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Development of a quality of life model based on the example of selected urban centers
No full textKvaliteta života sve je važnija tema jer izravno utječe na zadovoljstvo stanovnika, njihovo zdravlje i opću dobrobit. Teorijski okvir istraživanja kvalitete života obuhvaća razmatranje različitih modela i teorija koji se bave objektivnim i subjektivnim indikatorima kvalitete života. Istraživanje kvalitete života usmjereno je na definiranje i klasifikaciju različitih vrsta indikatora, uključujući objektivne i subjektivne, kvantitativne i kvalitativne. Posebna pažnja posvećena je funkcijama indikatora, kao što su procjena, praćenje, planiranje, donošenje odluka, komunikacija i participacija. Smjerniceglobalnih institucija, poput Ujedinjenih naroda i Europske unije, preporučuju da se mjerenja kvalitete života provode integriranim pristupom koji u obzir uzima dosad neistražene indikatore, poput održivog razvoja i pametnih gradova. Na temelju subjektivnih percepcija stanovnika Zagreba, Beča i Ljubljane, koji se razlikuju po socioekonomskom kontekstu i duljini članstva u Europskoj uniji, opisan je model mjerenja kvalitete života u urbanim centrima. Novi model mjerenja kvalitete života osmišljen je tako da osigura relevantnost za buduće političke odluke u urbanim centrima. Empirijskidio istraživanjauključujei mjerenjekvalitete života u tri gradska prstena i ukupno u Zagrebu. Obuhvatnom interpretacijom rezultata, istraživanje pruža dublje razumijevanje različitih dimenzija kvalitete života u različitim prstenima grada Zagreba. Zaključno, na temelju rezultata testiranja hipoteze izveden je zaključak da ne postoji razlika u ocjeni kvalitete života u Zagrebu između ispitanika iz tri gradska prstena. To znači da je model mjerenjakvaliteteživota u urbanimcentrimaprikladan za mjerenjekvalitete života u Zagrebu neovisno o tome u kojem dijelu grada se provodi mjerenje kvalitete života. Zaključci istraživanja ističu važnost kontinuiranog praćenja i prilagođavanja politika kako bi se osigurala dugoročna održivost urbanih sredina. Postavljaju se temelji za buduća istraživanja u području kvalitete života i nude se smjernice za primjenu modela u drugim urbanim centrima. Integracijom različitih indikatora i analizom suvremenih izazova, rad pridonosi razumijevanju kompleksnih dinamika kvalitete života u urbanim centrima i temelj je za kvalitetno upravljanje urbanim centrima.Quality of life is becoming an increasingly important topic because it directly affects the satisfaction of residents, their health and general well-being. The theoretical framework of quality of life research includes consideration of various models and theories that deal with objective and subjective indicators of quality of life. Quality of life research is focused on defining and classifying different types of indicators, including objective and subjective, quantitative and qualitative. Special attention is paid to the functions of indicators, such as assessment, monitoring, planning, decision-making, communication and participation. Guidelines from global institutions, such as the United Nations and the European Union, that quality of life measurements are carried out with an integrated approach that takes into account hitherto unexplored indicators, such as sustainable development and smart cities. Based on the subjective perceptions of the residents of Zagreb, Vienna and Ljubljana, who differ in socioeconomic context and length of membership in the European Union, a model for measuring the quality of life in urban centers is described. The new quality of life measurement model is designed to ensure relevance for future policy decisions in urban centers. The empiricalpart of the research includes measuring the quality of life in the three city rings and in Zagreb as a whole. Through a comprehensive interpretation of the results, the research provides a deeper understanding of the different dimensions of the quality of life in the different rings of the city of Zagreb. In conclusion, based on the results of the hypothesis testing, it was concluded that there is no difference in the assessment of the quality of life in Zagreb between respondents from the three city rings. This fact means that the model of measuring the quality of life in urban centers is suitable for measuring the quality of life in Zagreb, regardless of which part of the city the quality of life measurement is carried out. The research conclusionsemphasize the importance of continuous monitoring and adaptation of policies to ensure the long-term sustainability of urban environments. The foundations for future research in the area of quality of life are laid and guidelines are offered for the application of the model in other urban centers. Through the integration of various indicators and the analysis of contemporary challenges, the work contributes to the understanding of the complex dynamics of the quality of life in urban centers and represents the basis for quality management of urban centers
Utjecaj nošenja standardne policijske opreme na povećanu pojavu asimetrije u hodu i stajanju kod pristupnika temeljne policije Ministarstva unutarnjih poslova Republike Hrvatske
No full textAim The main objective of this doctoral thesis is to determine if standard police equipment affects the increase in walking and standing asymmetry. Regarding the primary objective, three specific objectives were established for three independent studies (Study 1, Study 2 and Study 3). Study 1 aims to assess whether standard police equipment affects the increase in asymmetry in the spatio-temporal parameters of the basic gait of police officers. Study 2 aimed to assess whether the standard police equipment affects the increase in the asymmetry of the forces and the pressures under the front, the middle and the back of the foot of the basic police. Study 3 aims to evaluate whether the standard police equipment affects the increased display of asymmetry during the stay of the basic police.
Study 1 methods In this cross-sectional study, we recruited police recruits who were part of a one-year academy training program intended to become part of the Croatian police service. Typically, a police academy recruits between 750 and 1000 people each year. 900 police recruits were screened and selected to participate in the study. The inclusion criteria strictly stipulate that all participants must be free of acute or chronic locomotor and mental diseases, which could prevent them from participating in the study. Exclusion criteria included participants suffering from locomotor disease (injury) or mental illness (depression or other illness) and who were ill at the time of the study. To analyse the spatial parameters of gait, we used the Zebris pedobarographic platform (FDM; GmbH, Munich, Germany). This advanced device includes 11,264 sensors with a sampling rate of 100 Hz and a sensor area of 149 cm × 54.2 cm. Its main function is to capture, process and produce gait characteristics in dynamic (lying) and static (resting) conditions. All procedures were anonymous and compliant in the Declaration of Helsinki. In addition, all participants provided written informed consent to participate in the study. This study was approved by the Ministry of the Interior and Police Academy "Josip Jovic" and the Ethical Committee of the Faculty of Kinesiology, University of Zagreb, Croatia (ethics code number: 511-01-128 -23-1).
Study 1 results Compared to the “no load” condition, a standardized load of 3.5 kg/7.5 kg/10 kg was administered. A load of 7 lb significantly increased asymmetries in the spatial parameters of gait, as follows: heavy gait phases (mean difference = 1.05), load response (mean difference = 0.31), single member support (mean difference = 0.31), single limb support (mean diff. = 0.56), pre-swing (average change = 0.22) and swing (average change = 0. 90), while no significant asymmetry was observed in leg rotation, step length and stride length. For gait time parameters, we observed a significant asymmetry in stride time (mean difference = -0.01), while no difference was observed in walking cadence and speed.
Study 1 conclusions Results indicate that the additional fee of 3. 5 kg / 7.7 lb are more likely to increase the asymmetries in the spatial components of the gait cycle, compared to the temporal parameters. Thus, external policing can have dangerous effects by increasing the general asymmetry of the body, which can lead to a higher risk of injury and reduced performance to perform specific daily tasks.
Study 2 method The sample of respondents for Study 2 was determined in Study 1 (see detailed information in Study 1). The absolute values of ground reaction forces and plantar pressures under different regions of the foot were evaluated with a pedobarographic platform (Zebris FDM). Skewness was calculated as (xright - xleft) / 0.5 × (xright + xleft) × 100%, where the term "x" denotes a specific parameterbeing computed, and if it is closer to 0, the value of x is more reflective.
Study 2 results Significant differences in ground reaction forces and plantar pressures between the left and right foot were observed when a "3.5 kg load" was added. Compared to the “no load” condition, carrying a “3.5 kg load” resulted in an increase in ground reaction force and plantar pressure. The load of 3.5 kg significantly increased the gait asymmetries for the peak ground reaction forces under the forefoot (ES = 0.29), midfoot (ES = 0) and hindfoot (ES = 0, 19) regions). For plantar pressure peaks, only the asymmetry under the midfoot region increased significantly (ES = 0.19).
Study 2 conclusion The results of this study show that a "3.5 kg load" significantly increases the ground reaction force and the asymmetry of the forefoot and midfoot pressure compared to the condition " without charge". Due to higher loads, increased kinetic gait asymmetry may have negative effects on future pain and discomfort in the leg region, possibly causing stress fractures and deviant gait biomechanics in police recruits.
Study 3 method The sample of respondents for Study 3 was determined in Study 1 (see detailed information in Study 1). The characteristics of the leg in a standing position were assessed with the Zebris FDM pedobarographic pressure platform.
Study 3 results Carrying a load of 3.5 kg significantly increased the area of the 95% confidence ellipse (Δ = 15.0%, p = 0.009), the path length of the centre of pressure (Δ = 3.3%, p = 0.009). 023) and the average speed (Δ = 11.1%, p = 0.014), the length of the minor axis (Δ = 8.2%, p 0.002). 05).
Study 3 conclusions The results of suggest that the spatial and temporal parameters of the foot may be more sensitive to change during the transport of heavy loads, especially the characteristics of the centre of pressure.Cilj Glavni cilj ovog doktorskog rada je utvrditi utječe li standardna policijska oprema na povećanje asimetrije hodanja i stajanja. Što se tiče primarnog cilja, utvrđena su tri specifična cilja za tri neovisne studije (Studija 1, Studija 2 i Studija 3). Studija 1 ima za cilj procijeniti utječe li standardna policijska oprema na povećanje asimetrije u prostorno-vremenskim parametrima osnovnog hoda policijskih službenika. Studija 2 imala je za cilj procijeniti utječe li standardna policijska oprema na povećanje asimetrije sila i pritisaka ispod prednjeg, srednjeg i stražnjeg dijela stopala temeljne policije. Studija 3 ima za cilj utvrditi utječe li standardna policijska oprema na povećanu pojavu asimetrije tijekom stajanja službenika temeljne policije.
Metode Studije 1 U ovoj presječnoj studiji regrutirali smo policijske novake koji su bili dio jednogodišnjeg programa obuke u akademiji s namjerom da postanu dio hrvatske policijske službe. Obično policijska akademija svake godine regrutira između 750 i 1000 ljudi. 900 policijskih novaka pregledano je i odabrano za sudjelovanje u studiji. Kriteriji uključivanja strogo propisuju da svi sudionici ne smiju imati akutne ili kronične lokomotorne i psihičke bolesti koje bi ih mogle spriječiti u sudjelovanju u istraživanju. Kriteriji za isključenje podrazumijevali su sudionike koji pate od bolesti lokomotornog sustava (ozljeda) ili mentalne bolesti (depresija ili druga bolest) i koji su bili bolesni u vrijeme istraživanja. Za analizu prostornih parametara hoda koristili smo pedobarografsku platformu Zebris (FDM; GmbH, München, Njemačka). Ovaj uređaj uključuje 11.264 senzora s brzinom uzorkovanja od 100 Hz i površinom senzora od 149 cm × 54.2 cm. Njegova glavna funkcija je prikupljanje, obrada i opis karakteristika hoda u dinamičkim (kretački) i statičkim (mirujući) uvjetima. Svi postupci bili su anonimni i u skladu s Helsinškom deklaracijom. Osim toga, svi su sudionici dali pisani informirani pristanak za sudjelovanje u studiji. Studiju su odobrili Ministarstvo unutarnjih poslova i Policijska akademija "Josip Jović" i Etičko povjerenstvo Kineziološkog fakulteta Sveučilišta u Zagrebu, Hrvatska (etički kod broj: 511-01-128 -23-1).
Rezultati studije 1 U usporedbi sa stanjem "bez opterećenja", primijenjeno je standardizirano opterećenje od 3.5 kg/7.5 kg/10 kg. Opterećenje od 7 lb značajno je povećalo asimetrije u prostornim parametrima hoda, kako slijedi: faze pojačanog hoda (srednja razlika = 1.05), odgovor na opterećenje (srednja razlika = 0.31), faza potpore jednog ekstremiteta (srednja razlika = 0.31), faza potpore jedne noge (srednja razlika = 0.56), predzamah (prosječna promjena = 0.22) i faza zamaha (prosječna promjena = 0.90), dok nije zabilježena značajna asimetrija u rotaciji donjeg ekstremiteta, duljina koraka i duljina dvokoraka. Za parametre vremena hoda, uočili smo značajnu asimetriju u vremenu koraka (srednja razlika = -0.01), dok nije primijećena razlika u kadenci i brzini hoda.
Zaključci studije 1. Rezultati pokazuju da dodatno opterećenje od 3,5 kg / 7,7 lb vjerojatnije povećava asimetrije u prostornim komponentama ciklusa hoda u usporedbi s vremenskim parametrima. Vanjsko opterećenje može imati negativne učinke povećanjem ukupne asimetrije tijela, što može dovesti do povećanog rizika ozljeda te smanjene sposobnosti za obavljanje specifičnih svakodnevnih zadataka.
Metoda Studije 2 Uzorak ispitanika za Studiju 2 određen je u Studiji 1 (pogledajte detaljne informacije u Studiji 1). Apsolutne vrijednosti sila reakcije podloge i plantarnih pritisaka pod različitim regijama stopala opisane su pedobarografskom platformom (Zebris FDM). Asimetrija je izračunata prema formuli (xdesno - xlijevo) / 0.5 × (xdesno + xlijevo) × 100%, pri čemu pojam "x" označava specifičan parametar koji se računa, a što je vrijednost bliža 0, to je parameter više stvaran.
Rezultati studije 2 Značajne razlike u silama reakcije podloge i plantarnom pritisku između lijevog i desnog stopala zabilježene su pri dodatku opterećenja od 3,5 kg. U usporedbi sa stanjem bez opterećenja, nošenje opterećenja od 3,5 kg rezultiralo je povećanjem sila reakcije podloge i plantarnog pritiska. Opterećenje od 3,5 kg značajno je povećalo asimetrije hoda u vršnim silama reakcije podloge ispod prednjeg dijela stopala (ES = 0,29), srednjeg dijela stopala (ES = 0) i stražnjeg dijela stopala (ES = 0,19). Što se tiče vršnih vrijednosti plantarnog pritiska, značajno je porasla samo asimetrija ispod srednjeg dijela stopala (ES = 0,19).
Zaključak studije 2 Rezultati ove studije pokazuju da opterećenje od 3,5 kg značajno povećava sile reakcije podloge te asimetriju pritiska prednjeg i srednjeg dijela stopala u usporedbi sa stanjem bez opterećenja. Zbog većih opterećenja, povećana kinetička asimetrija hoda može imati negativne učinke na pojavu bolove i nelagodu u području donjih ekstremiteta, potencijalno uzrokujući stres frakture i odstupanja u biomehanici hoda kod novih policijskih službenika.
Metoda Studije 3 Uzorak ispitanika za Studiju 3 određen je u Studiji 1 (pogledajte detaljne informacije u Studiji 1). Karakteristike nogu u stojećem položaju procijenjene su pomoću pedobarografske platforme Zebris FDM za mjerenje pritiska.
Rezultati studije 3 Nošenje opterećenja od 3,5 kg značajno je povećalo površinu 95%-tnog intervala pouzdanosti elipse (Δ = 15,0%, p = 0,009), duljinu puta središta pritiska (Δ = 3,3%, p = 0,023) i prosječnu brzinu (Δ = 11,1%, p = 0,014), duljinu manje osi (Δ = 8,2%, p 0,005).
