In recent years, the focus on augmented renal clearance increased as it was found by other researchers to result in subtherapeutic drug dosing concentrations. Accurate assessment of renal function is important for prescribing optimal dosis of pharmaceuticals for ARC patients. Objective of the work: The purpose of this quantitative retrospective comparative study was to register possible cases of Accelerated renal clearance in patients of Hospital of Lithuanian University of Health Sciences Kaunas Clinics and analyse the differences in assessments of cases of Augmented Renal Clearance and the possible risks of ARC for therapy. Tasks: To achieve the objective several tasks were raised: 1) to register possible ARC patients cases as assessed by Cocroft-Gault and their possible associated reasons; 2) to analyse differences in three for GFR estimation used equations (Cocroft-Gault, MDRD simplified, and CKD-EPI). 3) determine the risk drugs for changed renal elimination. Methodology: ARC survey (appendix 1) was filled about patients from various departments of Clinics during the period of 2013 03-04 – 2013 12-20. All patients were selected according serum creatinine values that were 50 µmol/l. or less. Two goups of patients were assigned for analysis: patients were grouped according Cocroft - Gault creatinine clearance values: (1) ARC group A CrCl >130 ml./min and (2) comparative Non-ARC group B CrCl 90-130 ml./min. In the group A were 31 and in the group B - 5 patients... [to full text] / Pastaraisiais metais labai išaugo tyrimų apie padidintą inkstų klirensą (PIK), nes pagal keleto tyrejų duomenis šios būklės pasekmė yra subterapinės vaistų koncentracijos. Tikslus inkstų funkcijos nustatymas yra labai svarbus norint parinkti optimalias terapines vaistų dozes padidinto inkstų klirenso pacientams. Darbo tikslas: Šio kiekybinio retrospektyvaus palyginamojo darbo tikslas buvo surinkti duomenis apie padidinto inkstų klirenso PIK atvejus Lietuvos sveikatos mokslų universiteto ligonines Kauno klinikose. Buvo siekiama išanalizuoti sirtumus tarp skirtingų PIK įvertinimo būdų ir įvertinti galimas PIK rizikas terapijai Uždaviniai: norint pasiekti užsibrėžtus tikslus šie uždaviniai buvo iškelti: 1) užregistruoti PIK atvejus ir nustatyti jų galimas priežastis. 2) apskaičiuoti GFG trimis skirtingomis formulėmis (Cocroft-Gault, MDRD, CKD-EPI) ir išanalizuoti skirtumus. 3) nustatyti vaistus, kurie gali būti pakitusios inksų eliminacijos rizikoje. Metodika: PIK anketa ( 1 priedas) buvo pildoma apie pacientus iš skirtingų Kauno klinikų skyrių, laikotarpiu nuo 2013 04 03 iki 2013 12 20. Visi pacientai buvo parinkti pagal kreatinino kiekį serume – 50 µmol/l.. ir mažiau. Dvi pacientų grupės buvo parinktos analizei: pacientai buvo sugrupuoti pagal kreatinino klirensą į (1) PIK A grupę – CrCl > 130 ml./min. ir (2) palyginamąją B grupę – CrCl 90-130 ml./min. A grupėje buvo parinktas 31 pacientas ir B grupėje 5 pacientai. Rezultatai: Vidutinės GFG reikšmės tiriamojoje... [toliau žr. visą tekstą]

In critically ill patients, the pathophysiology of sepsis can affect the interactions between the antibiotic, the bacteria and the patient, leading to potential therapeutic failure and the development of antibiotic resistance. It is well acknowledged that research that optimises antibiotic exposure will assist improvement of outcomes in this patient group. Although beta-lactam antibiotics, such as piperacillin and meropenem, are commonly selected for empiric therapy of sepsis, dosing is unlikely to be optimal. In patients without renal dysfunction, data suggests that disease-induced alterations to pharmacokinetic parameters result in low trough concentrations for significant periods within a dosing interval. Administration of these time-dependent antibiotics by continuous infusion has been suggested to improve the pharmacokinetic-pharmacodynamic profile. Knowledge of concentrations in the extracellular fluid of human tissue, which is the target site of most pathogens, is particularly instructive. Extracellular fluid concentrations can be determined using techniques such as microdialysis. Therefore, the principal aims of this Thesis were to determine the plasma and subcutaneous tissue pharmacokinetics of piperacillin and meropenem administered by bolus dosing and continuous infusion in critically ill patients with sepsis; and to use Monte Carlo simulations to compare the ability of different dosing strategies to achieve pharmacodynamic endpoints. This Thesis also sought to compare the clinical outcomes of bolus dosing and continuous infusion of a beta-lactam antibiotic, ceftriaxone, in a prospective randomised controlled trial and to perform a meta-analysis on clinical outcomes from other similar published studies. Finally, this Thesis aimed to systematically review the published literature to determine any correlation between antibiotic dosing and the development of antibiotic resistance. The results of the pharmacokinetic studies, using piperacillin and meropenem, indicate that beta-lactam distribution into subcutaneous tissue, in critically ill patients with sepsis, is less than that observed in previous studies in healthy volunteers yet superior to studies in patients with septic shock. This supports the notion that the peripheral concentration of drugs may be inversely related to the level of sickness severity. Administration by continuous infusion was found to maintain statistically significantly higher trough beta-lactam concentrations in both plasma and subcutaneous tissue. Further analysis of the plasma data using population pharmacokinetic modeling and Monte Carlo simulations described significant pharmacodynamic advantages for administering meropenem or piperacillin by continuous infusion to organisms with high minimum inhibitory concentrations. Given the documented pharmacodynamic advantages for administering beta-lactams by continuous infusion, a prospective randomized controlled clinical trial was conducted using the beta-lactam antibiotic ceftriaxone. In 57 critically ill patients, we found equivalence between continuous infusion and bolus dosing in the intention-to-treat analysis. However, our a priori analysis criteria, requiring patients receive at least 4-days antibiotic treatment, found significant clinical and bacteriological advantages for administration by continuous infusion. To further investigate any clinical differences between bolus dosing and continuous infusion of beta-lactam antibiotics, we performed a meta-analysis of all published studies. Our analysis of the 13 published prospective randomized controlled trials (846 hospitalised patients) showed equivalence of continuous infusion and bolus dosing. Possible confounders observed within, and between the studies, make interpretation of these results challenging. However, two large retrospective cohorts not included in the meta-analysis, found definitive clinical and bacteriological advantages suggesting further research may be appropriate. The possible relationship between antibiotic dosing, or exposures, on the development of resistance was investigated using a structured review of the published literature. Our analysis of relevant papers found a wealth of data describing increasing levels of resistance with sub-optimal antibiotic dosing, particularly for fluoroquinolone antibiotics, but also for other classes including beta-lactams. These results demonstrate the importance of optimizing antibiotic dosing to decrease the development of antibiotic susceptibility from sub-optimal dosing, particularly for critically ill patients who are likely to have low drug concentrations. The results of this Thesis, suggest that a large, prospective, multi-centre randomised controlled trial in critically ill patients with sepsis, is required to definitively determine the clinical utility of administration of beta-lactam antibiotics by continuous infusion.

Mikrodosering av psykedeliska droger är den senaste trenden som verkar ha fått en stor spridning, främst bland unga människor för att uppnå ökad produktivitet och kreativitet, men även för att uppnå allmän psykisk hälsa. Denna uppsats lägger fokus på lysergsyradietylamid (LSD) och psilocybin (magic mushroom). Mikrodosering innebär att användaren tar en väldigt låg dos av substansen. Dosen ger ingen psykedelisk effekt, d.v.s. inga visuella effekter, inget förändrat medvetandetillstånd,och ingen förändrad tids-eller rumsuppfattning. Deltagare (n=201) besvarade en elektronisk enkät som distribuerades i olika forum med intresse för psykedeliska substanser. I denna deskriptiva sambandsstudie undersöktes motiveringen av att mikrodosera LSD-och psilocybin, samt vilka positiva och negativa effekter mikrodosering av dessa substanser har på den psykiska hälsan.Deltagare uppgav upplevd minskad depression, ångest och stress, men att det inte var den primära anledningen till att de mikrodoserade trots att 62% hade självdiagnostiserat sig med någon form av upplevd ohälsa. De primära motiven med att mikrodosera, som angavs i enkäten, var att förbättra den allmänna hälsan, samt för att nå ökad kreativitet och produktivitet. Trots upplevda negativa bieffekter under mikrodoseringscykeln uppgav majoriteten att de ville fortsätta att mikrodosera. På grund av urvalet är studieresultatet inte generaliserbart och efterföljande undersökningar med hypoteser och frågor är att föreslå.

A toxicidade dos metais em ambientes aquáticos está relacionada à sua biodisponibilidade e esta, por sua vez, pode ser influenciada por diversos fatores. As características do sedimento fazem dele um importante compartimento para avaliação do nível de contaminação no ambiente aquático. A presente pesquisa teve por objetivo quantificar e avaliar a biodisponibilidade de metais em sedimentos da baía da Ribeira. Nessa região, encontram-se os bairros mais populosos de Angra dos Reis RJ. Essa baía está localizada na parte nordeste da baía da Ilha Grande, que consiste de um espaço pesqueiro, turístico e de importante valor econômico e industrial. Foram coletados 12 sedimentos na baía da Ribeira e determinados os teores dos metais Al, Cu, Cd , Cr, Fe, Mn, Ni, Pb e Zn, através da extração com água régia (protocolo BCR-701), e o potencial de toxicidade dos metais Cd, Cu, Ni, Pb e Zn pelo método de extração dos sulfetos voláteis em meio ácido e quantificação dos metais extraídos simultaneamente (em inglês Acid Volatile Sulfide and Simultaneously Extracted Metal, AVS/SEM). Também foram efetuadas medidas de pH, potencial redox (Eh), carbono orgânico, fósforo total e granulometria. Através desses dados, foi possível estudar correlações entre essas variáveis. As concentrações de cada metal são similares nas diferentes localizações dos sedimentos e não apresentam significativas diferenças com relação a estudos reportados para a área, com exceção do Pb que apresentou a mais alta concentração já reportada. Os valores de SEM/AVS (entre 0,02 e 0,2) menores que 1, indicam que há quantidade de sulfetos suficiente para o aprisionamento dos metais investigados. As correlações obtidas através da Análise dos Componentes Principais demonstram relação direta entre as concentrações da maioria dos metais extraídos por água-régia (Ni, Fe, Cr, Cu, Zn); entre os metais Mn, Pb, Al e o fósforo total; entre os teores de matéria orgânica, carbono orgânico total, fósforo total com as frações finas de silte e argila com o Eh. Os resultados sugerem que a região não sofre influência significativa de fontes antrópicas em relação a metais e que, segundo o AVS/SEM, esses se encontram pouco disponíveis para o ambiente e, portanto, apresentam baixo potencial tóxico / The toxicity of metals in aquatic environments is related to their bioavailability, and this can be influenced by several factors. The sediment characteristics make it an important compartment for assessment of the level of contamination in the aquatic environment. This study aimed to quantify and assess the bioavailability of metals in sediments from the Ribeira Bay. In this region, are the most populous districts of Angra dos Reis - RJ. This bay is located in the northeast part of the Ilha Grande Bay, which consists of a fishery, tourist space and important economic and industrial value. 