Process Mining for Dynamic Modeling of Smart Manufacturing Systems: Data Requirements

Modern manufacturing systems can benefit from the use of digital tools to support both short- and long-term decisions. Meanwhile, such systems reached a high level of complexity and are frequently subject to modifications that can quickly make the digital tools obsolete. In this context, the ability to dynamically generate models of production systems is essential to guarantee their exploitation on the shop-floors as decision-support systems. The literature offers approaches for generating digital models based on real-time data streams. These models can represent a system more precisely at any point in time, as they are continuously updated based on the data. However, most approaches consider only isolated aspects of systems (e.g., reliability models) and focus on a specific modeling purpose (e.g., material flow identification). The research challenge is therefore to develop a novel framework that systematically enables the combination of models extracted through different process mining algorithms. To tackle this challenge, it is critical to define the requirements that enable the emergence of automated modeling and simulation tasks. In this paper, we therefore derive and define data requirements for the models that need to be extracted. We include aspects such as the structure of the manufacturing system and the behavior of its machines. The paper aims at guiding practitioners in designing coherent data structures to enable the coupling of model generation techniques within the digital support system of manufacturing companies

Genetic diversity of the genus Prunus based on per se evaluation of peach clonal rootstocks.

A aplicação de análises multivariadas e quantificação da divergência genética fornecem parâmetros que favorecem a seleção de porta-enxertos superiores. O objetivo deste trabalho foi avaliar a viabilidade técnica do uso de parte da diversidade genética do gênero Prunus como porta-enxerto clonal do pessegueiro ?BRS-Libra?. O pomar experimental faz parte de uma rede nacional de avaliação de porta-enxertos para prunáceas, sob a coordenação geral da Embrapa Clima Temperado. O delineamento experimental foi em blocos ao acaso e a coleta de dados ocorreu no ciclo produtivo 2016/2017. Foram realizadas análises físicas (área de secção do tronco, massa média de frutos) e química (sólidos solúveis), além da quantificação da produtividade estimada das plantas. Os dados obtidos foram submetidos ao teste de normalidade de Shapiro-Wilk, ao nível 5% de probabilidade, sendo posteriormente realizado o agrupamento dos porta-enxertos através do método hierárquico UPGMA. A realização do agrupamento resultou na formação de cinco grupos. As cultivares do grupo I, Mirabolano 29C e Marianna 2624, apresentaram incompatibilidade de enxertia com a cultivar BRS-Libra. Semelhantemente, as cultivares do grupo II apresentaram sintomas característicos de incompatibilidade de enxertia, resultando em pouco desenvolvimento. Os grupos III e IV são compostos por cultivares que apresentaram baixo e médio vigor, com boas perspectivas de uso para formar pomares em alta densidade, enquanto as cultivares do grupo V destacaram-se por apresentar alto vigor, recomendadas para pomares de baixa densidade. O uso de diferentes porta-enxertos influencia no comportamento da cultivar BRS-Libra no vigor e produção de frutos, havendo divergência genética entre eles

Biliary cystic disease and neoplasia: surgical management

Background Congenital cystic dilatation of the extra- and intrahepatic bile ducts is a rare condition with several potential complications, especially a high risk of malignant degeneration, which may develop from an anomalous arrangement of the pancreatico-biliary ductal junction. Patients Twenty-two patients with cystic dilatation of the biliary tree, subdivided according to the Todani classification, were observed and treated during a 17-year period. The intrahepatic ducts were involved in 15 patients. Results Surgical treatment involved either total excision of extrahepatic cysts, hepatic resection in cases of segmental intrahepatic disease or, in the presence of diffuse intrahepatic disease, a wide biliary-digestive anastomosis performed onto the biliary confluence, with the intent of reducing the risk of neoplastic degeneration. One patient with extensive and symptomatic liver involvement complicated by biliary cirrhosis has already undergone liver transplantation, and another two patients who are currently asymptomatic may require this procedure in future. Neoplastic degeneration was found in three patients (one each of Todani type I, type IVa and type V), or 14% of the series. The postoperative course was complicated by cholangitis in only two patients, who were treated successfully with antibiotics. Except for one patient with a type I cyst complicated by carcinoma, who died 14 months post-operatively, all patients are alive and well at a mean follow-up of eight years (range 8 months to 17 years). Discussion The ideal surgical procedures to cure the disease and prevent malignant degeneration are: (a) complete excision of the extrahepatic biliary cysts; (b) hepatic resection in cases of segmental intrahepatic involvement; (c) wide bilio-digestive anastomosis in cases of multiple intrahepatic involvement, or liver transplantation when this is complicated by secondary biliary cirrhosis

