No Brasil, poucos estudos investigaram a prevalência de medicamentos potencialmente inapropriados (MPIs) em idosos ambulatoriais. Este estudo visa determinar a prevalência de MPIs prescritos para estes pacientes, identificando os mais comumente envolvidos e verificando se a idade, o sexo e o número de medicamentos estão relacionados à prescrição de tais medicamentos. Foram coletadas prescrições de 3070 pacientes idosos (60 anos) em banco de dados, provenientes dos ambulatórios de Geriatria e Clínica Geral de um hospital universitário de atenção terciária em São Paulo-Brasil entre fevereiro e maio de 2008, que foram divididas de acordo com o sexo e faixa etária (60-69; 70-79 e 80). Os critérios de Beers versão 2003 foram utilizados para a avaliação de MPIs. A maior parte da casuística foi composta por mulheres em ambos os ambulatórios (66,6% na Clínica Geral e 77,7% na Geriatria). Os pacientes da Clínica Geral apresentaram média de idade de 71,3 anos e os da Geriatria, 80,1 anos. Na Clínica Geral a prevalência média de prescrição de MPIs foi de 37,6% e na Geriatria de 26,9%, sendo que em ambos as mulheres de 60-69 foram as que apresentaram a maior prevalência destes medicamentos. Os MPIs mais prescritos nos dois ambulatórios foram o carisoprodol, a fluoxetina e a amitriptilina, sendo que houve diferenças nos perfis de prescrições entre homens e mulheres. A chance de uso de MPI no sexo feminino é maior que no masculino (p<0,001); a chance de uso de MPI na faixa de 70-79 anos é menor que na faixa de 60-69 anos (p=0,030), assim como na faixa de 80 (p=0,024). Estas conclusões não dependem do ambulatório (p=0,164).O efeito de ambulatório depende do número de medicamentos (p=0,009). Se o número de medicamentos é < 9 a chance de uso de MPI na Clínica Geral é maior que na Geriatria (p=0,041). Quando o número de medicamentos é 7 ou 8, a chance de uso de MPI é maior do que quando são prescritos 1-4 medicamentos (p<0,001), nos dois ambulatórios (p=0,098). Quando são usados 9 medicamentos, a chance de uso de MPI depende do ambulatório (p=0,044). Na Geriatria, a chance de uso de um MPI é 8,2 vezes a RC na categoria 1-4 medicamentos; enquanto que na Clínica Geral a razão de chances é 4,6. As prevalências de MPIs encontradas foram semelhantes ao relatado na literatura e estão correlacionadas ao sexo feminino. A chance de prescrição de MPIs foi menor em pacientes com 70 anos; observou-se que se o número de medicamentos for <9, a chance de uso de MPI na Clínica Geral é maior que na Geriatria, porém, se o número de medicamentos for 9 não há diferença entre as chances de uso de MPI nos dois ambulatórios / In Brazil, few studies have investigated the prevalence of potentially inappropriate medications (PIMs) among elderly outpatients. This study aimed to determine the prevalence of PIMs prescribed to such patients, identify the medications most commonly involved and investigate whether age, sex and number of medications are related to the prescription of such medications. Prescriptions issued to 3,070 elderly patients (60 years) were gathered from a database. These patients were attended at the geriatric and general clinical outpatient services of a tertiary-level university hospital in São Paulo, Brazil, between February and May 2008. They were divided according to sex and age group (60- 69; 70-79; and 80 years). The Beers criteria (2003 version) were used to evaluate PIMs. The majority of the sample comprised women, at both outpatient services (66.6% in the general clinic and 77.7% in geriatrics). The mean age of the general clinical patients was 71.3 years and the mean for the geriatric patients was 80.1 years. At the general clinic, the mean prevalence of prescriptions of PIMs was 37.6%, and it was 26.9% at the geriatric clinic. At both outpatient services, women aged 60-69 years presented the highest prevalence of such medications. The PIMs most prescribed at the two outpatient services were carisoprodol, fluoxetine and amitriptyline, and there were differences in the prescription profiles between the men and women. The chances of using PIMs were greater for the women than for the men (p < 0.001). The chances of using PIMs in the 70-79 years group were lower than in the 60-69 years group (p = 0.030), and likewise for the group 80 years (p = 0.024). These conclusions were independent of the outpatient service (p = 0.164). The outpatient effect depended on the number of medications (p = 0.009). If the number of medications was < 9, the chances of using PIMs at the general clinic were greater than the chances at the geriatric clinic (p = 0.041). When the number of medications was 7 or 8, the chances of using PIMs were greater than when prescribed 1-4 medications (p < 0.001), at both outpatient services (p = 0.098). When 9 medications were used, the chances of using PIMs depended on the outpatient service (p = 0.044). At the geriatric clinic, the chances of using PIMs were 8.2 times greater than the chances in the category of 1-4 medications; while at the general clinic, the odds ratio was 4.6. The prevalence of PIMs encountered was similar to what has been reported in the literature, and it correlated with female sex. The chances of being prescribed PIMs were lower among patients 70 years. If the number of medications was < 9, the chances of using PIMs at the general clinic were greater than the chances at the geriatric clinic. However, if the number of medications was 9, there was no difference in the chances of using PIMs between the two outpatient services