12 sediments were collected in the Ribeira Bay and determined the levels of the metals Al, Cu, Cd, Cr, Fe, Mn, Ni, Pb and Zn by aqua regia extraction protocol (BCR -701) and the potential toxicity of metals Cd, Cu , Ni , Pb and Zn by extraction of Acid Volatile Sulfide and Simultaneously Extracted Metal (AVS/SEM). Measurements of pH, redox potential (Eh), organic carbon , total phosphorus and particle size were also made. Through these data it was possible to study correlations between these variables. The concentrations of each metal are similar in the different locations of sediment and no significant differences with compared to published studies in the area. The values of ΣSEM/AVS (0.02 to 0.2) smaller than 1 indicate that there is amount of sulfides sufficient for trapping of the metals investigated. The correlations obtained by Principal Components Analysis show a direct relationship between the concentrations of most metals extracted by aqua regia (Ni, Fe, Cr, Cu, Zn); between the metals Mn, Pb, Al and total phosphorus; between organic matter content, total organic carbon, total phosphorus with the fractions fine silt and clay and the Eh. The results suggest that the region no suffer significant influence of anthropogenic sources in relation to metals and, according to the AVS/SEM, these are not readily available to the environment and therefore have low toxic potential

A toxicidade dos metais em ambientes aquáticos está relacionada à sua biodisponibilidade e esta, por sua vez, pode ser influenciada por diversos fatores. As características do sedimento fazem dele um importante compartimento para avaliação do nível de contaminação no ambiente aquático. A presente pesquisa teve por objetivo quantificar e avaliar a biodisponibilidade de metais em sedimentos da baía da Ribeira. Nessa região, encontram-se os bairros mais populosos de Angra dos Reis RJ. Essa baía está localizada na parte nordeste da baía da Ilha Grande, que consiste de um espaço pesqueiro, turístico e de importante valor econômico e industrial. Foram coletados 12 sedimentos na baía da Ribeira e determinados os teores dos metais Al, Cu, Cd , Cr, Fe, Mn, Ni, Pb e Zn, através da extração com água régia (protocolo BCR-701), e o potencial de toxicidade dos metais Cd, Cu, Ni, Pb e Zn pelo método de extração dos sulfetos voláteis em meio ácido e quantificação dos metais extraídos simultaneamente (em inglês Acid Volatile Sulfide and Simultaneously Extracted Metal, AVS/SEM). Também foram efetuadas medidas de pH, potencial redox (Eh), carbono orgânico, fósforo total e granulometria. Através desses dados, foi possível estudar correlações entre essas variáveis. As concentrações de cada metal são similares nas diferentes localizações dos sedimentos e não apresentam significativas diferenças com relação a estudos reportados para a área, com exceção do Pb que apresentou a mais alta concentração já reportada. Os valores de SEM/AVS (entre 0,02 e 0,2) menores que 1, indicam que há quantidade de sulfetos suficiente para o aprisionamento dos metais investigados. As correlações obtidas através da Análise dos Componentes Principais demonstram relação direta entre as concentrações da maioria dos metais extraídos por água-régia (Ni, Fe, Cr, Cu, Zn); entre os metais Mn, Pb, Al e o fósforo total; entre os teores de matéria orgânica, carbono orgânico total, fósforo total com as frações finas de silte e argila com o Eh. Os resultados sugerem que a região não sofre influência significativa de fontes antrópicas em relação a metais e que, segundo o AVS/SEM, esses se encontram pouco disponíveis para o ambiente e, portanto, apresentam baixo potencial tóxico / The toxicity of metals in aquatic environments is related to their bioavailability, and this can be influenced by several factors. The sediment characteristics make it an important compartment for assessment of the level of contamination in the aquatic environment. This study aimed to quantify and assess the bioavailability of metals in sediments from the Ribeira Bay. In this region, are the most populous districts of Angra dos Reis - RJ. This bay is located in the northeast part of the Ilha Grande Bay, which consists of a fishery, tourist space and important economic and industrial value. 12 sediments were collected in the Ribeira Bay and determined the levels of the metals Al, Cu, Cd, Cr, Fe, Mn, Ni, Pb and Zn by aqua regia extraction protocol (BCR -701) and the potential toxicity of metals Cd, Cu , Ni , Pb and Zn by extraction of Acid Volatile Sulfide and Simultaneously Extracted Metal (AVS/SEM). Measurements of pH, redox potential (Eh), organic carbon , total phosphorus and particle size were also made. Through these data it was possible to study correlations between these variables. The concentrations of each metal are similar in the different locations of sediment and no significant differences with compared to published studies in the area. The values of ΣSEM/AVS (0.02 to 0.2) smaller than 1 indicate that there is amount of sulfides sufficient for trapping of the metals investigated. The correlations obtained by Principal Components Analysis show a direct relationship between the concentrations of most metals extracted by aqua regia (Ni, Fe, Cr, Cu, Zn); between the metals Mn, Pb, Al and total phosphorus; between organic matter content, total organic carbon, total phosphorus with the fractions fine silt and clay and the Eh. The results suggest that the region no suffer significant influence of anthropogenic sources in relation to metals and, according to the AVS/SEM, these are not readily available to the environment and therefore have low toxic potential

