Explanation of the Charge Trapping Properties of Silicon Nitride Storage Layers for NVMs-Part II: Atomistic and Electrical Modeling

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Practical approach to respiratory emergencies in neurological diseases

Many neurological diseases may cause acute respiratory failure (ARF) due to involvement of bulbar respiratory center, spinal cord, motoneurons, peripheral nerves, neuromuscular junction, or skeletal muscles. In this context, respiratory emergencies are often a challenge at home, in a neurology ward, or even in an intensive care unit, influencing morbidity and mortality. More commonly, patients develop primarily ventilatory impairment causing hypercapnia. Moreover, inadequate bulbar and expiratory muscle function may cause retained secretions, frequently complicated by pneumonia, atelectasis, and, ultimately, hypoxemic ARF. On the basis of the clinical onset, two main categories of ARF can be identified: (i) acute exacerbation of chronic respiratory failure, which is common in slowly progressive neurological diseases, such as movement disorders and most neuromuscular diseases, and (ii) sudden-onset respiratory failure which may develop in rapidly progressive neurological disorders including stroke, convulsive status epilepticus, traumatic brain injury, spinal cord injury, phrenic neuropathy, myasthenia gravis, and Guillain-Barr\ue9 syndrome. A tailored assistance may include manual and mechanical cough assistance, noninvasive ventilation, endotracheal intubation, invasive mechanical ventilation, or tracheotomy. This review provides practical recommendations for prevention, recognition, management, and treatment of respiratory emergencies in neurological diseases, mostly in teenagers and adults, according to type and severity of baseline disease

Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

A Supernova Candidate at z=0.092 in XMM-Newton Archival Data

During a search for X-ray transients in the XMM-Newton archive within the EXTraS project, we discovered a new X-ray source that is detected only during a ~5 min interval of a ~21 h-long observation performed on 2011 June 21 (EXMM 023135.0-603743, probability of a random Poissonian fluctuation: ~$1.4\times10^{-27}$). With dedicated follow-up observations, we found that its position is consistent with a star-forming galaxy (SFR = 1-2 $M_\odot$ yr$^{-1}$) at redshift $z=0.092\pm0.003$ ($d=435\pm15$ Mpc). At this redshift, the energy released during the transient event was $2.8\times10^{46}$ erg in the 0.3-10 keV energy band (in the source rest frame). The luminosity of the transient, together with its spectral and timing properties, make EXMM 023135.0-603743 a gripping analog to the X-ray transient associated to SN 2008D, which was discovered during a Swift/XRT observation of the nearby ($d=27$ Mpc) supernova-rich galaxy NGC 2770. We interpret the XMM-Newton event as a supernova shock break-out or an early cocoon, and show that our serendipitous discovery is compatible with the rate of core-collapse supernovae derived from optical observations and much higher than that of tidal disruption events.Comment: 11 pages, 6 figures; Revised version accepted for publication in The Astrophysical Journa

Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma

The updated spectral catalogue of INTEGRAL Gamma-Ray Bursts

We present a catalogue with the properties of all the bursts detected and localized by the IBIS instrument onboard the INTEGRAL satellite from November 2002 to September 2008. The sample is composed of 56 bursts, corresponding to a rate of ~ 0.8 GRB per month. Thanks to the performances of the INTEGRAL Burst Alert System, 50% of the IBIS GRBs have detected afterglows, while 5% have redshift measurements. A spectral analysis of the 43 bursts in the INTEGRAL public archive has been carried out using the most recent software and calibration, deriving an updated, homogeneous and accurate catalogue with the spectral features of the sample. When possible also a time-resolved spectral analysis has been carried out. The GRBs in the sample have 20-200 keV fluences in the range 5 x 1E-8 --2.5 x 1E-4 erg cm-2, and peak fluxes in the range 0.11 - 56 ph cm-2 s-1. While most of the spectra are well fitted by a power law with photon index ~ 1.6, we found that 9 bursts are better described by a cut-off power law, resulting in Ep values in the range 35--190 keV. Altough these results are comparable with those obtained with BAT onboard Swift, there is a marginal evidence that ISGRI detects dimmer bursts than Swift/BAT. Using the revised spectral parameters and an updated sky exposure map that takes into account also the effects of the GRB trigger efficiency, we strengthen the evidence for a spatial correlation with the super galactic plane of the faint bursts with long spectral lag (Foley et al.,2008).Comment: Corrected some typos, added some references; Accepted by Astronomy & Astrophysics, in pres