Zaključci Studije 3 Rezultati sugeriraju da prostorni i vremenski parametri stopala mogu biti osjetljiviji na promjene tijekom prenošenja tereta, osobito karakteristike središta pritiska
Apoptosis and cell response to hypoxia in colon cancer
No full textCilj istraživanja. Poznato je da je razvoj kolorektalnog karcinoma karakteriziran nizom događaja tijekom kojih se normalni epitel debelog crijeva postupno transformira u karcinom, slijedom od adenoma do karcinoma. Apoptoza ima važnu ulogu u razvoju i održavanju homeostaze tkiva. Hipoksija postoji u solidnim tumorima i uzrokuje hiperpermeabilnost unutarnje mitohondrijske membrane što dovodi do otpuštanja citokroma c i cijepanja kaspaze 9 čime se aktivira apoptoza. Danas u literaturi nema dogovora o prognozi apoptoze i hipoksije kod kolorektalnog karcinoma. Broj studija koje ispituju ekspresiju kaspaza te HIF-1a u kolorektalnom karcinomu vrlo su ograničene i one nisu ispitivale korelaciju između ekspresije i preživljenja pacijenata. Ispitanici i metode. Ova studija uključivala je histološke uzorke 179 pacijenata kojima je dijagnosticiran rak debelog crijeva. Koristili smo TUNEL metodu i označavanje kaspazom-3 kako bismo identificirali stupanj apoptoze uz ispitivanje povezanosti između ekspresije HIF-1α i kaspaze-9 i tumorske patologije te utvrditi njihov prognostički značaj za kolorektalni karcinom. Rezultati. Rezultati pokazuju da je niži apoptotski indeks (AI) mjeren metodom TUNEL i niža imunohistokemijska ekspresija kaspaze-3 povezana s kraćim preživljenjem bez bolesti i ukupnim preživljenjem. Ekspresija HIF-1α i kaspaze-9 povezana je sa stadijem tumora, stupnjem tumora i vaskularnom invazijom te je povezana s lošim ukupnim preživljenjem i preživljenjem bez povrata bolesti. Povećana ekspresija HIF-1α i kaspaze-9 povezana je s rastom tumora, agresivnošću i lošim preživljavanjem bolesnika s kolorektalnim karcinomom. Zaključak. Samo je apoptotski indeks (AI) određen TUNEL metodom dokazano neovisni pokazatelj preživljavanja. Rezultati istraživanja u skladu su s predloženim modelima karcinogeneze kolorektalnog karcinoma koji naglašavaju otpornost na apoptozu kao odlučujući čimbenik u progresiji bolesti i otpornosti na liječenje.Objectives. It is known that the development of colorectal cancer is characterized by a series of events during which the normal epithelium of the colon gradually transforms into cancer, following the sequence from adenoma to carcinoma. Apoptosis plays an important role in the development and maintenance of tissue homeostasis. Hypoxia exists in solid tumors and causes hyperpermeability of the inner mitochondrial membrane leading to the release of cytochrome c and cleavage of caspase 9, thereby activating apoptosis. Currently, there is no agreement in the literature on the prognosis of apoptosis and hypoxia in colorectal cancer. The number of studies examining the expression of caspases and HIF-1a in colorectal cancer is very limited and they did not examine the correlation between expression and patient survival. Patients and Methods. This study included histological samples from 179 patients diagnosed with colon cancer. We used the TUNEL method and caspase-3 labeling to identify the degree of apoptosis while examining the association between the expression of HIF-1α and caspase-9 and tumor pathology and to determine their prognostic significance for colorectal cancer. Results. The results show that lower apoptotic index (AI) measured by the TUNEL method and lower immunohistochemical expression of caspase-3 are associated with shorter disease-free survival and overall survival. HIF-1α and caspase-9 expression correlated with tumor stage, tumor grade, and vascular invasion, and was associated with poor overall and disease-free survival. Increased expression of HIF-1α and caspase-9 is associated with tumor growth, aggressiveness and poor survival in patients with colorectal cancer. Conclusion. Only the apoptotic index (AI) determined by the TUNEL method proved to be an independent indicator of survival. The research results are consistent with the proposed models of colorectal cancer carcinogenesis that emphasize resistance to apoptosis as a determining factor in disease progression and resistance to treatment
Beatrice Speraz, life and literary output „between numbers and dreams“
No full textU ovoj doktorskoj disertaciji istražen je život i književno stvaralaštvo Beatrice Speraz, talijanske književnice hrvatskog podrijetla koja je živjela i književno djelovala u drugoj polovini 19. i prvim desetljećima 20. stoljeća. Bila je poznatija pod pseudonimom Bruno Sperani pod kojim je objavljivala svoja djela. U uvodnom dijelu rada prikazan je povijesni, društveni i kulturološki kontekst postunitarne Italije, vremena u kojem je Beatrice Speraz živjela i književno djelovala, a koji je neizostavan okvir za razumijevanje njezinog proznog stvaralaštva. U nastavku je dat kraći povijesni prikaz književnosti koju su pisale žene na talijanskom poluotoku i ukazano je na njihovu marginaliziranost u talijanskoj književnosti koja je bila uvjetovana njihovom pripadnosti ženskom spolu. Poglavlje o književnicama Ottocenta kojem je Beatrice Speraz kronološki i kulturološki pripadala, prikazuje razdiobu unutar samog perioda, naznačuje karakteristike njihova stvaralaštva, i ukazuje na izazove s kojima su se književnice ovog razdoblja susretale kako bi prodrle na književnu scenu. U drugom dijelu rada predstavljeni su književničin životopis i prozni opus te kritički osvrti na njezino prozno stvaralaštvo. U trećem dijelu težište rada je na analizi položaja žene u talijanskom društvu druge polovine Ottocenta, jer je žena tog razdoblja kao tema i kao lik u središtu autoričinog književnog stvaralaštva. Prije analize odabranih djela daje se i kratki osvrt na početke emancipacije te koncept i povijest braka kao kontekst za bolje razumijevanje autoričine proze. Opsežan prozni opus Beatrice Speraz pruža pogled u stoljećima zatvoreni i osamljeni ženski svijet te uvid u proces samospoznavanja i sazrijevanja ženskih likova. U njemu pratimo postupno osvješćivanje, prvo same potrebe za promjenom postojećeg stanja i položaja žene u društvu druge polovine 19. i prvih desetljeća 20. stoljeća, a potom njezino pokretanje, sam čin promjene, samoostvarenja i realizacije. Književno stvaralaštvo autorice u svom središtu ima podređen položaj žene u talijanskom društvu Ottocenta, stoga je u analizi odabranih romana težište postavljeno na procesu osvješćivanja i sazrijevanja svijesti ženskih likova. Kako je književnica bila angažirani pisac, duboko svjesna svog vremena, neka od njezinih proznih djela nose socijalistički predznak. U svom stvaralaštvu Beatrice Speraz također skreće pozornost na nepovoljne okolnosti i uvjete kojima su izloženi podređeni i marginalizirani dionici društva, radnici, seljaci i djeca te ukazuje na prijeko potrebnu promjenu u društvu postunitarne Italije. Zaključna razmatranja donose sintezu rada i nude prosudbu o književnom izričaju Beatrice Speraz te upućuju na potrebna daljnja izučavanja i revalorizaciju njezina književnog stvaralaštva čime bi se književnici dodijelilo zasluženo mjesto u kanonu talijanske književnosti.This doctoral thesis presents the results of research and study of the life and literary output of Beatrice Speraz, an Italian female writer of Croatian origins, who lived and worked in the second half of the 19th and the first decades of the 20th century. She was better known under the pseudonym of Bruno Sperani which she had chosen as her literary name. The introduction presents historical, social and cultural context of the post-Unification Italy, period in which Beatrice Speraz lived and literary worked and which serves as a framework for comprehension of her literary output. Further chapter provides the abridged historical view of the literature written by female authors on the Italian peninsula and points out their marginalization in Italian literary history caused by their belonging to female sex. The chapter entitled The women writers of Ottocento, to which Beatrice Speraz cronologicaly and culturaly belonged, reviews the division inside the period itself, denotes the features of their literary works and indicates the challenges these women writers encountered on their breakthrough in the literary scene. The second part of the doctoral thesis presents Beatrice Speraz's biography and the overview of her literary production, as well as the critical reviews of her novels and collection of short stories written by her contemporaries. The emphasis of the third part of the