Computer vision in aseptic pharmaceutical manufacturing: a deep learning-based approach to vial inspection and pack formation during a lyophilizer loading cycle

Vision systems are powerful tools playing an increasingly important role in modern industry, to detect errors and maintain product standards. With the enlarged availability of affordable industrial cameras, computer vision algorithms have been increasingly applied in industrial manufacturing processes monitoring. Until a few years ago, industrial computer vision applications relied only on ad-hoc algorithms designed for the specific object and acquisition setup being monitored, with a strong focus on co-designing the acquisition and processing pipeline. Deep learning has overcome these limits providing greater flexibility and faster re-configuration. In this work, the process to be inspected consists in vials’ pack formation entering a freeze-dryer, which is a common scenario in pharmaceutical active ingredient packaging lines. To ensure that the machine produces proper packs, a vision system is installed at the entrance of the freeze-dryer to detect eventual anomalies with execution times compatible with the production specifications. Other constraints come from sterility and safety standards required in pharmaceutical manufacturing. This work presents an overview about the production line, with particular focus on the vision system designed, and about all trials conducted to obtain the final performance. Transfer learning, alleviating the requirement for a large number of training data, combined with data augmentation methods, consisting in the generation of synthetic images, were used to effectively increase the performances while reducing the cost of data acquisition and annotation. The proposed vision algorithm is composed by two main subtasks, designed respectively to vials counting and discrepancy detection. The first one was trained on more than 23k vials (about 300 images) and tested on 5k more (about 75 images), whereas 60 training images and 52 testing images were used for the second one.

Machine Learning in Applicazione alla Prevenzione del Morbo di Alzheimer

Il morbo di Alzheimer è ancora una malattia incurabile. Negli ultimi anni l'aumento progressivo dell'aspettativa di vita ha contribuito a un'insorgenza maggiore di questa patologia, specialmente negli stati con l'età media più alta, tra cui l'Italia. La prevenzione risulta una delle poche vie con cui è possibile arginarne lo sviluppo, ed in questo testo vengono analizzate le potenzialità di alcune tecniche di Machine Learning atte alla creazione di modelli di supporto diagnostico per Alzheimer. Dopo un'opportuna introduzione al morbo di Alzheimer ed al funzionamento generale del Machine Learning, vengono presentate e approfondite due delle tecniche più promettenti per la diagnosi di patologie neurologiche, ovvero la Support Vector Machine (macchina a supporto vettoriale, SVM) e la Convolutional Neural Network (rete neurale convoluzionale, CNN), con annessi risultati, punti di forza e principali debolezze. La conclusione verterà sul possibile futuro delle intelligenze artificiali, con particolare attenzione all'ambito sanitario, e verranno discusse le principali difficoltà nelle quali queste incombono prima di essere commercializzate, insieme a plausibili soluzioni.

Manutenzione predittiva dei giunti mediante tecnologie di Intelligenza Artificiale per la prevenzione dei guasti nelle reti di distribuzione in MT

Lo scopo dell’elaborato è quello di valutare una prima applicazione di intelligenza artificiale per svolgere manutenzione predittiva sui giunti installati nella rete di distribuzione, al fine di prevenirne i guasti. L’estensione delle reti in cavo è infatti in costante aumento per supportare lo sviluppo della rete elettrica e, per l’installazione di nuove linee o nella manutenzione di cavi, si fa uso di giunti, spesso soggetti a guasti e di difficile manutenzione. Risulta quindi importante svolgere manutenzione predittiva su questi componenti, al fine di prevenirne i guasti ed ottenere un risparmio in termini di tempo e denaro. A seguito un’attenta analisi della struttura dei giunti, dei loro modi di guasto e dei parametri caratteristici, si è proceduto alla generazione sintetica di un dataset contenente misure sui giunti e, sulla base di specifici criteri applicati a questi valori, l’informazione sulla presenza o sull’assenza di un guasto. Il dataset è stato poi utilizzato per la fase di apprendimento e di test di sei algoritmi di machine learning, selezionati a partire da considerazioni sullo stato dell’arte, valutato tramite una Revisione Sistematica della Letteratura (SLR). I risultati così ottenuti sono stati analizzati tramite specifiche metriche e da questo caso di studio sono emerse le elevate potenzialità delle tecnologie di intelligenza artificiale ai fini della prevenzione dei guasti nelle reti di distribuzione, soprattutto se considerata la semplicità implementativa degli algoritmi.

