For the detection of secondary vertices of long lived particles containing bottom and charm quarks at the International Linear Collider (ILC), a DEPFET pixel detector is one of the technologically ...favored options. In a DEPFET sensor a MOSFET pixel detector is integrated on a sidewards depleted silicon bulk sensor, thus combining the advantages of a fully depleted silicon sensor with in-pixel amplification. DEPFET pixel matrices have been characterized in a high energy particle beam. Since the DEPFET is a very high precision device, given its large S/N (> 100) and small pixel size (36 × 22 ¿m 2 ), a DEPFET based pixel telescope consisting of 5 DEPFETs has been developed. The uncertainty on the predicted position for a device under test (DUT) positioned inside the telescope was found to be 1.4 ¿m with the existing device, due to the limited performance of two of the five DEPFET planes. A DEPFET telescope built of 5 modules equivalent to the best plane presented here, would have a track extrapolation error as low as 0.65 ¿m at the DUT plane.
For the HL-LHC, ATLAS 1 will install a new all-silicon tracking system. The strip part will be comprised of five barrel layers and seven end cap disks on each side. The detectors will be connected to ...highly integrated, low mass front-end electronic hybrids with custom-made ASICs in 130nm CMOS technology. The hybrids will be flexible four layer copper polyimide constructions. They will be designed and populated at the universities involved, while the flexible PCBs will be produced in industry. This paper describes the evolution of hybrid designs for the barrel and end cap, discusses their electrical performance, and presents results from prototype modules made with the hybrids.
We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010.
NETSARC (netsarc.org) is a ...network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients’ characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020.
A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers.
The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.
•The creation of nationwide network of reference centers in France was associated with improved survival of sarcoma patients.•The compliance to CPGs over 10 years and the quality of surgery nationwide increased significantly.•Improvement in compliance to CPG was seen both in and outside reference centers but the compliance was lower outside.•These observations support the systematic referral of sarcoma patients to a network of sarcoma reference centers.•Further work on improvement and monitoring of compliance to CPGs must be implemented.
For the Phase-II Upgrade of the ATLAS detector at CERN, the current ATLAS Inner Detector will be replaced with the ATLAS Inner Tracker (ITk). The ITk will be an all-silicon detector, consisting of a ...pixel tracker and a strip tracker. Sensors for the ITk strip tracker are required to have a low leakage current up to bias voltages of −500 V to maintain a low noise and power dissipation. In order to minimise sensor leakage currents, particularly in the high-radiation environment inside the ATLAS detector, sensors are foreseen to be operated at low temperatures and to be manufactured from wafers with a high bulk resistivity of several kΩ·cm. Simulations showed the electric field inside sensors with high bulk resistivity to extend towards the sensor edge, which could lead to increased surface currents for narrow dicing edges. In order to map the electric field inside biased silicon sensors with high bulk resistivity, three diodes from ATLAS silicon strip sensor prototype wafers were studied with a monochromatic, micro-focused X-ray beam at the Diamond Light Source (Didcot, U.K.). For all devices under investigation, the electric field inside the diode was mapped and its dependence on the applied bias voltage was studied.
Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront ...metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas.
Les sarcomes des tissus mous sont des tumeurs rares et hétérogènes. Pour la maladie localisée, le traitement repose sur l’association de chirurgie conservatrice et de radiothérapie, avec la possibilité d’associer une chimiothérapie dans certains cas, selon les facteurs de risque. Dans 7 à 20 % des cas, des métastases sont présentes au moment du diagnostic, et sont le plus souvent de localisation pulmonaire. La maladie disséminée est considérée en général incurable, mais dans certains cas, un traitement local agressif des métastases permet un allongement de la survie. Dans cette situation, le traitement local de la tumeur primaire est souvent débattu. Nous nous proposons d’évaluer la littérature sur le rôle de la radiothérapie dans la prise en charge des sarcomes métastatiques d’emblée.
