Efficient Expression of <i style="box-sizing: border-box;">Igf-1</i> from Lentiviral Vectors Protects <i style="box-sizing: border-box;">In Vitro</i> but Does Not Mediate Behavioral Recovery of a Parkinsonian Lesion in Rats

Gene therapy approaches delivering neurotrophic factors have offered promising results in both preclinical and clinical trials of Parkinson's disease (PD). However, failure of glial cell line-derived neurotrophic factor in phase 2 clinical trials has sparked a search for other trophic factors that may retain efficacy in the clinic. Direct protein injections of one such factor, insulin-like growth factor (IGF)-1, in a rodent model of PD has demonstrated impressive protection of dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity. However, protein infusion is associated with surgical risks, pump failure, and significant costs. We therefore used lentiviral vectors to deliver Igf-1, with a particular focus on the novel integration-deficient lentiviral vectors (IDLVs). A neuron-specific promoter, from the human synapsin 1 gene, excellent for gene expression from IDLVs, was additionally used to enhance Igf-1 expression. An investigation of neurotrophic effects on primary rat neuronal cultures demonstrated that neurons transduced with IDLV-Igf-1 vectors had complete protection on withdrawal of exogenous trophic support. Striatal transduction of such vectors into 6-OHDA-lesioned rats, however, provided neither protection of dopaminergic substantia nigra neurons nor improvement of animal behavior

Using the Health Belief Model to design a questionnaire aimed at measuring people’s perceptions regarding COVID-19 immunity certificates

This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.Copyright © 2021 The Author(s). The present short communication paper describes the methodological approach of applying the Health Belief Model to the use COVID-19 immunity certificates in the UK. We designed an online survey including an adaptation of the following Health Belief Model constructs: perceived COVID-19 susceptibility, perceived COVID-19 severity, perceived benefits of using immunity certificates, perceived barriers from using immunity certificates, perceived severity of not using immunity certificates, and perceived vaccination views. The online cross-sectional survey conducted on the 3rd of August 2021 gathered responses from 534 participants aged 18 and older, representative of the UK population in terms of gender, age, and ethnicity.AHRC/UKRI COVID-19 Rapid Response, IMMUNE or Immunity Passport Service Design project (Ref. AH/W000288/1)

Epidemiology of lobomycosis-like disease in bottlenose dolphins Tursiops spp. from South America and southern Africa

We report on the epidemiology of lobomycosis-like disease (LLD), a cutaneous disorder evoking lobomycosis, in 658 common bottlenose dolphins Tursiops truncatus from South America and 94 Indo-Pacific bottlenose dolphins T. aduncus from southern Africa. Photographs and stranding records of 387 inshore residents, 60 inshore non-residents and 305 specimens of undetermined origin (inshore and offshore) were examined for the presence of LLD lesions from 2004 to 2015. Seventeen residents, 3 non-residents and 1 inshore dolphin of unknown residence status were positive. LLD lesions appeared as single or multiple, light grey to whitish nodules and plaques that may ulcerate and increase in size over time. Among resident dolphins, prevalence varied significantly among 4 communities, being low in Posorja (2.35%, n = 85), Ecuador, and high in Salinas, Ecuador (16.7%, n = 18), and Laguna, Brazil (14.3%, n = 42). LLD prevalence increased in 36 T. truncatus from Laguna from 5.6% in 2007−2009 to 13.9% in 2013−2014, albeit not significantly. The disease has persisted for years in dolphins from Mayotte, Laguna, Salinas, the Sanquianga National Park and Bahía Málaga (Colombia) but vanished from the Tramandaí Estuary and the Mampituba River (Brazil). The geographical range of LLD has expanded in Brazil, South Africa and Ecuador, in areas that have been regularly surveyed for 10 to 35 yr. Two of the 21 LLD-affected dolphins were found dead with extensive lesions in southern Brazil, and 2 others disappeared, and presumably died, in Ecuador. These observations stress the need for targeted epidemiological, histological and molecular studies of LLD in dolphins, especially in the Southern Hemisphere.The Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to E.R.S. (PQ 307846/2014-8) and P.H.O. (Process 572180/2008-0), and L.F. was sponsored by Petrobras through Petrobras Socio Ambiental.http://www.int-res.com/journals/dao/dao-home/2020-11-30am201

Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging

BACKGROUND: Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. METHODS: We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. RESULTS: In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. CONCLUSION: There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

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