Effects of Menopause in Women With Multiple Sclerosis: An Evidence-Based Review

Over two thirds of all individuals who develop multiple sclerosis (MS) will be women prior to the age of menopause. Further, an estimated 30% of the current MS population consists of peri- or postmenopausal women. The presence of MS does not appear to influence age of menopausal onset. In clinical practice, symptoms of MS and menopause can frequently overlap, including disturbances in cognition, mood, sleep, and bladder function, which can create challenges in ascertaining the likely cause of symptoms to be treated. A holistic and comprehensive approach to address these common physical and psychological changes is often suggested to patients during menopause. Although some studies have suggested that women with MS experience reduced relapse rates and increased disability progression post menopause, the data are not consistent enough for firm conclusions to be drawn. Mechanisms through which postmenopausal women with MS may experience disability progression include neuroinflammation and neurodegeneration from age-associated phenomena such as immunosenescence and inflammaging. Additional effects are likely to result from reduced levels of estrogen, which affects MS disease course. Following early retrospective studies of women with MS receiving steroid hormones, more recent interventional trials of exogenous hormone use, albeit as oral contraceptive, have provided some indications of potential benefit on MS outcomes. This review summarizes current research on the effects of menopause in women with MS, including the psychological impact and symptoms of menopause on disease worsening, and the treatment options. Finally, we highlight the need for more inclusion of MS patients from underrepresented racial and geographic groups in clinical trials, including among menopausal women

Neuroprotective role of phosphoserine in primary open-angle glaucoma patients

OBJECTIVE: To evaluate the neuroprotective role of phosphoserine (P-Ser) in primary open-angle glaucoma (POAG) patients and to compare its therapeutic effectiveness to placebo treatment. PATIENTS AND METHODS: Fifty-one patients (24 males and 27 females) between 35 and 61 years (average 46 years ± 3.8 SD) affected by POAG were enrolled in this study. Patients were divided in two groups: group A included 28 subjects that received an oral P-Ser treatment for 12 months; and group B included 23 subjects that received an oral placebo treatment for 12 months. Complete ophthalmological examination, standard automated perimetric examination, analysis of ON fibers via scanning laser polarimetry and glaucoma staging was performed in all patients at enrolment and 1, 3, 6, and 12 months after. Statistical analysis was performed using STATA 14.0 (Collage Station, TX, USA). RESULTS: Mean deviation (MD) and pattern standard deviation (PSD) analysis by means of 30-2 full threshold of the visual fields (VFs), retinal nerve fiber layer (RNFL) thickness by means of GDx, and IOP were considered to evaluate P-Ser therapy effectiveness in both groups. A statistically significant improvement (p<0.05) in VF, RNFL thickness and IOP compared to pre-treatment was found in patients in group A. CONCLUSIONS: Our study shows a significant improvement in several variables in patients with glaucoma treated with P-Ser compared to placebo and suggests a potential neuroprotective effect of P-Ser in treating glaucoma patients in association with the traditional hypotonic topical therapy

Post-operative outcomes and predictors of mortality after colorectal cancer surgery in the very elderly patients

Background: The frailty of the very elderly patients who undergo surgery for colorectal cancer negatively influences postoperative mortality. This study aimed to identify risk factors for postoperative mortality in octogenarian and nonagenarian patients who underwent surgical treatment for colorectal cancer. Methods: This is a single institution retrospective study. The primary outcomes were risk factors for postoperative mortality. The variables of the octogenarians and nonagenarians were compared by using t-test, chi-square test, and Fisher exact test. A multivariate logistic regression analysis was carried out on the combined cohorts. Results: we identified 319 octogenarians and 43 nonagenarians (N = 362) who underwent surgery for colorectal cancer at the Sant'Orsola-Malpighi university hospital in Bologna between 2011 and 2015. The 30-day post-operative mortality was 6% (N = 18) among octogenarians and 21% (N = 9) for the nonagenarians. The groups significantly differed in the type of surgery (elective vs. urgent surgery, p < 0.0001), ASA score (p = 0.0003) and rates of 30-day postoperative mortality (6% vs. 21%, p = 0.0003). In the multivariate analysis ASA > III (OR 2.37, 95% CI [1.43\u20133.93], p < 0,001), and urgent surgery (OR 2.17, 95% CI [1.17\u20134.04], p = 0.014) were associated to post-operative mortality. On the contrary, pre-operative albumin 653.4 g/dL (OR 0.14, 95% CI [0.05\u20130.52], p = 0.001) was associated with a protective effect on postoperative mortality. Conclusions: In the very elderly affected by colorectal cancer, preoperative nutritional status and pre-existing comorbidities, rather than age itself, should be considered as selection criteria for surgery. Preoperative improvement of nutritional status and ASA risk assessment may be beneficial for stratification of patients and ultimately for optimizing outcomes

