The Model Matching Problem for Max-Plus Linear Systems: a Geometric Approach

Linear systems over the max-plus algebra provide a suitable formalism to model discrete event systems where synchronization, without competition, is involved. In this paper, we consider a formulation of the model matching problem for systems of such class, in which the output of a given system, called the plant, is forced, by a suitable input, to track exactly that of a given model. A necessary and sufficient condition for its solvability is obtained by making a suitable use of geometric methods in the framework of systems over the max-plus algebra

Robotic intracorporeal urinary diversion: practical review of current surgical techniques

In this practical review, we discuss current surgical techniques reported in the literature to perform Intracorporeal Urinary Diversion (ICUD) after Robotic Radical Cystectomy (RARC), emphasizing criticisms of single approaches and making comparisons with Extracorporeal Urinary Diversion (ECUD). Although almost 97% of all RARCs use an ECUD, ICUD is gaining in popularity, in view of its potential benefits (i.e., decreased bowel exposure, etc.), although there are a few studies comparing ICUD and ECUD. Analysing single experiences and the data from recent metanalyses, we emphasize the current critiques to ICUD, stressing particular technical details which could reduce operative time, lowering the postoperative complications rate, and improving functional outcomes. Only analysis of long-term follow-up data from large-scale homogeneous series can ascertain whether robotic intracorporeal urinary diversion is superior to other approaches

5G-Based Multi-Sensor Platform for Monitoring of Workpieces and Machines: Prototype Hardware Design and Firmware

In this paper, we introduce a 5G-based multi-sensor platform for monitoring workpieces and machines. The prototype is realized within the EU-funded 5G-SMART project, which aims to enable smart manufacturing through 5G, demonstrating and validating new generation network technology in industrial processes. There are already state-of-the-art solutions, but with drawbacks such as limited flexibility, brief real-time capability, and sensors aimed at single applications. The 5G-SMART multi-sensor platform is designed to overcome these points and meet the requirements of Industry 4.0. The device is equipped with different sensors to acquire multiple data from workpieces and machines of the shop floor, wirelessly connected by 5G to the factory cloud. A hardware design description of the prototype is provided, focusing on the electronic components and their interaction with the microcontroller. Verification of the correct functioning of the board is given, with a basic library for the main peripherals used as a basis for the final firmware

The cellular prion protein increases the uptake and toxicity of tdp-43 fibrils

Cytoplasmic aggregation of the primarily nuclear TAR DNA-binding protein 43 (TDP-43) affects neurons in most amyotrophic lateral sclerosis (ALS) and approximately half of frontotemporal lobar degeneration (FTLD) cases. The cellular prion protein, PrPC, has been recognized as a common receptor and downstream effector of circulating neurotoxic species of several proteins involved in neurodegeneration. Here, capitalizing on our recently adapted TDP-43 real time quaking induced reaction, we set reproducible protocols to obtain standardized preparations of recombinant TDP-43 fibrils. We then exploited two different cellular systems (human SH-SY5Y and mouse N2a neuroblastoma cells) engineered to express low or high PrPC levels to investigate the link between PrPC expression on the cell surface and the internalization of TDP-43 fibrils. Fibril uptake was increased in cells overexpressing either human or mouse prion protein. Increased internalization was associated with detrimental consequences in all PrP-overexpressing cell lines but was milder in cells expressing the human form of the prion protein. As described for other amyloids, treatment with TDP-43 fibrils induced a reduction in the accumulation of the misfolded form of PrPC, PrPSc, in cells chronically infected with prions. Our results expand the list of misfolded proteins whose uptake and detrimental effects are mediated by PrPC, which encompass almost all pathological amyloids involved in neurodegeneration

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT.EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p &lt; 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.</p

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT.EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p &lt; 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.</p

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer

Purpose: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. Methods: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center’s adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. Conclusion: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. Clinical trial registration: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641)

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group

OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content 65 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein ( 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p  28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice