Risk factors for severe outcomes in patients with systemic vasculitis & COVID‐19: a bi‐national registry‐based cohort study

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and so may be at risk of severe outcomes following COVID-19. It is important to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multi-centre cohort was developed through the participation of centres affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes were described. Logistic regression was used to evaluate associations between potential risk factors and severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, invasive ventilation, or death. RESULTS: Sixty-five cases of patients with systemic vasculitis who developed COVID-19 were reported (median age 70 years, 49% female) of whom 25 (38%) experienced a severe outcome. Most cases (55/65, 85%) had ANCA-associated vasculitis (AAV). Almost all patients required hospitalization (59/65, 91%), 7 patients (11%) were admitted to intensive care and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcome (adjusted odds ratio [aOR] 3.7 (1.1-14.9, p=0.047)) as was comorbid respiratory disease (aOR 7.5 (1.9-38.2, p=0.006)). Vasculitis disease activity and non-glucocorticoid immunosuppression were not associated with severe outcome. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision making relating to risk of severe COVID-19 in this vulnerable patient group

Determination of the Carrier-Envelope Phase of Few-Cycle Laser Pulses with Terahertz-Emission Spectroscopy

The availability of few-cycle optical pulses opens a window to physical phenomena occurring on the attosecond time scale. In order to take full advantage of such pulses, it is crucial to measure and stabilise their carrier-envelope (CE) phase, i.e., the phase difference between the carrier wave and the envelope function. We introduce a novel approach to determine the CE phase by down-conversion of the laser light to the terahertz (THz) frequency range via plasma generation in ambient air, an isotropic medium where optical rectification (down-conversion) in the forward direction is only possible if the inversion symmetry is broken by electrical or optical means. We show that few-cycle pulses directly produce a spatial charge asymmetry in the plasma. The asymmetry, associated with THz emission, depends on the CE phase, which allows for a determination of the phase by measurement of the amplitude and polarity of the THz pulse

The Effect of Plant Inbreeding and Stoichiometry on Interactions with Herbivores in Nature: Echinacea angustifolia and Its Specialist Aphid

Fragmentation of once widespread communities may alter interspecific interactions by changing genetic composition of interacting populations as well as their abundances and spatial distributions. In a long-term study of a fragmented population of Echinacea angustifolia, a perennial plant native to the North American prairie, we investigated influences on its interaction with a specialist aphid and tending ants. We grew plant progeny of sib-matings (I), and of random pairings within (W) and between (B) seven remnants in a common field within 8 km of the source remnants. During the fifth growing season, we determined each plant's burden of aphids and ants, as well as its size and foliar elemental composition (C, N, P). We also assayed composition (C, N) of aphids and ants. Early in the season, progeny from genotypic classes B and I were twice as likely to harbor aphids, and in greater abundance, than genotypic class W; aphid loads were inversely related to foliar concentration of P and positively related to leaf N and plant size. At the end of the season, aphid loads were indistinguishable among genotypic classes. Ant abundance tracked aphid abundance throughout the season but showed no direct relationship with plant traits. Through its potential to alter the genotypic composition of remnant populations of Echinacea, fragmentation can increase Echinacea's susceptibility to herbivory by its specialist aphid and, in turn, perturb the abundance and distribution of aphids

Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

BACKGROUND: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. METHODS: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. RESULTS: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0–13.8) at 6 months (n = 90), and 16.2 (IQR 9.6–20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ≤ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ≤ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. CONCLUSION: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The Effects of Cognitive Therapy versus ‘No Intervention’ for Major Depressive Disorder

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: We used The Cochrane systematic review methodology with meta-analyses and trial sequential analyses of randomized trials comparing the effects of cognitive therapy versus 'no intervention' for major depressive disorder. Participants had to be older than 17 years with a primary diagnosis of major depressive disorder to be eligible. Altogether, we included 12 trials randomizing a total of 669 participants. All 12 trials had high risk of bias. Meta-analysis on the Hamilton Rating Scale for Depression showed that cognitive therapy significantly reduced depressive symptoms (four trials; mean difference -3.05 (95% confidence interval (Cl), -5.23 to -0.87; P<0.006)) compared with 'no intervention'. Trial sequential analysis could not confirm this result. Meta-analysis on the Beck Depression Inventory showed that cognitive therapy significantly reduced depressive symptoms (eight trials; mean difference on -4.86 (95% CI -6.44 to -3.28; P = 0.00001)). Trial sequential analysis on these data confirmed the result. Only a few trials reported on 'no remission', suicide inclination, suicide attempts, suicides, and adverse events without significant differences between the compared intervention groups. DISCUSSION: Cognitive therapy might be an effective treatment for depression measured on Hamilton Rating Scale for Depression and Beck Depression Inventory, but these outcomes may be overestimated due to risks of systematic errors (bias) and random errors (play of chance). Furthermore, the effects of cognitive therapy on no remission, suicidality, adverse events, and quality of life are unclear. There is a need for randomized trials with low risk of bias, low risk of random errors, and longer follow-up assessing both benefits and harms with clinically relevant outcome measures

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration