A flexible readout board for HEP experiments

This thesis will present my contributions to the development of the PiLUP board along with a general overview of its features and capabilities. The PiLUP board is a general-purpose FPGA-based readout board for data acquisition systems under development by the University of Bologna and the Instituto Nazionale Fisica Nucleare (INFN) and intended for high energy physics experiments, where the sheer amount of data generated by detectors often requires custom hardware solutions. This board was initially proposed for the next upgrade of the ATLAS Pixel detector. In this context its purpose would be to interface the Front-End readout chip RD53A with the FELIX card and provide advanced testing features such as an emulator for the RD53A that will help the development of the other parts of the data acquisition chain. Nonetheless, since the early stages of development, the hardware has been designed to offer great flexibility so that the same hardware platform could be directly used in other applications. To this purpose an important feature of the board is the great extendibility offered by the presence of different interfaces, such as and 3 FMC connectors (two low density and one high density), a PCI Express x8 interface, gigabit ethernet and an integrated SFP connector. The computing power of the PiLUP is provided by of two FPGAs, a Zynq-7 SoC and a Kintex-7 produced by Xilinx, intended to be used in master-slave configuration. In this case the Zynq, with its dual-core ARM processor and the possibility to run an embedded linux distribution, would be used as main interface with the other functionalities in the board. The main objective of this thesis is the development of such software and firmware control infrastructure, starting from the firmware solutions for the inter-FPGA communication to the low-level software to control the system

Correlation between basal bilirubin levels and survival in advanced colorectal carcinoma treated with CPT-11-based chemotherapy: A study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.)

AbstractBackgroundThis study was carried out to evaluate total basal bilirubin levels as a predictive factor for survival and toxicity in patients with advanced colorectal carcinoma treated with CTP-11-based regimens.Patients and methodsThe analysis was carried out on a data base including 287 patients affected by advanced colorectal carcinoma all treated with CPT-11 plus bolus and continuous venous infusion intravenous folinic acid and 5-fluorouracil on a biweekly schedule (FOLFIRI regimen). Patients were divided into four groups according to basal bilirubin levels as follows: 0.50 and 1.00 and 1.50mg/dl. Analysis of overall median survival and time-to-progression were correlated to performance status at entry, volume of liver metastases, and carcinoembrionary antigen.ResultsGlobal statistical analysis showed that bilirubin levels were strongly correlated with time-to-progression and overall survival in a statistically significant fashion (p<0.0001). The size of liver metastases represents the only study parameter which is correlated to basal bilirubin levels in a statistically significant fashion. Neutropaenia and diarrhoea were also correlated to baseline bilirubin levels in a statistically significant manner (p=0.001).ConclusionsData reported in this study support the observation that basal bilirubin levels are a biomarker able to predict, at least in part, the clinical efficacy and toxicity of CPT-11-based chemotherapy in patients with advanced colorectal carcinoma

General purpose readout board {\pi} LUP: overview and results

This work gives an overview of the PCI-Express board $\pi$LUP, focusing on the motivation that led to its development, the technological choices adopted and its performance. The $\pi$LUP card was designed by INFN and University of Bologna as a readout interface candidate to be used after the Phase-II upgrade of the Pixel Detector of the ATLAS and CMS experiments at LHC. The same team in Bologna is also responsible for the design and commissioning of the ReadOut Driver (ROD) board - currently implemented in all the four layers of the ATLAS Pixel Detector (Insertable B-Layer, B-Layer, Layer-1 and Layer-2) - and acquired in the past years expertise on the ATLAS readout chain and the problematics arising in such experiments. Although the $\pi$LUP was designed to fulfill a specific task, it is highly versatile and might fit a wide variety of applications, some of which will be discussed in this work. Two 7$^{th}$-generation Xilinx FPGAs are mounted on the board: a Zynq-7 with an embedded dual core ARM Processor and a Kintex-7. The latter features sixteen 12.5$\,$Gbps transceivers, allowing the board to interface easily to any other electronic board, either electrically and/or optically, at the current bandwidth of the experiments for LHC. Many data-transmission protocols have been tested at different speeds, results will be discussed later in this work. Two batches of $\pi$LUP boards have been fabricated and tested, two boards in the first batch (version 1.0) and four boards in the second batch (version 1.1), encapsulating all the patches and improvements required by the first version.Comment: 6 pages, 10 figures, 21th Real Time Conference, winner of "2018 NPSS Student Paper Award Second Prize

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM- patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM- patients (BC: AUC = 0.71 +/- 0.09, P = 0.03; PC: AUC = 0.73 +/- 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease

Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases.

Background: The effects of the bisphosphonate derivative zoledronic acid (ZA) on the > circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 > (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in > patients with bone metastasis (BMTS) and the possible correlation with the symptomatic > response induced by this drug in these patients were evaluated. Patients and Methods: > Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the > plasma of 30 patients with painful bone metastases from breast or prostate cancer > undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects > (HS) of both genders (12 female and 30 male) served as the control group. The > symptomatic response to ZA was assessed by the visual analog scale score (VAS). > Results: The median MMP-2 and MMP-9 pretreatment levels were more elevated in BMTS as > compared to HS (p¡Ü0.0001). Conversely, uPA levels were lower in BMTS p=0.0033; no > significant difference was observed for Cath B. ZA administration was associated with > a symptomatic response (VAS score¡Ü4) in 25/30 patients (83.3%) (p<0.0001). This > phenomenon paralleled a decrease of Cath B and MMP-2 plasma concentrations from > baseline values on week 12 (p=0.05). A similar trend, although not statistically > significant, was also noted for MMP-9 and uPA. However, no direct relationship was > observed between the analgesic effect induced by ZA and changes in the circulating > levels of these enzymes. Conclusion: These data show that ZA administration may > provide relief from bone pain in patients with diffuse skeletal metastases and confirm > a possible implication of cysteine proteinases and matrix metalloproteinases in bone > metastasis formation, but not in the pathogenesis of metastatic bone pain

Bisphosphonate-related osteonecrosis of the jaw (BRONJ): run dental management designs and issues in diagnosis.

Recently, jawbone osteonecrosis has been largely reported as a potential adverse effect of bisphosphonate (BP) administration. Because of the peculiar pharmacokinetic and pharmacodynamic features of the BF (mainly for i.v. administration), their efficacy and large use, some major issues have to be taken into account extendedly both by oncologists and by dentists: 1) therapeutic dental protocol for patients with diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ); 2) dental strategies for patients in former or current i.v. BF treatment and in absence of BRONJ signs; 3) strategies for patients before i.v. BF treatment. Clinical features and guidelines for the management of this condition have been investigated and reported, sometimes with unclear indications; hence, on the basis of the literature and our clinical experience, major end points of this paper are providing our run protocols for the issues above described and, finally, focusing on a crucial, but not extensively investigated point: the early and correct diagnosis of BRONJ versus metastatic jaw lesions in cancer patients

MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.

Background: The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. Patients and Methods: MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Results: Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy. Conclusion: Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better define

WHATSAPP MESSENGER AS A REAL-TIME TOOL FOR A LONG-DISTANCE ACTIVITY OF A MULTIDISCIPLINARY

Introduction: Communication between doctors is traditionally conducted by written clinical charts. Mobile health is becoming an integral part of modern medical systems, improving accessibility and quality of medical care. Recent papers suggest that an increasing number of doctors are using in their clinical practice mobile tools to communicate clinical informations (1, 2). The aim of our study was to verify the adoption of WhatsApp Messenger in everyday clinical practice to obtain a real-time multidisciplinary collaboration among medical centers located in different areas of the city. Materials and Methods: In January 2016 a WhatsApp Messenger group was created among 25 specialists: 9 urologists, 9 oncologists, 3 urology residents, 3 radiotherapists and 1 general practitioner. A general coordinator and a group coordinator for each specialty was monthly appointed. The participants were invited to interact within the group clinical cases of genitourinary tumors of particular complexity requiring a multidisciplinary approach. All the chats were registered. A preliminary analysis of the activity of the group was planned after the first 10 entered patients. An evaluation questionnaire was sent after 6 months to evaluate the level of appreciation. The questionnaire was composed of a first section investigating the appreciation among the members of the group and a second section analyzing the impact in their everyday clinical practice of whatsapp multidisciplinary consultation. Results: In 10 (91%) out of 11 patients the WhatsApp consultation was completed, one case was not of oncological interest. An average of 8 (range=2-13) specialists joined the chat for each patient. An average of 17.6 (range: 4-43) interventions for each clinical case was recorded. On the average, 27%, 54% and 19% of the interventions for each clinical case were provided by oncologists, urologists and radiotherapists respectively. In 9 (81.8%) cases a final agreement on the patient's management was reached. At the evaluation questionnaire in a scale 1-10, the average rating score of appreciation was 7.8 (range=4-10). Relevant suggestions to improve the Whatsapp Messenger consultation were obtained and will be considered for future application the ameliorate the tool. Discussion: WhatsApp is a useful alternative and powerful complementary communication tool because of its capability to rapidly transfer large amount of clinical and radiological data. In our experience this new approach for multidisciplinary consultations improved collaboration among different specialist in different areas of the city through an easier and more informal change of opinions. In difficult and complex cases a rapid multidisciplinary approach allowed to offer the patient a personalized and tailored therapy management. GSTU Foundation. 1Sidhoum N, Dast S, Abdulshakoor A, Assaf N, Herlin C and Sinna R: WhatsApp: Improvement tool for surgical team communication. J Plast Reconstr Aesthet Surg 69: 1562-1563, 2016. 2 Gould G and Nilforooshan R: WhatsApp Doc? BMJ Innov 2(3): 109-110, 201

Ductal lavage: a way of carefully tracing the breast-secreting duct

Background: Breast cancer is the most commonly diagnosed neoplasia in women after nonmelanoma skin tumors. Unfortunately, present-day diagnostic methods are unable to identify the presence of a cancer until it has been developing for several years. Currently, ductal lavage seems to represent a new method of reaching an early diagnosis of breast cancer. Materials & methods: This study analyzed 30 patients with ages ranging from 40 to 55 years; and in 26 of these patients, we were able to obtain a sufficient quantity of material for cytological and biomolecular analysis. Results & conclusion: We propose an easy, reproducible method that makes it possible to obtain a detailed map of the nipple, in order to re-identify the duct orifice and take a series of repeated samples from it over a period of time. This procedure is a promising screening and translational research tool since it provides the quantity and quality of ductal fluid required for subsequent cytological and biomolecular analyse

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC