The clinical and immunological basis of early food introduction in food allergy prevention

IgE-mediated food allergy has an estimated prevalence of 6%–10% in developed countries. Allergen avoidance has long been the main focus in the prevention of food allergy and late solid food introduction after 6–12 months of age was recommended in high-risk infants. However, the rising prevalence of food allergy despite delayed exposure to allergens and the observations that IgE-mediated sensitization to food products could even occur before the introduction of solid foods resulted in a shift towards early solid food introduction as an attempt to prevent IgE-mediated food allergy. Since then, many trials focused on the clinical outcome of early allergen introduction and overall seem to point to a protective effect on the development of IgE-mediated food allergies. For non-IgE-mediated diseases of food allergy, evidence of early food introduction seems less clear. Moreover, data on the underlying immunological processes in early food introduction is lacking. The goal of this review is to summarize the available data of immunological changes in early food introduction to prevent IgE and non-IgE mediated food allergy

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment

The Short-term Car Flow Planning Model in Rail Freight Company – Case Study

AbstractWith the promotion of the environmentally friendly transportation modes (the European Commission supports the freight transport operations in the rail sector), an increase in the diversification of the demand is observed. While most rail freight companies tend to apply fixed schedules, this approach is not effective turns out to be ineffective due to the need to meet the customer's specific requirements.The purpose of this paper is to present a case study of empty wagon flow planning over a medium term horizon and to discuss the opportunities of improvement of this plans by discrete optimization. In order to increase the utilization and availability of wagons, the planning procedure with a rolling horizon has to be implemented. Unfortunately, since the plan has to be updated ca. every 4hours, this planning approach needs effective optimization tools. Our hybrid two-stage approach is designed to be implemented in such business environment. This formulation allows us to solve real life instances even for a 7-day time horizon

Catalog of Galactic Beta Cephei Stars

We present an extensive and up-to-date catalog of Galactic Beta Cephei stars. This catalog is intended to give a comprehensive overview of observational characteristics of all known Beta Cephei stars. 93 stars could be confirmed to be Beta Cephei stars. For some stars we re-analyzed published data or conducted our own analyses. 61 stars were rejected from the final Beta Cephei list, and 77 stars are suspected to be Beta Cephei stars. A list of critically selected pulsation frequencies for confirmed Beta Cephei stars is also presented. We analyze the Beta Cephei stars as a group, such as the distributions of their spectral types, projected rotational velocities, radial velocities, pulsation periods, and Galactic coordinates. We confirm that the majority of these stars are multiperiodic pulsators. We show that, besides two exceptions, the Beta Cephei stars with high pulsation amplitudes are slow rotators. We construct a theoretical HR diagram that suggests that almost all 93 Beta Cephei stars are MS objects. We discuss the observational boundaries of Beta Cephei pulsation and their physical parameters. We corroborate that the excited pulsation modes are near to the radial fundamental mode in frequency and we show that the mass distribution of the stars peaks at 12 solar masses. We point out that the theoretical instability strip of the Beta Cephei stars is filled neither at the cool nor at the hot end and attempt to explain this observation

An asteroseismic study of the beta Cephei star 12 Lacertae: multisite spectroscopic observations, mode identification and seismic modelling

We present the results of a spectroscopic multisite campaign for the beta Cephei star 12 (DD) Lacertae. Our study is based on more than thousand high-resolution high S/N spectra gathered with 8 different telescopes in a time span of 11 months. In addition we make use of numerous archival spectroscopic measurements. We confirm 10 independent frequencies recently discovered from photometry, as well as harmonics and combination frequencies. In particular, the SPB-like g-mode with frequency 0.3428 1/d reported before is detected in our spectroscopy. We identify the four main modes as (l1,m1) = (1, 1), (l2,m2) = (0, 0), (l3,m3) = (1, 0) and (l4,m4) = (2, 1) for f1 = 5.178964 1/d, f2 = 5.334224 1/d, f3 = 5.066316 1/d and f4 = 5.490133 1/d, respectively. Our seismic modelling shows that f2 is likely the radial first overtone and that the core overshooting parameter alpha_ov is lower than 0.4 local pressure scale heights.Comment: 16 pages, 11 figures, accepted in MNRA

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Risk management of biosimilars in oncology: each medicine is a work in progress

Drug licensing and drug safety monitoring for standard chemical entities have been established and are routinely used. These have resulted in a solid foundation of knowledge from which confident therapeutic decisions can be made. For many chemical entities, this advanced level of experience is also present for the generic products. The expertise surrounding the development of biosimilar competitor versions is increasing and progress is encouraging. To address the re-engineering and comparability complexities of biosimilars, the European Union imposed a requirement that risk management plans be included in the medications’ marketing applications. This paper summarizes and discusses the circumstances complicating the public’s view of drug safety, historical incidents during the transition from innovative to competitor products, as well as retrospective assessments of the development and post-marketing experiences thus far with two biosimilars. Through assessing the market entries and post-marketing experiences of biosimilars used in oncology, the healthcare field can better prepare for the next wave of comparator-products: biosimilar monoclonal antibodies

Socioeconomic inequalities in cancer survival in Scotland 1986–2000

We analysed trends in 5-year survival of the 18 commonest cancers in Scotland diagnosed between 1986 and 2000 and followed up to 2004 in each of five deprivation groups based on patients postcode of residence at diagnosis. We estimated relative survival up to 5 years after diagnosis, adjusting for the different background mortality in each deprivation group by age, sex and calendar period. We estimated trends in overall survival and in the deprivation gap in survival up to 2004. Five-year survival improved for all malignancies except bladder cancer and was associated with a widening in the deprivation gap in survival. For 25 of 30 cancer–sex combinations examined, 5-year survival was lower among more deprived patients diagnosed during 1996–2000, and the deprivation gap in survival had widened since 1986–1990 for 15 of these 25 cancers, similar to the trends seen in England and Wales

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. METHODS: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. RESULTS: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. CONCLUSIONS: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry