Three wastewater treatment systems (WWTS) situated on Cayes in the Belize Barrier Reef System were assessed in terms of the unique public health and environmental circumstances of being a tourist destination surrounded by fragile coral reef. Laughing Bird Caye, Silk Caye, and Little Water Caye are three small cayes that are the staging points for local diving, fishing, and other recreational tourism. All three systems are based upon pour-flush toilets, semi-anaerobic biodigesters and drainage fields. Limitations in cost, available resources, useable area, high infiltration rates of the sand, and salinity of the water have played a major factor in the construction and performance of the WWTS on the Cayes. This thesis aims to form an understanding of treatment efficiency of the WWTS, investigate the effectiveness of decentralized saltwater-based WWTS in comparison to freshwater-based WWTS, and provide recommendations to improve the performance and resource recovery in a manner appropriate for the context in which the systems are deployed. A mathematical model was developed to predict the performance of the WWTS based on available operational and water-quality input data. The model is based on the mass balances of six species: inert solids, fecal solids, bacterial biomass, soluble substrate (i.e. dissolved organic carbon), ammonium and nitrate. Effects of salinity were estimated for the two saltwater-based WWTS. The model predicted the effluent concentrations of fecal solids, soluble biological oxygen demand (BOD), ammonium, and nitrate. A sensitivity analysis was also performed on the predicted effluent treatment efficiency based upon influent load, oxygen concentration and system salinity. Results from Silk Caye and Laughing Bird Caye indicate that varying the number of visitors from seasonal lows to highs has a moderate impact on the effluent fecal solids and soluble BOD in the effluent. Due to the relatively large volume of the WWTS at Little Water Caye, and thus high HRT, varying the number of visitors did not have a significant effect. The model predicted a reduction of nitrogen from the effluent due to settled solids and the assimilation of the nitrogen into bacteria. However the model consistently projected an effluent nitrate concentration (as mg/L as N) between 60 and 63 across the three WWTS. The oxygen concentration within the WWTS had the greatest effect on effluent BOD of the three parameters tested in the sensitivity analysis. Results from the sensitivity analysis indicate that a minimum concentration of 0.95 mg/L of oxygen is required before the model can accurately predict the effluent BOD concentration. The concentration of effluent fecal solids did not significantly change with changes in oxygen concentration. Salinity had a significant effect on the predicted fecal solids and soluble BOD in the effluent. Predicted fecal solids in the effluent wastewater increased approximately 60 percent from freshwater conditions to 4 percent salinity. Similarly, effluent BOD concentration increased strongly with increasing salinity. The increase in concentration is due to the major reduction of substrate-consuming bacteria by cell-die-off. The model predicts that a significant increase in cell die-off begins to occur at 2.4 percent salinity. The predicted effluent of the freshwater-based WWTS on Little Water Caye was compared to 166 wastewater treatment plants operating in Brazil. Comparison between the WWTS on the Caye and the decentralized WWTS in Brazil indicate that the predicted removal efficiencies of total suspended solids and soluble BOD are higher than the measured efficiencies of the WWTS. However, the total nitrogen removal efficiency for the WWTS on the Caye was the least effective; most-likely because the model does not account for denitrification within the biodigester. The comparison between the WWTS illustrates that the predicted removal efficiency of BOD and TSS solids is most likely less in the actual measurement than predicted value from the model. The WWTS on the Cayes were constructed to mitigate the impacts of the wastewater produced by visitors on the general health of the pubic and the environment. Considering the reports of the eutrophication affecting the coral reefs surrounding the Cayes, the WWTS have largely failed in at least one aspect of their purpose. The effluent water quality predicted by the model also suggests that significant concentrations of nitrogen are entering the surrounding ocean habitat as ammonia and nitrate. Recommendations to improve the effluent wastewater quality were separated into three categories based upon the required level of input to realize the recommendation. The input includes the capital cost and labor of the change, the level of buy-in from the users of the system, and the resulting maintenance requirements. The implementation of a urine separation toilet system was proposed as a method to reduce effluent nitrogen entering the environment and to create a resource recovery system (RR) from the already constructed WWTS.

Le pronostic à court terme des patients d'oncohématologie admis en réanimation s'est notablement amélioré au cours des deux dernières décennies. Ces progrès sont le fait d'une diversification importante de l'arsenal thérapeutique relatif à l'oncologie et l'hématologie mais aussi d'une meilleure prise en charge de ces patients au sein des réanimations. Notre travail de recherche s'est centré sur la devenir de ces malades et les facteurs associés à celui-ci.Dans ce cadre, nous avons conduit plusieurs études observationnelles pronostiques portant sur des patients neutropéniques admis en réanimation. Nous avons montré que les facteurs indépendamment associés à la mortalité hospitalière étaient une allogreffe de moelle, le recours à la ventilation mécanique invasive, le recours à l'épuration extra-rénale ainsi qu'une documentation microbiologique positive. De plus, chez les patients neutropéniques admis en réanimation pour sepsis sévère/choc septique, les facteurs indépendamment associés à la mortalité en réanimation étaient une antibiothérapie initiale inappropriée, un délai d'initiation de l'antibiothérapie en réanimation > 1h, une documentation microbiologique positive à bacille gram négatif non fermentant et à un score SOFA élevé dès l'admission en réanimation. La désescalade du traitement antibiotique initial, réalisable dans 44% des cas,était sans répercussion significative sur le pronostic à court et long-terme. Enfin, chez les patients neutropéniques admis en réanimation pour détresse respiratoire aiguë, le seul facteur indépendant associé à la mortalité hospitalière était le recours à la ventilation mécanique alors que l'utilisation de corticostéroïdes les jours précédant l'admission en réanimation et l'une admission dans un contexte de sortie d'aplasie étaient protecteurs.Finalement, nous avons montré dans une récente revue de la littérature que le pronostic du patient d'oncohématologie admis en réanimation s'était amélioré au cours du temps et que la neutropénie ne semblait pas être un facteur pronostique dans ce contexte.En conclusion, nous avons montré que le patient neutropénique est à haut risque de complications sévères infectieuses, respiratoires et immunologiques. Ces complications impactent le pronostic des patients de manière significative. Nos résultats vont donner lieu à plusieurs essais randomisés chez le patient neutropénique admis en réanimation notamment autour de la désescalade antibiotique au cours du sepsis et des stratégies d'oxygénothérapie en cas de détresse respiratoire. / The short-term prognosis of patients with onco-hematological diseases and neutropenia admitted to intensive care has significantly improved over the last two decades. This progress is the fact of a significant diversification of the armamentarium on oncology and hematology but also a better management of these patients in the ICUs. Our research has focused on the outcome of these patients and its prognostic factors. In this context, we have conducted several prognostic observational studies of neutropenic patients admitted to intensive care units. We showed that factors independently associated with hospital mortality were the bone marrow transplantation, the use of invasive mechanical ventilation, the use of renal replacement therapy and a positive microbiological documentation. Moreover, in neutropenic patients admitted to intensive care for severe sepsis / septic shock, factors independently associated with ICU mortality were inappropriate initial antibiotic therapy, a delay of antibiotic treatment > 1h, a positive microbiological documentation with non-fermenting gram negative bacilli, a high SOFA score on admission in ICU. The de-escalation of initial antibiotic treatment feasible in 44% of cases had no significant impact on the short and long-term outcomes. Otherwise, in neutropenic patients admitted to intensive care for acute respiratory failure, the only independent factor associated with hospital mortality was the need for mechanical ventilation, while the use of corticosteroids in the days before ICU admission and a admission during neutropenia recovery period were protective. Finally, we have shown in a recent review of the literature that the outcome of hematology-oncology patient admitted to intensive care had improved over time and that neutropenia did not seem to be a prognostic factor in this context. In conclusion, we have shown that the neutropenic patient is at high risk of severe infectious,respiratory and immunological complications. These complications significantly impact the outcome of these patients. Our results could lead to the planning of several randomized trials in neutropenic patients admitted to intensive care in particular about the escalation antibiotic in sepsis and oxygentherapy strategies for respiratory distress.

Elizabethkingia Meningoseptica (E. Meningoseptica) an oxidase-positive gram-negative aerobic rod.1-2 Although ubiquitous in nature and widely distributed in soil and water, it is not a part of normal human flora. Cases of outbreaks of meningitis in premature neonates or infants have been reported, however, very few cases have been reported in adults.3 Infection is primarily nosocomial, or hospital acquired and has been implicated in bacteremia, meningitis, pneumonia, endocarditis especially in immunocompromised individuals.2-4 We report a 29-year-old male with past medical history significant for intravenous drug abuse, hepatitis C, oxymorphone induced hemolytic uremic syndrome, who presented to hospital with altered mental status. On admission, patient was unresponsive to vocal commands, febrile (102.3 F), tachycardic and tachypneic. He had pinpoint pupils and diffuse petechiae. In addition, he had erythematous flat macular lesions on his palms and dorsum of hands as well as injection marks in left cubital fossa. Cardiac examination was significant for a grade III systolic murmur at apical region and diastolic murmur at left second intercostal space. Laboratory studies revealed thrombocytopenia (43,000m/microL), lactic acidosis (4.9mmol/L), serum creatinine (Cr) of 6.6 mg/dL, glomerular filtration rate (GFR) of 10 ml/min. Transthoracic echocardiogram (TTE) revealed large mobile vegetation on aortic valve measuring 3.6 x 0.72 cm. Patient’s presentation was consistent with infective endocarditis with the vegetation seen on TTE and patient’s physical findings. Magnetic Resonance Imaging of the brain showed numerous small hemorrhagic infarcts, likely secondary to emboli from aortic valve vegetation. Patient required intubation for airway protection and started on hemodialysis. He was initially started on Meropenem and Vancomycin for infective endocarditis and later switched to Ciprofloxacin based on blood cultures and sensitivities which revealed methicillin sensitive staphylococcus aureus and multi-drug resistant E. Meningoseptica. Patient was transferred to long term care facility after acute care at the hospital. The increasing incidence of polymicrobial infective endocarditis and increasing resistance to antibiotic therapy pose challenges to the rapid assessment and treatment to mitigate the multi-organ involvement with septic emboli. Reports of pathogenicity associated with native valve endocarditis with this organism is scarce and exist primarily in a very few case reports and is resistant to many traditional antibiotics.5,6 E. Meningoseptica has shown antimicrobial susceptibility to the newer quinolones, rifampin, trimethoprim/sulfamethoxazole and ciprofloxacin with reasonable activity.7 Due to the unusual pattern of antibiotic resistance, early switching to appropriate antibiotics based on sensitivities is crucial for survival in patients with E. Meningoseptica. References 1..Kim KK, Kim MK, Lim JH, Park HY, Lee ST. Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov. Int J Syst Evol Microbiol.2005 May;55(Pt 3):1287-93. 2:Shinha T, Ahuja R. Bacteremia due to Elizabethkingia meningoseptica. IDCases. 2015 Jan 17;2(1):13-5. doi: 10.1016/j.idcr.2015.01.002. eCollection 2015. 3..Jung SH, Lee B, Mirrakhimov AE, Hussain N. Septic shock caused by Elizabethkingia meningoseptica: a case report and review of literature. BMJ Case Rep. 2013 Apr 3;2013. pii: bcr2013009066. doi: 10.1136/bcr-2013-009066. 4.Ratnamani MS, Rao R. Elizabethkingia meningoseptica: Emerging nosocomial pathogen in bedside hemodialysis patients. Indian J Crit Care Med. 2013 Sep;17(5):304-7. 5.Bomb K, Arora A, Trehan N. Endocarditis due to Chryseobacterium meningosepticum. Indian J Med Microbiol. 2007 Apr;25(2):161-2. 6.Yang J, Xue W, Yu X. Elizabethkingia meningosepticum endocarditis: A rare case and special therapy. Anatol J Cardiol. 2015 May;15(5):427-8. 7. Hsu MS, Liao CH, Huang YT, Liu CY, Yang CJ, Kao KL, Hsueh PR. Clinical features, antimicrobial susceptibilities, and outcomes of Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) bacteremia at a medical center in Taiwan,1999-2006. Eur J Clin Microbiol Infect Dis. 2011 Oct;30(10):1271-8.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22768号 / 工博第4767号 / 新制||工||1745(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 田中 宏明, 教授 清水 芳久, 教授 藤井 滋穂 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Myocardial dysfunction is an important manifestation of sepsis/septic shock. Activation of Phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) signaling pathway has been shown to improve cardiac performance during sepsis/septic shock. We have reported previously that α-lipoic acid (LA) activates PI3K/Akt pathway in neuronal cells. It is possible, therefore, that treatment with LA will attenuate cardiac dysfunction during sepsis/septic shock through a PI3K/Akt-dependent mechanism. To test this possibility, we treated mice with LA prior to lipopolysaccharide (LPS) challenge. Cardiac function was analyzed by echocardiography 6 h after LPS challenge. LPS significantly suppressed cardiac function as evidenced by decreases in EF% and FS% in mice. However, LA pretreatment significantly attenuated cardiac dysfunction following LPS challenge. LA pretreatment also improved survival in LPS-challenged mice. Furthermore, LA markedly attenuated the LPS-induced inflammatory response in myocardium, as evidenced by decreases in the upregulation of VCAM-1, ICAM-1 and iNOS, as well as myocardial leucocytes infiltration. Moreover, LPS challenge significantly decreased the phosphorylation levels of Akt and Gsk-3β, which was prevented by LA pretreatment. More importantly, inhibition of PI3K/Akt signaling by Wortmannin (WM) completely abrogated the LA-induced protection in cardiac dysfunction following LPS challenge. Collectively, our results demonstrated that LA improved cardiac function during endotoxemia. The mechanism was through, at least in part, preserved activation of the PI3K/Akt signaling.

Myocardial dysfunction is an important manifestation of sepsis/septic shock. Activation of Phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) signaling pathway has been shown to improve cardiac performance during sepsis/septic shock. We have reported previously that α-lipoic acid (LA) activates PI3K/Akt pathway in neuronal cells. It is possible, therefore, that treatment with LA will attenuate cardiac dysfunction during sepsis/septic shock through a PI3K/Akt-dependent mechanism. To test this possibility, we treated mice with LA prior to lipopolysaccharide (LPS) challenge. Cardiac function was analyzed by echocardiography 6 h after LPS challenge. LPS significantly suppressed cardiac function as evidenced by decreases in EF% and FS% in mice. However, LA pretreatment significantly attenuated cardiac dysfunction following LPS challenge. LA pretreatment also improved survival in LPS-challenged mice. Furthermore, LA markedly attenuated the LPS-induced inflammatory response in myocardium, as evidenced by decreases in the upregulation of VCAM-1, ICAM-1 and iNOS, as well as myocardial leucocytes infiltration. Moreover, LPS challenge significantly decreased the phosphorylation levels of Akt and Gsk-3β, which was prevented by LA pretreatment. More importantly, inhibition of PI3K/Akt signaling by Wortmannin (WM) completely abrogated the LA-induced protection in cardiac dysfunction following LPS challenge. Collectively, our results demonstrated that LA improved cardiac function during endotoxemia. The mechanism was through, at least in part, preserved activation of the PI3K/Akt signaling.

Bakgrund: Sepsis definieras som en kroppslig reaktion på infektion och klassificeras som ett livshotande medicinskt tillstånd. Post-sepsis kännetecknas av hög mortalitet och morbiditet samt svår återhämtning. Därför är det viktigt att identifiera och sammanställa de problem patienter träffar på efter sepsis vård genom att bedöma deras livskvalitet efter sepsis. Syfte: Syftet med studien var att beskriva skillnader i livskvalitet efter genomgången sepsis, vid olika tidpunkter och i jämförelse med andra grupper i befolkningen. Metod: Litteraturstudien innefattar åtta empiriska studier med kvantitativ metod och sökning gjordes i databaserna Pubmed och Cinahl. Artiklarna kvalitetsgranskades, analyserades och sammanställdes i text och tabeller. Resultat: Artiklarna använde olika mätinstrument som inkluderar Short-Form Health Survey (SF-36), EuroQol-5 Dimensions (EQ-5D) och Sickness Impact Profile (SIP).Domänerna i mätinstrumentet omgrupperades för att anpassa resultaten till varandra och SF-36 användes som grundparametrar. Deltagarna upplevde ett signifikant nedsatt fysiskt och psykisk förmåga efter genomgången sepsis. Konklusion: Sepsis är en livshotande sjukdom som visade sig ha en hög grad påverkan på patienternas fysiska och mentala livskvalitet, under en lång period och återhämtning kan vara svår. Detta innebär att sepsis överlevande behöver vård under sjukhusvistelse samt även efter utskrivning. Ökad förståelse och kunskap behövs för att främja insatser som lindrar samt förbättrar livskvalitet hos sepsis överlevande. / Background: Sepsis is defined as a disturbed bodily reaction to infection and is classified as a life-threatening medical condition. Post-sepsis is characterized by high mortality and morbidity as well as difficult recovery. Therefore, it is important to identify and compile the problems patients encounter after sepsis care by assessing patients’ quality of life after sepsis. Aim: The purpose of the study was to describe differences in quality of life after surviving sepsis, at different times and in comparison, with other population groups. Methods: The literature study contains eight empirical studies with quantitative methods found in Pubmed and Cinahl. The articles were cross-examined, analyzed, and compiled in text and tables. Results: The articles used various quality-of-life measuring instruments that include the Short-Form Health Survey (SF-36), EuroQol-5 Dimensions (EQ-5D) and the Sickness Impact Profile (SIP). The domains in the measuring instrument were regrouped, and domains from SF-36 were used as base parameters. Patients experienced impaired physical and mental ability after sepsis. Conclusion: Sepsis is a life-threatening disease that has been shown to have a high degree of impact on patients’ physical and mental quality of life over a long period of time, and recovery can be difficult. This shows that sepsis survivors need care during the hospital stay and after discharge. Increased understanding and knowledge are needed to promote efforts that alleviate and improve the quality of life of sepsis survivors.

Sepsis is a severe blood stream infection that claim the lives of almost 220,000 Americans annually. Delayed patient treatment results in multi-organ failure, morbidity, mortality, and increased hospital length of stay. Timely sepsis management enables hospitals to have decreased expenses, increased patient survival, and judicious interventions. The problem addressed in this project was the lack of sepsis- training for registered nurses (RNs) working in the emergency department (ED) of a 628-bed hospital in the southeastern United States. Under the direction of the director of the ED, 269 patient charts were reviewed during 2014 to February 2015 for data related to a sepsis diagnosis. Data showed that 19.4% (n = 103) of patients diagnosed with sepsis had the sepsis order set implemented by the ED nurse. The purpose of this project was to create an educational sepsis-training program for ED nurses. The program included a 2-hour educational module on signs and symptoms of sepsis, including guidelines from the Surviving Sepsis Campaign and the Emergency Nurses' Association. Stetler's Model of Research Utilization and Benner's Novice to Expert conceptual frameworks supported the project. The director of professional practice provided formative feedback on module content and the program evaluation tool. Director feedback indicated that content was beneficial in educating ED nurses on the signs and symptoms of early sepsis recognition. The ED director has now mandated that all ED nurses take the training module and posttest. The project has the potential to improve early sepsis recognition by ED staff and to improve patient outcomes, thus promoting positive social change for patients, families, and nurses.

Sepsis is an organ dysfunction life-threatening disease that is caused by a dysregulated body response to infection. Sepsis is difficult to detect at an early stage, and when not detected early, is difficult to treat and results in high mortality rates. Developing improved methods for identifying patients in high risk of suffering septic shock has been the focus of much research in recent years. Building on this body of literature, this dissertation develops an improved method for septic shock prediction. Using the data from the MMIC-III database, an ensemble classifier is trained to identify high-risk patients. A robust prediction model is built by obtaining a risk score from fitting the Cox Hazard model on multiple input features. The score is added to the list of features and the Random Forest ensemble classifier is trained to produce the model. The Cox Enhanced Random Forest (CERF) proposed method is evaluated by comparing its predictive accuracy to those of extant methods.

京都大学 / 0048 / 新制・課程博士 / 博士(地球環境学) / 甲第18629号 / 地環博第124号 / 新制||地環||25(附属図書館) / 31529 / 京都大学大学院地球環境学舎環境マネジメント専攻 / (主査)教授 藤井 滋穂, 教授 高岡 昌輝, 准教授 田中 周平 / 学位規則第4条第1項該当 / Doctor of Global Environmental Studies / Kyoto University / DFAM