Patient-rated suitability of a novel electronic device for self-injection of subcutaneous interferon beta-1a in relapsing multiple sclerosis: an international, single-arm, multicentre, Phase IIIb study

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) currently requires long-term treatment with disease-modifying drugs, administered parenterally up to once daily. The need for regular self-injection can be a barrier to treatment for many patients. Autoinjectors can help patients overcome problems or concerns with self-injection and could, therefore, improve treatment adherence. This study was performed to assess the suitability of a new electronic device for the subcutaneous (sc) administration of interferon (IFN) beta-1a, 44 mcg three times weekly, for relapsing MS.</p> <p>Methods</p> <p>In this Phase IIIb, multicentre, single-arm study, patients with relapsing MS who had been consistently self-injecting sc IFN beta-1a using an autoinjector for at least 6 weeks were taught to use the new device and self-administered treatment for 12 weeks thereafter. Patient-rated suitability of the device was assessed at the end of Week 12 using the Patient User Trial Questionnaire. Patient satisfaction with, and evaluation of, the injection process was assessed using the MS Treatment Concern Questionnaire. Trainers evaluated the device using the Trainer User Trial Questionnaire.</p> <p>Results</p> <p>At Week 12, 71.6% (73/102) of patients considered the device 'very suitable' or 'suitable' for self-injection; 92.2% (94/102) reported some degree of suitability and only 7.8% (8/102) found the device 'not at all suitable'. At Weeks 4, 8 and 12, most patients reported that injection preparation and clean-up, performing injections and ease of device use in the previous 4 weeks compared favourably with, or was equivalent to, their previous experience of self-injection. Injection-related pain, injection reactions and 'flu-like' symptoms remained stable over the 12 weeks. Each device feature was rated 'very useful' or 'useful' by at least 80% of patients. All trainers and 95.2% (99/104) of patients found device functions 'very easy' or 'easy' to use. Overall convenience was considered the most important benefit of the device.</p> <p>Conclusions</p> <p>Most patients considered the new electronic injection device suitable for the sc injection of IFN beta-1a. They found the device easy to use with useful features, and reported benefits such as overall convenience. The device may, therefore, increase treatment adherence in patients with MS, particularly those with injection-related issues.</p> <p>Trial registration</p> <p>NCT00735007</p

Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

<p>Abstract</p> <p>Background</p> <p>Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS).</p> <p>Methods</p> <p>BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device.</p> <p>Results</p> <p>Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (<it>P </it>= 0.821) or PASAT (<it>P </it>= 0.952) scores, or pre-study therapy (<it>P </it>= 0.303). No significant changes (baseline-Week 12) in mean HADS depression (<it>P </it>= 0.482) or anxiety (<it>P </it>= 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated. Mean MSTCQ scores for 'flu-like' symptoms (<it>P </it>= 0.022) and global side effects (<it>P </it>= 0.002) significantly improved from Week 4-12. Mean MSTCQ scores for pain at injection site and injection pain increased from Week 4-12 (<it>P </it>< 0.001). Adverse events were mild/moderate. No new safety signals were identified.</p> <p>Conclusion</p> <p>Convenience and ease of use of the autoinjection device may improve adherence and, therefore, outcomes, in patients with RRMS receiving sc IFN β-1a.</p> <p>Trial registration</p> <p>EU Clinical Trials Register (EU-CTR; <url>http://www.clinicaltrialsregister.eu</url>): 2009-013333-24</p

An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects

<p>Abstract</p> <p>Background</p> <p>The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients.</p> <p>Methods</p> <p>This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout.</p> <p>Results</p> <p>Seventy-one (96%) patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3) on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy). Ninety-four percent of patients preferred the prefilled pen over the prefilled syringe. Induction of serum neopterin levels, serving as a biomarker for type 1 interferon action, was similar to that of the prefilled syringe. The prefilled pen demonstrated a safety profile comparable to the prefilled syringe.</p> <p>Conclusions</p> <p>The prefilled pen is a safe and effective device for administration of IM IFNβ-1a and represents an alternative method for self-injection for MS patients using this therapy.</p> <p>Trial registration</p> <p>This study is registered at clinicaltrials.gov, identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00828204">NCT00828204</a></p