertion tool pre-loaded with the small ICM. The implantation procedure involves incision, creation of a device pocket, insertion of the ICM, verification of sensing, and incision closure. Patients receive a mobile device with a preloaded App, connecting to their ICM and transmitting data to the management system. Data collected at European centers were analyzed at the time of implantation and before patient discharge. RESULTS: A total of 368 implantation procedures were conducted across 23 centers. Syncope (235, 64%) and cryptogenic stroke (34, 9%) were the most frequent indications for ICM. Most procedures (338, 92%) were performed in electrophysiology laboratories. All ICMs were successfully implanted in the left parasternal region, oriented at 45° in 323 (88%) patients. Repositioning was necessary after sensing verification in 9 (2%) patients. No procedural complications were reported, with a median time from skin incision to suture of 4 min (25th-75th percentiles 2-7). At implantation, the mean R-wave amplitude was 0.39 ± 0.30 mV and the P-wave visibility was 91 ± 20%. Sensing parameters remained stable until pre-discharge and were not influenced by patient characteristics or indications. Procedural times were fast, exhibited consistency across patient groups, and improved after an initial experience with the system. Operator Operator feedback on the system was positive. Patients reported very good ease of use of the App and low levels of discomfort after implantation. CONCLUSIONS: LUX-Dx™ implantation appears efficient and straightforward, with favorable post-implantation sensing values and associated with positive feedback from operators and patients.

Cosmic-ray positron energy spectrum measured by PAMELA.

Precision measurements of the positron component in the cosmic radiation provide important information about the propagation of cosmic rays and the nature of particle sources in our Galaxy. The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray positron flux and fraction that extends previously published measurements up to 300 GeV in kinetic energy. The combined measurements of the cosmic-ray positron energy spectrum and fraction provide a unique tool to constrain interpretation models. During the recent solar minimum activity period from July 2006 to December 2009, approximately 24,500 positrons were observed. The results cannot be easily reconciled with purely secondary production, and additional sources of either astrophysical or exotic origin may be required.