Instrument transformers with Digital outputting high voltage power networks

In recent years, energy modernization has focused on smart engineering advancements. This entails designing complicated software and hardware for variable-voltage digital substations. A digital substation consists of electrical and auxiliary devices, control and monitoring devices, computers, and control software. Intelligent measurement systems use digital instrument transformers and IEC 61850-compliant information exchange protocols in digital substations. Digital instrument transformers used for real-time high-voltage measurements should combine advanced digital, measuring, information, and communication technologies. Digital instrument transformers should be cheap, small, light, and fire- and explosion-safe. These smaller and lighter transformers allow long-distance transmission of an optical signal that gauges direct or alternating current. Cost-prohibitive optical converters are a problem. To improve the tool's accuracy, amorphous alloys are used in the magnetic circuits and compensating feedback. Large-scale voltage converters can be made cheaper by using resistive, capacitive, or hybrid voltage dividers. In known electronic voltage transformers, the voltage divider output is generally on the low-voltage side, facilitating power supply organization. Combining current and voltage transformers reduces equipment size, installation, and maintenance costs. These two gadgets cost less together than individually. To increase commercial power metering accuracy, current and voltage converters should be included into digital instrument transformers so that simultaneous analogue-to-digital samples are obtained. Multichannel ADC microcircuits with synchronous conversion start allow natural parallel sample drawing. Digital instrument transformers are created adaptable to substation operating circumstances and environmental variables, especially ambient temperature. An embedded microprocessor auto-diagnoses and auto-calibrates the proposed digital instrument transformer.

Proposal for the acoustic requalification of a site of the "Bologna Engineering School", including the design of a noise barrier

Il lavoro di questa tesi ha riguardato lo studio e l'analisi acustica del sito della Scuola di Ingegneria di Bologna in Via Terracini con l’obiettivo di trovare una soluzione per mitigare il disturbo sonoro rilevato nella zona. Dalle diverse misurazioni fonometriche si è stabilita l’entità numerica di partenza che ha richiesto un’implentazione attraverso delle misurazioni di tipo qualitativo con delle registrazioni in formato wave ed annotando al contempo il numero ed il tipo di veicoli che circolavano. Attraverso l'implementazione dei vari dati ricavati dai rilievi delle diverse sezioni, è stata convalidata la consapevolezza del principale problema dell'area: l'inquinamento acustico causato dal traffico stradale. Lo studio è proseguito monitorando le bande di frequenza che interessavano questo tipo di rumore e quantificando il livello in dB che superava i limiti imposti dalla normativa. Non essendo possibile ridurre il traffico acustico direttamente alla fonte, si è optato per misure di protezione del recettore che si sono configurate nell'inserimento dell'asfalto fonoassorbente e nella progettazione di una barriera acustica. Dopo aver ricercato i diversi tipi di barriere, si è deciso per la barriera con cristalli sonici. Si è indagato quali fattori influissero sulle proprietà dei cristalli sonici: la distribuzione geometrica, la frazione di riempimento e la dimensione degli elementi periodici influenzano la formazione delle bande proibite, la loro larghezza e quindi la capacità fonoisolante del cristallo sonico. In base all'altezza degli edifici e alla loro distanza dalla strada, Via Terracini è stata suddivisa in quattro sezioni. Infine, per le varie sezioni, è stato riprodotto il grafico frequenza/perdita di inserzione che ha confermato una riduzione del livello sonoro di quasi 15 dB. Il progetto ha previsto anche il dimensionamento e la verifica delle azioni statiche (carichi e azione del vento) e dell'azione sismica del sistema strutturale della barriera.

