Performance of Delta4 Phantom+ using Flattening-Filter and Flattening Filter-Free beams

EnThe goal of this study was to evaluate the performances of the new pre-treatment system Delta4 Phantom+ in terms of a stable and sensitive tool for achieving a reliable verification. Delta4+ was evaluated for verification with 6FFFMV beams using static beam arrangement. The accelerator output was monitored with the ionization chamber. The device was tested for dose-rate dependence, linearity and stability using its daily output correction. The response of Delta4+ was evaluated for energy 6FFFMV, measuring the gamma index of four Volumetric Modulated Arc Therapy (VMAT) plan. The response of Delta4+ as a function of accelerator dose rate is in agreement with the ionization chamber with a difference smaller than 0,1%. The output is constant for different MU. VMAT plan analysis show values within 98,3%-100% with a threshold of 3%-3mm, while with a threshold of 2%-2mm the values are within 93,5%-97,5%. Delta4+ is an accurate device. For all the measurements made, uncertainties below 1% were obtained.ItLo scopo di questo studio è stato quello di valutare la risposta in termini di stabilità e sensibilità del nuovo sistema pre-trattamento Delta4 Phantom+. La risposta del sistema è stato studiata utilizzando fasci di fotoni da 6MVsenza filtro di flattening (6FFFMV). L'output dell'acceleratore è stato monitorato con una camera a ionizzazione. La dipendenza dal dose rate, la linearità e la stabilità sono state verificate utilizzando il fattore di correzione giornaliera fornito dal sistema. La risposta è stata verificata su 4 piani di trattamento con tecnica VMAT. La risposta del Delta4+ al variare del dose rate è in accordo con quella della camera a ionizzazione con una scarto minore dello 0.1%. La risposta al variare delle UM è costante con una differenza entro lo 0.4%. L'analisi dei piani VMAT mostra valori di indice gamma per soglia 3%-3mm compresi tra 98.3%-100%, mentre per 2%-2mm i valori sono tra 93,5%-97,5%. Il Delta4+ risulta essere un sistema accurato in quanto l'incertezza ottenuta su tutte le misure non supera l'1%

Initial operation of the International Gravitational Event Collaboration

The International Gravitational Event Collaboration, IGEC, is a coordinated effort by research groups operating gravitational wave detectors working towards the detection of millisecond bursts of gravitational waves. Here we report on the current IGEC resonant bar observatory, its data analysis procedures, the main properties of the first exchanged data set. Even though the available data set is not complete, in the years 1997 and 1998 up to four detectors were operating simultaneously. Preliminary results are mentioned.Comment: 8 pages, 2 figures, 3 tables; Proceeding of the GWDAW'99. Submitted to the International Journal of Modern Physic

Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression

: Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the -200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy - even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies

Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes: an Italian multicenter study

OBJECTIVE— To estimate the prevalence of biopsy-confirmed celiac disease in Italian children and adolescents with type 1 diabetes and to assess whether age at onset of type 1 diabetes is independently associated with diagnosis of celiac disease. RESEARCH DESIGNANDMETHODS— The study group was a clinic-based cohort of children and adolescents with type 1 diabetes cared for in 25 Italian centers for childhood diabetes. Yearly screening for celiac disease was performed using IgA/IgG anti-gliadin and IgA anti-endomysium antibodies. RESULTS— Of the 4,322 children and adolescents (age 11.8 4.2 years) identified with type 1 diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%, 95% confidence interval [CI] 6.0 –7.6), with a higher risk seen in girls than in boys (odds ratio [OR] 1.93, 1.51–2.47). In 89% of these, diabetes was diagnosed before celiac disease. In logistic regression analyses, being younger at onset of diabetes, being female, and having a diagnosis of a thyroid disorder were independently associated with the risk of having diabetes and celiac disease. In comparison with subjects who were older than 9 years at onset of diabetes, subjects who were younger than 4 years at onset had an OR of 3.27 (2.20–4.85). CONCLUSIONS— We have provided evidence that 1) the prevalence of biopsy-confirmed celiac disease in children and adolescents with type 1 diabetes is high (6.8%); 2) the risk of having both diseases is threefold higher in children diagnosed with type 1 diabetes at age 4 years than in those age 9 years; and 3) girls have a higher risk of having both diseases than boys

Random time-changes and asymptotic results for a class of continuous-time Markov chains on integers with alternating rates

