Plasma applications in medicine and dentistry

U fizici, plazma je ioniziran, kvazineutralan plin za koji se često kaže da je četvrto stanje materije. Dugo vremena se plazma u medicini koristila zbog svojih termalnih svojstava, primjerice za sterilizaciju kirurškog i medicinskog pribora te za rezanje i kauterizaciju tkiva. Generiranjem hladne plazme u atmosferskim uvjetima započelo je novo razdoblje u primjeni plazme u biomedicini. Plazma medicina novo je interdisciplinarno znanstveno područje koje kombinira spoznaje fizike plazme s biomedicinskim i kliničkim znanostima. Hladna atmosferska plazma emitira elektromagnetno zračenje te se sastoji od mnoštva nabijenih i nenabijenih čestica, među kojima su najznačajnije reaktivne kisikove i dušikove vrste. Smatra se da su upravo reaktivne kisikove vrste najvažnije za biološke učinke plazme kao što su inaktivacija mikroorganizama i biofilmova. U dermatologiji se pokazalo da hladna atmosferska plazma pozitivno utječe na zacjeljivanje kroničnih rana. Prvi instrumenti za primjenu hladne plazme na ljudima već su i komercijalno dostupni. Primjena hladne plazme ima velik potencijal za primjenu u onkologiji, ali i u stomatologiji. Mnogobrojne studije dale su vrlo obećavajuće rezultate za primjenu hladne plazme u medicini, no treba imati na umu da mehanizmi međudjelovanja plazme s biološkim tkivom još uvijek nisu u potpunosti razjašnjeni, da nema dogovorom prihvaćene definicije doze koju plazma predaje materiji, da još uvijek nema standardiziranih instrumenata za generiranje i karakterizaciju plazme te da za pravu procjenu potencijala primjene atmosferske plazme u medicini i stomatologiji nedostaje više detaljnih in vivo studija.Physical plasma is an ionized, quasi-neutral gas. It is often said to be the fourth state of matter. For a long time, plasma was used in medicine exclusively because of its thermal properties for sterilization purposes of surgical equipment and medical supplies, and also to cut and cauterize tissue. The possibility to generate cold plasma in atmospheric conditions marked the beginning of a completely new era in the application of plasma in biomedicine. Plasma medicine is a new interdisciplinary field of science that combines the knowledge of plasma physics to biomedical and clinical sciences. Cold atmospheric plasma emits electromagnetic radiation and it consists out of charged and uncharged particles, among those reactive oxygen and nitrogen species are the most important ones. It is considered that reactive oxygen species cause the most important biological plasma effects, such as inactivation of microorganisms and biofilms. It has been shown in dermatology that cold atmospheric plasma has a healing effect on chronic wounds. First instruments for the application of cold plasma in humans are already commercially available. Cold plasma has a great potential for application in oncology and in dentistry. Numerous studies have yielded very promising results for the application of cold plasma in medicine, but it should be kept in mind that the mechanisms of interaction between plasma and biological tissue are still not fully understood. There is no agreement on the accepted plasma dosages and there are still no standardized instruments for the generation and characterization of plasma. And lastly, for a comprehensive assessment of the potential application of atmospheric plasma in medicine and dentistry we lack more detailed in vivo studies

Characterization of a karst aquifer based on the spatial and temporal variations of hydrogen and oxygen stable isotopes

Kako bi se okarakterizirao krški vodonosnik provedeno je istraživanje izotopnog sastava vode izvora uključenih u vodoopskrbni sustav grada Rijeke i okolice te izotopnog sastava oborine na pretpostavljenom području prihranjivanja. Mjerenje δ2H i δ18O vrijednosti vode obavljeno je u Laboratoriju za stabilne izotope Zavoda za fiziku Medicinskog fakulteta Sveučilišta u Rijeci. Za mjerenje je korišten maseni spektrometar izotopnih omjera IRMS DeltaplusXP u sprezi s ekvilibratorskom jedinicom i jedinicom dvostrukog ulaza. Na vremenske nizove δ18O vrijednosti primijenjene su statističke metode modeliranja: određivanje gustoća vjerojatnosti modeliranjem Gaussove mješavine, analiza autokorelacijske i kroskorelacijske funkcije te ARIMA modeliranje. Navedene statističke metode do sada nisu bile primijenjene na δ18O vrijednosti voda u krškim sustavima. Utvrđeno je da je voda na izvorima oborinskog podrijetla te da se vodonosnici primarno prihranjuju zimskom oborinom. Vremenske promjene δ18O vrijednosti pokazuju različite stupnjeve okršenosti zaleđa izvora. Voda na izvorištima se prema izotopnom sastavu može razdvojiti na vodu baznog toka i brzu komponentu kojoj doprinosi novoinfiltrirana oborinska voda. Komponenta baznog toka je dominantna kod svih ispitivanih izvora i bunara, a njen izotopni sastav ukazuje na to da izvori pojedinih slivova dijele zajedničke vodne zalihe. Rezultati provedenog istraživanja važni su za uvođenje metode dvostruko obilježene vode u medicinsku praksu jer uočene promjene izotopnog sastava pitke vode mogu utjecati na promjenu bazne razine izotopa kod ispitanika.Due to karst hydrological systems’ heterogeneity and complexity, its investigation is quite demanding. Use of artificial tracers on karst terrains provides an insight into the functioning of short groundwater channels, while environmental tracers enable the analysis of different karst subsystems. Stable isotopes of water are perfect environmental tracers and they serve as water molecule tracers through the hydrological cycle. There are three stable isotopes of oxygen (16O, 17O and 18O) and two stable isotopes of hydrogen (1H and 2H), that form nine possible configurations of stable water molecules. Stable isotope composition of water is expressed in terms of δ-values (δ2H, δ18O) that represent a relative difference between ratios of less abundant and predominant isotopes in a sample and in an internationally accepted standard: δ (‰)=(Rsample/Rstandard)-1. Construction of Local Meteoric Water Line (LMWL, the linear regression line for δ2H and δ18O in precipitation of certain area) and its comparison to the Global Meteoric Water Line (GMWL, δ2H=8∙δ18O+10 ‰), as well as an analysis of deuterium excess (d-excess= δ2H-8∙δ18O) are essential parts of one of the main isotope hydrology applications that is identification of a groundwater origin. The differences in slope and intercept between the GMWL and the LMWL are the consequences of climate conditions and geographical parameter variations. Stable isotopes of water have been applied in investigations of karst aquifers to understand recharge processes, reservoir mixings, to determine mean recharge area elevations, for identification of water sources in karst springs, etc

Incremental cost-effectiveness pharmacoeconomic assessment of hepatitis C virus therapy: an approach for less wealthy members of the common market

Aim To develop a new method of health-economic analysis based on a marginal approach. Methods We tested the research hypothesis that a detailed comparative a priori incremental cost-effectiveness analysis provides the necessary input for budget impact analysis about the proper order of introduction of new therapies, and thus maximizes the cost-effectiveness bounded by the total budget constraint. For the analysis we chose a combination therapy for the treatment of hepatitis C virus (HCV) genotype 1 (GT1) infection, which was approved by the European Medicine Agency in 2015. We used the incremental cost-effective approach to assess the increase in the percentage of patients achieving sustained virological response (SVR) and the expenditure per additional SVR modulated by the new therapy’s market entrance dynamics. Patient subpopulations were differentiated by their response to previous treatment, presence of cirrhosis, and HCV GT1 subtype. Final parameters were estimated by Monte Carlo simulations. Results The new combination therapy had high efficacy, shorter duration, and was better tolerated than alternative interventions. The research hypothesis was confirmed: gradual introduction of the new therapy on the market, based on a priori incremental cost-effectiveness analysis, would result in average increase in successfully treated patients by 20%-40%, while additional costs would approximately be between 8%-40%, ie, €21 000-52 000 per additional patient achieving SVR. Conclusion We showed the new combination therapy to be cost-effective for certain patient subpopulations, especially for experienced cirrhotic HCV GT1 patients. Results of the analysis are in agreement with the latest recommendations for HCV patients’ treatment in Croatia. This economic evaluation could serve as a starting point for negotiations between pharmaceutical industry and insurance companies