thesis is on the analysis of the woman's status and condition in the Italian society of the second half of the 19th century, since the woman of the mentioned period was in the focus of Beatrice Speraz's literary work as a major theme and a main character. Before the analysis of the selected works, the short review of the beginnings of emancipation movement is given, as well as the concept and history of marriage which provides the context for better understanding of the author's prose. The prolific Speraz's output provides the insight in previously isolated and lonely woman's world as well as the view in the process of self-consciousness and maturing of the female characters. Through it the process of gradual rise of woman's self-awareness is followed, firstly a very need for changing of the present position and condition for the woman of the second half of 19th and the first decades of 20th century, then her motion, the act of change, self-recognition and realization. Although the author is strongly concerned with „the woman's question“ and required changes and modes in which they can be obtained, Speraz's literary works bear the pedagogical message as well. It is contained in the author's intention to draw attention to circumstances to which girls and women are exposed to and the ways how they can achieve better position in their families and society. As the author was an engaged writer, deeply aware of her time, some of her works bear the socialistic sign. Nevertheless, Speraz's preoccupation is primarily focused on the position of the woman and needed emancipation in the society of the second half of Ottocento, she also draws attention to unfavourable and difficult conditions in the lives of other marginalized members of the society like workers, peasants and children and points out the need for indispensable change in the society of post-Unification Italy. The concluding remarks synthesize the results of the researched and studied theme and offer the opinion of Beatrice Speaz's literary work. They point out the necessity of further studies and the revaluation of the author's literary output which hopefully would lead to the recognition of Beatrice Speraz, awarding her with the merited and deserved place in the canon of the Italian literature
A comparison of detection methods for multidimensional polytomous differential item functioning
No full textMetode za otkrivanje DIF-a tradicionalno su se koristile za jednodimenzionalne mjerne instrumente, pretpostavljajući da sama prisutnost višedimenzionalnosti u podacima upućuje na prisustvo DIF-a. Međutim, brojni psihološki instrumenti su inherentno višedimenzionalni jer mjere složene konstrukte kroz različite skupine čestica, što može dovesti do netočnih zaključaka o prisutnosti DIF-a kada se koriste jednodimenzionalni modeli. Dosad je nekoliko metoda za detekciju DIF-a adaptirano za upotrebu na višedimenzionalnim podacima, no njihova učinkovitost provjeravana je samo na višedimenzionalnim dihotomnim podacima. Stoga se u ovom istraživanju učinkovitost željela provjeriti na višedimenzionalnim politomnim podacima. Pritom su uspoređivane 4 metode: omjer izglednosti iz okvira teorije odgovora na zadatak (IRT-LR), MIMIC model s interakcijom, logistička regresija s latentnom procjenom i logistička regresija s bruto rezultatima. Učinkovitost ovih metoda provjeravana je na računalno simuliranim, ali i na realnim podacima koji su dobiveni pomoću kraće verzije Upitnika emocionalne kompetentnost UEK-27. Evaluacija metoda obuhvatila je analizu stope pogrešaka tipa I i statističke snage (osjetljivosti) svake metode. Rezultati istraživanja pokazuju da je logistička regresija s procjenom latentne varijable bila najučinkovitija u otkrivanju DIF-a na politomnim višedimenzionalnim podacima, posebno efikasna u otkrivanju niskog DIF-a te otporna na stvarne razlike u grupnim sposobnostima i razlike u veličini grupa. S druge strane, MIMIC metoda s interakcijom pokazala je tendenciju povećanja stope pogrešaka tipa I. Empirijski nalazi djelomično su potvrdili rezultate simulacije, no ograničenje na jedan uzorak u empirijskom dijelu upozorava na potrebu opreznog tumačenja i generalizacije rezultata. Buduća istraživanja trebala bi nastaviti razvijati i testirati metodologije za detekciju DIF-a, proširujući njihovu primjenjivost i adresirajući postojeća ograničenja u različitim testnim situacijama i populacijama.This dissertation evaluates the effectiveness of various Differential Item Functioning (DIF) detection methods in multidimensional testing environments, particularly focusing on their application to polytomous data settings. The study aims to address the complexities that arise when traditional unidimensional approaches are used for inherently multidimensional constructs. Data for the study were gathered through both computer-simulated scenarios and real data collected via the shortened form of Emotional Skills and Competence Questionnaire (ESCQ-27). Four DIF detection methods were compared: Item Response Theory-Likelihood Ratio (IRT-LR), MIMIC with interaction, logistic regression with latent trait estimation, and logistic regression with observed total scores. The efficacy of these methods was assessed through their Type I error rates and statistical power (sensitivity). The findings revealed that logistic regression with latent trait estimation was most effective in identifying DIF in multidimensional polytomous data, efficiently detecting low DIF and demonstrating robustness against actual differences in group abilities and group sizes. Conversely, the MIMIC method with interaction tended to increase Type I error rates, indicating potential issues with false positives. Although simulated data supported the effectiveness of the logistic regression methods, the empirical results from the ESCQ-27 questionnaire emphasized the need for cautious interpretation and generalization due to the sample limitation in the empirical component of the study. The research highlights the necessity of using appropriate multidimensional DIF detection methods for complex constructs measured by psychometric instruments and recommends logistic regression with latent trait estimation for its superior performance in diverse testing scenarios. Future studies should focus on further developing and testing DIF detection methodologies to enhance their applicability and address existing limitations in different test situations and populations. This aim would improve the accuracy and reliability of psychometric evaluations across varied demographic groups
Effect of C19H16ClN3O2S on the expression of glycosphingolipids, cytotoxicity, apoptosis, and metabolomics in the ovarian adenocarcinoma cell lines
No full textCiljevi doktorske disertacije "Učinak C19H16ClN3O2S na izražaj glikosfingolipida, citotoksičnost, apoptozu i metabolomiku u staničnim linijama adenokarcinoma jajnika" su istražiti potencijal antitumorskog spoja na staničnim linijama karcinoma jajnika SK-OV-3 i OVCAR -3 s fokusom na citotoksičnost, apoptozu, postotak matičnih stanica raka (CSC), izražaj glikosfingolipida (GSL) i metabolomiku. Proučavani spoj, 3-amino-N-(3-klor-2-metilfenil)-5-okso-5,6,7,8-tetrahidrotieno[2,3-b]kinolin-2-karboksamid (Spoj 1), sintetiziran je umjetno i upotrijebljen je za procjenu njegovih potencijalnih inhibicijskih učinaka na stanične linije raka jajnika. Citotoksičnost spoja je provedena korištenjem MTT testa koji je pokazao da je Spoj 1 bio znatno toksičan za obje stanične linije, IC50 vrijednosti od 5,5 μM za SK-OV-3 i 5,0 μM za OVCAR-3 stanične linije prilikom izloženosti Spoju 1 u trajanju od 48 sati. Nadalje, Spoj 1 dovodi do indukcije apoptoze, pri čemu je primijećeno da je statistički značajno veći udio i ranih i kasnih apoptotskih stanica u obje linije nakon tretmana. Osim toga, udio CSC (matične stanice karcinoma) se značajno smanjio nakon tretmana Spojem 1, čime se ukazuje na potencijalnu značajnu ulogu u smanjenju recidiva tumora i neuspjeha liječenja. Promjene u izražaju GSL-a zabilježene su i na CSC i na ne-CSC. U SK-OV-3 staničnoj liniji, sedam od osam promatranih GSL-a pokazalo je smanjenje CSC-a, dok su ne-CSC-i pokazali povećanje izražaja GSL-a. Stanična linija OVCAR-3 pokazala je slične trendove, iako su promjene bile manje statistički značajne. Metaboličko profiliranje provedeno uz pomoć GC-MS na staničnim linijama raka jajnika prije i nakon tretmana Spojem 1 pronašla je specifične metaboličke promjene u tretiranim stanicama u odnosu na netretirane. Metabolomika je otkrila 20 metabolita u OVCAR-3 i 21 u SK-OV-3 staničnim