Global characteristics of GRBs observed with INTEGRAL and the inferred large population of low-luminosity GRBs

INTEGRAL has two sensitive gamma-ray instruments that have detected 46 gamma-ray bursts (GRBs) up to July 2007. We present the spectral, spatial, and temporal properties of the bursts in the INTEGRAL GRB catalogue using data from the imager, IBIS, and spectrometer, SPI. Spectral properties of the GRBs are determined using power-law, Band model and quasithermal model fits to the prompt emission. Spectral lags, i.e. the time delay in the arrival of low-energy gamma-rays with respect to high-energy gamma-rays, are measured for 31 of the GRBs. The photon index distribution of power-law fits to the prompt emission spectra is consistent with that obtained by Swift. The peak flux distribution shows that INTEGRAL detects proportionally more weak GRBs than Swift because of its higher sensitivity in a smaller field of view. The all-sky rate of GRBs above ~0.15 ph cm^-2 s^-1 is ~1400 yr^-1 in the fully coded field of view of IBIS. Two groups are identified in the spectral lag distribution, one with short lags <0.75 s (between 25-50 keV and 50-300 keV) and one with long lags >0.75 s. Most of the long-lag GRBs are inferred to have low redshifts because of their long spectral lags, their tendency to have low peak energies and their faint optical and X-ray afterglows. They are mainly observed in the direction of the supergalactic plane with a quadrupole moment of Q=-0.225+/-0.090 and hence reflect the local large-scale structure of the Universe. The rate of long-lag GRBs with inferred low luminosity is ~25% of Type Ib/c supernovae. Some of these bursts could be produced by the collapse of a massive star without a supernova or by a different progenitor, such as the merger of two white dwarfs or a white dwarf with a neutron star or black hole, possibly in the cluster environment without a host galaxy.Comment: 22 pages, 13 figures and appendix, accepted for publication in A&A, added and updated reference

The magnetar candidate AX J1818.8-1559

In October 2007 a hard X-ray burst was detected by the INTEGRAL satellite from a direction consistent with the position of AX J1818.8-1559, an X-ray source at low Galactic latitude discovered with the ASCA satellite in 1996-1999. The short duration (0.8 s) and soft spectrum (power law photon index of 3.0+/-0.2) of the burst in the 20-100 keV range are typical of Soft Gamma-ray Repeaters and Anomalous X-ray Pulsars. We report on the results of an observation of AX J1818.8-1559 obtained with the Suzaku satellite in October 2011. The source spectrum, a power law with photon index 1.5, and flux 2x10^{-12} erg cm^-2 s^-1 (2-10 keV), do not show significant variations with respect to the values derived from archival data of various satellites (ROSAT, XMM-Newton, Chandra, Swift) obtained from 1993 to 2011. We discuss possible interpretations for AX J1818.8-1559 and, based on its association with the INTEGRAL burst, we propose it as a new member of the small class of magnetar candidates.Comment: Accepted for publication in Astronomy and Astrophysic

Risk of Getting COVID-19 in People With Multiple Sclerosis

Background and Objectives Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administeredDMT, previousDMTsequences, or the place where the last treatment was administered. Results A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p &lt; 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last DMT(OR[95%CI]: 2.38 [1.66–3.42], p &lt; 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p &lt; 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. Discussion This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. Classification of Evidence This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective