643 research outputs found
Vstopanje Slovenije v EU in trajnostni razvoj
Osnovna tema prispevka je vpraÅ”anje, ali vstopanje v Evropsko unijo že samo posebi zagotavlja uveljavljanje trajnostnega razvoja. V prvem delu ugotavljam,da približevanje Slovenije Evropski uniji samo po sebi Å”e ne zagotavlja tudi uveljavljanja razvoja v skladu z naÄeli trajnosti. V nadaljevanju to ugovotitev nekoliko relativiziram z navajanjem dejstev. ki kažejo na to, da uveljavljanje pravnega reda EU odpralja nekatere slabosti dosedanje okoljske politike. Prav te spremembe, skupaj z dobrim izhodiÅ”Änim stanjem okolja ter že sprejeto Strategijo gospodarskega razvooja, vidim kot priložnost, da se priÄakovani hitrejÅ”i razvoj po vstopu v EU izkoristi tudi za uveljavljanje trajnostnega razvoja
ToksikoloŔke lastnosti kanabinoidov
Cannabis sativa L. contains more than 100 phytocannabinoids that can interact with cannabinoid receptors CB1 and CB2. None of the cannabinoid receptor ligands is entirely CB1- or CB2-specific. The effects of cannabinoids therefore differ not just because of different potency at cannabinoid receptors but also because they can interact with other non-CB1 and non-CB2 targets, such as TRPV1, GPR55, and GPR119. The most studied phytocannabinoid is Ī9-tetrahydrocannabinol (THC). THC is a partial agonist at both cannabinoid receptors, but its psychotomimetic effect is produced primarily via activation of the CB1 receptor, which is strongly expressed in the central nervous system, with the noteworthy exception of the brain stem. Although acute cognitive and other effects of THC are well known, the risk of irreversible neuropsychological effects of THC needs further research to elucidate the association. Unlike THC, phytocannabinoid cannabidiol (CBD) does not appear to have psychotomimetic effects but may interact with some of the effects of THC if taken concomitantly. CBD administered orally has recently undergone well-controlled clinical trials to assess its safety in the treatment of paediatric epilepsy syndromes. Their findings point to increased transaminase levels as a safety issue that calls for postmarketing surveillance for liver toxicity. The aim of this review is to summarise what is known about acute and chronic toxicological effects of both compounds and address the gaps in knowledge about the safety of exogenous cannabinoids that are still open.Iz rastline Cannabis sativa L. so do sedaj izolirali že veÄ kot 100 fitokanabinoidov, poleg njih pa obstaja veÄ kot 550 sintetiÄnih spojin, ki delujejo na kanabinoidne receptorje CB1 in CB2. Prav tako je treba omeniti, da nobeden od ligandov kanabinoidnih receptorjev ni popolnoma CB1- ali CB2-specifiÄen. Zato se uÄinki vsakega od njih razlikujejo ne le zaradi razliÄne moÄi na kanabinoidnih receptorjih, ampak tudi zato, ker lahko delujejo na druga ne-CB1 in ne-CB2 prijemaliÅ”Äa. Najpogosteje prouÄevani kanabinoid je Ī9-tetrahidrokanabinol (THC). THC je delni agonist na obeh kanabinoidnih receptorjih, vendar je njegov psihoaktivni uÄinek povezan predvsem z aktivacijo receptorjev CB1. Receptor CB1 je eden izmed metabotropnih receptorjev z najveÄjo ekspresijo v osrednjem živÄevju, z izjemo možganskega debla. Äeprav so akutni uÄinki na osrednji živÄni sistem THC jasno opredeljeni, je tveganje za ireverzibilne nevropsiholoÅ”ke uÄinke THC kot neodvisnega dejavnika potrebno nadalje raziskati za pojasnitev povezave. Za razliko od THC, fitokanabinoid kanabidiol (CBD) nima psihoaktivnih uÄinkov, vendar lahko pri soÄasni uporabi vpliva na nekatere uÄinke THC. CBD, ki nima pomembne afinitete za CB1 in CB2, aktivira ali zavira Å”tevilne uveljavljene in domnevne farmakoloÅ”ke tarÄe. CBD je kot aktivna snov v zdravilu EpidiolexĀ® pred kratkim opravil nadzorovana kliniÄna preskuÅ”anja, da so ocenili njegovo varnost pri zdravljenju redkih epileptiÄnih sindromov pri otrocih. NajveÄjo zaskrbljenost glede varnosti so predstavljale poviÅ”ane vrednosti transaminaz. Zato je treba izvesti postmarketinÅ”ki nadzor toksiÄnosti za jetra. Älanek bo povzel kar je znano o akutnih in kroniÄnih toksikoloÅ”kih uÄinkih, katere Å”tudije Å”e manjkajo in kaj so negotovosti v zvezi z varnostjo eksogenih kanabinoidov
MATHEMATICAL MODELING OF MOLECULAR TRANSMEMBRANE TRANSPORT AND CHANGES OF TISSUESĀ“ DIELECTRIC PROPERTIES DUE TO ELECTROPORATION
Visokonapetostni elektriÄni pulzi poveÄajo prepustnost celiÄne membrane (Tsong 1991Weaver 1993Kotnik et al. 2012) skozi pore (Abidor et al. 1979), ki nastanejo na tistih njenih delih, kjer vsiljena
transmembranska napetost preseže kritiÄno vrednost (Towhidi et al. 2008Kotnik et al. 2010).
Elektroporacija je reverzibilna, Äe si celica po pulzih opomore, in ireverzibilna, Äe je Å”koda preobsežna in
celica odmre (Pakhomova et al. 2013bJiang et al. 2015a). Trenutne optiÄne metode por ne morejo zaznati,
zato njihov nastanek zaznavamo posredno, bodisi z meritvami vnosa razliÄnih molekul v celice ali z
meritvami elektriÄnih lastnosti celic (Napotnik in MiklavÄiÄ 2017).
Uporaba elektroporacije
V živilski industriji (Toepfl 2012Toepfl et al. 2014) uporabljamo elektroporacijo oziroma pulzirajoÄa
elektriÄna polja (angl. pulsed electric fields), kar je uveljavljen izraz v tej industriji, za uniÄevanje patogenih
organizmov in njihovih produktov (encimov in toksinov). V nasprotju s termiÄno obdelavo hrane elektriÄni
pulzi ne vplivajo na okus, barvo ali hranilno vrednost. V biotehnologiji uporabljamo elektroporacijo za
ekstrakcijo molekul iz mikroorganizmov in rastlin, s Äimer se izognemo uporabi kemiÄnih sredstev in ne
uniÄimo celiÄnih organelov, torej se izognemo tudi dodatnemu ÄiÅ”Äenju konÄnega produkta (Sack et al.
2010Haberl et al. 2013aMahniÄ-Kalamiza et al. 2014bKotnik et al. 2015). Primeri: ekstrakcija DNK iz
bakterijsladkorja iz sladkorne pese (Haberl et al. 2013b), sokov iz sadjapolifenolov iz grozdja za
izboljÅ”anje kvalitete vina (PuĆ©rtolas et al. 2010)vode pri suÅ”enju zelene biomase, ki služi kot vir za
biogorivo (Golberg et al. 2016). Elektroporacija je tudi nova metoda pri zamrzovanju celic in tkiv, angl.
cryopreservation (Galindo in Dymek 2016Dovgan et al. 2017).
Elektroporacijo uporabljamo tudi v medicini (MiklavÄiÄ et al. 2010Yarmush et al. 2014), in sicer pri
elektrokemoterapiji (MiklavÄiÄ et al. 2012Mali et al. 2013Cadossi et al. 2014MiklavÄiÄ et al. 2014Campana et al. 2014SerÅ”a et al. 2015), netermiÄnem odstranjevanju tkiva z ireverzibilno elektroporacijo
(Davalos et al. 2005Garcia et al. 2010JosƩ et al. 2012Cannon et al. 2013Scheffer et al. 2014bJiang et
al. 2015aRossmeisl et al. 2015), genski terapiji (Golzio et al. 2002Vasan et al. 2011Gothelf in Gehl
2012Calvet et al. 2014Heller in Heller 2015Trimble et al. 2015) in vnosu uÄinkovin v kožo in skoznjo
(Denet et al. 2004Zorec et al. 2013b). Pri genski terapiji vnesemo v celice plazmide, v katerih je zapisana
sinteza doloÄenega proteina, ki lahko spremeni bioloÅ”ko funkcijo celice (Aihara in Miyazaki 1998Heller in
Heller 2015). Z elektroporacijo poviŔamo varnost genske terapije, saj se izognemo uporabi virusov in
kemikalij. Mehanizmi genske terapije z elektroporacijo Ŕe niso popolnoma pojasnjeni, osnovni koraki so
opisani v literaturi (Rosazza et al. 2016). Z elektroporacijo lahko zlivamo razliÄne celice, s Äimer
pridobivamo celice, ki proizvajajo monoklonska protitelesa ali inzulin (Ramos in TeissiƩ 2000Trontelj et
al. 2008Rems et al. 2013).
V doktorski disertaciji sem se osredotoÄila na uporabo elektroporacije v medicini, predvsem pri
elektrokemoterapiji, netermiÄnem odstranjevanju tkiva z ireverzibilno elektroporacijo in pri vnosu
uÄinkovin v kožo in skoznjo je, zato so ti trije posegi podrobneje opisani v naslednjem poglavju.
Medicinski posegi z elektroporacijo ā elektrokemoterapija, netermiÄno odstranjevanje tkiva z
ireverzibilno elektroporacijo in vnos uÄinkovin v kožo in skoznjo
Elektrokemoterapija je kombinacija kemoterapije in elektriÄnih pulzov, dovedenih neposredno na tarÄno
tkivo. ElektriÄni pulzi poveÄajo prepustnost celiÄne membrane za kemoterapevtike, zato poveÄamo
uÄinkovitost zdravljenja, obenem pa zmanjÅ”amo dovedeno dozo kemoterapevtika in omilimo stranske
uÄinke. Celoten tumor mora biti pokrit z dovolj visokim elektriÄnim poljem, da poveÄamo prepustnost vseh
tumorskih celic (MiklavÄiÄ et al. 2006a), zagotoviti pa moramo tudi dovolj visoko koncentracijo
kemoterapevtika znotraj tumorja (MiklavÄiÄ et al. 2014). OkoliÅ”ko tkivo ne sme biti uniÄeno, torej mora biti
elektriÄno polje okoli tumorja pod mejo za ireverzibilno elektroporacijo. Pri elektrokemoterapiji obiÄajno
dovajamo osem pulzov dolžine 100 Ī¼s s ponavljalno frekvenco 1 Hz. S poskusi doloÄena meja za poviÅ”anje
prepustnosti tumorskega tkiva je 0,4 kV/cm (MiklavÄiÄ et al. 2010). Osem pulzov je bilo doloÄenih kot
optimalno Å”tevilo pulzov (Marty et al. 2006Mir et al. 2006), veÄje Å”tevilo dovedenih pulzov namreÄ Å¾e
zmanjÅ”uje preživetje (Dermol in MiklavÄiÄ 2015). Za zdravljenje tumorjev z elektrokemoterapijo so bili
definirani standardni postopki (angl. standard operating procedures) (Marty et al. 2006Mir et al. 2006),
kjer so glede na Å”tevilo tumorjev, njihovo velikost in lokacijo (na koži ali pod kožo) doloÄeni tip elektrod,
kemoterapevtik, anestezija in naÄin dovajanja kemoterapevtika. Kemoterapevtik lahko dovedemo lokalno
ali sistemsko. V elektrokemoterapiji oz. terapiji z elektriÄnimi pulzi sta najbolj razÅ”irjena kemoterapevtika
cisplatin in bleomicin. Z elektrokemoterapijo je možno zdraviti tudi globlje ležeÄe tumorje (MiklavÄiÄ et al.