linijama. Stanice OVCAR-3 pokazale su značajnije promjene, s osam metabolita koji su se značajno razlikovali u tretiranim naspram netretiranih stanica, dok su samo dva metabolita pokazala značajne razlike u SK-OV-3 liniji. Rezultati pokazuju da Spoj 1 ne samo da dovodi do značajne stanične smrti, već također utječe na nekoliko ključnih signalnih puteva odgovornih za regulaciju izražaja GSL-a u staničnim linijama raka jajnika. Naglašavajući njegovu sposobnost da inducira apoptozu, smanji populaciju CSC-a i promijeni metaboličke puteve tumorskih stanica, potencijal Spoja 1 kao terapeutskog agensa protiv raka jajnika je izniman.The objectives of the doctoral dissertation "Effect of C19H16ClN3O2S on the expression of glycosphingolipids, cytotoxicity, apoptosis and metabolomics in the ovarian adenocarcinoma cell lines" are to investigate the potential of the antitumor compound on the ovarian cell lines SK-OV-3 and OVCAR-3 with a focus on cytotoxicity, apoptosis, percentage of cancer stem cells (CSC), glycosphingolipid (GSL) expression and metabolomics. The studied compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1), is artificially synthesized and we used it to evaluate its potential inhibitory effects on ovarian cancer cell lines. The cytotoxicity of the compound was performed using the MTT assay which showed that Compound 1 was significantly toxic to both cell lines, with IC50 values of 5.5 μM for SK-OV-3 and 5.0 μM for OVCAR-3 cell lines when exposed to the compound in duration of 48 hours. Furthermore, Compound 1 leads to the induction of apoptosis, with a statistically significantly higher proportion of both early and late apoptotic cells observed in both lines after treatment. In addition, CSCs show that their proportion significantly decreased after treatment with Compound 1, thus indicating the important role of Compound 1 in tumor recurrence and treatment failure. Changes in the expression of GSLs were noted in both CSCs and non-CSCs. In the SK-OV-3 cell line, seven of the eight observed GSLs showed a decrease in CSCs, while non-CSCs showed increased GSL expression. The OVCAR-3 cell line showed similar trends, although the changes were less statistically significant. Metabolic profiling performed with GC-MS on ovarian cancer cell lines before and after treatment with Compound 1 found specific metabolic changes only in treated cells. Metabolomics revealed 20 metabolites in OVCAR-3 and 21 in SK-OV-3 cell lines. OVCAR-3 cells showed more significant changes, with eight metabolites significantly different in treated versus untreated cells, while only two metabolites showed significant differences in the SK-OV-3 line. The results show that Compound 1 not only induces significant cell death, but also affects several key signaling pathways responsible for the regulation of GSL expression in ovarian cancer cell lines. Emphasizing its ability to induce apoptosis, reduce the population of CSCs, and alter the metabolic pathways of tumor cells, the potential of Compound 1 as a therapeutic agent against ovarian cancer is exceptional
Von Willebrand factor and Factor VIII in chronic Graft-versus-Host Disease
No full textKronična bolest presatka protiv primatelja (cGvHD) kasna je komplikacija alogenične transplantacije krvotvornih matičnih stanica (alo-PKMS) koju karakterizira imuna disregulacija. U svakodnevnoj kliničkoj praksi istaknuta je potreba za neinvazivnim i lako dostupnim biomarkerom koji bi pouzdano pokazivao aktivnost bolesti i pomogao u modulaciji terapijske strategije. Von Willebrandov faktor (VWF) i faktor VIII (FVIII) su koagulacijski faktori koji djeluju kao upalni markeri koji mogu odražavati i endotelnu aktivaciju, inače poznati etiopatogenetski čimbenik nastanka cGvHD-a. Njihov biomarkerski potencijal u procjeni aktivnosti bolesti opisivan je ranije u autoimunim bolestima koje klinički nalikuju cGvHD-u. Rezultati naše studije pokazali su kako su razine VWF i FVIII značajno više kod bolesnika oboljelih od cGvHD-a u odnosu na kontrole koji nisu razvili cGvHD (VWF:Ag 268,2% vs 191,9%, p=0,003; VWF:RCo 261,8% vs 178,2%, p= 0,003; FVIII 2,17 vs 1,82, p=0,006). Daljnom analizom pokazano je kako su razine VWF:Ag iznad 246,3% i VWF:RCo iznad 271,4% u inicijalnoj fazi bolesti dijagnostički pokazatelj pojave cGvHD-a visoke specifičnosti (92,3%) i dobre osjetljivosti (67,5%). Pokazano je i da su razine faktora povezane s postojanjem manifestacija cGvHD u jetri, ustima i gastrointestinalnom traktu. Ovim longitudinalnim istraživanjem po prvi put je pokazano kako su razine VWF i FVIII povišene dugo nakon postavljanja dijagnoze cGvHD-a i da su povezane s aktivnošću bolesti. Navedeni rezultati ukazuju na moguću dugotrajnu ulogu endotela u aloimunom odgovoru povezanim s cGvHD-om čime se dodatno ističe potreba za bazičnim istraživanjima koji bi dodatno objasnili biologiju bolesti. Potrebno je provesti dodatna istraživanja biomarkerskog potencijala VWF kao dijagnostičkog sredstva u predmanifestnoj fazi bolesti te u procjeni odgovora na terapiju čime bi se mogla omogućiti ranija terapijska intervencija i smanjenje nastanka ireverzibilih i teških sekvela bolesti.Chronic Graft-versus-Host Disease (cGvHD) is a late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by immune dysregulation. In clinical practice, there is a critical need for a non-invasive and easily accessible biomarker that can reliably indicate disease activity and assist in tailoring therapeutic strategies. Von Willebrand factor (VWF) and factor VIII (FVIII) are coagulation factors that function as inflammatory markers and can reflect endothelial activation, a known etiopathogenetic factor in the development of cGvHD. Their biomarker potential in assessing disease activity has been previously described in autoimmune diseases that clinically resemble cGvHD. Our study results showed that VWF and FVIII levels were significantly higher in patients with cGvHD compared to controls who did not develop cGvHD (VWF 268.2% vs 191.9%, p=0.003; VWF 261.8% vs 178.2%, p=0.003; FVIII 2.17 vs 1.82, p=0.006). Further analysis revealed that VWF levels above 246.3% and VWF levels above 271.4% in the initial phase of the disease are diagnostic indicators of cGvHD with high specificity (92.3%) and good sensitivity (67.5%). It was also shown that these factor levels are associated with the presence of cGvHD manifestations in the liver, mouth, and gastrointestinal tract. This longitudinal study demonstrated for the first time that VWF and FVIII levels remain elevated long after the diagnosis of cGvHD and correlate with ongoing disease activity. These findings suggest a possible long-term role of the endothelium in the alloimmune response related to cGvHD, highlighting the need for basic research to further explain the biology of the disease. Additional studies are needed to investigate the biomarker potential of VWF as a diagnostic tool in the pre-manifestation phase of the disease and in assessing response to therapy, which could enable earlier therapeutic intervention and reduce the occurrence of irreversible and severe disease sequelae
Development of criteria for selection of batch distillation operation mode
No full textNajvažnija kontrolna varijabla kod vođenja procesa šaržne destilacije je omjer pretoka. U konvencionalnom režimu rada, omjer pretoka se tijekom pokretanja procesa postavlja na maksimalnu vrijednost sve do postizanja stacionarnog sastava, nakon čega ostaje konstantan do završetka procesa. Cilj ovog rada je razviti metodu za određivanje optimalnog vremenskog profila omjera pretoka, počevši od faze pokretanja, kojim se u minimalnom vremenu može proizvesti proizvod zadanih karakteristika.
Za tu svrhu razvijen je matematički model procesa s bezdimenzijskom nezavisnom varijablom. Predložene su dvije metode za rješavanje problema optimalnog vođenja s ciljem minimizacije trajanja procesa. Prva metoda diskretizira omjer pretoka na veliki broj linearnih segmenata, dok druga metoda koristi parametrizaciju manjim brojem jednostavnijih krivulja. Usporedba metoda pri različitim procesnim parametrima pokazala je da metoda s diskretiziranim omjerom pretoka daje najbolje rezultate prema funkciji cilja i minimalnoj eksergijskoj destrukciji, ali je i računalno najzahtjevnija. S druge strane, metoda s parametriziranim profilom omjera pretoka predstavlja dobro kompromisno rješenje, postižući slične rezultate uz znatno smanjenje računalne složenosti. Obje metode omogućuju značajne uštede u odnosu na konvencionalno vođenje procesa, pri čemu potencijalna ušteda varira ovisno o parametrima procesa.
Eksperimentalnim istraživanjem uspješno je validiran razvijeni model u parametriziranom režimu rada. Pokazano je da simulacija može reproducirati eksperimentalne rezultate, kao i da se proces može eksperimentalno voditi na temelju rezultata simulacije. Regresijskom analizom ispitani su glavni i interakcijski utjecaji sedam parametara procesa na karakteristike konvencionalnog i optimalnog vođenja procesa.
Na kraju, razvijene su dvije metode za optimizaciju procesa uz nesigurne parametre i početne uvjete, temeljene na proračunu propagacije nesigurnosti metodom Koopmanovog očekivanja. Prva metoda koristi propagaciju nesigurnosti u unutarnjoj optimizacijskoj petlji, dok druga modificira funkciju cilja, koja se zatim minimizira determinističkom optimizacijom. Obje metode daju slične rezultate, ali je druga metoda računalno učinkovitija.Distillation remains one of the most widely used separation processes in the chemical and process industries. Batch distillation stands out as an extremely flexible process, especially suited for processing small quantities of mixtures, as well as for applications where feed and product compositions fluctuate significantly. Industries such as pharmaceuticals, fine chemicals, and specialty chemicals frequently rely on batch distillation due to its adaptability to varying production needs.
Despite these advantages, batch distillation is often less energy-efficient than continuous distillation. The frequent startup and shutdown phases inherent in batch operation contribute to higher energy consumption. Given the rising focus on energy efficiency and sustainable practices, there is a growing need to optimize batch distillation processes. This research focuses on optimizing the reflux ratio, a key control variable in batch distillation, to enhance operational efficiency. In conventional operations, the reflux ratio is set to maximum value during startup until a steady-state composition is achieved, after which it is maintained at a constant value until the end of the process. However, such a simplistic approach leaves substantial room for improvement.
The objective of this study is to develop a method for determining the optimal time-dependent reflux ratio profile, starting from the startup phase. The aim of this optimized control strategy is to produce a product meeting specified purity and recovery requirements in the shortest possible time, thereby enhancing overall process efficiency.
Mathematical Modelling and Optimization Problem
The foundation of this work is the development of a mathematical model for the batch distillation process. The model is built on rigorous mass and energy balance equations and employs a dimensionless independent variable, with process duration included as a parameter. In designing the model, a careful balance is struck between complexity and computational efficiency to ensure its suitability for use in iterative optimization algorithms.
Two distinct iterative methods were proposed to solve the optimization problem:
1.
Discretized reflux ratio method
This method discretizes the reflux ratio profile into a large number of linear segments. The optimization problem is solved by iteratively adjusting the values of these segments using gradient-based optimization techniques. The gradients of the objective function with respect to the control variables are computed using the necessary conditions for optimality.
2.
Parameterized Reflux Ratio Method
In this method, the reflux ratio profile is represented by a smaller number of simpler parametric curves, such as piecewise linear or polynomial functions. By reducing the number of decision variables, this approach lowers the computational complexity. Gradients are computed using automatic differentiation, which is efficient for reduced number of control parameters.
Comparative Analysis of Methods
Both methods were applied to a range of process conditions, which included variations in tray and reflux drum holdup, and product specifications. The discretized reflux ratio method provided the best results in terms of minimizing objective function values and destruction of exergy. However, this method is very computationally intensive. On the other hand, the parametric approach offered a near-optimal solution with significantly reduced computational effort. Both methods demonstrate significant savings compared to the conventional operation, with the potential savings varying substantially depending on the process parameters.
Experimental Validation
To validate the developed model and optimization strategies, an extensive experimental study was conducted. The experimental setup included a pilot-scale batch distillation column equipped with process control and measurement systems. A custom-built software platform was used to implement and monitor the control strategies.
Experiments were conducted for conventional reflux control as well as optimized reflux profiles. The TLZ (total-linear-zero) profile, identified as the most efficient parametrization, was tested alongside other profiles. The experimental results were in excellent agreement with simulation predictions, confirming the model’s accuracy. Additionally, the ability to guide experimental operation using simulation-based control profiles was demonstrated, highlighting the practical applicability of the proposed methods.
Impact of Process Parameters
A detailed regression analysis was conducted to evaluate the influence of seven key process parameters on both optimal and conventional operations. These parameters include product purity, product recovery, initial feed composition, number of trays, tray holdup, reflux drum holdup, and tray efficiency. The analysis revealed that the number of trays had the most significant impact on potential time savings, with higher tray counts enabling greater efficiency gains. Initial feed composition primarily influenced the duration of the optimal process, while reflux drum holdup had the most pronounced effect on conventional process duration. These insights provide a comprehensive understanding of the process dynamics and the factors that govern optimization potential.
Optimization Under Uncertainty
The final phase of the study addresses the challenge of optimizing the batch distillation process under uncertain conditions. In real-world operations, parameters such as feed composition, tray efficiency, and holdup volumes inevitably exhibit a degree of uncertainty. To account for this, two uncertainty-based optimization methods were developed, both leveraging Koopman expectation propagation to quantify the impact of parameter uncertainties.
1.
Direct iterative optimization
In this method, uncertainty propagation is performed within an inner optimization loop. The objective function and constraints are evaluated considering the distribution of uncertain parameters.
2.
Backoff–assisted iterative optimization
This method leverages uncertainty propagation to adjust the objective function, incorporating the impact of uncertainties directly into its formulation. This enables a deterministic optimization approach that remains robust under uncertain conditions.
Both methods were validated through Monte Carlo simulations, which confirmed their effectiveness in providing robust solutions under uncertainty. While both approaches yielded comparable results, the second method demonstrated superior computational efficiency
Utjecaj ventilacije na širenje aerosola u zatvorenim prostorima
No full textThe COVID-19 pandemic caused one of the most severe health, societal, and economic downturns in recent history, exposing significant vulnerabilities in society’s preparedness for such crises. Given that this pandemic is unlikely to be the last, with some researchers estimating a 40% chance of encountering another COVID-like pandemic within our lifetimes, addressing these vulnerabilities has become even more critical. A major route for the spread of many diseases is airborne transmission, where viruses and bacteria are carried by small (<5 μm) droplets of saliva. Due to their small size and light weight, these droplets are primarily affected by air drag rather than gravity, allowing them to remain suspended in the air and be carried by indoor airstreams. Building ventilation systems, which are designed to replace stale indoor air with fresh outdoor air and alter indoor airflow patterns, have become crucial in reducing the risk of airborne transmission. This increased focus on ventilation has led to a significant shift in public attention, making indoor air quality a primary concern in indoor environments, moving beyond the traditional focus on thermal comfort. As the pandemic progressed, leading organizations in the HVAC field, such as ASHRAE (American Society of Heating, Refrigerating, and Air-Conditioning Engineers) and REHVA (Federation of European Heating, Ventilation, and Air Conditioning Associations), issued guidelines on HVAC system operation and design to help reduce the spread of the virus. However, these guidelines often lacked empirical support and specific operational details, relying instead on broad recommendations such as increasing airflow, which may not always be optimal or efficient.
The existing scientific literature on the impact of ventilation systems on aerosol dispersion is characterized by significant ambiguities and contradictions. Many studies advocate for displacement ventilation over mixing systems, citing its advantages due to the thermally stratified environment it creates. Such environments facilitate upward buoyant flow, which helps remove contaminants and aerosols from the breathing zone and directs them towards the ceiling. However, other studies point out the drawbacks of displacement ventilation, particularly under certain environmental conditions, and argue for the benefits of mixing ventilation systems. A major issue in current literature is the heavy reliance on Computational Fluid Dynamics (CFD) simulations, which are often inadequately validated against experimental data. Many studies use limited datasets focusing narrowly on specific physical properties, failing to capture the full complexity of indoor environments and leaving critical questions about optimal ventilation strategies unresolved. This study aimed to address these limitations by integrating rigorous experimental methods with comprehensive CFD validation, ensuring robust findings supported by extensive and reliable simulation results.
Experiments were primarily focused on validating CFD simulations, which were subsequently used for extensive and time-efficient analyses due to the resource-intensive and time-consuming nature of physical experiments. These experiments were conducted in a specialized ventilation test room,
which was equipped with three fully independent ventilation systems: mixing ventilation, displacement ventilation from the walls, and displacement ventilation from the floor. To simulate human interaction with the surrounding air, simplified models designed as cylinders with hemispherical tops were employed. Each model, fitted with two 25 W lightbulbs to generate heat, effectively replicated the thermal effects of a human body on the surrounding air. The primary focus was on accurately simulating the thermal plume ‒ the buoyant air rise caused by the temperature difference between the human body and the surrounding air. Extensive analysis confirmed the accuracy of this approach, as velocity measurements above the models closely matched those observed for real human subjects. A total of four such models were used in the experiments. Exhaled aerosols were simulated using the tracer gas method, a well-established technique known for its simplicity and accuracy in aerosol dispersion studies. Carbon dioxide (CO₂) was chosen as the tracer gas in experiments, due to its non-toxic nature and availability. CO₂ was introduced into one model designated as the infected source. Concentrations and temperatures were measured at strategic locations to ensure that the data collected was suitable for comparison with CFD simulations. Two sets of experiments were conducted: one with mixing ventilation and another with displacement ventilation from the walls. CFD simulations identical to these processes were performed, and the results were compared with experimental data. The comparison revealed a high degree of similarity, with the normalized root mean square error being 11% for the mixing ventilation test and 10% for the displacement ventilation from the walls. These results validated the CFD models, establishing a firm foundation for trusting the numerical simulations as accurate representations of real-world conditions.
A comprehensive set of CFD simulations was then designed to analyze the impact of ventilation on aerosol dispersion in closed environments and to assess various influential parameters. A total of 24 simulations were conducted, covering all combinations of the key parameters: three types of ventilation systems (mixing, displacement from the walls, and displacement from the floor) and four airflow rates (0.5, 1, 2, and 4 air changes per hour) chosen to encompass those recommended by HVAC standards ASHRAE 62.1-2022 and EN 16798-1:2019. The simulations also considered two distinct occupancy patterns ‒ office and classroom ‒ which differ primarily in the occupancy density.
The results indicate that displacement ventilation from the floor consistently outperformed other ventilation types, regardless of the occupancy pattern. On average, the infection probability at breathing height for displacement ventilation from the floor was 10% lower compared to displacement ventilation from the walls and 21% lower compared to mixing ventilation. Although displacement ventilation systems demonstrated superior performance compared to mixing ventilation, they exhibited greater variability in infection probabilities throughout the breathing zone. In some instances, the localized infection risk was up to five times higher than the average, with these variations becoming more pronounced at higher airflow rates.
This highlights that, while displacement ventilation provides better protection on average, mixing ventilation still holds value. Specifically, mixing ventilation offers practical advantages in environments with unpredictable occupancy dynamics or frequent spatial changes. Furthermore, a transient analysis examined the scenario of an infected person leaving the room after an extended period. The results showed that displacement ventilation from the floor provides the shortest time before the room is safe to reenter, further demonstrating its superiority. These findings highlight the advantages of displacement ventilation from the floor across all types but also emphasize the importance of customized ventilation solutions. Instead of a one-size-fits-all approach, each system should be carefully tailored to the specific needs and conditions of the space.Pandemija COVID-19 uzrokovala je jednu od najvećih zdravstvenih, društvenih i ekonomskih kriza u novijoj povijesti, ukazujući na nespremnost društva da reagira na krizu takvih razmjera. S obzirom na to da pandemija COVID-19 nije posljednja te da neki istraživači procjenjuju 40% vjerojatnosti za pojavu još jedne pandemije sličnih razmjera za vrijeme naših života, od iznimne je važnosti pripremiti društvo za sljedeću pandemiju. Jedan od načina širenja zaraze je putem aerosola, sitnih kapljica sline (<5 μm) koje putuju zrakom i na taj način omogućuju širenje virusa i bakterija. Zbog svoje male veličine i mase, ove su kapljice pod većim utjecajem otpora zraka nego gravitacije, što im omogućuje da ostanu suspendirane i prenose se strujanjem zraka u prostoru. Ventilacija u zgradama, čija je uloga zamjena ustajalog unutarnjeg sa svježim vanjskim zrakom, pri čemu utječe na strujanje zraka u prostoru, postala je ključan čimbenik za smanjenje rizika od prijenosa zaraze aerosolom. Povećana svijest o važnosti ventilacije dovela je do toga da kvaliteta zraka u zatvorenim prostorima postane važnija od tradicionalnog fokusa na toplinsku udobnost. Tijekom pandemije, vodeće organizacije u području grijanja, ventilacije i klimatizacije (GViK), poput ASHRAE-a (American Society of Heating, Refrigerating, and Air-Conditioning Engineers) i REHVA-e (Federation of European Heating, Ventilation, and Air Conditioning Associations), izdale su smjernice za rad i projektiranje GViK sustava s ciljem smanjenja širenja virusa. Međutim, te su smjernice često bile preopćenite i temeljene na ograničenim dokazima, oslanjajući se na jednostavne preporuke poput povećanja protoka svježeg vanjskog zraka, a što nije uvijek optimalno niti energetski učinkovito.
Znanstvena literatura u ovom području ukazuje na značajne nejasnoće i kontradikcije. Mnoge studije zagovaraju potisnu ventilaciju koja stvara temperaturnu stratifikaciju zraka u prostoru, pri čemu je cilj uzlazno strujanje zraka u prostoru sa svrhom uklanjanja nečistoća iz zone udisaja ljudi. S druge strane, neka istraživanja ukazuju na ograničenja takvog pristupa u određenim uvjetima i predlažu miješajuću ventilaciju kao bolju opciju. Nadalje, jedan od glavnih nedostataka u literaturi je snažno oslanjanje na numeričke simulacije računalnom dinamikom fluida (eng. Computational Fluid Dynamics, CFD), koje često nisu dovoljno validirane eksperimentalnim mjerenjima. Primjerice, mnoge studije koriste ograničena eksperimentalna mjerenja koja su fokusirana na specifična fizikalna svojstva, ne obuhvaćajući složenost strujanja zraka u prostor. To dovodi do netočnih rezultata istraživanja i nejasnoća oko optimalnih strategija ventilacije. Ovo istraživanje nastoji unaprijediti znanje u ovom području kombiniranjem opsežnih eksperimentalnih mjerenja i CFD simulacija, s naglaskom na validaciju i osiguravanje pouzdanih i točnih rezultata.
Eksperimenti su prvenstveno bili usmjereni na validaciju CFD simulacija, koje su potom korištene za opsežne i vremenski učinkovite analize, uzimajući u obzir dugotrajnost i kompleksnost provođenja eksperimenata. Eksperimenti su provedeni u posebno opremljenoj prostoriji s tri neovisna ventilacijska sustava: miješajuća ventilacija, potisna ventilacija iz zida i potisna ventilacija iz poda.
Kako bi se utjecaj čovjeka na okolni zrak točno simulirao, korišteni su pojednostavljeni modeli u obliku cilindara s polusferom na vrhu. Svaki je model bio opremljen s dvije žarulje od 25 W s ciljem generiranja topline sličnoj toplini koju generira ljudsko tijelo i time utječe na strujanje zraka u neposrednoj blizini. Posebna je pažnja usmjerena na točno simuliranje uzgonskog kretanja zraka iznad čovjeka – posljedica temperaturne razlike između ljudskog tijela i zraka u prostoriji. Detaljna analiza potvrdila je točnost ovog modela čovjeka, a što je potvrđeno mjerenjem brzine zraka iznad modela koje su bile vrlo slične onima zabilježenima iznad stvarnih ljudi. U eksperimentima su korištena ukupno četiri takva modela čovjeka. Širenje aerosola je simulirano metodom plina za praćenje – dobro poznatom tehnikom u ovom području koja se ističe jednostavnošću i točnošću. Specifično, korišten je ugljikov dioksid (CO₂) zbog svoje netoksičnosti i dostupnosti. CO₂ je ispuštan iz jednog od modela čovjeka, odabranog kako bi predstavljao zaraženu osobu. Na odabranim mjestima u prostoru mjerena je koncentracija CO2 i temperatura, a ta su mjerenja poslužila za usporedbu s rezultatima CFD simulacija. Provedena su eksperimentalna mjerenja korištenjem miješajuće ventilacije i potisne ventilacije iz zida. Usporedba s CFD rezultatima pokazala je visok stupanj podudarnosti (normalizirana srednja kvadratna pogreška od 11% za slučaj gdje se koristila miješajuća ventilacija i 10% za slučaj gdje se koristila potisna ventilacija sa zida).
Nakon validacije s eksperimentalnim mjerenjima, provedene su 24 CFD simulacije koje su analizirale utjecaj ventilacije na širenje aerosola u zatvorenim prostorima, uzimajući u obzir tri tipa ventilacijskih sustava (miješajuća, potisna iz zida i potisna s poda) i četiri različita protoka svježeg vanjskog zraka (0.5, 1, 2 i 4 izmjene zraka na sat). Ovi su specifični iznosi odabrani kako bi pokrili vrijednosti preporučene od strane relevantnih normi u ovom području – ASHRAE 62.1-2022 i EN 16798-1:2019. U simulacijama su analizirana dva scenarija korištenja prostora ‒ ured i učionica, a koji su se značajno razlikovali po broju ljudi koji borave u tim prostorima.
Rezultati simulacija pokazali su da je rizik od zaraze putem aerosola najmanji za slučaj potisne ventilacije s poda, neovisno o načinu korištenja prostora. Vjerojatnost zaraze na visini zone udisaja bila je u prosjeku 10% niža u odnosu na potisnu ventilaciju iz zida te 21% niža u odnosu na miješajuću ventilaciju. Međutim, iako je u prosjeku vjerojatnost zaraze putem aerosola manja za slučaj potisne ventilacija u odnosu na miješajuću, potisna je ventilacija uzrokovala značajnije varijacije unutar zone udisaja. Varijabilnost u rezultatima bila je značajnija za slučajeve s većom količinom svježeg zraka koja se ubacivala u prostor, pri čemu je u nekim simuliranim slučajevima korištenjem potisne ventilacije vjerojatnost zaraze bila i do 5 puta veća od prosječne.
Ovi rezultati pokazuju da, iako potisna ventilacija u prosjeku osigurava manji rizik od zaraze putem aerosola, miješajuća ventilacija svejedno ima neke prednosti. Miješajuća ventilacija nudi praktične prednosti u slučajevima gdje je teško predvidjeti raspored ljudi u prostoru ili u prostorima s učestalim premještanjem ljudi. Nadalje, tranzijentnim je simulacijama analiziran scenarij gdje zaražena
osoba napusti prostor nakon određenog perioda boravka u njemu. Rezultati su pokazali da je vrijeme koje je potrebno da se rizik od zaraze putem aerosola u toj prostoriji minimizira najkraće za slučaj korištenja potisne ventilacije iz poda, dodatno pokazujući prednost ovog sustava u odnosu na ostale tipove ventilacije. Konačno, rezultati potvrđuju prednosti potisne ventilacije iz poda u odnosu na druge tipove ventilacije, ali također naglašavaju važnost prilagođavanja ventilacijskih sustava za svaki specifični slučaj. Umjesto definiranja jedinstveno optimalnog rješenja za sve slučajeve, potrebno je pristupiti pažljivo svakom slučaju i prilagoditi ventilacijski sustav specifičnim potrebama i uvjetima prostora
THE ROLE OF NEURONS AND GLIAL CELLS IN PRODUCTIVE AND LATENT CYTOMEGALOVIRUS INFECTION
No full textCilj istraživanja: Humani citomegalovirus (HCMV) je vodeći uzročnik prirođenih virusnih infekcija koji često uzrokuje trajna oštećenja živčanog sustava u djece. Tipovi stanica i mehanizmi uključeni u uspostavljanje cjeloživotne latencije citomegalovirusa (CMV) u mozgu još uvijek su nepoznati. Glavni cilj ovog istraživanja je razjasniti diseminaciju virusa i stanični tropizam, te imunološke mehanizme koji nadziru infekciju i uspostavljanje latencije CMV-a u mozgu. Materijali i metode: U ovom istraživanju koristili smo mišji model prirođene CMV infekcije, u kojem su novookoćeni miševi inficirani mišjim citomegalovirusom (MCMV). Kako bismo izučavali biologiju infekcije MCMV-om u mozgu, koristili smo rekombinantne reporterske viruse i transgenične miševe koji ispoljavaju rekombinazu Cre ili im nedostaju ključni elementi efektorskih funkcija limfocita T. Tropizam, anatomska lokacija i reaktivacija virusa određeni su imunohistokemijskim metodama. Kako bismo testirali ulogu imunoloških medijatora u sprečavanju infekcije neurona HCMV-om, koristili smo staničnu liniju humanog neuroblastoma SH-SY5Y i organotipsku kulturu tkiva ljudskog fetalnog mozga (hfOBSC). Rezultati: Pokazali smo da je tijekom akutne faze infekcije u novookoćenih miševa hipokampus glavno mjesto produktivne infekcije MCMV-om. Infektivni virus prvo su proizveli astrociti, zatim mikroglije i konačno neuroni, koji su bili glavna mjesta replikacije virusa tijekom kasne faze akutne infekcije. Pokazali smo da su CD4+ limfociti T i citokin IFN-γ potrebni za razrješenje produktivne infekcije u neuronima. Citokin IFN-γ također može spriječiti infekciju stanica SH SY5Y i neurona u hfOBSC HCMV-om. Konačno, pokazali smo da MCMV uspostavlja latenciju u neuronima i da su CD4+ limfociti T ključni za sprječavanje reaktivacije virusa iz neurona. Zaključak: Rezultati ovog istraživanja po prvi put pokazuju da CMV uspostavlja latenciju u neuronima, te da su CD4+ limfociti T i citokin IFN-γ ključni za nadzor produktivne i latentne infekcije u neuronima. Ova studija ima važan translacijski potencijal s obzirom da ukazuje na to da bi poticanje odgovora posredovanog CD4+ limfocitima T moglo spriječiti neurološke posljedice uzrokovane prirođenom CMV infekcijom.Objectives: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infections, frequently accompanied with long-term neurological sequelae in children. The cell types and mechanisms involved in establishing lifelong CMV latency in the brain, from which the virus reactivates intermittently, remain enigmatic. This research aims to elucidate viral dissemination and cell tropism, immune mechanisms controlling the infection, and the establishment of MCMV latency in the brain. Materials and methods: In this research, we used mouse model of congenital CMVinfection, in which newborn mice are infected with MCMV postnatally. To study the biology of MCMV infection in the brain, we utilized recombinant reporter viruses and transgenic mouse lines that express Cre recombinase or lack critical elements of T-cell effector functions. Viral tropism, anatomical location, and reactivation were determined with immunohistochemical methods. We employed human cell line SH-SY5Y and human fetal organotypic brain slices cultures (hfOBSCs) to test the role of immune mechanisms in preventing HCMV infection of neurons. Results: We found that the hippocampus is a major site of productive MCMV infection during the acute phase in newborn mice. Infectious virus was first produced by astrocytes, then microglia, and finally by neurons, which were the major sites of viral replication during the late phase of infection. CD4+ T-cells and IFN-γ were pivotal in resolving a productive infection in neurons. IFN-γ can also suppress HCMV infection of SH-SY5Y cell line and neurons in hfOBSCs. Finally, we show that MCMV establishes latency in neurons and that CD4+ T-cells are crucial to prevent virus reactivation. Conclusion: This research shows for the first time that neuron-restricted cytomegalovirus latency in the central nervous system is regulated by CD4+ T cells and IFN-γ. This study has important translational potential as it demonstrates that boosting CD4+ T-cell-mediated immunity could prevent neurological sequelae following congenital CMV infection