Atmospheric CO₂ enrichment is employed by greenhouse tomato growers to increase fruit yields, and CO₂ applications are managed according to atmospheric set points or CO₂ injection rates. These methods do not immediately focus on the targets of CO₂ applications: plant performance and the regulation of plant carbon status. This thesis explores several plant-based approaches that may have potential for use in the management of CO₂ in greenhouse tomato production. Three plant-based approaches to CO₂ management were explored in commercial and experimental tomato greenhouses. These were: (1) simulation modeling, (2) non-destructive analysis of growth and (3) the status of plant carbon reserves. A cost and benefit analysis (c/b) using simulation modeling was carried out using grower-collected greenhouse environment and yield data. Simulation modeling was useful for retrospectively determining c/b of several CO₂ scenarios. The model was effective in predicting long term yields, but not short term yield variations, which limits its application for CO₂ management. Non-destructive measures of growth: stem length and diameter, leaf area and fruit load were found to be too sluggish for daily CO₂ dosing decision-making. Finally, plants growing under CO₂ enrichment can deposit substantial carbon as starch in their leaves. Plant carbon status was evaluated by determining the spatial distribution of leaf starch in the shoot and by following its variation diurnally and after the onset of CO₂ enrichment. As starch is difficult to measure by a grower, leaf mass per unit area (LMA) was also monitored for assessment as a surrogate measure for starch. Leaves in positions 7 to 9 were identified as the most meaningful in the shoot to sample. Diurnal profiles indicated these leaves carryover substantial starch from one day to the next. Monitoring starch at its peak time of accumulation (14 h to 16 h), at sunset and sunrise will indicate how much the peak starch reserves are used overnight. If starch remains high between peak and sunrise the following day, then the plants are in a carbon-surplus state and CO₂ enrichment could be postponed. For upper canopy leaves LMA is substantially influenced by starch and thus is a promising surrogate. / Land and Food Systems, Faculty of / Graduate

>Magister Scientiae - MSc / To address the urgent need for safe potable water in South Africa’s rural areas, sustainable systems for water disinfection at the village-scale of operation are required.In this thesis, the development of a small-scale water chlorination system that runs on salt and solar panels is described. The system combines a membrane-based hypochlorite generator, or “membrane electrolyser”, with an automated hypochlorite dosing system.The system was designed to (i) coordinate hypochlorite production and dosing automatically in a flow-through system, and (ii) fit inline with low pressure pipelines from overhead storage tanks or raised water sources. Low cost materials were used for construction, and water-powered mechanisms were devised to control both brine supply to the electrolyser and regulation of water flow. The capacity of the system was based on the maximum daily output of the electrolyser at ~20 g of sodium hypochlorite. This was sufficient chlorinate up to 10 kL of water per day using less than 80 g of salt and less than 0.1 kW.h of electricity. The cost of the system was estimated at ~R10 000 and therefore potentially affordable for communities up to 100 people, e.g. small farms and villages.Testing of the system was carried out at a farm site in Worcester (Western Cape) using remote monitoring of current levels in the electrolyser. Operation of the system over a two month test period, dosing at ~4 mg/L, produced consistent chlorination measured as(FAC). Community participation in maintenance of the brine supply was managed and chlorinated water was made available to the community after a brief social survey was conducted. Community awareness of chlorination was minimal. No significant history of diarrhoea was reported. However, the community regularly boiled their tap water in response to turbidity increase in summer.The system was affected by turbidity increase in the local water, which caused a drop in electrolyser current and chlorine production due to particle blockage of the membrane in the electrolyser. However, turbidity at acceptable levels for chlorination was found to have no detrimental effect on the system’s performance. The system showed promise for rural implementation providing low turbidity was maintained. Therefore,groundwater sites, and surface waters with appropriate clarification systems are recommended for the system’s installation. Further testing of the system will be required to establish its long term viability in the hands of a rural community.