En studie om medveten memorering av harmonik inom klassiskt pianospel. Arbetet bygger på observationer av en tolv veckors lång instuderingsprocess, sett i relation till ett urval av tidigare litteratur och forskning inom området. Studien har i syfte att ge en djupare bild och förståelse av memoreringens påverkan vid konsertsituationen samt vilka fördelar respektive nackdelar det kan finnas med medveten memorering av harmonik. För att uppnå syftet tar studien utgångspunkt i tre frågeställningar. Frågeställningarna berör medveten memorering av harmonik som metod att instudera ett stycke, vilka fördelar och nackdelar det kan få samt om det kan hjälpa en musicerande att känna sig tryggare på scen. Som blivande lärare hoppas jag att detta dels ska hjälpa mig vid egna uppspel men också att jag ska kunna förmedla en bra memoreringsmetod till de elever som jag kommer att möta under min tid som lärare. / A study about conscious memorization of harmony in classical piano playing. The study is based on observations of a twelve week period and on chosen literature from previous research in this field. The purpose of the study is to get a deeper knowledge and understanding in how memorizing can effect the results at a performance and also what other benefits and disadvantages there could be. The study has as a starting point three questions. These questions are about memorization of harmonics as a method to learn a music piece, the benefits and disadvantages with conscious memorization and also if a pianist can feel safer on stage after consciously memorizing harmony. As a future teacher I hope this study will help me with my own performances and also the pupils that I will teach and meet during my professional work as a musicteacher.

Resistance to glucocorticoid (GC) therapy results in poor prognosis for acute lymphoblastic leukemia (ALL) patients. Utilizing a whole genome shRNA screen our lab identified several novel mechanisms of GC resistance. My thesis work established that an orphan nuclear receptor, the Estrogen Related Receptor Beta (ESRRB), is critical for induction of apoptotic genes following treatment with the GC dexamethasone. ESRRB has mostly been implicated in maintenance of pluripotency in mouse embryonic stem cells. We find that repression of ESRRB results in GC resistance in ALL and define ESRRB as a novel cooperating transcription factor in GC-induced gene expression. We also show that agonists to ESRRB synergize with dexamethasone and increase dexamethasone induced apoptosis in relapse ALL patient samples. Interestingly, our shRNA screen identified another factor important in stem cell maintenance: SOX2. While we originally hypothesized that ESRRB and SOX2 may cooperate in ALL, RNA-sequencing studies revealed that these factors mediate GC resistance by independent mechanisms. Our data define SOX2 as a repressor of key signaling pathways in ALL. Upon SOX2 knockdown, we observe activation of pro-survival gene expression including activation of the MAPK pathway, which has previously been implicated in GC resistance. MAPK activation may be explained by an increase in EGFR expression observed in Sox2 knockdown cells and GC resistant patients, suggesting EGFR inhibitors may re-sensitize patients to GCs. Overall my thesis work identifies mechanisms of GC resistance in ALL and utilizes these findings to define novel therapeutic strategies for GC resistant ALL patients.

