Assessing Binary Measurement Systems

Binary measurement systems (BMS) are widely used in both manufacturing industry and medicine. In industry, a BMS is often used to measure various characteristics of parts and then classify them as pass or fail, according to some quality standards. Good measurement systems are essential both for problem solving (i.e., reducing the rate of defectives) and to protect customers from receiving defective products. As a result, it is desirable to assess the performance of the BMS as well as to separate the effects of the measurement system and the production process on the observed classifications. In medicine, BMSs are known as diagnostic or screening tests, and are used to detect a target condition in subjects, thus classifying them as positive or negative. Assessing the performance of a medical test is essential in quantifying the costs due to misclassification of patients, and in the future prevention of these errors. In both industry and medicine, the most commonly used characteristics to quantify the performance a BMS are the two misclassification rates, defined as the chance of passing a nonconforming (non-diseased) unit, called the consumer's risk (false positive), and the chance of failing a conforming (diseased) unit, called the producer's risk (false negative). In most assessment studies, it is also of interest to estimate the conforming (prevalence) rate, i.e. probability that a randomly selected unit is conforming (diseased). There are two main approaches for assessing the performance of a BMS. Both approaches involve measuring a number of units one or more times with the BMS. The first one, called the "gold standard" approach, requires the use of a gold-standard measurement system that can determine the state of units with no classification errors. When a gold standard does not exist, is too expensive or time-consuming, another option is to repeatedly measure units with the BMS, and then use a latent class approach to estimate the parameters of interest. In industry, for both approaches, the standard sampling plan involves randomly selecting parts from the population of manufactured parts. In this thesis, we focus on a specific context commonly found in the manufacturing industry. First, the BMS under study is nondestructive. Second, the BMS is used for 100% inspection or any kind of systematic inspection of the production yield. In this context, we are likely to have available a large number of previously passed and failed parts. Furthermore, the inspection system typically tracks the number of parts passed and failed; that is, we often have baseline data about the current pass rate, separate from the assessment study. Finally, we assume that during the time of the evaluation, the process is under statistical control and the BMS is stable. Our main goal is to investigate the effect of using sampling plans that involve random selection of parts from the available populations of previously passed and failed parts, i.e. conditional selection, on the estimation procedure and the main characteristics of the estimators. Also, we demonstrate the value of combining the additional information provided by the baseline data with those collected in the assessment study, in improving the overall estimation procedure. We also examine how the availability of baseline data and using a conditional selection sampling plan affect recommendations on the design of the assessment study. In Chapter 2, we give a summary of the existing estimation methods and sampling plans for a BMS assessment study in both industrial and medical settings, that are relevant in our context. In Chapters 3 and 4, we investigate the assessment of a BMS in the case where we assume that the misclassification rates are common for all conforming/nonconforming parts and that repeated measurements on the same part are independent, conditional on the true state of the part, i.e. conditional independence. We call models using these assumptions fixed-effects models. In Chapter 3, we look at the case where a gold standard is available, whereas in Chapter 4, we investigate the "no gold standard" case. In both cases, we show that using a conditional selection plan, along with the baseline information, substantially improves the accuracy and precision of the estimators, compared to the standard sampling plan. In Chapters 5 and 6, we investigate the case where we allow for possible variation in the misclassification rates within conforming and nonconforming parts, by proposing some new random-effects models. These models relax the fixed-effects model assumptions regarding constant misclassification rates and conditional independence. As in the previous chapters, we focus on investigating the effect of using conditional selection and baseline information on the properties of the estimators, and give study design recommendations based on our findings. In Chapter 7, we discuss other potential applications of the conditional selection plan, where the study data are augmented with the baseline information on the pass rate, especially in the context where there are multiple BMSs under investigation

The surgical approach of advanced esophageal cancers

Clinica l-a Chirurgi U.M.F, Iaşi, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Lucrarea este un studiu retrospectiv a neoplasmelor esofagiene internate în Clinica I Chirurgie Iaşi între 2000 - 2009. După trecerea în revistă a datelor generale (sex, vârstă, posibilități de explorare, decizii terapeutice) a celor 71 de cazuri de neoplasme esofagiene internate în ultimii 10 ani, sunt prezentate sintetic cazurile care au beneficiat de abord chirurgical. Sunt expuse elementele care au concurat la luarea unei anumite decizii terapeutice şi analizate evoluția şi complicațiile postoperatorii. Nu au fost incluse în observații tumorile eso-cardiotuberozitare care constituie un subiect al patologiei joncțiunii esogastrice. Procent de rezecabilitate al leziunilor avansate este extrem de redus (24,13%). Dacă în cancerele avansate pentru exereză nu se porneşte pe ideea radicalității oncologice, având în vedere vârsta şi fragilitatea acestor bolnavi considerăm utilă fracționatea gestului chirurgical în două sau trei etape, atitudine care pe seria noastră a redus mortalitatea perioperatorie. În cazurile inoperabile, by-pass-ul este o soluție valoroasă de rezolvare a disfagiei, dar complexitatea intervenției trebuie să pună în balanță beneficiul net al pacientului; de aceea se indică pentru bolnavii bine compensați biologic şi funcțional, de vârste acceptabile.The therapeutical option was adapted to each case so for resectable tumors we apply a multimodal approach in 21 cases, a palliative approach in 12 cases and gastro or jejunostomy in 25 cases.The location of resectable tumors was cervical in 3 cases, mid third of esophagus in 11 cases, inferior third of esophagus in 4 cases and multiple tumor locations in 3 cases. The T.N.M. stages of operated tumors were especially stage III with 14 cases, Stage I one case, Stage II, 2 cases and Stage IV. 4 cases. A R0 resection was realized in 17 cases associated with a two field lymphadenectomy. We perform the operations in one step in 14 cases and in two steps in 7 cases. Considering esophagectomy with esophagoplasty the best palliation for esophageal cancers, we consider very important to adapt the surgical technique to the nutritional and biological status of the patient. So performing the operation in two steps we succeed to improve the survival rate as shown in our group of patients. The post operative mortality is of 4% In case of unresectable esophageal lesion the eso-gastric by-pass represents a good relief of dysphagia. We recommend this palliative attitude in case of patients with a good nutritional and biological status.The authors present a retrospective study of 58 epidermoid esophageal cancers treated in the l st Surgical Clinic U.M.F. Iasi, in the last decade 2000-2009.The eso-cardial tumors are excluded. The resectability of epidermoid esophageal cancers at the moment of the diagnosis was about 24, 13 %.The tumor location was: upper third of esophagus 10 cases, mid esophagus 33 cases, inferior third of esophagus 12 cases, multiple 3 cases.51 cases (87, 9%) were complicated at the moment of the diagnosis: malnutrition 39 cases, bleeding 2 cases, pneumonia 6 cases (aspiration), eso-tracheal fistula 4 cases

Features of hemostasis in patients with non-ST-elevation myocardial infarction

Background: Coronary thrombosis is the key pathogenic mechanism of acute heart attack, including non-ST segment elevation (NSTEMI). Given that, the detection of reliable markers of hemostasis disorders is important in the process of optimizing the diagnosis of NSTEMI. Material and methods: The study was conducted on 54 patients with NSTEMI (average age 69.7±1.5 years). In 60% of cases, 3-vessel disease was noted; 56% of patients had ejection fraction >50%, and Killip class I of heart failure was revealed in 78% of patients. With the help of the STA-Liatest (France) equipment, the blood tests determined the following hemostasis markers: fibrin monomers (FM), thrombotic complex activity of factors II, VII and X. Additional markers like Procoag, the coagulation indicator dependent on circulating phospholipids or SPA, D-dimers, as well as factors C, S and antithrombin III were appreciated. The values of these markers determined by the same method in 20 healthy persons (control group) were used as normal values. Results: Circulating level of FM on admission was increased twice, while the values of Procoag and SPA were significantly decreased by 35.3% compared to the control. Factors C, S and antithrombin III were 54-80% of the control value range, and D-dimers were within the permissible values. In the acute phase of the heart attack, a deterioration of hemostasis indicators was noted, excepting the D-dimers. The levels of FM determined 24 and 72 hours after revascularization were consistently increased (up to 3.8 times) compared to the control, while Procoag and SPA decreased by 54-57%. Further reduction of factors C, S and antithrombin III accounted for 42-54% of normal indicators. After 5 days, an improvement in hemostasis markers was observed, but a significant difference still remained comparing to the control group. Conclusions: The hemostasis particularities discovered in patients with NSTEMI indicate the features of an activated prothrombotic status, and FM could be an important diagnostic marker of NSTEMI, due to its most significant deviation from the normal value (>100%). It can reliably reflect the thrombin level, which triggers the last enzymatic phase of thrombus formation

