U ovom se radu obrađuju toponimi, odnosno mikrotoponimi Semeljaca, sela istočne Đakovštine, na osnovi dostupne literature, proučavanja dostupne arhivske građe te terenskoga rada. Obrađuju se i ...jezične osobitosti koje su relevantne s povijesnojezičnoga i dijalektološkoga stajališta, utvrđuje se etimološki razvitak mikrotoponima (gdje je to moguće) te se bilježi pučka etimologija pojedinih mikrotoponima.
Doktorski rad Toponimije Đakovštine proučava toponimiju Đakova i sela koja pripadaju prostoru Đakovštine. Riječ je o cjelovitoj analizi toponima navedenoga prostora. Cilj je rada zabilježiti toponime ...Đakovštine te ih motivacijski analizirati. Toponimi su odraz kulture, društva, gospodarstva i duhovnosti određenoga kraja, a ujedno su okamenjeni jezični spomenici mjesnih govora Đakovštine. Nakon uvodnoga dijela slijedi geomorfološki i fitomorfološki opis Đakovštine, a potom povijesni i demografski pregled Đakovštine. U radu se analizira govor Đakovštine s fonološkoga, morfološkoga, sintaktičkoga i leksičkoga stajališta. Središnje poglavlje Toponimija dijeli se na analizu ojkonima i analizu svih preostalih toponima. Riječ je o motivacijskoj analizi. Toponimijski je korpus prikupljen terenskim radom s ispitanicima te dijelom preuzet s ARKOD-a. Zabilježen je naglasak te stavljena oznaka sela kojemu toponim pripada. Opisana su i naselja, njihov smještaj i povijesni razvitak u poglavlju Mjestopis Đakovštine. Popisani su toponimi Đakovštine te etnici i ktetici što je razvidno u prilozima. Prikupljena i istražena onimijska građa važna je zbog toga što dolazi do velikih promjena u poljoprivredi i gospodarstvu općenito. Dolazi do okrupnjivanja zemljišta, zbog čega se pomalo gube onimi koji su nekada bili mnogo važniji za život slavonskoga čovjeka, nego danas kada se poljoprivreda usmjerava na velike poduzetnike, a mali se poljoprivrednik gubi pa imenovanje zemljišta ima sve manju važnost. Napose, gubi se i emotivna nota kod imenovanja objekta koji je pripadao pojedincu, a sada pripada gospodarstvu. Ovim korpusom veliki će se broj onima sačuvati od zaborava i pribrojiti hrvatskoj onimijskoj građi.
The doctoral dissertation Toponymies of the Đakovo area studies the toponymy of Đakovo and villages which are located in the Đakovo area. It is an integral analysis of the toponyms that can be found in this region. The aim of this paper is to record the toponyms of the Đakovo area and analyze the motivation behind them. Toponyms are a reflection of the culture, society, economy and spirituality of a particular place, and they represent petrified linguistic monuments of the vernacular of the Đakovo area. After the introductory part, there is a geomorphological and phytomorphological description of the Đakovo area, followed by a historical and demographic overview of the Đakovo area. The subsequent chapter analyzes the Đakovo area vernacular from the phonological, morphological, syntactic and lexical aspects. The central chapter of Toponymies is divided into two parts: the analysis of oikonyms and the analysis of all other toponyms. All items are analyzed motivationally. The toponymic corpus was collected through field work with respondents and partly taken from ARKOD. Each toponym entry lists the village area where it was found and its specific stress. The dissertation also describes settlements, their location and historical development in the chapter Mjestopis Đakovštine. All toponyms of the Đakovo area, as well as all demonyms and adjectival forms, have been listed and can be found in the appendices. The collected and analyzed onymic corpus is significant because of some major ongoing changes in agriculture and the economy in general. Lately there has been a tendency of small farms merging, which leads to the gradual loss of onyms that once had a much greater importance for the life of the Slavonian man than they do now. Today, when farming focuses on large enterprises and the small farmer is lost, naming the land has less and less significance. Finally, the emotional component of naming an object is missing when it no longer belongs to an individual, but to a business. With the help of this corpus, a large number of onyms will be preserved and added to the Croatian onymic corpus.
Doktorski rad Toponimije Đakovštine proučava toponimiju Đakova i sela koja pripadaju prostoru Đakovštine. Riječ je o cjelovitoj analizi toponima navedenoga prostora. Cilj je rada zabilježiti toponime Đakovštine te ih motivacijski analizirati. Toponimi su odraz kulture, društva, gospodarstva i duhovnosti određenoga kraja, a ujedno su okamenjeni jezični spomenici mjesnih govora Đakovštine. Nakon uvodnoga dijela slijedi geomorfološki i fitomorfološki opis Đakovštine, a potom povijesni i demografski pregled Đakovštine. U radu se analizira govor Đakovštine s fonološkoga, morfološkoga, sintaktičkoga i leksičkoga stajališta. Središnje poglavlje Toponimija dijeli se na analizu ojkonima i analizu svih preostalih toponima. Riječ je o motivacijskoj analizi. Toponimijski je korpus prikupljen terenskim radom s ispitanicima te dijelom preuzet s ARKOD-a. Zabilježen je naglasak te stavljena oznaka sela kojemu toponim pripada. Opisana su i naselja, njihov smještaj i povijesni razvitak u poglavlju Mjestopis Đakovštine. Popisani su toponimi Đakovštine te etnici i ktetici što je razvidno u prilozima. Prikupljena i istražena onimijska građa važna je zbog toga što dolazi do velikih promjena u poljoprivredi i gospodarstvu općenito. Dolazi do okrupnjivanja zemljišta, zbog čega se pomalo gube onimi koji su nekada bili mnogo važniji za život slavonskoga čovjeka, nego danas kada se poljoprivreda usmjerava na velike poduzetnike, a mali se poljoprivrednik gubi pa imenovanje zemljišta ima sve manju važnost. Napose, gubi se i emotivna nota kod imenovanja objekta koji je pripadao pojedincu, a sada pripada gospodarstvu. Ovim korpusom veliki će se broj onima sačuvati od zaborava i pribrojiti hrvatskoj onimijskoj građi.
U ovom se radu obrađuju toponimi, odnosno mikrotoponimi Semeljaca, sela istočne Đakovštine, na osnovi dostupne literature, proučavanja dostupne arhivske građe te terenskoga rada. Obrađuju se i ...jezične osobitosti koje su relevantne s povijesnojezičnoga i dijalektološkoga stajališta, utvrđuje se etimološki razvitak mikrotoponima (gdje je to moguće) te se bilježi pučka etimologija pojedinih mikrotoponima.
On the basis of field research there has been noted the microtoponyms of Semeljci, a village placed on the east part of Dakovstina, or to be more precise, 14 km east of Dakovo and in the direction of ...Vinkovci. Microtoponyms of the archival cadastral maps are noted as well in the paper. Special linguistic features, relevant from the language-historical and dialectical point of view are also elaborated. Where possible, etiologic development of the microtoponyms is determined and folk etymology of particular microtoponyms is noted. Systematicness in naming is not noted in the toponyms of Semeljci. It is common that the names are motivated by the former or present owners of particular areas (Ded Piciljev Izvor, Elekovo) or by the names of the people that used to live there (Ivkino, Jelino). It is also learned what field crops have been cultivated (Vinakovci). It is commonely noted that the microtoponyms are motivated by the names of the plants (Glogovaca, Grabina, Osatina). A large number of toponyms is completely nontransparent to the local people because those toponyms have origins in the more distant past, and their interpretation in the oral tradition has not been preserved. Adapted from the source document
Purpose:
Unpredictable drug efficacy and safety of combined antiepileptic therapy is a major challenge during pharmacotherapy decisions in everyday clinical practice. The aim of this study was to ...describe the pharmacokinetics of valproic acid (VA), lamotrigine (LTG), and levetiracetam (LEV) in a pediatric population using nonlinear mixed-effect modeling, while machine learning (ML) algorithms were applied to identify any relationships among the plasma levels of the three medications and patients’ characteristics, as well as to develop a predictive model for epileptic seizures.
Methods:
The study included 71 pediatric patients of both genders, aged 2–18 years, on combined antiepileptic therapy. Population pharmacokinetic (PopPK) models were developed separately for VA, LTG, and LEV. Based on the estimated pharmacokinetic parameters and the patients’ characteristics, three ML approaches were applied (principal component analysis, factor analysis of mixed data, and random forest). PopPK models and ML models were developed, allowing for greater insight into the treatment of children on antiepileptic treatment.
Results:
Results from the PopPK model showed that the kinetics of LEV, LTG, and VA were best described by a one compartment model with first-order absorption and elimination kinetics. Reliance on random forest model is a compelling vision that shows high prediction ability for all cases. The main factor that can affect antiepileptic activity is antiepileptic drug levels, followed by body weight, while gender is irrelevant. According to our study, children’s age is positively associated with LTG levels, negatively with LEV and without the influence of VA.
Conclusion:
The application of PopPK and ML models may be useful to improve epilepsy management in vulnerable pediatric population during the period of growth and development.
Plain language summary
Pharmacokinetics and machine learning in epilepsy
Abstract: Nowadays, combined antiepileptic therapy is the best option for a number of pediatric patients. Furthermore, there are no standard procedures in the therapy management of this complex treatment. Besides therapeutic monitoring, the population pharmacokinetic (PopPK) approach and machine learning (ML) are useful sources of information regarding the optimization of therapy. The aim of this study was to describe the pharmacokinetics of valproic acid (VA), lamotrigine (LTG), and levetiracetam (LEV) in a pediatric population using nonlinear mixed-effect modeling, while ML algorithms were applied to identify any relationships among the plasma levels of the three medications and patients’ characteristics. The study included 71 pediatric patients of both genders, aged 2–18 years, on combined antiepileptic therapy. Population pharmacokinetic (PopPK) models were developed separately for VA, LTG, and LEV. Based on the estimated pharmacokinetic parameters and the patients’ characteristics, three ML approaches were applied (principal component analysis, factor analysis of mixed data, and random forest). According to our study, children’s age is positively associated with LTG levels, negatively with LEV and without influence from VA. However, the gender of patients has no influence on drug plasma concentration. Findings demonstrated that the application of PopPK and ML models may be useful to improve epilepsy management in vulnerable pediatric population during the period of growth and development.
Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine ...Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed
Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.
Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. ...While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice.
Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients.
We retrospectively investigated a real-life cohort of ...325 DOAC anticoagulated patients with atrial fibrillation 179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%). Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI <30 kg/m2), class I obesity (71 with BMI 30–34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2).
Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED.
Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.
•Patients with higher BMI receiving DOACs have higher thrombotic and bleeding risks.•Loss of efficacy might be associated with dabigatran.•Higher risk of major bleeding might be associated with Xa inhibitors.
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