2010Pavliha et al. 2013EdhemoviÄ et al. 2014MiklavÄiÄ in Davalos 2015). V zadnjem Äasu se
uveljavlja tudi uniÄevanje tumorskih celic z visokimi koncentracijami kalcija in elektriÄnimi pulzi
(Frandsen et al. 2015Frandsen et al. 2016Frandsen et al. 2017). Pri elektrokemoterapiji se pojavijo Ŕe
dodatni uÄinki, ki poviÅ”ajo uÄinkovitost elektroporacije. Vazokonstrikcija zmanjÅ”a spiranje kemoterapevtika
iz tumorja in s tem ohranja visoko koncentracijo kemoterapevtika v tumorju, obenem se zmanjŔa pretok
krvi skozi tumor, kar povzroÄi hipoksijo in pomanjkanje hranilnih snovi (Mir 2006SerÅ”a et al. 2008).
Elektrokemoterapija sproži tudi odziv imunskega sistema, ki nato odstrani preostale tumorske celice (SerŔa
et al. 2015).
Z ireverzibilno elektroporacijo netermiÄno odstranjujemo tumorje brez uporabe kemoterapevtika (Jiang et
al. 2015a). Tako se popolnoma izognemo stranskim uÄinkom kemoterapevtikov, vendar na raÄun veÄ
dovedene energije in poslediÄno Joulovega gretja. Pri ireverzibilni elektroporaciji dovajamo veÄ (okoli 90)
elektriÄnih pulzov, dolgih od 50 Ī¼s do 100 Ī¼s, s ponavljalno frekvenco 1 Hz. Dovedeno elektriÄno polje je v
rangu nekaj kV/cm, kar je dosti veÄ kot pri elektrokemoterapiji. Pri ireverzibilni elektroporaciji lahko z
visoko natanÄnostjo odstranimo želeno tkivo ā obmoÄje med uniÄenim in nepoÅ”kodovanim tkivom je Å”iroko
le nekaj premerov celic (Rubinsky et al. 2007). Za odstranjevanje tumorjev tradicionalno uporabljamo
termiÄne metode (Hall et al. 2014) ā radiofrekvenÄno odstranjevanje in odstranjevanje s tekoÄim duÅ”ikom,
kjer tkivo uniÄujemo z visoko oz. z nizko temperaturo. Prednost ireverzibilne elektroporacije pred
uveljavljenimi termiÄnimi metodami je krajÅ”i Äas zdravljenja, izognemo se uÄinkom hlajenja oz. gretja tkiva
zaradi bližine žil (Golberg et al. 2015), pri Äemer ostanejo okoliÅ”ke pomembne strukture (žile, živci)
nedotaknjene (Jiang et al. 2015a). Tudi pri ireverzibilni elektroporaciji je v dokonÄno odstranitev tumorskih
celic vpleten imunski sistem (Neal et al. 2013).
Pri elektrokemoterapiji in ireverzibilni elektroporaciji se zaradi daljŔih pulzov in ponavljalne frekvence
1 Hz pojavljajo težave zaradi krÄenja miÅ”ic (MiklavÄiÄ et al. 2005), boleÄine med dovajanjem pulzov,
heterogenosti elektriÄnih lastnosti tkiv v tem frekvenÄnem podroÄju ter zaradi možnosti srÄnih aritmij (Ball
et al. 2010). BoleÄini in krÄenju miÅ”ic se lahko izognemo, Äe pulze dovajamo z viÅ”jo frekvenco, npr. 5 kHz
(ŽupaniÄ et al. 2007SerÅ”a et al. 2010). SrÄnim aritmijam se izognemo tako, da s sinhroniziramo dovedene
elektriÄne pulze z elektriÄno aktivnostjo srÄne miÅ”ice (Mali et al. 2008Deodhar et al. 2011aMali et al.
2015). BoleÄini, krÄenju miÅ”ic in heterogenosti elektriÄnih lastnosti tkiv se lahko izognemo z dovajanjem
1 Ī¼s bipolarnih pulzov (Arena et al. 2011Arena in Davalos 2012Sano et al. 2015). V zadnjem Äasu so se
pojavile tudi metode, s katerimi so vnos barvil v celico dosegli brezkontaktno s t. i. magnetoporacijo (Chen
et al. 2010Towhidi et al. 2012Kardos in Rabussay 2012Novickij et al. 2015Kranjc et al. 2016Novickij et al. 2017bNovickij et al. 2017a).