Innovative Biomaterials Based on Collagen-Hydroxyapatite and Doxycycline for Bone Regeneration

Bone regeneration is a serious challenge in orthopedic applications because of bone infections increase, tumor developing, and bone loss due to trauma. In this context, the aim of our study was to develop innovative biomaterials based on collagen and hydroxyapatite (25, 50, and 75%) which mimic bone composition and prevent or treat infections due to doxycycline content. The biomaterials were obtained by freeze-drying in spongious forms and were characterized by water uptake capacity and microscopy. The in vitro release of doxycycline was also determined and established by non-Fickian drug transport mechanism. Among the studied biomaterials, the most suitable one to easily deliver the drug and mimic bone structure, having compact structure and lower capacity to uptake water, was the one with 75% hydroxyapatite and being cross-linked

Management of patients with acute myocardial infarction without ST-segment elevation in the Republic of Moldova

Purpose: To evaluate the quality of NSTEMI care in AMI centers and to identify potential gaps in the management of patients with this diagnosis.Material and methods: 550 patients with NSTEMI, hospitalized in 3 coronary angioplasty centers were enrolled in the study. The information was collected using a questionnaire composed of 179 questions, developed according to the standards of the EORP NSTEMI Registry. The research took place in two stages: retrospective observational study during 2019 and prospective in the period 01.2020-09.2022.Results. The NSTEMI rate from the total number of patients hospitalized with AMI in the Institute of Cardiology and SP Novamed, in the period 2019-2022 was 21,6%. The results of the evaluation of NSTEMI management in the studied AMI centers are close to those reported by equivalent international registries (EORP NSTEMI, FAST-MI, PLACS, MINAP), excepting some differences in certain chapters: the diagnostic strategy of NSTE-ACS, risk stratification, diagnosis and treatment of hypercholesterolemia and the antiplatelet treatment indicated at discharge. The mortality rate in the hospital was 4,2%, at 30 days m8k6,0%, at 6 months after hospitalization 10,2%, and at 12 months 12,8%. Conclusions. The rate of NSTEMI in the Republic of Moldova is lower than that reported by the international registers of IMA, while the mortality indicators are higher. These discrepancies are largely explained by gaps in NSTEMI management identified within the studied AMI centers.Scop: Evaluarea calității managementului NSTEMI în cadrul centrelor responsabile de IMA și identificarea unor potențiale lacune în conduita pacienților cu acest diagnostic. Material și metode: În studiu au fost înrolați 550 de pacienți cu NSTEMI, spitalizați în 3 centre de angioplastie coronariană: Institutul de Cardiologie, SP Novamed și SCM Sfânta Treime. Informația a fost colectată cu ajutorul unui chestionar compus din 179 de întrebări, elaborat conform standardelor Registrului EORP NSTEMI. Cercetarea a derulat în două etape: studiu observațional retrospectiv pe parcursul anului 2019 și prospectivîn perioada 01.2020-09.2022. Rezultate. Rata NSTEMI din numărul total de pacienți spitalizați cu IMA în cadrul Institutului de Cardiologie, în perioada 2019-2022 a fost de 21,6%. Rezultatele evaluării managementului NSTEMI în centrele de IMA studiate sunt apropiate de cele raportate de registrele internaționale echivalente (EORP NSTEMI, FAST-MI, PL-ACS, MINAP), dar cu unele diferențe la anumite capitole: strategia de diagnostic a SCA fără elevarea segmentului ST, stratificarea riscului, diagnosticul și tratamentul hipercolesterolemiei, dar și în tratamentul antiplachetar indicat la externare. Rata mortalității în spital a fost de 4,2%, la 30 de zile 6,0%, la 6 luni de la spitalizare 10,2%, iar la 12 luni 12,8%. Concluzii. Rata NSTEMI în Republica Moldova este mai mică decât cea raportată de către registrele internaționale ale IMA, în timp ce indicatorii mortalității sunt mai mari. Aceste divergențe sunt explicate în mare parte de lacunele din managementul NSTEMI, identificate în cadrul centrelor de IMA studiate. Cuvinte cheie: Sindrom coronarian acut, NSTEMI, troponina înalt sensibilă, evenimente cardiovasculare majore