Marine Pollution Differentiation with Stable Isotopes of Groundwater

Stock and flow pollution differentiation is the basis for efficient pollution-abatement mechanism designs. The focus of our research has been marine pollution from land-based sources. Stable isotope analysis of groundwater is an acknowledged method for karst aquifer characterisation. We have tested whether stable isotopes of water, when used as a proxy for groundwater dynamics in the karst, could also be used as an indicator of marine pollution differentiation in terms of flow and stock pollution. The focus has been on two close coastal locations characterized by differences in terms of open and closed sea as well as anthropogenic pressure. A static Estimated General Least Squares (EGLS) statistical model described the closed bay location suggesting stock pollution. For a good description of the open sea location, we have had to resort to dynamic Generalised Method of Moments (GMM) statistical modelling, indicating flow pollution. Stable isotopes of groundwater together with appropriate statistical tools have proved to be a useful tool of marine pollution differentiation into stock or flow

Marine Pollution Differentiation with Stable Isotopes of Groundwater

Stock and flow pollution differentiation is the basis for efficient pollution-abatement mechanism designs. The focus of our research has been marine pollution from land-based sources. Stable isotope analysis of groundwater is an acknowledged method for karst aquifer characterisation. We have tested whether stable isotopes of water, when used as a proxy for groundwater dynamics in the karst, could also be used as an indicator of marine pollution differentiation in terms of flow and stock pollution. The focus has been on two close coastal locations characterized by differences in terms of open and closed sea as well as anthropogenic pressure. A static Estimated General Least Squares (EGLS) statistical model described the closed bay location suggesting stock pollution. For a good description of the open sea location, we have had to resort to dynamic Generalised Method of Moments (GMM) statistical modelling, indicating flow pollution. Stable isotopes of groundwater together with appropriate statistical tools have proved to be a useful tool of marine pollution differentiation into stock or flow

Marine Pollution Differentiation with Stable Isotopes of Groundwater

Stock and flow pollution differentiation is the basis for efficient pollution-abatement mechanism designs. The focus of our research has been marine pollution from land-based sources. Stable isotope analysis of groundwater is an acknowledged method for karst aquifer characterisation. We have tested whether stable isotopes of water, when used as a proxy for groundwater dynamics in the karst, could also be used as an indicator of marine pollution differentiation in terms of flow and stock pollution. The focus has been on two close coastal locations characterized by differences in terms of open and closed sea as well as anthropogenic pressure. A static Estimated General Least Squares (EGLS) statistical model described the closed bay location suggesting stock pollution. For a good description of the open sea location, we have had to resort to dynamic Generalised Method of Moments (GMM) statistical modelling, indicating flow pollution. Stable isotopes of groundwater together with appropriate statistical tools have proved to be a useful tool of marine pollution differentiation into stock or flow

Marine Pollution Differentiation with Stable Isotopes of Groundwater

Stock and flow pollution differentiation is the basis for efficient pollution-abatement mechanism designs. The focus of our research has been marine pollution from land-based sources. Stable isotope analysis of groundwater is an acknowledged method for karst aquifer characterisation. We have tested whether stable isotopes of water, when used as a proxy for groundwater dynamics in the karst, could also be used as an indicator of marine pollution differentiation in terms of flow and stock pollution. The focus has been on two close coastal locations characterized by differences in terms of open and closed sea as well as anthropogenic pressure. A static Estimated General Least Squares (EGLS) statistical model described the closed bay location suggesting stock pollution. For a good description of the open sea location, we have had to resort to dynamic Generalised Method of Moments (GMM) statistical modelling, indicating flow pollution. Stable isotopes of groundwater together with appropriate statistical tools have proved to be a useful tool of marine pollution differentiation into stock or flow

Okolišni izotop (^18 O) u vodi priobalnih krških izvora kao moguća prediktorska varijabla mikrobiološkog onečišćenja mora