Elektroporacijo lahko uporabljamo ne le za zdravljenje tumorjev, temveÄ tudi za vnos uÄinkovin v kožo in
skoznjo. Vnos uÄinkovin skozi kožo je neinvaziven, poleg tega pa se izognemo degradaciji uÄinkovin pri
prehodu skozi prebavni trakt. Skozi kožo lahko preide le malo molekul, zato uporabljamo razliÄne metode
za poveÄanje prehoda uÄinkovin ā iontoforezo, radiofrekvenÄno mikroablacijo, laser, mikroigle, ultrazvok
in elektroporacijo (Zorec et al. 2013b). Proces elektroporacije kože je slabo razumljen. Predpostavljamo, da
pri dovajanju visokonapetostnih elektriÄnih pulzov v roženi plasti nastanejo lokalna transportna obmoÄja,
kjer sta poviÅ”ani elektriÄna prevodnost in prepustnost (Pliquett et al. 1996Pliquett et al. 1998Pliquett et
al. 1998PavÅ”elj in MiklavÄiÄ 2008a). Skozi lokalna transportna obmoÄja lahko nato uÄinkovine Å”e nekaj ur
po dovedenih pulzih vstopajo skozi kožo v krvni obtok (Zorec et al. 2013a). Gostota teh obmoÄij je odvisna
od elektriÄnega polja v koži ā viÅ”je elektriÄno polje jih povzroÄi veÄ. Velikost lokalnih transportnih obmoÄij
je odvisna od trajanja pulza. Med samim pulzom se zaradi Joulovega gretja topijo lipidi v roženi plasti, kar
povzroÄi njihovo Å”irjenje (Pliquett et al. 1996Prausnitz et al. 1996Pliquett et al. 1998Weaver et al. 1999Vanbever et al. 1999Gowrishankar et al. 1999b).
NaÄrtovanje posegov elektrokemoterapije in netermiÄnega odstranjevanja tkiva z ireverzibilno
elektroporacijo
Pri zdravljenju tumorjev z elektroporacijo lahko uporabimo standardne oblike in postavitve elektrod z že
doloÄenimi parametri elektriÄnih pulzov (Marty et al. 2006Mir et al. 2006Campana et al. 2014). Äe
zdravimo velike tumorje ali tumorje nepravilnih oblik, ki pogosto ležijo globlje, s standardno postavitvijo
elektrod ne moremo zagotoviti ustrezne pokritosti tumorja z dovolj visokim elektriÄnim poljem. V tem
primeru lahko elektrode med samim posegom veÄkrat premaknemo ali pa prilagodimo njihovo Å”tevilo in
postavitev. Pri tem moramo prej pripraviti naÄrt posega (Kos et al. 2010MiklavÄiÄ et al. 2010Pavliha et
al. 2012Linnert et al. 2012EdhemoviÄ et al. 2014). V njem zagotovimo, da bo cel tumor izpostavljen
dovolj visokemu elektriÄnemu polju (MiklavÄiÄ et al. 2006a), obenem pa Å”koda na okoliÅ”kem tkivu
minimalna.
NaÄrtovanje posega poteka v veÄ korakih: 1. zajem medicinskih slik (raÄunalniÅ”ka tomografija, magnetna
resonanca) tumorja in okoliÅ”kega tkiva2. obdelava slik3. razgradnja slik in doloÄitev geometrije tkiva4.
vzpostavitev tridimenzionalnega modela5. optimizacija postavitve elektrod glede na obliko in velikost
tumorja6. izdelava modela elektroporacije (izraÄun elektriÄnega polja in spremembe elektriÄne
prevodnosti tkiva)7. optimizacija napetosti med elektrodami in položaja elektrod (Pavliha et al. 2012). Na
sliki 1 lahko vidimo izraÄunano elektriÄno polje v tumorju in okoliÅ”kem tkivu pri eni izmed možnih
postavitev elektrod.Electroporation is a phenomenon, which occurs when short high voltage pulses are applied to cells and tissues
resulting in a transient increase in membrane permeability or cell death, presumably due to pore formation. If
cells recover after pulse application, this is reversible electroporation. If cells die, this is irreversible
electroporation. Electroporation is used in biotechnology for biocompound extraction and cryopreservation, in
food processing for sterilization and pasteurization of liquid food and in medicine for treating tumors by
electrochemotherapy or irreversible electroporation as an ablation technique, for gene electrotransfer,
transdermal drug delivery, DNA vaccination, and cell fusion.
In electroporation-based medical treatments, we can treat tumors with predefined electrode geometry and
parameters of electric pulses. When we treat larger tumors of irregular shape treatment plan of the position of the
electrodes and parameters of the electric pulses has to be calculated before each treatment to assure coverage of
the tumor with a sufficient electric field. In treatment plans, currently, 1) we assume that above an
experimentally determined critical electric field all cells are affected and below not, although, in reality, the
transition between non-electroporated and electroporated state is continuous. 2) We do not take into account the
excitability of some tissues. 3) The increase in tissuesā conductivity is described phenomenologically and does
not include mechanisms of electroporation. 4) Transport of chemotherapeutics into the tumor cells in
electrochemotherapy treatments is not included in the treatment plan although it is vital for a successful
treatment. We focused on the mathematical and numerical models of electroporation with the aim of including
them in the treatment planning of electroporation-based medical treatments.
We aimed to model processes happening during electroporation of tissues, relevant in the clinical procedures, by
taking into account processes happening at the single cell level. First, we used mathematical models of cell
membrane permeability and cell death which are phenomenological descriptions of experimental data. The
models were chosen on the basis of the best fit with the experimental data. However, they did not include
mechanisms of electroporation, and their transferability to tissues was questionable. We modeled time dynamics
of dye uptake due to increased cell membrane permeability in several electroporation buffers with regard to the
electrosensitization, i.e., delayed hypersensitivity to electric pulses caused by pretreating cells with electric
pulses. We also modeled the strength-duration depolarization curve and cell membrane permeability curve of
excitable and non-excitable cell lines which could be used to optimize pulse parameters to achieve maximal drug
uptake at minimal tissue excitation.
Second, we modeled change in dielectric properties of tissues during electroporation. Model of change in
dielectric properties of tissues was built for skin and validated with current-voltage measurements. Dielectric
properties of separate layers of skin before electroporation were determined by taking into account geometric
and dielectric properties of single cells, i.e., keratinocytes, corneocytes. Dielectric properties of separate layers
during electroporation were obtained from cell-level models of pore formation on single cells of lower skin
layers (keratinocytes in epidermis and lipid spheres in papillary dermis) and local transport region formation in
the stratum corneum. Current-voltage measurements of long low-voltage pulses were accurately described taking
into account local transport region formation, pore formation in the cells of lower layers and electrode
polarization. Voltage measurements of short high-voltage pulses were also accurately described in a similar way
as with long low-voltage pulseshowever, the model underestimated the current, probably due to
electrochemical reactions taking place at the electrode-electrolyte interface.
Third, we modeled the transport of chemotherapeutics during electrochemotherapy in vivo. In
electrochemotherapy treatments, transport of chemotherapeutics in sufficient amounts into the cell is vital for a
successful treatment. We performed experiments in vitro and measured the intracellular platinum mass as a
function of pulse number and electric field by inductively coupled plasma ā mass spectrometry. Using the dualporosity
model, we calculated the in vitro permeability coefficient as a function of electric field and number of
applied pulses. The in vitro determined permeability coefficient was then used in the numerical model of mouse
melanoma tumor to describe the transport of cisplatin to the tumor cells. We took into account the differences in
the transport of cisplatin in vitro and in vivo caused by the decreased mobility of molecules and decreased
membrane area available for the uptake in vivo due to the high volume fraction of cells, the presence of cell
matrix and close cell connections. Our model accurately described the experimental results obtained in
electrochemotherapy of tumors and could be used to predict the efficiency of electrochemotherapy in vitro thus
reducing the number of needed animal experiments.
In the thesis, we connected the models at the cell level to the models at the tissue level with respect to cell
membrane permeability and depolarization, cell death, change in dielectric properties and transport.