Nowadays, probiotic lactic acid bacteria (LAB) and bifidobacteria are plentifully exploited in food processing industry. LAB and bifidobacteria are important part of microflora of gastro intestinal tract (GIT). Probiotics (most often just lactobacilli and bifidobakteria) can be supplied to the GIT of the organism like food complements. Species identification is therefore very important. New methods of identification of LAB and bifidobacteria are based on analysis of DNA. Mostly exploited method is polymerase chain reaction (PCR). In my diploma work, genus and species specific PCRs were used for identification of different species of bacteria of genus Lactobacillus and Bifidobacterium in complex matrices of six food supplements (Zenflo, Linex Forte, Probian, Nutra Bona, GS lactobacillus Forte, Pangamin Bifi plus). Total DNA was isolated from crude lysates of cells present in tablets by magnetic particles coated by carboxyl groups . The preparation of cell lysates was optimalised. Different amounts of lysozyme (3 mg/ml, 10 mg/ml), time of incubation at laboratory temperature (1,5 hour, 3 hour) and time of incubation with SDS and proteinase K at 55 °C (1 hour, 3 hour, over all night) were tested. Isolated DNA was quantified and checked in PCR. Primers specific for genus Lactobacillus and Bifidobacterium and for species Lb. acidophilus, Lb. casei, Lb. rhamnosus and Lb. plantarum and B. animalis, B. bifidum, B. infantis, B. longum were used, respectively. All identified bacteria were in accord with the data declared by producer in 3 food supplements (Zenflo, Linex Forte and Pangamin Bifi Plus). The genus indentification was in accord with declaration of producer in other food products only (Probian, Nutra Bona, GS Laktobacily Forte).

The aim of the thesis was to analyze the historical pharmaceutical preparations, including the determination of the active substance and identify theirs possible degradation products. A historical pharmaceutical preparation of naloxone was analyzed by mass spectrometry. Historical pharmaceutical preparations of adrenaline and ephedrine were analyzed by UHPLC-MS and were quantified using a calibration curve. In the historical injection solution of naloxone, "NARCAN", dated around 1980, there were no significant degradation products and the measured mass and UV spectrum was consistent with the spectrum of naloxone. The analyzed sample of naloxone was stable even after 35 years of storage. In the analyzed historical injection solution of adrenaline, "Adrenalin Hydrochlor., Dr. Heisler" (dated between 1917 and 1938) was determined 5.26 ± 0.11 % of the declared amount of adrenaline. In the measured spectras were noticeable degradation products, which have not been described in the literature yet and their identification was beyond the scope of this paper. The analyzed sample of adrenaline was almost completely degraded during about ninety years. The stability test carried out with four standard solutions of adrenaline proved influence of oxygen, light, temperature and time on the degradation of adrenaline. In...

HIV-1 protease is a very important drug target for AIDS therapy. Nine protease inhibitors have been proved by FDA and used in AIDS treatment. Due to the high replication rate and the lack of fidelity of the HIV-1 reverse transcriptase, HIV-1 virus developed various drug-resistant variants. Although experimental methods such as crystallography and isothermal titration calorimetry provide structural and thermodynamic data on drug-resistant variants, they are unable to discern the mechanism by which the mutations confer resistance to inhibitors. Understanding the drug-resistance mechanism is crucial for developing new inhibitors more tolerant to the drug-resistant mutations. Computational methods such as free energy calculations and molecular dynamic simulations can provide insights to the drug resistance mechanism at an atomic level. In this thesis, I have focused on the elucidation of the energetic and dynamics of key drug-resistant variants of HIV-1 protease. Two multi-drug resistant variants, in comparison with wild-type HIV-1 protease were used for the comparisons: Flap+ (L10I, G48V, I54V, and V82A) which contains a combination of flap and active site mutations and ACT (V82T, I84V) that only contains active site mutations. In Chapter II, I applied free energy simulations and decomposition methods to study the differential mechanism of resistance to the two variants, Flap+ and ACT, to the recently FDA-approved protease inhibitor darunavir (DRV). In this study, the absolute and relative binding free energies of DRV with wild-type protease and the two protease variants were calculated with MM-PB/GBSA and thermodynamic integration methods, respectively. And the predicted results are in good agreement with the ITC experimental results. Free energy decomposition elucidates the mutations alter not only its own interaction with DRV but also other residues by changing the geometry of binding pocket. And the VdW interactions between the bis-THF group of DRV is predominant even in the drug-resistant variants. At the end of this chapter, I offer suggestions on developing new inhibitors that are based on DRV but might be less susceptible to drug-resistant mutations. In Chapter III, 20-ns MD simulations of the apo wildtype protease and the apo drug-resistant protease variant Flap+ are analyzed and compared. In these studies, these mutations have been found to decrease the protease flexibility in the apo form but increase the mobility when the protease is binding with inhibitor. In Chapter IV, more details of the free energy simulation and decomposition are discussed. NMR relaxation experiments were set up as a control for the MD simulation study of the dynamics of the Flap+ variant. The difficulty of finishing the NMR experiment is discussed and the solution and some preliminary results are shown. In summary, the scope of this thesis was to use computational methods to study drug-resistant protease variants’ thermodynamic and dynamic properties to illuminate the mechanism of protease drug resistance. This knowledge will contribute to rational design of new protease inhibitors which bind more tightly to the protease and hinder the development of drug-resistant mutations.