We consider continuous-time Markov chains on integers which allow transitions to adjacent states only, with alternating rates. This kind of processes are useful in the study of chain molecular diffusions. We give explicit formulas for probability generating functions, and also for means, variances and state probabilities of the random variables of the process. Moreover we study independent random time-changes with the inverse of the stable subordinator, the stable subordinator and the tempered stable subordinator. We also present some asymptotic results in the fashion of large deviations. These results give some generalizations of those presented in [Journal of Statistical Physics 154 (2014), 1352–1364]

SYNCHRONOUS SPERMATOGENESIS IN APPENDICULARIANS

Spermatogenesis was studied in appendicularians belonging to the families Fritillariidae (Fritillaria borealis, Fritillaria pellucida) and Oikopleuridae (Oikopleura dioica, Oikopleura albicans, Oikopleura longicauda). Particular attention was given to specimen of Fritillaria borealis collected in the fjord of Bergen (Norway) and to Oikopleura dioica reared in a laboratory at the Station Zoologique in Villefranche-sur-Mer. In all species, spermatogenesis proceeds in a highly synchronized way in the whole testis, thanks to the presence of syncytial structures. Two models were identified: 1) In Fritillaria borealis, the syncytium contains organelles and two populations of large and small nuclei. The large somatic nuclei produce "nuage" and occupy the center of wide cytiplasmic areas, at the periphery of which the small nuclei of the germ cells lie. As spermatogenesis progresses, large nuclei and syncytial cytoplasm reduce volume, while germ cells greatly proliferate and undergo meiosis and spermiogenesis. Lastly, the large nuclei degenerate while late spermatids, all possessing a single mitochondrion and a flagellum, segregate from the syncytium. 2) In Oikopleura dioica, the large cytoplasmic area contains most of the organelles and germ cell nuclei hanging at the periphery. Germ cells undergo series of mitosis, meiosis and spermiogenesis, whereas mitochondria migrate from the common cytoplasmic area through bridges. Lastly, the syncytial area is markedly reduced, and spermatozoa segregate and mature all together. In all species, spermatozoa are small and flagellate. They mature in great numbers and are appropriately arranged in the testis, thus exploiting to fulest extent the space for the imminent spawning

The appendicularian alimentary tract: a comparative study

Species belonging to the three families of appendicularians (Oikopleuridae, Fritillariidae, Kowalevskiidae) reveal general simplification of trunk organs, especially Fritilalriidae and Kowalevskiidae. In particular, the alimentary tract, studied by light and electron microscopy using specimens cut with complete series of sections, shows that no connective or muscle tissue accompanies the gut epithelium, and no cell-renewing regions nor endocrine-like cells can be identified. In the pharynx, the endostyle varies in complexity from Oikopleura to Fritillaria, but is absent in Kowalevskia. The post-pharyngeal tract is always composed of an oesophagus, a stomach and an intestine, the latter subdivided into two or three regions. In Oikopleura, several cell types with different functions are recognisable. In the other families, the cells are very few, mostly giant, and poorly diversified. Food passage depends upon ciliary activity. Absorption, digestion and epithelial transport are also evident. The gut tracts are always separated by valves (usually cardiac, pyloric and rectal) although their importance varies among species. In general, oikopleurids possess common features in the histology of the alimentary tract, completely distinc from fritillarids and kowalevskids, which have othe features in common

Gut ultrastructure of the appendicularian Oikopleura dioica (Tunicata)

The appendicularians, planktonic tunicates, possess a specialized, external filtering system that captures food particles <1 \u3bcm in size. In this work the alimentary canal of Oikopleura dioica has been studied by serial sections of whole animals and ultrastructure. The gut includes a dorsal esophagus, a bilobed saccular stomach, and a curved intestine, divided into vertical, mid-, and distal intestine (or rectum). No multicellular glands or cellular proliferative centers were found. Three main cell types were recognized, ciliated microvillar cells, globular cells and gastric band cells, with specializations reflecting different physiological roles in the various regions. Ciliated microvillar cells, the most diffuse, are considered to be involved in food propulsion, fecal pellet formation, absorption, and nutrient storage. Pinocytotic features and vacuoles suggest that absorption of macromolecules and intracellular digestion occur in the globular cells of the stomach and rectum. The large gastric band cells of the left lobe have typical features of intense protein synthesis and probably produce enzymes for extracellular digestion. Diffuse interdigitations of many cells enormously increase the plasmalemma surface and may be involved in liquid/ion exchange. Despite the apparent structural simplicity of the gut epithelium, O. dioica efficiently processes food to fulfill the energy requirements of its exceptionally rapid life-cycle