We present the update of the recommendations of the French society of radiation oncology on soft tissue sarcomas. Currently, the initial management of sarcomas is very important as it may impact on ...patients’ quality of life, especially in limb soft tissue sarcomas, and on overall survival in trunk sarcomas. Radiotherapy has to be discussed within a multidisciplinary board meeting with results of biopsy, eventually reexamined by a dedicated sarcoma pathologist. The role of radiotherapy varies according to localization of soft tissue sarcoma. It is part of the standard treatment in grade 2 and 3 sarcomas of the extremities and superficial trunk>5cm. In case of R1 or R2 resection, reexcision should be discussed. In such cases, it may be delivered preoperatively (50Gy/25 fractions of 2Gy) or postoperatively. In retroperitoneal sarcomas, preoperative conformal radiotherapy with or without modulated intensity cannot be proposed systematically in daily practice. Concomitant chemoradiotherapy cannot be considered a standard treatment. Intensity-modulated radiotherapy has become widely available. Other soft tissue sarcoma sites such as trunk, head and neck and gynaecological soft tissue sarcomas will be addressed, as well as other techniques that may be used such as brachytherapy and proton therapy.
Nous présentons la mise à jour des recommandations de la Société française de radiothérapie oncologique sur la radiothérapie des sarcomes des tissus mous. La qualité de la prise en charge initiale des sarcomes est fondamentale, car elle conditionne la qualité de vie du patient et sa survie globale. La radiothérapie doit être donc discutée en réunion de concertation pluridisciplinaire après relecture histologique dans le cadre du Réseau de référence en pathologie des sarcomes des tissus mous et des viscères (RRePS). La place de la radiothérapie chez les adultes atteints d’un sarcome des tissus mous dépend de la localisation tumorale, en sachant qu’elle est le plus souvent associée à la chirurgie, qui est le traitement essentiel. Elle fait partie du traitement standard des sarcomes des membres et sarcomes tronculaires superficiels de grades II et III, de taille égale ou supérieure à 5cm. En cas d’exérèse R1 et a fortiori R2, une reprise chirurgicale doit être discutée. La radiothérapie peut être réalisée en situation préopératoire (50Gy en 25 séances de 2Gy) ou postopératoire dans ces indications. Pour les sarcomes rétropéritonéaux, la radiothérapie préopératoire conformationnelle avec ou sans modulation d’intensité ne doit pas être réalisée systématiquement. D’autres localisations de sarcome des tissus mous touchant le tronc, la tête et le cou, la sphère gynécologique sont également abordées, ainsi que d’autres techniques de radiothérapie : curiethérapie et protonthérapie. La chimioradiothérapie concomitante n’est pas un standard. La radiothérapie conformationnelle avec modulation d’intensité est de plus en plus utilisée.
Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of ...genetic testing for patients with IDC in the primary tumour.
To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case–control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.
No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1–16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1–13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7–19.3).
While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.
•Presence of gBRCA2 mutations was not associated with IDC and CRIB patterns.•Results do not support germline BRCA2 testing only based on presence of IDC and/or CRIB.•IDC and CRIB patterns were associated with bi-allelic BRCA2 alterations in our study.
To better understand the molecular and physiological mechanisms underlying maintenance and release of seasonal bud dormancy in perennial trees, we identified differentially expressed genes during ...dormancy progression in reproductive buds from peach (Prunus persica L. Batsch) by suppression subtractive hybridization (SSH) and microarray hybridization. Four SSH libraries were constructed, which were respectively enriched in cDNA highly expressed in dormant buds (named DR), in dormancy-released buds (RD) and in the cultivars with different chilling requirement, ‘Zincal 5’ (ZS) and ‘Springlady’ (SZ), sampled after dormancy release. About 2500 clones picked from the four libraries were loaded on a glass microarray. Hybridization of microarrays with the final products of SSH procedure was performed in order to validate the selected clones that were effectively enriched in their respective sample. Nearly 400 positive clones were sequenced, which corresponded to 101 different unigenes with diverse functional annotation. We obtained DAM4, 5 and 6 genes coding for MADS-box transcription factors previously related to growth cessation and terminal bud formation in the evergrowing mutant of peach. Several other cDNAs are similar to dormancy factors described in other species, and others have been related to bud dormancy for the first time in this study. Quantitative reverse transcription polymerase chain reaction analysis confirmed differential expression of cDNAs coding for a Zn-finger transcription factor, a GRAS-like regulator, a DNA-binding protein and proteins similar to forisome subunits involved in the reversible occlusion of sieve elements in Fabaceae, among others.
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