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial – CADOT

IntroductionAmong treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines.MethodOut of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity – QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning – GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st – 3rd quartile) of 4 (1–9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11–33) months after remission.ResultsAt the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38–66%]). After DATA step 2, 37 patients were in remission (77% [65–89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78–97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62–95%]).ConclusionThese results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s)

Cancer data quality and harmonization in Europe: the experience of the BENCHISTA Project – international benchmarking of childhood cancer survival by stage

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans

CYTOGENETIC EFFECTS INDUCED BY PHENOLIC COMPOUNDS IN LYCOPERSICON ESCULENTUM MILL

The aim of this paper is to evaluate the effects of the phenolic compounds extracted from spruce bark on cells from the radicular apex of Lycopersicon esculentum Mill. We found that different concentrations of polyphenols and the time of treatment modified the frequency of cells division and the number of mitotic ana-telophases with aberrations

Нарушения гемостаза у больных с NSTEMI, диагностические маркеры.

Actualitate. Tulburarea hemostazei este un mecanism important al afecțiunilor cardiovasculare, iar aportul patogenetic al acestuia în evoluția NSTEMI este îndeosebi notabil în contextul semnificației paternului fiziopatologic determinat de dereglarea microcirculației coronariene. Evidențierea markerilor iminenți va facilita diagnosticul și prognosticul NSTEMI. Scopul. Relatarea datelor de sinteză a literaturii privind markerii circulanți ai tulburării hemostazei la pacienții cu NSTEMI. Rezultate. Markerii principali ai dereglării hemostazei în NSTEMI și cu valoare predictivă asupra diagnosticului și evoluției post-infarct sunt:vizavi de sistemul procoagulant: elevarea microparticulelor derivate de endoteliocite și plachete ce expresează fosfotidilserină, activarea complexului factorilor de coagulare II, VII și X, formarea agregatelor dintre plachete și leucocite;vizavi de sistemul anticoagulant: creșterea trombomodulinei solubile în asociere cu micșorarea plasmatică a antitrombinei și a proteinelor C și S;vizavi de sistemul fibrinolitic: elevarea nivelului plasmatic al monomerilor și D-dimerilor ai fibrinei, al inhibitorului activatorului plasminogenului în asociere cu deprecierea cantitativă a activatorului plasminogenului.Background. Hemostasis disorder is an important mechanism of cardiovascular disease, and its pathogenetic contribution to the evolution of NSTEMI is particularly notable in the context of the significance of the pathophysiological pattern caused by coronary microcirculation disorder. Highlighting imminent markers will facilitate the diagnosis and prognosis of NSTEMI. Object. Reporting literature summary data on markers with definite predictive value on proven hemostasis disorder in patients with NSTEMI. Results. The main markers of hemostasis disorder in NSTEMI and with predictive value on the diagnosis and evolution of post-infarction are:opposite the procoagulant system: elevation of microparticles derived from endotheliocytes and platelets expressing phosphotidylserine, activation of the complex of coagulation factors II, VII and X, formation of aggregates between platelets and leukocytes;opposite the anticoagulant system: increase in soluble thrombomodulin in combination with plasma decrease in antithrombin and C and S proteins;opposite the fibrinolytic system: elevation of the plasma levels of fibrin monomers and D-dimers of the plasminogen activator inhibitor in association with quantitative impairment of the plasminogen activator.Вступление. Нарушение гемостаза является важным патогенетическим фактором развития многих сердечно-сосудистых заболеваний, в частности NSTEMI. Определение маркеров гемостаза облегчает диагностику и прогнозирование NSTEMI.Цель. Представлены основные данные о диагностической и прогностической ценности определения маркеров нарушения гемостаза у пациентов с NSTEMI. Результаты. Основные маркеры нарушения гемостаза, имеющие диагностическое и прогностическое значение при NSTEMI, являются:факторы прокоагулянтной системы: повышение содержания микрочастиц эндотелиоцитов и тромбоцитов, экспрессирующие фосфатидилсерин, активация комплекса факторов свертывания крови II, VII и X, образование агрегатов тромбоцитов с лейкоцитами;- факторы антикоагулянтной системы: повышение содержания растворимого тромбомодулина в сочетании со снижением в плазме антитромбина и белков С и S;- факторы фибринолитической системы: повышение содержания в плазме крови мономеров фибрина и D-димеров, ингибитора активатора плазминогена на фоне снижения активатора плазминогена