Observations of Forbush Decreases of Cosmic-Ray Electrons and Positrons with the Dark Matter Particle Explorer

The Forbush decrease (FD) represents the rapid decrease of the intensities of charged particles accompanied with the coronal mass ejections or high-speed streams from coronal holes. It has been mainly explored with the ground-based neutron monitor network, which indirectly measures the integrated intensities of all species of cosmic rays by counting secondary neutrons produced from interaction between atmospheric atoms and cosmic rays. The space-based experiments can resolve the species of particles but the energy ranges are limited by the relatively small acceptances except for the most abundant particles like protons and helium. Therefore, the FD of cosmic-ray electrons and positrons have just been investigated by the PAMELA experiment in the low-energy range (<5 GeV) with limited statistics. In this paper, we study the FD event that occurred in 2017 September with the electron and positron data recorded by the Dark Matter Particle Explorer. The evolution of the FDs from 2 GeV to 20 GeV with a time resolution of 6 hr are given. We observe two solar energetic particle events in the time profile of the intensity of cosmic rays, the earlier, and weaker, one has not been shown in the neutron monitor data. Furthermore, both the amplitude and recovery time of fluxes of electrons and positrons show clear energy dependence, which is important in probing the disturbances of the interplanetary environment by the coronal mass ejections

First detection of X-ray polarization from the accreting neutron star 4U 1820-303

This paper reports the first detection of polarization in the X-rays for atoll-source 4U 1820-303, obtained with the Imaging X-ray Polarimetry Explorer (IXPE) at 99.999% confidence level (CL). Simultaneous polarimetric measurements were also performed in the radio with the Australia Telescope Compact Array (ATCA). The IXPE observations of 4U 1820-303 were coordinated with Swift-XRT, NICER, and NuSTAR aiming to obtain an accurate X-ray spectral model covering a broad energy interval. The source shows a significant polarization above 4 keV, with a polarization degree of 2.0(0.5)% and a polarization angle of -55(7) deg in the 4-7 keV energy range, and a polarization degree of 10(2)% and a polarization angle of -67(7) deg in the 7-8 keV energy bin. This polarization also shows a clear energy trend with polarization degree increasing with energy and a hint for a position-angle change of about 90 deg at 96% CL around 4 keV. The spectro-polarimetric fit indicates that the accretion disk is polarized orthogonally to the hard spectral component, which is presumably produced in the boundary/spreading layer. We do not detect linear polarization from the radio counterpart, with a 99.97% upper limit of 50% at 7.25 GHz

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

The Viral Tegument Protein pp65 Impairs Transcriptional Upregulation of IL-1β by Human Cytomegalovirus through Inhibition of NF-kB Activity

Interleukin-1&beta; (IL-1&beta;) is a key effector of the inflammasome complex in response to pathogens and danger signals. Although it is well known that assembly of the inflammasome triggers proteolytic cleavage of the biologically inactive precursor pro-IL-1&beta; into its mature secreted form, the mechanism by which human cytomegalovirus (HCMV) regulates IL-1&beta; production via the inflammasome is still poorly understood. Here, we show that the infection of human foreskin fibroblasts (HFFs) with a mutant HCMV lacking the tegument protein pp65 (v65Stop) results in higher expression levels of mature IL-1&beta; compared to its wild-type counterpart, suggesting that pp65 mediates HCMV immune evasion through downmodulation of IL-1&beta;. Furthermore, we show that enhanced IL-1&beta; production by the v65Stop mutant is due in part to induction of DNA binding and the transcriptional activity of NF-&kappa;B. Lastly, we demonstrate that HCMV infection of HFFs triggers a non-canonical IL-1&beta; activation pathway where caspase-8 promotes IL-1&beta; maturation independently of caspase-1. Altogether, our findings provide novel mechanistic insights into the interplay between HCMV and the inflammasome system and raise the possibility of targeting pp65 to treat HCMV infection

Daily, weekly, monthly, and seasonal patterns in the occurrence of vasovagal syncope in an older population

AIMS: The aim of this study was to assess the frequency of vasovagal episodes over the day, week, month, and seasons. METHODS AND RESULTS: This study was part of the multi-centre International Study on Syncope of Uncertain Etiology-2 (ISSUE-2), which included patients, aged 30 years or older, with severe neurally mediated syncope between June 2002 and July 2004. The Implantable Loop Recorder (ILR) was used to document the syncope-related ECG periods. For this study patients with recorded syncopal episodes after ILR-implantation was selected. At least one episode was documented in 106 patients. A higher number of episodes were documented during the morning than during other periods of the day (P < 0.01). There was no difference between various days of the week, episodes per month, or between seasons. There was no difference between age and gender groups, although elderly patients seemed to be responsible for the peak in the morning. CONCLUSION: A circadian pattern in the frequency of vasovagal episodes exists, with a peak in the morning. This is in accordance with reports of diurnal variations in blood pressure and heart rate. No difference was observed in syncope distribution between days of the week, months, or season

Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study

Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause. Given the lack of effective treatment for VVA in BC survivors, we retrospectively evaluated the efficacy and tolerability of fractional microablative CO2 laser therapy in these patients