Increasing freshwater scarcity across the world means that wastewater reclamation is being considered as a key method in which to meet the growing demand. Evolution of water reuse schemes where high quality product is required such as for indirect potable reuse has led to the adoption in recent years of the integrated membrane scheme using a combination of microfiltration or ultrafiltration with reverse osmosis membrane. However, despite technological advancements, these membranes are still prone to fouling resulting in increased costs through cleaning or replacement. This thesis aims to look at pretreatment to reduce the fouling propensity of the microfiltration membranes via a 600m3 /d pilot plant which was commissioned to investigate indirect potable reuse. A range of pretreatments including pre-screening, pre-coagulation, powdered activated carbon and granular activated carbon were assessed based on fouling amelioration, water quality improvement and cost analysis. Results showed that ferric sulphate dosing was the most effective in terms of reducing the reversible fouling rate especially at high turbidity loads enabling higher flux to be realised leading to a small cost benefit. Activated carbon proved the most effective pretreatment in terms of organic removal and a significant reduction in the irreversible fouling rate. However, the cost involved in using this as a pretreatment is significant compared to possible cost savings through reduced requirement for chemical cleaning. This pretreatment is only viable if it obviates the need for a separate organic removal process.

The thesis deals with the possibility of specific weight lowering of kaolin suspensions using air-entraining agents. These agents are usually used as concrete admixtures. The goal of the thesis is to verify an alternative possibility of creating porous structure in kaolin suspensions in order to prepare heat insulating moulded refractory concretes without using lightweight fillers. The effect of several air-entraining agents was compared, after that the dosage of agent and mixing conditions were optimized. The stabilization of prepared foams and practical application of selected agents were also part of the thesis.

Background: The effectiveness of inhaled salbutamol in routine care depends particularly on prescribed dosage and applied inhalation technique. To achieve maximum effectiveness and to prevent drug-related problems, prescription and administration need to work in concert. Methods: We performed a controlled intervention pilot study with 4 consecutive groups in a general paediatric unit and assessed problems in salbutamol prescribing and administration. Control group [i]: Routine care without additional support. First intervention group [ii]: We carried out a teaching session for nurses aimed at preventing problems in inhalation technique. Independently from this, a pharmacist counselled physicians on problems in salbutamol prescribing. Second intervention group [iii]: Additionally to the first intervention, physicians received standardised feedback on the inhalation technique. Follow-up group [iv]: Subsequently, without any delay after the second intervention group had been completed, sustainability of the measures was assessed. We performed the chi-square test to calculate the level of significance with p ≤ 0.05 to indicate a statistically significant difference for the primary outcome. As we performed multiple testing, an adjusted p ≤ 0.01 according to Bonferroni correction was considered as significant. Results: We included a total of 225 patients. By counselling the physicians, we reduced the number of patients with problems from 55% to 43% (control [i] vs. first intervention [ii], n.s.). With additional feedback to physicians, this number was further reduced to 25% ([i] vs. [iii], p < 0.001). In the follow-up [iv], the number rose again to 48% (p < 0.01 compared to feedback group). Conclusions: Teaching nurses, counselling physicians, and providing feedback on the quality of inhalation technique effectively reduced problems in salbutamol treatment. However, for success to be sustained, continuous support needs to be provided. Trial registration: German Clinical Trials register: DRKS00006792.