We tested the validity of the traditional hypothesis of a causal effect between rainfall occurrence, groundwater discharging into the sea, and marine microbial contamination. For groundwater characterization, we used the (^18 O) isotope. This stable isotope, together with 2 H, proved to be a useful physical, naturally occurring tracer primarily due to its abundance variations at different stages of water cycle. Test locations include Bakar Bay and selected adjacent Rijeka city beaches (Croatia). To test for statistical associations, we used the Panel Data Pairwise Granger Causality test. At examined locations, we found statistically significant relationships between the amount of rainfall and the abundance of (^18 O) isotope in groundwater, as well as relationships between the abundance of (^18 O) isotope in groundwater and faecal bacteria concentrations. Accordingly, (^18 O) isotope, when used as an indicator for the functioning of karstic groundwater systems, may also be used as the predictor of faecal contamination of bathing waters in associated karst littoral areas. We believe this physical method could be a valuable addition to present methods of predicting microbiological contamination and economic allocation of stock and flow pollutants in scarce common pool resources as fresh water basins, springs and beaches.Testirali smo hipotezu o statističkoj povezanosti između kiše, podzemnih voda koje utječu u more i mikrobiološkog onečišćenja mora. Kao varijablu koja opisuje podzemne vode odabrali smo stabilni izotop (^18 O). Stabilni izotop (^18 O) vode je okolišni obilježivač koji se često korisiti u hidrologiji, osobito u krškim područjima kakav je obalni pojas Jadranskog mora. Testiranje je provedeno na lokacijama u Bakarskom zaljevu i odabranim plažama u gradu Rijeci. Panel analizom “Granger kauzalnosti” utvrdili smo postojanje statistički značajne povezanosti između količine oborina i izdašnosti (^18 O) izotopa u podzemnim vodama, kao i statistički značajnu povezanost između izdašnosti (^18 O) u podzemnim vodama i koncentracije fekalnih bakterija u moru. U skladu s dobivenim rezultatima možemo zaključti da se stabilni izotop (^18 O), u slučaju kada se koristi kao obilježivač za proučavanje krških podzemnih voda, također može koristiti i kao prediktorska varijabla fekalnog onečišćenja mora u koje se te podzemne vode ulijevaju. Pretpostavljamo da bi ova fizikalna metoda mogla biti vrijedan dodatak metodama predviđanja mikrobioloških zagađenja i ekonomske alokacije oskudnih zaliha zajedničkih prirodnih resursa kao što su vodonosnici, izvori pitke vode i plaže

Northern Velebit (Croatia) karst hydrological system: results of a preliminary 2H and 18O stable isotope study

Researching the hydrogeological properties of karst systems is very challenging due to their extreme heterogeneity. A grey-box approach in karst research combines the results from classical hydrogeological methods with direct observations within the karstic underground, i.e. in the caves. Isotope research has become a widely used method in the investigation of karst systems. The results presented are of a preliminary 2H and 18O stable isotope study of the Northern Velebit karst system (Croatia) employing the grey-box approach. Groundwater samples were collected during two summer expeditions in deep caves within the karst massif. Monthly precipitation samples were also collected (at three locations between approx. 900 m and 1600 m altitude), as well as water samples at some of the most significant springs, i.e. discharge outlets of the system. For a single expedition, the stable isotope composition is almost constant, i.e. the stable isotope measurements are within the measurement error across the complete cave profile. Similar characteristics across different caves during the same year were also noted. Samples of water from the springs were taken during base-flow conditions and they have similar isotopic contents to the cave water. The results obtained indicate that homogenization of the water already occurs within the subsurface epikarst zone above the sampling locations in the caves, but a future extended sampling campaign during variable hydrologic conditions is needed to confirm this. The final research goal is to establish a conceptual grey-box model for the functioning of this complex hydrogeological system.</p

Isotope Studies of Karst Springs Included in the Water Supply System of the City of Rijeka (Croatia)

Aim: To inform about the results of isotopic analyses of karstic springs, Rječina Spring and Zvir, that ensure potable water for more than 200,000 people in Rijeka County (Croatia) Methods: Specific activities of selected radionuclides were determined by high resolution gamma spectrometric analysis and radiochemical separation method. Values of hydrogen and stable isotope contents were determined by water equilibration method on isotope ratio mass spectrometer in conjunction with dual inlet and equilibration peripheral unit. Results: Anthropogenic radionuclides were detected in trace amounts. The results of the analysis show that the calculated yearly dose introduced to an adult human consuming 2 liters of water per day is approximately 20 mSv. Stable isotopes content of the spring waters indicate a dominant recharge of the analyzed hydrological system by winter precipitation. Different isotopic variations of spring water as a consequence of sudden precipitation inputs in summer and autumn indicate that water discharged at Rječina Spring mainly originates from a big water reservoir situated in the wide mountain region in the hinterland of the spring. Conclusion: The examined water is potable and radiologically safe. Stable isotope variations of the spring water show a fast reaction to sudden precipitation inputs, confirming the ecological vulnerability of karstic springs. In light of recent heavy precipitation and flooding in different parts of Croatia, a more systematic research on isotopic water composition should be encouraged