Immediate Decision-Making and Information Needs in Intensive Care Coordination

The aim of this study was to develop a theoretical model for information integration to support the deci¬sion making of intensive care charge nurses, and physicians in charge – that is, ICU shift leaders. The study focused on the ad hoc decision-making and immediate information needs of shift leaders during the management of an intensive care unit’s (ICU) daily activities. The term ‘ad hoc decision-making’ was defined as critical judgements that are needed for a specific purpose at a precise moment with the goal of ensuring instant and adequate patient care and a fluent flow of ICU activities. Data collection and research analysis methods were tested in the identification of ICU shift leaders’ ad hoc decision-making. Decision-making of ICU charge nurses (n = 12) and physicians in charge (n = 8) was observed using a think-aloud technique in two university-affiliated Finnish ICUs for adults. The ad hoc decisions of ICU shift leaders were identified using an application of protocol analysis. In the next phase, a structured online question¬naire was developed to evaluate the immediate information needs of ICU shift leaders. A national survey was conducted in all Finnish, university-affiliated hospital ICUs for adults (n = 17). The questionnaire was sent to all charge nurses (n = 515) and physicians in charge (n = 223). Altogether, 257 charge nurses (50%) and 96 physicians in charge (43%) responded to the survey. The survey was also tested internationally in 16 Greek ICUs. From Greece, 50 charge nurses out of 240 (21%) responded to the survey. A think-aloud technique and protocol analysis were found to be applicable for the identification of the ad hoc decision-making of ICU shift leaders. During one day shift leaders made over 200 ad hoc decisions. Ad hoc decisions were made horizontally, related to the whole intensive care process, and vertically, concerning single intensive care incidents. Most of the ICU shift leaders’ ad hoc decisions were related to human resources and know-how, patient information and vital signs, and special treatments. Commonly, this ad hoc decision-making involved several multiprofessional decisions that constituted a bundle of immediate decisions and various information needs. Some of these immediate information needs were shared between the charge nurses and the physicians in charge. The majority of which concerned patient admission, the organisation and management of work, and staff allocation. In general, the information needs of charge nurses were more varied than those of physicians. It was found that many ad hoc deci-sions made by the physicians in charge produced several information needs for ICU charge nurses. This meant that before the task at hand was completed, various kinds of information was sought by the charge nurses to support the decision-making process. Most of the immediate information needs of charge nurses were related to the organisation and management of work and human resources, whereas the information needs of the physicians in charge mainly concerned direct patient care. Thus, information needs differ between professionals even if the goal of decision-making is the same. The results of the international survey confirmed these study results for charge nurses. Both in Finland and in Greece the information needs of charge nurses focused on the organisation and management of work and human resources. Many of the most crucial information needs of Finnish and Greek ICU charge nurses were common. In conclusion, it was found that ICU shift leaders make hundreds of ad hoc decisions during the course of a day related to the allocation of resources and organisation of patient care. The ad hoc decision-making of ICU shift leaders is a complex multi-professional process, which requires a lot of immediate information. Real-time support for information related to patient admission, the organisation and man¬agement of work, and allocation of staff resources is especially needed. The preliminary information integration model can be applied when real-time enterprise resource planning systems are developed for intensive care daily management

Análise interactômica da VDAC (voltage-dependent anion selective channel) nos cérebros aviar, bovino e murino

A VDAC é a proteína mais abundante na membrana mitocondrial externa. Exerce o controle da atividade desta organela através da regulação da troca de metabólitos e tem função crucial no mecanismo de apoptose. Em nosso caso, os estudos dos complexos protéicos, das interações entre a VDAC e outras proteínas presentes no interior do neurônio que auxiliam na manutenção das funções das organelas e da célula, fazem parte da chamada interactômica. O presente estudo determinou o interactoma do complexo protéico Hexoquinase-VDAC-ANT presente em cérebros murino, bovino e aviar. Nosso objetivo foi identificar se as expressões diferenciadas da VDAC1 e VDAC2 verificadas nos cérebros murino, aviar e bovino, estão associadas a diferenças nos interactomas dessas proteínas. Este estudo revelou que as espécies aviar e bovina apresentaram o maior número de complexos protéicos contendo VDACs (5) quando comparadas com os neurônios de rato (1), o que é indicativo de uma cinética diferencial de montagem ou desmontagem do complexo. Além disso, a VDAC mitocondrial neuronal aviar também interage com mais proteínas em relação à VDAC mitocondrial neuronal bovina, o que é resultado de uma composição de subunidades diferenciada. Tais resultados indicam diferenças significativas quanto ao metabolismo energético e apoptótico no cérebro aviar, bovino e murino, existindo interações diferenciais da VDAC no cérebro aviar.

The Effects of Estradiol, Androgens and the Selective Estrogen Modulators: Ospemifene, Raloxifene and Tamoxifen on Explant Cultures of Human Breast Tissue

The impact of menopausal hormone therapy (MHT) on increasing the risk for breast cancer (BC) remains controversial. To understand MHT-elicited cellular breast effects and the potential risks, included with using this therapy, a further investigation into this controversy is the subject of this thesis. In this thesis, to study the effects of estrogen, progestin, androgens and selective estrogen receptor modulators (SERMs), a modified tissue explant culture system was used. The different types of human breast tissues (HBTs) used in this study were normal HBTs, obtained from reduction mammoplasties of premenopausal women (prem-HBTs) or postmenopausal (postm-HBTs) women and peritumoral HBTs (peritum-HBTs) which were obtained from surgeries on postmenopausal BC patients. The explants were cultured up to three weeks in the presence or absence of estradiol (E2), medroxyprogesterone acetate (MPA), testosterone (T), dihydrotestosterone (DHT) and SERMs - ospemifene (OSP), raloxifene (RAL) and tamoxifen (TAM). The cultured HBTs maintained morphological integrity and responded to hormonal treatment in vitro. E2, MPA or E2/MPA increased proliferative activity and was associated with increased cyclin-D1 and caused changes in the cell cycle inhibitors p21 and p27, whereas the androgens T and DHT inhibited proliferation and increased apoptosis in HBT epithelia and opposed E2-stimulated proliferation and cell survival. The postm-HBTs were more sensitive to E2 than prem-HBTs. The effects of OSP, RAL and TAM on HBT epithelium were antiproliferative. E2, androgens and SERMs were associated with marked changes in the proportions of epithelial cells expressing steroid hormone receptors: E2 increased ERα expressing cells and decreased androgen receptor (AR) positive cells, whereas T and DHT had opposite effects. The OSP, RAL and TAM, also decreased a proportion of ERα positive cells in HBT epithelium. At 100 nM, these compounds maintained the relative number of AR positive cells, present at control level, which may partly explain proliferative inhibition. In conclusion, the proliferative activity of E2, in the epithelium of postm-HBTs, is opposed by T and DHT, which suggests that the inclusion of androgens in MHT may decrease the risk for developing BC.

Aqueous-phase reforming of renewables for selective hydrogen production in the presence of supported platinum catalysts

The evolution of our society is impossible without a constant progress in life-important areas such as chemical engineering and technology. Innovation, creativity and technology are three main components driving the progress of chemistry further towards a sustainable society. Biomass, being an attractive renewable feedstock for production of fine chemicals, energy-rich materials and even transportation fuels, captures progressively new positions in the area of chemical technology. Knowledge of heterogeneous catalysis and chemical technology applied to transformation of biomass-derived substances will open doors for a sustainable economy and facilitates the discovery of novel environmentally-benign processes which probably will replace existing technologies in the era of biorefinary. Aqueous-phase reforming (APR) is regarded as a promising technology for production of hydrogen and liquids fuels from biomass-derived substances such as C3-C6 polyols. In the present work, aqueous-phase reforming of glycerol, xylitol and sorbitol was investigated in the presence of supported Pt catalysts. The catalysts were deposited on different support materials, including Al2O3, TiO2 and carbons. Catalytic measurements were performed in a laboratory-scale continuous fixedbed reactor. An advanced analytical approach was developed in order to identify reaction products and reaction intermediates in the APR of polyols. The influence of the substrate structure on the product formation and selectivity in the APR reaction was also investigated, showing that the yields of the desired products varied depending on the substrate chain length. Additionally, the influence of bioethanol additive in the APR of glycerol and sorbitol was studied. A reaction network was advanced explaining the formation of products and key intermediates. The structure sensitivity in the aqueous-phase reforming reaction was demonstrated using a series of platinum catalysts supported on carbon with different Pt cluster sizes in the continuous fixed-bed reactor. Furthermore, a correlation between texture physico-chemical properties of the catalysts and catalytic data was established. The effect of the second metal (Re, Cu) addition to Pt catalysts was investigated in the APR of xylitol showing a superior hydrocarbon formation on PtRe bimetallic catalysts compared to monometallic Pt. On the basis of the experimental data obtained, mathematical modeling of the reaction kinetics was performed. The developed model was proven to successfully describe experimental data on APR of sorbitol with good accuracy.

Selective inhibition of human tankyrases

Tankyrases belong to the Diphtheria toxin-like ADP-ribosyltransferase (ARTD) enzyme superfamily, also known as poly(ADP-ribose) polymerases (PARPs). They catalyze a covalent post-translational modification reaction where they transfer ADP-ribose units from NAD+ to target proteins. Tankyrases are involved in many cellular processes and their roles in telomere homeostasis, Wnt signaling and in several diseases including cancers have made them interesting drug targets. In this thesis project, selective inhibition of human tankyrases was studied. A homogeneous fluorescence-based assay was developed to screen the compound libraries. The assay is inexpensive, operationally easy, and performs well according to the statistical analysis. Assay suitability was confirmed by screening a natural product library. Flavone was identified as the most potent inhibitor in the library and this motivated us to screen a larger flavonoid library. Results showed that flavones were indeed the best inhibitor of tankyrases among flavonoids. To further study the structure-activity relationship, a small library of flavones containing single substitution was screened and potency measurements allowed us to generate structure-activity relationship. Compounds containing substitutions at 4´-position were more potent in comparison to other substitutions, and importantly, hydrophobic groups improved isoenzyme selectivity as well as the potency. A flavone derivative containing a hydrophobic isopropyl group (compound 22), displayed 6 nM potency against TNKS1, excellent isoenzyme selectivity and Wnt signaling inhibition. Protein interactions with compounds were studied by solving complex crystal structures of the compounds with TNKS2 catalytic domain. A novel tankyrase inhibitor (IWR-1) was also crystallized in complex with TNKS2 catalytic domain. The crystal structure of TNKS2 in complex with IWR-1 showed that the compound binds to adenosine site and it was the first known ARTD inhibitor of this kind. To date, there is no structural information available about the substrate binding with any of the ARTD family members; therefore NAD+ was soaked with TNKS2 catalytic domain crystals. However, analysis of crystal structure showed that NAD+ was hydrolyzed to nicotinamide. Also, a co-crystal structure of NAD+ mimic compound, EB-47, was solved which was used to deduce some insights about the substrate interactions with the enzyme. Like EB-47, other ARTD1 inhibitors were also shown to inhibit tankyrases. It indicated that selectivity of the ARTD1 inhibitors should be considered as some of the effects in cells could come from tankyrase inhibition. In conclusion, the study provides novel information on tankyrase inhibition and presents new insight into the selectivity and potency of compounds.

The role of network coordination in business incubation - Comparative evidence from Finland and Russia

Business incubators (BIs) have an important role in promoting entrepreneurship and innovation. Networks have been identified as one of the main factors influencing business incubation success; however, their management has not been widely covered in previous business incubation research. Therefore, the main objective of this research is to investigate the role of network coordination in business incubation. Thus, the research aims to understand how the BI as a hub firm coordinates, i.e. manages and orchestrates, the business incubation process. As business incubation is also claimed to be affected by country specific factors, a cross-country comparison of Finland and Russia is conducted. Based on previous scientific literature on networks, network management, network orchestration and business incubation, a theoretical model combining business incubation and network coordination is developed. Through a qualitative multiple-case study evidence from a cross-country sample of BI managers and their residents was collected via semi-structured interviews. Based on the empirical data the network coordination mechanisms used by BIs are identified, yet only minor differences in network coordination in different countries are found. The results suggest that network coordination enables value creation in business incubation.

Selective leaching of multimetal tailings

Depletion of high grade mineral resources, tightening of environmental regulations and the environmental impact of acid mine drainage caused by sulfidic minerals continuously increase the interest in processing tailings and other mine waste. Treating waste requires additional capital and operational input, but the decrease in size and need of tailings ponds and permits decrease the overall costs. Treatment and utilization of the tailings could also bring added revenue by the recovery of valuables. Leaching of metal sulfides is very demanding and time consuming and hence process conditions need to be carefully optimized. The leaching of sulfides is affected by for example the choice of leaching agent, its concentration and temperature, pH, the redox potential, pressure, pulp density and particle size distribution. With reference to the mine case study the leaching of nickel and copper sulfides, especially the primary minerals pentlandite and chalcopyrite were investigated. Leaching behavior and recoveries for nickel, copper and iron were found out by sulfuric and citric acid leaching experiments using tailings samples of high and low sulfur content. Moderate recoveries were obtained and citric acid seemed more attractive. Increase in temperature and decrease in pulp density had positive effect on the recovery and pH was also proven to have a significant effect on the recovery of valuables. The rate determining step was determined through kinetic modeling in case of all valuables separately. Leaching was controlled by diffusion. The investigated multimetal tailing showed moderate potential in recovering of metal valuables from low grade tailing deposits. The process conditions should however be further optimized.

Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 ± 0.31 vs CL = 23.64 ± 0.30 g/l, P<0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 ± 26 vs CL = 535.41 ± 54 mg, P<0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 ± 3.2 vs CL = 227.14 ± 1.7 mg/g, P<0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ± 1.1 vs CL = -10.2 ± 1.9 g, P<0.05). This was associated with a marked decrease in fat stores (P = 5.35 ± 0.81 vs CL = 2.02 ± 0.16 g, P<0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ± 16.20 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05), was still much higher than in control rats (C = 159.55 ± 11.54 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7) in water-loaded rats

In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7) (Ang-(1-7)) in water-loaded rats. Water diuresis was induced in male Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage). Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight): 1) vehicle (0.05 ml 0.9% NaCl); 2) graded doses of 20, 40 or 80 pmol Ang-(1-7); 3) 200 nmol Losartan; 4) 200 nmol Losartan combined with 40 pmol Ang-(1-7); 5) 1.1 or 4.4 nmol A-779; 6) 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 7) 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 8) 95 nmol CGP 42112A, or 9) 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7). The antidiuretic effect of Ang-(1-7) was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 ± 0.04 ml/min vs 1.45 ± 0.18 ml/min in vehicle-treated rats, P<0.05). A-779 and Losartan completely blocked the effect of Ang-(1-7) on water diuresis (2.93 ± 0.34 ml/60 min and 3.39 ± 0.58 ml/60 min, respectively). CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7). The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7)-treated rats. When Ang-(1-7) was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7) alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7) suggests that the kidney effects of Ang-(1-7) are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.

Effect of SX-3228, a selective ligand for the BZ1 receptor, on sleep and waking during the light-dark cycle in the rat

The effects of the benzodiazepine1 (BZ1) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning of the light phase of the light-dark cycle induced a significant reduction of rapid-eye-movement sleep (REMS) during the third recording hour. Moreover, slow wave sleep (SWS) was increased during the fourth recording hour after the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the light-dark cycle caused a significant and maintained (6-h recording period) reduction of waking (W), whereas SWS and light sleep (LS) were increased. REMS values tended to increase during the entire recording period; however, the increase was statistically significant only for the 1.0 mg/kg dose during the first recording hour. In addition, a significant and dose-related increase of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX-3228 is a potent hypnotic when given to the rat during the dark period of the light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat.

Effect of training on the ability of dual-task coordination

Within the framework of the working memory model proposed by A. Baddeley and G. Hitch, a dual-task paradigm has been suggested to evaluate the capacity to perform simultaneously two concurrent tasks. This capacity is assumed to reflect the functioning of the central executive component, which appears to be impaired in patients with dysexecutive syndrome. The present study extends the investigation of an index ("mu"), which is supposed to indicate the capacity of coordination of concurrent auditory digit span and tracking tasks, by testing the influence of training on the performance in the dual task. The presentation of the same digit sequence lists or always-different lists did not differently affect the performance. The span length affected the mu values. The improved performance in the tasks under the dual condition closely resembled the improvement in the single-task performance. So, although training improved performance in the single and dual conditions, especially for the tracking component, the mu values remained stable throughout the sessions when the single tasks were performed first. Conversely, training improved the capacity of dual-task coordination throughout the sessions when dual task was performed first, addressing the issue of the contribution of the within-session practice to the mu index.

Effect of practice and span length on the dual-task coordination executive test

The measure "mu", proposed as an index of the ability to coordinate concurrent box-crossing (BC) and digit-span (DS) tasks in the dual task (DT), should reflect the capacity of the executive component of the working memory system. We investigated the effect of practice in BC and of a change in the digit span on mu by adding previous practice trials in BC and diminishing, maintaining or increasing the digit sequence length. The mu behavior was evaluated throughout three trials of the test. Reported strategies in digit tasks were also analyzed. Subjects with diminished span showed the best performance in DT due to a stable performance in DS and BC in the single- and dual-task conditions. These subjects also showed a more stable performance throughout trials. Subjects with diminished span tended to employ effortless strategies, whereas subjects with increased span employed effort-requiring strategies and showed the lowest means of mu. Subjects with initial practice trials showed the best performance in BC and the most differentiated performance between the single- and dual-task conditions in BC. The correlation coefficient between the mu values obtained in the first and second trials was 0.814 for subjects with diminished span and practice trials in BC. It seems that the within-session practice in BC and the performance variability in DS affect the reliability of the index mu. To control these factors we propose the introduction of previous practice trials in BC and a modification of the current method to determine the digit sequence length. This proposal should contribute to the development of a more reliable method to evaluate the executive capacity of coordination in the dual-task paradigm.

Application of isotope-selective non-dispersive infrared spectrometry for the evaluation of the 13C-urea breath test: comparison with three concordant methods

The aim of this work was to compare the performance of isotope-selective non-dispersive infrared spectrometry (IRIS) for the 13C-urea breath test with the combination of the 14C-urea breath test (14C-UBT), urease test and histologic examination for the diagnosis of H. pylori (HP) infection. Fifty-three duodenal ulcer patients were studied. All patients were submitted to gastroscopy to detect HP by the urease test, histologic examination and 14C-UBT. To be included in the study the results of the 3 tests had to be concordant. Within one month after admission to the study the patients were submitted to IRIS with breath samples collected before and 30 min after the ingestion of 75 mg 13C-urea dissolved in 200 ml of orange juice. The samples were mailed and analyzed 11.5 (4-21) days after collection. Data were analyzed statistically by the chi-square and Mann-Whitney test and by the Spearman correlation coefficient. Twenty-six patients were HP positive and 27 negative. There was 100% agreement between the IRIS results and the HP status determined by the other three methods. Using a cutoff value of delta-over-baseline (DOB) above 4.0 the IRIS showed a mean value of 19.38 (minimum = 4.2, maximum = 41.3, SD = 10.9) for HP-positive patients and a mean value of 0.88 (minimum = 0.10, maximum = 2.5, SD = 0.71) for negative patients. Using a cutoff value corresponding to 0.800% CO2/weight (kg), the 14C-UBT showed a mean value of 2.78 (minimum = 0.89, maximum = 5.22, SD = 1.18) in HP-positive patients. HP-negative patients showed a mean value of 0.37 (minimum = 0.13, maximum = 0.77, SD = 0.17). IRIS is a low-cost, easy to manage, highly sensitive and specific test for H. pylori detection. Storing and mailing the samples did not interfere with the performance of the test.

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.