Lifetime Exposure to Environmental Tobacco Smoke among Urban Women: Differences by Socioeconomic Class

This study sought to determine cumulative lifetime exposure to environmental tobacco smoke (ETS) among urban women in relation to sociodemographic factors. In a population survey carried out in Geneva, Switzerland, during 1993-1995, a representative sample of 1, 883 women aged 35-74 years answered interview questions on lifetime ETS exposure. Exposed women were defined as those who had spent at least 1 hour daily in a smoky environment during 1 or more years. The prevalence of current ETS exposure was 31.0% among 1, 458 never or former smokers. Lifetime prevalence was 58.3% among 1, 061 never smokers. The home (42.1%) and the workplace (39.6% of employed women) were the most frequent sources of ETS exposure, leisure time activity being a secondary source. Throughout a lifetime, work accounted for the greatest average intensity of exposure (on average, 19 hours of exposure per week), while the longest duration of exposure (on average, 18 years) was in the home. Cumulative lifetime exposure (intensity (in hours/week) x duration) from all sources combined was 308 hours/week-years, which can correspond to 30.8 hours/week over a period of 10 years or 20.5 hours/week over a period of 15 years. Women from low socioeconomic classes had more intense and longer exposures than women from higher socioeconomic classes, mainly because of work exposure. Both the intensity and the duration of lifetime ETS exposure were greater than previously suspected. Reduction of ETS exposure in the workplace should be a public health priority. Am J Epidemiol 1998; 148: 1040-

Relation of BMI to a dual-energy X-ray absorptiometry measure of fatness

Dual-energy X-ray absorptiometry (DXA) is a valid technique for measuring the fat, bone and lean (muscle, organs and water) masses of the body. We evaluated relationships of BMI (kg/m2) with independent measurements of fat and lean masses using DXA in 226 adult volunteers. The evaluation was an application of a general approach to compositional data which has not previously been used for describing body composition. Using traditional regression analyses, when lean mass was held constant, BMI varied with fat mass (men r 0·75, P < 0·05 ; women r 0·85, P < 0·05); when fat mass was held constant, BMI varied with lean mass (men r 0·63, P < 0·05; women r 0·47, P < 0·05). In contrast, a regression model for compositional data revealed that BMI was: (a) strongly associated with log fat mass in both sexes (b1 4·86, P < 0·001 for all women and b1 5·96, P < 0·001 for all men); (b) not associated with bone mass, except in older men; (c) related to lean mass in women but not in men (b3 −4·04, P < 0·001 for all women and b1 −2·59, P < 0·15 for all men). Women with higher BMI tended to have more fat mass and more lean mass than women with lower BMI. Men with higher BMI had more fat mass but similar lean mass to men with lower BMI. Investigators need to be alert to the inaccuracy of BMI to assign a fatness risk factor to individuals, especially among wome

Investigation of the size of plastic zones in nano indentation and nano scratching

Friction and the associated wear are important but still poorly understood phenomena with strong impacts on our every day lives. Several mechanisms, such as plasticity, lattice vibration, and third-body interactions contribute to the dissipation of energy in friction phenomena. This physical complexity is further increased by the inherently multiscale nature of contact. Indeed, it is well known that roughness exists over multiple length scales, which imposes a multiscale numerical treatment. Our objective in this study is to analyse the development of plastic events at contacting asperities in fcc metals. Dislocation nucleation can happen at the contact surface or – in special cases – as bulk nucleation [1] underneath the surface. We capture these dislocations by molecular dynamics (MD) mod- elling of the contact zones. As dislocation activity extends far away from the contact, it is not feasible to tackle this problem via MD alone. Therefore, to reduce computational cost, we resort to coupling MD to a discrete dislocation dynamics (DD) domain [2], into which MD dislocations may enter. The coupling method used is the recently proposed coupled atomistics and discrete dislocations (CADD) method [3, 4, 5]. It has so far been implemented only in 2D and therefore effectively models asperities with an infinite third dimension (cylindrical asperities). In the first part of our presentation, we evaluate the systematic differences between 2D and 3D contact in pure MD calculations. We use this comparison to motivate 2D simulations. Finally, we present simulation results obtained at different scratching speeds for several normal forces and indenter sizes and shapes. We monitor the friction coefficient and scratching forces and relate them to the energy dissipated in the form of discrete plasticity events

Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

Monoclonal antibodies (mAbs) play an increasing important role in the therapeutic armamentarium against multiple sclerosis (MS), an inflammatory and degenerative disorder of the central nervous system. Most of the mAbs currently developed for MS are immunomodulators blocking the inflammatory immune process. In contrast with mAbs targeting immune function, GNbAC1, a humanized IgG4 mAb, targets the multiple sclerosis associated retrovirus envelope (MSRVEnv) protein, an upstream factor in the pathophysiology of MS. MSRV-Env protein is of endogenous retroviral origin, expressed in MS brain lesions, and it is pro-inflammatory and toxic to the remyelination process, by preventing the differentiation of oligodendrocyte precursor cells. We present the preclinical and early clinical development results of GNbAC1. The specificity of GNbAC1 for its endogenous retroviral target is described. Efficacy of different mAb versions of GNbAC1 were assessed in MSRV-Env induced experimental allergic encephalitis (EAE), an animal model of MS. Because the target MSRV-Env is not expressed in animals, no relevant animal model exists for a proper in vivo toxicological program. An off-target 2-week toxicity study in mice was thus performed, and it showed an absence of safety risk. Additional in vitro analyses showed an absence of complement or antibody-dependent cytotoxicity as well as a low level of cross-reactivity to human tissues. The first-in-man clinical study in 33 healthy subjects and a long-term clinical study in 10 MS patients showed that GNbAC1 is well tolerated in humans without induction of immunogenicity and that it induces a pharmacodynamic response on MSRV biomarkers. These initial results suggest that the mAb GNbAC1 could be a safe long-term treatment for patients with MS with a unique therapeutic mechanism of action.GeNeuro SA, Geneva, Switzerlandhttp://www.tandfonline.com/loi/kmab202016-01-31hb201

Linking Discrete Dislocations and Molecular Dynamics in 3D: a Start

Many phenomena in crystalline metals such as friction, nano-indentation and ductile fracture are plasticity-driven and poorly understood. The physical complexity is further increased by the inherently multiscale nature of contact and fracture [1]. This study is aimed at a realistic numerical treatment of plasticity during nanoscale scratching of crystalline metal. The principal mechanism of plasticity is dislocation nucleation and motion. Nucleation is an atomic nanoscale phenomenon and is often localised at interfaces, crack tips, etc., while dislocation motion is a microscale phenomenon occurring within grains in a polycrystalline microstructure [2]. The molecular dynamics (MD) method is able to accurately predict dislocation nucleation, however the time and length scale limitations [3] of MD do not permit for the description of the motion of entire dislocation networks. The latter are computed much more efficiently [4] with the discrete dislocation dynamics (DD) method where the details of the atomistic core are eliminated from consideration. We present a method to extend to 3D the coupled atomistics and discrete dislocations (CADD) method [5, 6, 7]. To date, CADD has been restricted to plane strain problems with straight disloca- tions. In 3D CADD, the solid is split into two regions (e.g. Figure 1(a)): the MD region, where highly non-linear deformations (i.e. dislocation nucleation) and complex defect interactions are expected that require atomic resolution, and the DD region, where plastic behaviour due to dislocation motion can be computed at much lower cost. To couple these regions, the MD/DD interface (see Figure 1(b)) uses a layer in the MD region where approaching dislocations are detected and a layer in the DD region where fictitious pad atoms serve as boundary conditions for the MD region. An iterative solution permits for the tracking of dislocation lines that span the MD and DD regions, with minimal spurious forces due to the interface coupling. We apply the 3D coupling scheme to the simplest problem - motion of a straight edge dislocation under a uniform applied shear. The results will be used to show capabilities and limitations of the method, and will guide the extension to more complex problems

The role of local dimensionality measures in benchmarking nearest neighbor search

This paper reconsiders common benchmarking approaches to nearest neighbor search. It is shown that the concepts of local intrinsic dimensionality (LID), local relative contrast (RC), and query expansion allow to choose query sets of a wide range of difficulty for real-world datasets. Moreover, the effect of the distribution of these dimensionality measures on the running time performance of implementations is empirically studied. To this end, different visualization concepts are introduced that allow to get a more fine-grained overview of the inner workings of nearest neighbor search principles. Interactive visualizations are available on the companion website.1 The paper closes with remarks about the diversity of datasets commonly used for nearest neighbor search benchmarking. It is shown that such real-world datasets are not diverse: results on a single dataset predict results on all other datasets well

Sub-second periodicity in a fast radio burst

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light-years. The nature of their progenitors and their emission mechanism remain open astrophysical questions. Here we report the detection of the multi-component FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components with a significance of 6.5 sigmas. The long (~3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere, as opposed to emission regions located further away from the star, as predicted by some models.Comment: Updated to conform to the accepted versio

The Role of Regulatory T Cells in Cancer

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA