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Paediatric community-acquired pneumonia (CAP) is common in North America. It is often treated with beta-lactam antimicrobials targeting S. pneumoniae, the most important cause of CAP in young children. Current guidelines recommend 10 days of therapy for paediatric CAP, regardless of severity; in contrast, mild CAP in adults is routinely treated with only 5 days of antimicrobials. There have been no definitive studies of 5-day vs. 10-day therapy for CAP in children. The objective of this thesis was to conduct a pilot RCT comparing 5 to 10 days of amoxicillin for the treatment of mild paediatric CAP and then design the multicentre follow-up trial. Children aged 6 months - 10 years with no significant past medical history presenting to the McMaster Children's Hospital emergency department with mild CAP were eligible for enrollment. All participants were randomized to either 10 days high-dose amoxicillin (90 mg/kg/day divided bid) or 5 days of high-dose amoxicillin + 5 days placebo. The primary outcome was clinical cure at day 14-18 post-enrollment. In total, 61 participants were recruited. The median participant age was 2.64 y. Only 60% of chest radiographs were reported by the radiologist as showing evidence of pneumonia. There were six treatment failures; one participant failed to defervesce on day 4, one participant had recurrent fevers leading to re-presentation to the emergency, and the other four participants did not meet clinical cure criteria but were essentially well at the time of follow-up. Study blinding has been maintained. The majority of previously healthy children with mild CAP who are well enough to be treated as outpatients appear to do well, regardless of duration of antimicrobial treatment. Feasibility and safety of the trial protocol have been demonstrated; the follow-up multicentre trial is slated to begin in mid-2015. / Thesis / Master of Science (MSc)

Indiana University-Purdue University Indianapolis (IUPUI) / Fibromyalgia (FMS) is a complex, chronic condition involving persistent and widespread pain of unknown origin. FMS is sometimes mistaken as psychiatric in origin; however, the precise origin and cause of FMS is unknown (Klippel et al., 1998). Worldwide prevalence rates range from 0.18-12%, with 0.18% in the United Kingdom (UK) (Hughes et al., 2006), 2% in the United States (US) (Wolfe et al., 1997), and 12% in Spain (Carmona et al., 2001). In the UK, there is debate over the existence of FMS (Bohr, 1995), and the reluctance of a general practitioner (GP) to diagnose conditions that are poorly defined (Hughes et al., 2006). Primary symptoms of FMS include generalized muscular pain, multiple tender points, sleep disruption and excessive fatigue. Additional symptoms include headaches, memory and concentration problems, dizziness, numbness/tingling, itching, fluid retention, abdominal cramps or pelvic pain and diarrhea (Hudson et al., 1992). Clearly, these symptoms may have an immense impact on daily life, limiting an individual’s functioning and emotional well-being. FMS is associated with significant societal and health care costs. Patients with FMS may repeatedly present to the general practitioner with various symptoms before a definitive diagnosis of FMS is made. As a result, general practitioners may be more likely to diagnose FMS in patients who frequently present with symptoms related to FMS, while patients who meet the diagnostic criteria but who rarely present at the practice may be missed (Ehrlich, 2003). The condition is of unknown etiology, and this, together with the lack of verifiable diagnostic criteria (i.e. lab tests), has led some to speculate that the disease does not or is at best a surrogate marker for underlying psychosocial problems. As such, the very process of diagnosing a patient with FMS may exacerbate symptoms and lead to increased dependence on health care providers (Ehrlich, 2003). This study examined the diagnoses of FMS made in “real-life” clinical practice and recorded by general practitioners in a large primary care population in the UK.

Stockholms länsstyrelse genomför en regional miljöövervakning för att kartlägga kvaliteten på grundvattnet. Det här arbetet har tagits fram på länsstyrelsens initiativ tillsammans med Kungliga Tekniska Högskolan och vars syfte har varit att identifiera och diskutera lösningar på eventuella kvalitetsproblem.   Undersökningen har varit fokuserad på kloridhalter i vattnet och en fallstudie har gjorts av Hammarby källa i Upplands Väsby norr om Stockholm. Det finns flera tidigare undersökningar om förorening kopplat till vägsalt, och den här studien har avgränsats till klorid och i mindre utsträckning andra ämnen som kan relateras till vägsaltning. Arbetet har inneburit en sammanställning och granskning av material om kloridhalter i grundvatten, lagstiftning om föroreningar, halkbekämpning och åtgärder mot vattenföroreningar.   Undersökningen visade att kloridhalten i källorna i Stockholmsregionen har ökat, med förhöjda värden i vissa enstaka källor. År 2014 var medelvärdet och medianvärdet på 51,6 respektive 24,4 milligram klorid per liter vatten. Vatten får kvalitetsanmärkningar och kan orsaka korrosionsproblem i ledningar när halten går upp till 100 milligram per liter. Dock ska åtgärdsprogram införas redan vid en kloridhalt på 50 mg/l eller vid en markant stigande trend av kloridhalten. Kloridkoncentrationerna i Hammarby källa har länge legat nära eller över 100 mg/l. På grund av de höga koncentrationerna tätades dikena intill vägen och saltningen minskade i området. Det har lett till att kloridhalten i vattnet har sjunkit, men väldigt långsamt, och halterna betraktas fortfarande som höga.   Det finns ett flertal åtgärder för att minimera kloridhalter i grundvatten, dels alternativ till natriumklorid eller andra metoder, t.ex. att hålla vägbanorna isfria med bergvärme. De är många gånger dyra och lättast att tillämpa vid konstruktion av nya vägar. Resultaten från undersökningen kan utgöra en grund för mer detaljerade undersökningar, både av specifika källor, möjliga åtgärder som kan genomföras och vilka andra föroreningar som förekommer i grundvattnet i Stockholmsområdet. / The Stockholm county administrative board is continuously perform regional environmental monitoring with regards to groundwater quality. The county board and the Royal Institute of Technology developed this project, and its aim was to survey the situation based on chemical analysis and discuss solutions to potential problems.   The study has focused on chloride concentrations in the groundwater and the Hammarby spring, situated in Upplands Väsby north of Stockholm, was used as a case study. Earlier, chloride concentrations had been studied in connection to deicing salts, and this study has been limited to chloride with some attention paid to other elements affected by deicing salts. The study has resulted in a summary and discussion on research on chloride in groundwater, laws regulating pollution, deicing efforts and countermeasures aimed at water pollution.   The study showed that chloride concentration has increased in springs found in the greater Stockholm area, with elevated concentrations found in specific sites. The overall concentrations are below the ones found in legal guidelines. 2014 showed a mean and a median on 51.6 and 24.4 milligrams of chloride per liter of water, respectively. Sampled water gets remarks on quality and cause corrosion in pipes at concentrations higher than 100 mg/l. The chloride concentration in the Hammarby spring has for a long been at or above 100 mg/l. Due to the high concentrations of chloride, the roadside ditches have been sealed and road salting has been limited. This has caused chloride concentrations to decrease slowly, but the concentrations are still regarded as high.   There are numerous kinds of countermeasures, both alternatives to deicing salts to decrease pollution or other methods, such as keeping roads free of ice through energy storage in the ground. These are often expensive and easier to implement when constructing new roads. The results from the project may be the base for more investigations, both with regards to specific springs and the countermeasures that can be used, and what other pollutants that are present in the groundwater in the Stockholm region.

Although there is significant prevalence of serious emotional disturbance in adolescents, research concerning the determination of appropriate levels of care is lacking. This study examined predictors of successful treatment completion in male adolescents (n=132) who were admitted to a suburban residential treatment center during a ten year period. Data on pre-treatment client variables, family participation in treatment, and length of stay were collected on each subject. Data were collected by sequentially reviewing 132 file records of previously discharged clients. Five variables (age upon admission, family constellation, family participation, previous out-of-home placements, criminal involvement) did not predict successful treatment completion. A significant relationship was found between length of stay in residential treatment and successful treatment completion. Implications for decision-making regarding admissions to residential treatment programs and needs for future research are discussed. / Master of Science

PURPOSE: Previous studies have established an association between pre-treatment drinking goals (abstinence vs. non-abstinence) and alcohol treatment outcome. The purpose of this study is to better understand that characteristics of individuals who choose abstinence compared to non-abstinence as a drinking goal prior to treatment. This study explores the characteristics as predictor variables of drinking goal choice prior to entering a Phase II research study in Boston, Massachusetts. METHODS: The participant population consisted ot individuals who called about entry into a Phase II alcohol dependence research study and completes a telephone screening questionnaire (n=608). Desired drinking goal was measured in the telephone screening form and categorized as either abstinence (n=206) or non-abstinence (n=308). Differences between the 2 goal groups were explored by univariate calculations. In the final stage of the analysis potential predictor variables were entered into a backwards elimination logistic regression model to determine significant relationships between predictor variables and drinking goal choice. RESULTS: A total of 206 (40.1%) participants selected abstinence and 308 (59.9%) selected non-abstinence as a pre-treatment drinking goal. In the univariate analysis, participants' selecting a goal of abstinence were significantly more likely to have had previous alcohol treatment (including rehabilitation, outpatient counseling, detoxification, and Alcoholics Anonymous), have had alcohol related seizures, were currently on probation or parole, had higher average of drinks per drinking day, and more heavy drinking days as compared to the non-abstinence group. In the logistic regression model the strongest predictors of a participant choosing a goal of abstinence are previous alcohol treatment, previous detoxification, current probation or parole, and absence of recreational drug use. CONCLUSIONS: Several predictor variables were found to be associated with an individual choosing a drinking goal of abstinence prior to entry into an alcohol research study. These results can be helpful for researchers conducting future clinical trials. Based on the strongest predictors, those variables can be used in stratification to prevent confounding in future research studies.

Micro ribonucleic acids (miRNAs) are pivotal post-transcriptional regulators of gene expression and if research continues to reveal positive results, they will soon be used as therapeutic targets in the clinical setting for the treatment of a variety of cancers. They are evolutionarily conserved small noncoding RNAs that range from 18 to 24 nucleotides in length. There are over 1,400 miRNAs for which abundant evidence has demonstrated fundamental importance in normal cell development and up- or downregulation when they become deregulated. The deregulation of miRNAs, which can function as tumor suppressors or oncogenes, contributes to the development of cancer, among other diseases. Deregulation of tumor suppressor miRNA can occur in many different tissues of the body and lead to a variety of cancers. Tumor suppressor let-7 negatively regulates expression of an oncogenic mRNA named RAS. In lung cancer, a decrease in let-7 produces an increase in expression of RAS, which contributes to cell proliferation and tumorigenesis. In chronic lymphocytic leukemia, Bcl2 protein becomes overexpressed due to the down-regulation of tumor suppressors miRNA-15 and miRNA-16. MicroRNA-34 plays an important role in neuroblastoma in which its expression is decreased due to mutations that decrease a tumor suppressor protein, p53. Upon deregulation of oncogenic miRNAs, tumor suppressor mRNA expression is decreased and leads to multiple types of cancer. Up-regulation of the miRNA-17-92 cluster in lung cancer leads to increased cell proliferation and contributes to angiogenesis in many cancers. In B cell lymphoma, miRNA-155 becomes up-regulated along with an RNA named BIC. This up-regulation accelerates pathogenesis and up-regulation of an oncogenic protein, c-myc. MicroRNA-21 acts as an anti-apoptotic factor by downregulating apoptosis-related genes and contributing to the development of human glioblastoma. This review summarizes the present understanding of how miRNAs function at the molecular level in the body, how their deregulation contributes to tumor formation, maintenance and metastasis and how they can be used for cancer diagnosis, prognosis and therapy. With the mass amounts of knowledge gained from the current research done on miRNAs, a cancer cure may soon be developed based on the targeting of specific miRNAs. The promise of miRNAs in cancer therapeutics will depend on the development of proper delivery strategies of miRNA mimics and inhibitors, in addition to evaluation of safe usage and toxicity of therapeutic dosages.

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder and has a rapidly increasing prevalence. It is characterized by motor deficits, primarily resting tremor, rigidity, postural instability, and bradykinesia, associated with the progressive loss of dopaminergic neurons and formation of Lewy bodies. Current pharmacological treatments address mainly the primary motor symptoms of the disease and do not provide protection against further neurodegeneration. Therefore, complementary interventions are examined for their potential role in reducing symptoms, both motor and non-motor, and rate of PD progression. The Mediterranean, ketogenic, and MIND diets are promising interventions that simulate fasting states, thereby inducing adaptive and protective cellular stress responses. The large quantities of foods high in antioxidants, anti-inflammatory effects, and healthy fats recommended by these diet plans may combat PD pathology, particularly neuroinflammation, oxidative stress, and mitochondrial dysfunction. Ketogenic diets, in addition, provide more efficient brain energy sources, in the form of ketone bodies, that may further curb effects of mitochondrial dysfunction. Fats, omega-3 fatty acids in particular, provide significant, clinically relevant neuroprotection from the disease and supplementation is recommended. PD patients, on average, have insufficient serum levels of certain vitamins which may contribute to PD progression. When supplemented in large amounts, these vitamins may have the opposite effect. Certain foods, such as dairy products, red meats, and highly processed foods, are associated with increased risk of PD and may be considered neurodegenerative. Sodas, especially diet sodas, are significantly correlated with more rapid disease progression and increased symptom severity. Physical activity is highly recommended for PD patients for its motor and non-motor benefits and neuroprotective roles. Among the most effective forms of PA are suggested to be aerobic exercise and progressive training programs. Consistent exercise is advised for consistent cognitive benefits and alleviation of other symptoms. The potential benefits of cognitive training for individuals with PD remain to be seen. Further research in all areas is needed to elucidate the most effective complementary interventions in combating PD.

Increasing demands for hyperthermia (HT) as an adjuvant therapy is caused from the contributions of thermal therapy to the traditional treatments. Latest improvements in hyperthermia make it popular among thermal therapies to cure cancer in any organ or body parts. HT takes advantage of EM radiation inside the tumor that provides temperature and blood perfusion increment that helps radiation therapy and chemotherapy to be more efficient. Therefore, some advantages makes HT preferred when compared to similar treatments. Being noninvasive and painless with an efficient cooling system, and helping to shorten the application period and session number of conventional treatments are most important advantages of HT. However, existing HT systems require high input power per elements on the applicators and long application time. Designing conformal and patient specific applicators with mild application can solve this issue. Moreover, mild HT application can make cancer treatment cheaper and more accessible. The main goal in this study is to design conformal HT applicators through optimization for liver and provide a patient specific and cost-effective local hyperthermia treatment that can be widely used in local clinical cancer treatment centers without expensive applicators.