Our models
offer a step forward in modeling and understanding electroporation at the tissue level. In future, our models
could be used to improve treatment planning of electroporation-based medical treatments
Authentic leadership, employeesā job satisfaction, and work engagement: a hierarchical linear modelling approach
The purpose of this study is to develop and test empirically a multilevel model of cross-level interactions between authentic leadership at the team level and job satisfaction and work engagement at the individual level. Using data from 23 team supervisors and 289 team members, the study also investigates the mediating role of perceived supervisor support in the proposed cross-level relationships. For validation of the measurement instrument, we first applied confirmatory factor analysis using LISREL 8.80 software. The hierarchical linear modelling analysis demonstrated a positive relationship between authentic leadership, employeesā job satisfaction, and work engagement. In addition, the relationship between authentic leadership and job satisfaction is fully mediated by perceived supervisor support, whereas we have also found support for partial mediation of perceived supervisor support in the relationship between authentic leadership and employeesā work engagement. A key originality and the theoretical and methodological contribution of this study lies in a multilevel approach that builds upon a sample of leaders and a number of their followers. We also address managerial implications and discuss future research suggestions
Exploratory and exploitative innovation: the moderating role of partner geographic diversity
The aim of this study is to explore the effect of exploratory and exploitative innovation separately and ambidexterity premise simultaneously relating to firmsā innovation performance. To test these relationships, we applied a hierarchical linear regression analysis to a large sample of international organisations (by using the Community Innovation Survey [CIS] 2006 micro data). We show that the relationship between exploratory innovation and a firmās innovation performance is moderated by geographically different partners. We found that ambidexterity premise in innovation context undermines innovation performance
Oxidative stress assays for disease risk stratification
Despite the fact that oxidative stress is a significant aetiological factor in several degenerative diseases, its measurement is rarely a part of "routine analyses" performed in hospital clinical chemistry laboratories. This situation is likely to change, as interest in this topic is increasing rapidly. Here we review the pertinent literature, with an assessment to assays for oxidative stress, and categorize them under: (i) assays for monitoring lipid peroxidation, (ii) assays for measuring oxidized amino acids, (iii) assays for measuring oxidized nucleic acids, (iv) assays based on physicochemical and immunological properties of oxidized low-density lipoprotein, and (v) assays for measuring the antioxidant capacity of body fluids and tissues. Our overview should be of help when choosing appropriate laboratory assays for oxidative stress and for routine disease risk stratification
The influence of family income on studentsā family resilience in Croatia
The study basically examines if there are differences in the factors
of studentsā family resilience regarding the level of their familiesā
income. Two additional hypotheses have also been tested, concerning
influence of income level on studentsā expression of problems
and difficulties to family members and on religiosity. The
study has been done on a sample of students from the Faculty of
Educational Sciences of the Juraj Dobrila University of Pula,
Croatia. The results have shown that students from families with
no income or below-average income, are likely forbidden to show
certain emotions in their family. On the other hand, students
from average or above-average income families consider the fact
that everyone can āventā without upsetting the others and is able
to discuss problems until the solution is found as a significant factor
of family resilience. The hypothesis concerning relationship
between religion and income has not been confirmed. The average
family income was taken from publicly available databases.
The category of family income and decisions about its spending
is very important for the quality of life, but also for communication
within the family. The results offer guidelines for interventions
which encourage family involvement, especially in financial
contributions to their childrenās wellbeing
Oxidative stress assays for disease risk stratification
Despite the fact that oxidative stress is a significant aetiological factor in several degenerative diseases, its measurement is rarely a part of "routine analyses" performed in hospital clinical chemistry laboratories. This situation is likely to change, as interest in this topic is increasing rapidly. Here we review the pertinent literature, with an assessment to assays for oxidative stress, and categorize them under: (i) assays for monitoring lipid peroxidation, (ii) assays for measuring oxidized amino acids, (iii) assays for measuring oxidized nucleic acids, (iv) assays based on physicochemical and immunological properties of oxidized low-density lipoprotein, and (v) assays for measuring the antioxidant capacity of body fluids and tissues. Our overview should be of help when choosing appropriate laboratory assays for oxidative stress and for routine disease risk stratification
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