Background To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. Methods Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. Results We distinguished numerous, unique plasma miRNAs both up- and down-regulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and down-regulated miRNAs, included, but were not limited to, 574-5p, 466g, 466f-3p, 375, 29c, and 148a. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point ( P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point ( P = 0.011). Conclusion We identified unique plasma miRNAs both up- and down-regulated in lethally dosed APAP poisoned mice.

Title: Treatment of CMV Vitritis in a Preterm Newborn Author’s Section: Remil Simon1, Darshan Shah1, Peter Blosser1, Demetrio Macariola1, Jeffrey Carlsen2 1.Department of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 2.Johnson City Eye Clinic, Johnson City, TN Body: Cytomegalovirus (CMV) infection in the neonate is an infrequent occurrence in the developing world, and observing the symptoms of ocular CMV infection such as vitritis is rare. Treating CMV infection promptly is necessary to prevent mortality and potential neurological deficits including blindness and hearing loss. We encountered a preterm infant presenting with CMV sepsis immediately after birth. Our question was: will the current standard of treatment for CMV sepsis prevent CMV ocular infection? With our method of treatment, we followed the current standard of treatment for CMV infection by administering intravenous Gancyclovir for 6 weeks and oral Valgancyclovir for 6 months. Despite using the standard treatment to prevent neurological sequelae, the patient developed CMV vitritis and retinitis bilaterally. Although the treatment did not prevent CMV ocular infection, the severity of CMV retinitis and vitritis improved with treatment, and full resolution of vitritis was noted by day of life 61.

I byggbranschen är planering en viktig del för att säkert och effektivt genomföra byggnads- och anläggningsarbeten. En form av planeringsverktyg är arbetsberedning. Med en arbetsberedning görs det analyser på enskilda arbetsmoment, med målet att genomföra arbetet inom rätt tid, ekonomi, kvalitet och bra arbetsmiljö.Syftet med denna rapport är, ur ett arbetsmiljöperspektiv, att kartlägga hur NCC:s arbetsberedningar fungerar i dagsläget, med målet att ge förbättringsförslag. Detta sker genom intervjuer och enkätundersökningar på personalen på NCC.Resultatet visar att personalen på NCC ser arbetsberedningar som ett bra hjälpmedel för att förbättra arbetsmiljön. Däremot finns det brister i dagens arbetssätt kring arbetsberedningar som bör förbättras. Vi rekommenderar NCC att förbättra sitt arbete kring planering, genomförandet och uppföljning av arbetsberedningar. Våra egna förbättringsförslag finns att läsa om under avsnitt ”Rekommendationer”. / To safely and effectively carry through within the construction industry, planning plays an important part. Work preparation is one form of planning. When using the model of work preparations, one analyzes the specific work preparation with the intent and goal to carry through the labor within the beforehand estimated time, budget and quality, while still maintaining satisfying work environment.The aim of this paper is to, from a perspective of work environment, map out how NCC: s work preparations function today. The goal is to provide suggestions for improvement. This can be done by performing interviews and surveys on the NCC employees.The results indicate that the staff of NCC see work preparation as a helping aid in improving work environment. However, there are also shortcomings in the way work preparations are done at NCC, and these could be improved. We therefore recommend NCC to make improvements in the planning, realization and the follow-up phase when setting up a work preparation. Our suggestions for improvement can be found under “recommendations”.

Sammanfattning Examensarbete, Civilekonomprogrammet, Ekonomihögskolan vid Linneuniversitetet i Växjö, Vårtermin 2024. Författare: Elma Ibricic &amp; Elvisa Smajic Handledare: Natalia Berg Examinator: Ola Nilsson Titel: Från små till stora revisionsbyråer: Utmaningar med hållbarhetsrevision och vägen till CSRD-efterlevnad Sökord: Revisionsbyråer, CSRD, utmaningar, förberedelser, legitimitet, institutionell teori. _______________________________________________________________________ Bakgrund &amp; Problem: Inom en snar framtid förväntas det nya direktivet CSRD träda i kraft, vilket kommer att göra revision av hållbarhetsrapporter obligatorisk. Detta innebär att auktoriserade revisorer måste förbereda sig för att möta de nya kraven i detta direktiv. En utmaning uppstår då revisorer vanligtvis är utbildade för att granska finansiella rapporter och har bristande kompetens inom området hållbarhet. Vidare är det brist på standardiserade granskningsprocesser för hållbarhetsrevisioner och en bristfällig vägledning genom revisionsprocessen, vilket ytterligare komplicerar situationen för revisionsbranschen. Syfte: Studiens syfte är att undersöka vilka utmaningar och förberedelser revisionsbyråer av olika storlekar står inför när det kommer till den obligatoriska hållbarhetsrevisionen som införs i samband med implementeringen av CSRD. Metod: För att uppnå syftet har vi använt en deduktiv forskningsansats och tillämpat en kvalitativ metod. Empirisk data har samlats in genom semistrukturerade intervjuer med auktoriserade revisorer som har erfarenhet av revisionsyrket. Slutsats: Slutsatsen från studien är att bristande kompetens uppfattas som den främsta utmaningen för revisorer, då de saknar nödvändiga kunskaper inom hållbarhetsområdet för att effektivt granska innehållet i hållbarhetsrapporterna. Utmaningen är särskilt påtaglig för små revisionsbyråer, vilka möter större resursbegränsningar jämfört med de stora Big 4 byråerna som har tillgång till interna utbildningsprogram och expertis. Vidare noteras att förberedelserna för det nya direktivet varierar beroende på revisionsbyråns storlek, där de stora Big 4-byråerna ofta befinner sig i framkant av förberedelseprocessen. Återigen är det bristande resurser som begränsar icke Big 4-byråerna från att genomföra adekvata förberedelser inför det nya direktivet. / Abstract Master Thesis, Master of Science in Business and Economics, School of Business and Economics at Linnaeus University in Växjö, Spring 2024. Authors: Elma Ibricic &amp; Elvisa Smajic Supervisor: Natalia Berg Examiner: Ola Nilsson Title: From small to large audit firms: Challenges in sustainability auditing and the path to CSRD  compliance Keyword: Audit firms, CSRD, challenges, preparations, legitimacy, institutional Theory._____________________________________________________________________ Background &amp; problem: In the near future, the new CSRD directive is expected to come into effect, mandating the audit of sustainability reports. This requires certified auditors to prepare for meeting the new requirements set by this directive. A challenge arises as auditors are typically trained to review financial reports and lack expertise in the field of sustainability. Additionally, there is a lack of standardized auditing processes for sustainability audits and insufficient guidance throughout the auditing process, further complicating the situation for the auditing profession. Purpose: The purpose of this study is to investigate the challenges and preparations faced by audit firms of various sizes in relation to the mandatory sustainability auditing introduced with the implementation of the CSRD. Method: To achieve this objective, we employed a deductive research approach and applied a qualitative method. Empirical data were collected through semi-structured interviews with certified auditors who have experience in the auditing profession. Conclusion: The conclusion of the study is that a lack of expertise is perceived as the primary challenge for auditors, as they lack the necessary knowledge in the field of sustainability to effectively review the content of sustainability reports. This challenge is particularly pronounced for smaller audit firms, which face greater resource constraints compared to the larger Big 4-firms that have access to internal training programs and expertise. Furthermore, it is noted that preparations for the new directive vary based on the size of the audit firm, with the larger Big 4-firms often being at the forefront of the preparation process. Once again, it is the limited resources that hinder smaller non-Big 4-firms from adequately preparing for the new directive.