Assessing the impact of increasing lung screening eligibility by relaxing the maximum years-since-quit threshold. A simulation modeling study

BackgroundIn 2021, the US Preventive Services Task Force expanded its lung screening recommendation to include persons aged 50–80 years who had ever smoked and had at least 20 pack-years of exposure and less than 15 years since quitting (YSQ). However, studies have suggested that screening persons who formerly smoked with longer YSQ could be beneficial.MethodsThe authors used two validated lung cancer models to assess the benefits and harms of screening using various YSQ thresholds (10, 15, 20, 25, 30, and no YSQ) and the age at which screening was stopped. The impact of enforcing the YSQ criterion only at entry, but not at exit, also was evaluated. Outcomes included the number of screens, the percentage ever screened, screening benefits (lung cancer deaths averted, life-years gained), and harms (false-positive tests, overdiagnosed cases, radiation-induced lung cancer deaths). Sensitivity analyses were conducted to evaluate the effect of restricting screening to those who had at least 5 years of life expectancy.ResultsAs the YSQ criterion was relaxed, the number of screens and the benefits and harms of screening increased. Raising the age at which to stop screening age resulted in additional benefits but with more overdiagnosis, as expected, because screening among those older than 80 years increased. Limiting screening to those who had at least 5 years of life expectancy would maintain most of the benefits while considerably reducing the harms.ConclusionsExpanding screening to persons who formerly smoked and have greater than 15 YSQ would result in considerable increases in deaths averted and life-years gained. Although additional harms would occur, these could be moderated by ensuring that screening is restricted to only those with reasonable life expectancy

A New Computational Tool for the Phenomenological Analysis of Multipassage Tumor Growth Curves

Multipassage experiments are performed by subcutaneous implantation in lab animals (usually mice) of a small number of cells from selected human lines. Tumor cells are then passaged from one mouse to another by harvesting them from a growing tumor and implanting them into other healthy animals. This procedure may be extremely useful to investigate the various mechanisms involved in the long term evolution of tumoral growth. It has been observed by several researchers that, contrary to what happens in in vitro experiments, there is a significant growth acceleration at each new passage. This result is explained by a new method of analysis, based on the Phenomenological Universalities approach. It is found that, by means of a simple rescaling of time, it is possible to collapse all the growth curves, corresponding to the successive passages, into a single curve, belonging to the Universality Class U2. Possible applications are proposed and the need of further experimental evidence is discussed

Time periodicity and dynamical stability in two-boson systems

We calculate the period of recurrence of dynamical systems comprising two interacting bosons. A number of theoretical issues related to this problem are discussed, in particular, the conditions for small periodicity. The knowledge gathered in this way is then used to propose a notion of dynamical stability based on the stability of the period. Dynamical simulations show good agreement with the proposed scheme. We also apply the results to the phenomenon known as coherent population trapping and find stability conditions in this specific case.Comment: 7+ pages, 5 figure

Singlet-doublet Higgs mixing and its implications on the Higgs mass in the PQ-NMSSM

We examine the implications of singlet-doublet Higgs mixing on the properties of a Standard Model (SM)-like Higgs boson within the Peccei-Quinn invariant extension of the NMSSM (PQ-NMSSM). The SM singlet added to the Higgs sector connects the PQ and visible sectors through a PQ-invariant non-renormalizable K\"ahler potential term, making the model free from the tadpole and domain-wall problems. For the case that the lightest Higgs boson is dominated by the singlet scalar, the Higgs mixing increases the mass of a SM-like Higgs boson while reducing its signal rate at collider experiments compared to the SM case. The Higgs mixing is important also in the region of parameter space where the NMSSM contribution to the Higgs mass is small, but its size is limited by the experimental constraints on the singlet-like Higgs boson and on the lightest neutralino constituted mainly by the singlino whose Majorana mass term is forbidden by the PQ symmetry. Nonetheless the Higgs mixing can increase the SM-like Higgs boson mass by a few GeV or more even when the Higgs signal rate is close to the SM prediction, and thus may be crucial for achieving a 125 GeV Higgs mass, as hinted by the recent ATLAS and CMS data. Such an effect can reduce the role of stop mixing.Comment: 26 pages, 3 figures; published in JHE

SPIN90 associates with mDia1 and the Arp2/3 complex to regulate cortical actin organization

Cell shape is controlled by the submembranous cortex, an actomyosin network mainly generated by two actin nucleators: the Arp2/3 complex and the formin mDia1. Changes in relative nucleator activity may alter cortical organization, mechanics and cell shape. Here we investigate how nucleation-promoting factors mediate interactions between nucleators. In vitro, the nucleation-promoting factor SPIN90 promotes formation of unbranched filaments by Arp2/3, a process thought to provide the initial filament for generation of dendritic networks. Paradoxically, in cells, SPIN90 appears to favour a formin-dominated cortex. Our in vitro experiments reveal that this feature stems mainly from two mechanisms: efficient recruitment of mDia1 to SPIN90-Arp2/3 nucleated filaments and formation of a ternary SPIN90-Arp2/3-mDia1 complex that greatly enhances filament nucleation. Both mechanisms yield rapidly elongating filaments with mDia1 at their barbed ends and SPIN90-Arp2/3 at their pointed ends. Thus, in networks, SPIN90 lowers branching densities and increases the proportion of long filaments elongated by mDia1

Distinguishing Various Models of the 125 GeV Boson in Vector Boson Fusion

The hint of a new particle around 125 GeV at the LHC through the decay modes of diphoton and a number of others may point to quite a number of possibilities. While at the LHC the dominant production mechanism for the Higgs boson of the standard model and some other extensions is via the gluon fusion process, the alternative vector boson fusion is more sensitive to electroweak symmetry breaking through the gauge-Higgs couplings and therefore can be used to probe for models beyond the standard model. In this work, using the well known dijet-tagging technique to single out the vector boson fusion mechanism, we investigate its capability to discriminate a number of models that have been suggested to give an enhanced inclusive diphoton production rate, including the standard model Higgs boson, fermiophobic Higgs boson, Randall-Sundrum radion, inert-Higgs-doublet model, two-Higgs-doublet model, and the MSSM. The rates in vector-boson fusion can give more information of the underlying models to help distinguishing among the models.Comment: 31 pages, 3 figures; in this version some wordings are change

Co-Design of Business and IT Services – a Tool-Supported Approach

Service modeling is an important step in designing service-oriented systems. There are multiple levels of design because service sci-ence includes both the business rationale and the IT implementation ofthe services. As business and IT perspectives differ, the modeling tech-niques are different, and often the respective modeling languages aredisconnected or ad-hoc. We propose a new service-modeling approachfor connecting the business modeling and the web service modeling bypresenting these two perspectives in a single model. We present a multi-stage modeling process for capturing different perspectives and creatingmodels iteratively by working with levels of abstraction from higher tolower. The model is then used as an input in order to generate a RESTAPI specification in the OpenAPI format to feed the next stages of theservice life-cycle

Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children

Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration <= 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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