Augmented Reality for Airport Control Tower: Analysis and Implementation of Safety Nets

With the development of new technologies, Air Traffic Control, in the nearby of the airport, switched from a purely visual control to the use of radar, sensors and so on. As the industry is switching to the so-called Industry 4.0, also in this frame, it would be possible to implement some of the new tools that can facilitate the work of Air Traffic Controllers. The European Union proposed an innovative project to help the digitalization of the European Sky by means of the Single European Sky ATM Research (SESAR) program, which is the foundation on which the Single European Sky (SES) is based, in order to improve the already existing technologies to transform Air Traffic Management in Europe. Within this frame, the Resilient Synthetic Vision for Advanced Control Tower Air Navigation Service Provision (RETINA) project, which saw the light in 2016, studied the possibility to apply new tools within the conventional control tower to reduce the air traffic controller workload, thanks to the improvements in the augmented reality technologies. After the validation of RETINA, the Digital Technologies for Tower (DTT) project was established and the solution proposed by the University of Bologna aimed, among other things, to introduce Safety Nets in a Head-Up visualization. The aim of this thesis is to analyze the Safety Nets in use within the control tower and, by developing a working concept, implement them in a Head-Up view to be tested by Air Traffic Control Operators (ATCOs). The results, coming from the technical test, show that this concept is working and it could be leading to a future implementation in a real environment, as it improves the air traffic controller working conditions also when low visibility conditions apply.

Functional safety concept di un sistema di controllo elettronico per sospensioni motociclistiche semi-attive

Il seguente elaborato si pone l’obiettivo di presentare l’analisi sulla sicurezza di un sistema di sospensioni semi-attivo per motoveicoli basato sulla tecnologia ad orifizio variabile. Essendo un sistema comprendente numerosi apparecchi elettrici ed elettronici, si rende necessario seguire la normativa di riferimento ISO_26262. Una descrizione approfondita del sistema e un’analisi dei potenziali guasti permetteranno di dedurre gli obiettivi di sicurezza e successivamente assegnare dei requisiti specifici ai singoli componenti o sotto-assiemi. Strategie di riconoscimento e contrasto dei malfunzionamenti renderanno il sistema sicuro e funzionale.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Ecosystem Engineering Effects On Species Diversity Across Ecosystems: A Meta-analysis.

Ecosystem engineering is increasingly recognized as a relevant ecological driver of diversity and community composition. Although engineering impacts on the biota can vary from negative to positive, and from trivial to enormous, patterns and causes of variation in the magnitude of engineering effects across ecosystems and engineer types remain largely unknown. To elucidate the above patterns, we conducted a meta-analysis of 122 studies which explored effects of animal ecosystem engineers on species richness of other organisms in the community. The analysis revealed that the overall effect of ecosystem engineers on diversity is positive and corresponds to a 25% increase in species richness, indicating that ecosystem engineering is a facilitative process globally. Engineering effects were stronger in the tropics than at higher latitudes, likely because new or modified habitats provided by engineers in the tropics may help minimize competition and predation pressures on resident species. Within aquatic environments, engineering impacts were stronger in marine ecosystems (rocky shores) than in streams. In terrestrial ecosystems, engineers displayed stronger positive effects in arid environments (e.g. deserts). Ecosystem engineers that create new habitats or microhabitats had stronger effects than those that modify habitats or cause bioturbation. Invertebrate engineers and those with lower engineering persistence (<1 year) affected species richness more than vertebrate engineers which persisted for >1 year. Invertebrate species richness was particularly responsive to engineering impacts. This study is the first attempt to build an integrative framework of engineering effects on species diversity; it highlights the importance of considering latitude, habitat, engineering functional group, taxon and persistence of their effects in future theoretical and empirical studies.

Efficacy And Safety Of Intravitreal Bevacizumab In Eyes With Neovascular Glaucoma Undergoing Ahmed Glaucoma Valve Implantation: 2-year Follow-up.

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

Long-term Efficacy And Safety Of Tenofovir Disoproxil Fumarate In Hiv-1-infected Adolescents Failing Antiretroviral Therapy: The Final Results Of Study Gs-us-104-0321.

Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.

Segurança no circo : questão de prioridade = Circus safety: a priority issue

Universidade Estadual de Campinas . Faculdade de Educação Física

Reviewed evidence about the safety of the daily use of alcohol-based mouthrinses

Current scientific knowledge provides clear evidence that alcohol-based mouthwashes can be beneficial in a daily oral health routine, including dental hygiene and plaque control. Several issues are worth discussing, in spite of the wealth of supporting evidence. Despite some undesirable effects to some people, like burning sensation, and some contraindications, like the use by infants, alcohol addicts and patients with mucosal injuries, there is no reason to avoid the use of alcohol-containing mouthwashes as long as they are used following proper guidance by dental professionals and the manufacturers' instructions. The alleged correlation between oral cancer and alcohol-based mouthrinses presents so little, weak, inconsistent and even contradictory evidence in the literature that any kind of risk warning to patients would be uncalled for. Antimicrobial mouthrinses are safe and effective in reducing plaque and gingivitis, and should be part of a comprehensive oral health care regimen that includes brushing, flossing and rinsing to prevent or minimize periodontal disease.

Fire management and the nesting of Athene cunicularia (Aves, Strigidae) in grasslands in central Cerrado, Brazil

Fire management is a common practice in several reserves in the Cerrado, but its influences on bird reproduction remain unknown. In addition, the nesting biology of the Burrowing Owl (Athene cunicularia) has been studied in numerous environments, but not in tropical grasslands managed by fire. This study examined the effects of fire management on the nesting biology of A. cunicularia in Emas National Park, State of Goias, central Brazilian Cerrado. We compared the number of breeding pairs and their burrows in October and November 2009 at 15 study sites in grasslands managed by fire (firebreaks) and unmanaged grasslands adjacent to and distant from firebreaks. We visited active burrows two-four times and described the burrow entrances and sentinel sites and counted and observed adults and young. A total of 19 burrows were found at firebreaks. One and two burrows were found in grasslands adjacent to and distant from firebreaks, respectively. For all burrows found, one to three young reached the adult size, being able to fly and/or run in early November. The 22 burrows found were in the ground, associated or not with termite and ant nests. Most (86.4%) burrows had only one entrance. Only three burrows had two or three entrances. Structures used as sentinel perches by adults were mounds in front of the burrow entrances, termite nests, shrubs and trees. Most of these sentinel sites were shorter than 2 m high and located less than 10 m from the burrow entrance. At Emas National Park, firebreaks appear to provide more attractive conditions to the nesting of A. cunicularia than unmanaged grasslands, likely because of the short herbaceous stratum due to frequent burning of firebreaks. This study suggests that fire management provides suitable conditions for the successful reproduction of A. cunicularia in firebreaks at Emas National Park.

Safety Assessment of Potentially Inappropriate Medications (PIM) use in Older People and the Factors Associated with Hospital Admission

Purpose: Potentially Inappropriate Medications (PIM) use in elderly people may be responsible for the development of Adverse Drug Reaction (ADR) which, when severe, leads to hospital admissions. Objectives: to estimate the prevalence of elderly who had used PIM before being admitted to hospital and to identify the risk factors and the hospitalizations related to ADR arising from PIM. Methods: A descriptive and cross-sectional study was performed in the internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of a validated form, patients aged >= 60 years, with length of hospital stay >= 24 hours, were interviewed about drugs taken prior to the hospital admission and the complaints/reasons for hospitalization. Results: 19.1% (59/308) of older patients had taken PIM before hospital admission and in 4.9%; there were a causal relation between the PIM taken and the complaint reported. PIM responsible for admissions were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin, estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0% of the clinical manifestations of PIM-related ADR were: dizziness, fatigue, digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor for the occurrence of ADR of PIM (p = 0.02). Conclusion: PIM use in elderly people is not a risk factor for ADR-related hospital admission. Probably, severe ADR, which lead to hospitalizations of older people, can be explained by idiosyncratic response or the predisposition of these patients to develop adverse drug events, whether or not drugs are classed as PIM.