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Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background There are limited oral treatment options for patients with fungal infections who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with fungal disease refractory to, standard antifungal therapy. We present an interim analysis of patient outcomes from the FURI study by fungal disease type. Methods FURI patients are eligible for enrollment if they have proven or probable: severe mucocutaneous candidiasis, invasive candidiasis, chronic or invasive aspergillosis, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (e.g., due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for 113 enrolled patients in the FURI study from 27 centers in US, UK, and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016-2021. A total of 56 patients (49.5%) had invasive candidiasis/candidemia, 32 (28.3%) had mucocutaneous candidiasis, 14 (12.4%) had vulvovaginal candidiasis (VVC), and 11 (9.7%) patients had aspergillosis. Upon DRC review, the percentage of patients with complete or partial response, or for VVC, clinical improvement (defined as vulvovaginal signs and symptoms score ≤ 1) was 58.4%; stable disease was 23.9%; and 11.5% had disease progression (including 2 VVC patients not meeting the criteria for clinical improvement). There was one death due to underlying causes, and six outcomes were indeterminate. Table 1 shows outcomes by disease type. Conclusions Analysis of 113 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options.

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background There are limited oral treatment options for patients with high-mortality fungal infections such as candidemia or invasive candidiasis who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with invasive fungal disease refractory to, standard antifungal therapy. We present an interim analysis of all-cause mortality within 30 days post-treatment from the FURI study by fungal disease type for patients with candidemia or invasive candidiasis, who completed therapy up until October 2021. Methods FURI patients are eligible for enrolment if they have proven or probable: severe mucocutaneous candidiasis or invasive candidiasis, or candidemia, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (eg, due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible. Patients were followed through 30 days post-treatment for all-cause mortality. Results Out of the 113 patients who completed therapy in the FURI study through October 2021, 56 (50%) had invasive candidiasis or candidemia and were treated with ibrexafungerp. The most common infections in this group were candidemia (15/56, 26.8%), intra-abdominal infection (13/56, 23.2%), and bone infection (10/56, 17.9%). Overall survival within 30 days post-treatment in this group of 56 patients was 94.6%. Of the 56 patients with candidemia or invasive candidiasis, three (5.3%) died within 30 days after completion of treatment with ibrexafungerp, a fourth died at 31 days, a fifth died at 50 days, and a sixth died at 56 days. The mean age of the expired patients was 56 years. All 4 patients had candidemia (3 with C. parapsilosis and 1 with C. albicans), and 2 had intra-abdominal candidiasis, (both with C. glabrata). The average time on therapy with ibrexafungerp was 15.7 days. The mean time to death post-treatment for these patients was 27 days (median, 21 days). In five cases, the deaths were due to causes other than the underlying fungal disease. For the other case, the cause of death was not disclosed. Conclusions Analysis of all-cause mortality in these patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal diseases and limited treatment options.

Canadian bitumen is too viscous to transport by rail and pipeline to markets. One approach to solve this viscosity issue is to dilute the bitumen with a thinning agent to meet transport specifications, but the addition of diluent underutilizes pipeline capacity and increases production cost. A second approach involves the partial refinement of bitumen to produce synthetic crude, which better utilizes pipeline capacity; however, capital and operational costs are high. A third alternative is a new technology that involves wrapping bitumen in a polymer layer to form a solid “puck” termed Canapux, but transportation of this product to coastal ports is limited to rail. Also, greenhouse gas emissions are greater when oil is transported by rail rather than pipeline. In the end, a variety of bitumen products will be transported in Canada, but not all of these products will respond to remediation equally when spilled. In order to ensure effective spill contingency planning, we recommend that engineered bitumen products have physical properties that are resilient to change, within the range of typical response times, after a spill.

The effects of mixing time and energy on Alaska Northern Slope (ANS) and diluted bitumen Cold Lake Blend (CLB) were investigated using EPA baffled flask test. Dispersion effectiveness and droplet size distribution were measured after 5–120 min. A modeling method to predict the mean droplet size was introduced for the first time to tentatively elucidate the droplet size breakup mechanism. The ANS dispersion effectiveness greatly increased with dispersant and mixing energy. However, little CLB dispersion was noted at small energy input (e = 0.02 Watt/kg). With dispersant, the ANS droplet size distribution reached quasi-equilibrium within 10 min, but that of CLB seems to reach quasi-equilibrium after 120 min. Dispersants are assumed ineffective on high viscosity oils because dispersants do not penetrate them. We provide an alternative explanation based on the elongation time of the droplets and its residence in high intensity zones. When mixing energy is small, CLB did not disperse after 120 min, long enough to allow the surfactant penetration. Our findings suggest that dispersants may disperse high viscosity oils at a rougher sea state and a longer time. The latter could determine how far offshore one can intervene for effective responses to a high viscosity oil spill offshore.

Hibernia is Canada’s largest offshore oil platform. Produced water is the major waste byproduct discharged into the ocean. In order to evaluate different potential disposal methods, a comprehensive study was performed to determine the impact from the discharge. Microorganisms are typically the first organisms to respond to changes in their environment. The objectives were to characterize the microbial communities and the chemical composition in the produced water and to characterize changes in the seawater bacterial community around the platform. The results from chemical, physicochemical, and microbial analyses revealed that the discharge did not have a detectable effect on the surrounding seawater. The seawater bacterial community was relatively stable, spatially. Unique microorganisms like Thermoanaerobacter were found in the produced water. Thermoanaerobacter-specific q-PCR and nested-PCR primers were designed, and both methods demonstrated that Thermoanaerobacter was present in seawater up to 1000 m from the platform. These methods could be used to track the dispersion of produced water into the surrounding ocean.

Canada's production, transport, and sale of diluted bitumen (dilbit) products are expected to increase by a million barrels per day over the next decade. The anticipated growth in oil production and transport increases the risk of oil spills in aquatic areas and places greater demands on oil spill capabilities to respond to spills, which have raised stakeholder concerns. Current oil spill models only predict the transport of bitumen blends that are used in contingency plans and oil spill response strategies, rather than changes in the oil's physical properties that are relevant to spill response. We conducted weathering studies of five oil products (two conventional oils and three bitumen blends) in the Department of Fisheries and Oceans' flume tank. We also considered two initial oil slick thicknesses, 4.0 mm and 7.0 mm. We found that there is a major difference in the time evolution of oil properties (density and viscosity), raising doubts on weathering models that do not consider the thickness of oil. We also developed empirical expressions for the evolution of the density and viscosity of these oil products. The findings from the 4.0 mm results were incorporated with data from the literature to provide an update on the factors to consider during the decision making for spills of diluted bitumen products. The matrix indicated that most response options, including chemical dispersants, work much more effectively within 48 hours of the initiation of weathering. After this window of opportunity closes, natural attenuation or in situ burning is the only option remaining, but containment of oil is a limiting factor for in situ burning.

Antenatal screening has led to early detection of posterior urethral valves (PUV). However, despite early intervention, a proportion of children will develop chronic renal insufficiency. We studied the trend of serum creatinine following urinary tract decompression during the neonatal period in infants as a possible predictor of chronic renal insufficiency.Patients treated by endoscopic resection of posterior urethral valves between 1993 and 2004 were identified. From these, infants treated within the first 30 days of life were identified. Serum creatinine values taken within the first 5 days following initial drainage were recorded. A creatinine velocity for each patient was calculated by linear regression analysis. Creatinine was considered rising if velocity was3 μmol/L/day, or falling if velocity was-3 μmol/L/day. Chronic renal insufficiency was defined as CKD2 or higher.Sixty-four neonates had decompression of the urinary tract. Of these, 16 had rising creatinine despite drainage, 10 had a plateau in creatinine level, and 36 had falling creatinine following drainage. Insufficient data were available in two to calculate creatinine velocity. Progression to renal insufficiency was significantly higher in patients with an initial rise in creatinine (62.5%) than in those with plateau creatinine (40%) or falling creatinine (8.6%) (P ≤ 0.0005 by Fisher exact test). Mean follow-up was 9.2 years.Rising creatinine, even transiently, following urinary tract drainage in neonates with posterior urethral valves is significant and is a new and important indicator of long-term prognosis.

There is currently a need in the health care industry to develop and implement strategies to improve both the quality and cost effectiveness of health care delivery. Continuing medical education (CME), like other components of the health care system, is being pressured for more accountability in physician education programs. Specifically, CME professionals are being asked to address quality assurance issues (either physician performance or health care outcomes) as measures of the impact of educational programs and activities. Major research studies reported in the CME literature have pointed to the importance of determination of practice or real learning needs as a prerequisite for effective education. Furthermore, it has been suggested that research in CME should focus on evaluating the effects of CME interventions on major causes of morbidity and mortality. The funded, on-going project described in this paper is a continuing medical education efsort designed to address and correct dejiciencies in clinical quality and cost effectiveness documented by a mandatory statewide hospital data collection system. The database measures quality and effectiveness of care using two specific data elements: severity of illness upon admission and patient outcome upon discharge, in terms of morbidity and mortality for selected Diagnostic Related Groups. Key clinical findings are the focus. This article provides a conceptual framework and descriptive analysis of (1) the rationale for using large administrative databases in designing, implementing, and evaluating continuing medical education programs, and (2) the replicable problem-solving process that can be used in identifying the real learning needs of physicians from large administrative databases.

Produced water (PW) is the main discharge from the offshore oil industry and contains oil-derived compounds such as poly-aromatic hydrocarbons, phenols, alkylphenols, and heavy metals. Studies suggest that PW discharges may affect the biota over larger areas from the oil drilling sites at sea than originally predicted. We investigated the effects of chronic exposure to PW on some aspects of juvenile Atlantic cod immunity, stress response and growth by intermittently exposing fish to 0, 100 or 200 ppm of PW for 22 weeks. No significant effects of PW were observed on growth, hepatosomatic index, condition factor or plasma cortisol. The respiratory burst (RB) of circulating leukocytes was significantly elevated in the 100 ppm group only, while the RB of head–kidney leukocytes was significantly decreased in both the 100 and 200 ppm groups. Significant up-regulation of the mRNA expression of β-2-microglobulin, immunoglobulin-M light chain and interleukins-1β and −8 was observed in the 200 ppm group, while the down-regulation of interferon stimulated gene 15 was obvious for both the 100 and 200 ppm groups. The results suggest that chronic exposure to environmentally relevant concentrations of PW causes modulations of the immune system of juvenile Atlantic cod with most immune parameters being stimulated, potentially resulting in an energetic cost that may be detrimental to the fish.

The in vitro effect of produced water released by oil and gas platforms was assessed by exposing cod sperm cells to realistic concentrations of this mixture (100, 200, 500 ppm). We investigated produced water impact on enzymes of the aerobic (citrate synthase) and glycolytic metabolism (lactate dehydrogenase), lipid catabolism (lipase), as well as an anti-oxidant enzyme (catalase). Fertilization rates, viability, respiration, ATP, and total motility duration were also evaluated. To explore correlations between these parameters, we have also tested the effect of conserving sperm for 24 h at 4 degrees C. After conservation, fertilization success was decreased but other parameters were not affected. Produced water did not result in a significant change in fertilization; a significant increase in sperm protein amounts and citrate synthase activity can be observed. No correlations are found between parameters showing that sperm viability and unchanged energy levels do not translate into equivalent fertilization capacity. To conclude, exposure of sperm to produced water resulted only in subtle effects on cells. These findings bring information on the effect of produced water on sperm itself rather than on spermatogenesis or testis development of an exposed fish.

Heightened concerns about industry influence on continuing medical education (CME) have prompted tighter controls on the management of commercial funding and conflict of interest. As a result, CME providers must closely monitor their activities and intervene if bias or noncompliance with accreditation standards is likely. Potential for industry influence can be difficult to assess at a stage in the planning process when mitigation strategies can assure balance and content validity. Few tools exist to aid providers in this regard.A 12-item instrument was designed to assess risk for commercial influence on CME. To determine reliability and validity, a cohort of experienced CME professionals applied the tool to standardized "cases" representing CME activities in the early stages of planning. Results were compared with the experts' assignment of the same cases to one of four risk categories. A survey of study participants was conducted to ascertain usefulness and potential applications of the tool.Analysis demonstrated strong intraclass correlation across cases (0.90), interrater reliability (94%), and correlation between assessment of risk with and without the tool (Spearman coefficient, 0.93, p0.01; weighted kappa, 0.59). Participants found the tool easy to use and of potential benefit to their CME office.The Consortium for Academic Continuing Medical Education (CACME) risk stratification tool can help CME providers identify activities that must be closely monitored for potential industry influence, remain aware of factors that place programming at risk for noncompliance with accreditation standards, and substantiate the allocation of resources by the CME office.

To determine the response rate and toxicities of Herceptin and gemcitabine for patients with metastatic pancreatic adenocarcinomas that overexpress HER-2/neu.Patients with metastatic pancreatic cancer with 2+/3 + HER-2/neu expression by immunohistochemistry were eligible. Patients received gemcitabine, 1 g/m2/week, for 7 of 8 weeks followed by 3 of every 4 weeks, and Herceptin, 4 mg/kg loading dose, followed by 2 mg/kg/week.Screening logs demonstrated the rate of HER-2/neu overexpression was 16%. Thirty-four patients were enrolled. Thirty patients (88%) had pancreatic cancers with 2+ overexpression and 4 patients (12%) had 3+ overexpression. Toxicity was similar to gemcitabine alone. Confirmed partial responses were observed in 2 of 32 patients (6%). Thirteen of 32 patients (41%) had either a partial response or a50% reduction in CA 19-9. The median survival for all 34 patients was 7 months, and the 1-year survival was 19%.The response rate of Herceptin and gemcitabine is similar to gemcitabine alone. The 7-month median survival in patients with metastatic pancreatic cancer suggests there may be a modest benefit for some patients. Infrequent HER-2/neu overexpression limits the role of targeting the HER-2/neu gene and prevents definitive conclusions on the addition of Herceptin to gemcibine for patients with pancreatic cancer.

Surficial sediments and blue mussels were collected around the perimeter of Halifax Harbour. Samples were analysed for the levels and fingerprint of polycyclic aromatic compounds (PACs). The objective was to explore the relationship between contaminant profiles in sediments and in mussels and to explore the possibility of deducing their sources, pattern of deposition and circulation in the harbour. Combustion derived compounds predominated in both sets of samples, with more variability observed in the level of petroleum derived hydrocarbons in mussel samples. Biota-sediment accumulation factors (BSAF, dry/dry wt.) varied throughout the harbour, ranging from means of 0.006 to 1.26, where generally fluoranthene displayed the highest BSAF. Sediments and mussels give complementary views of the geographical distribution of contaminants, they reflect the state of benthic and pelagic habitats. Results observed for Halifax Harbour are discussed from the perspective of published data.

Brian Patrick Dillon was educated at Beaumont College. He was commissioned into the Coldstream Guards, serving with distinction in Malaya. At medical school he played in winning United Hospitals Cup teams in …

A 70 year old woman presented to the head and neck unit with a three month history of intermittent haemoptysis, progressive dysphagia, and odynophagia. On further questioning she reported no dysphonia or dyspnoea but complained of left sided otalgia. She had a 40 pack year history of smoking. Apart from controlled hypertension her medical history was unremarkable. Physical examination showed a 3 cm lymph node in the anterior triangle of the neck but no other findings. Fibre optic laryngoscopy performed in the outpatient department showed a large epiglottic mass with normal vocal cords. She was admitted for examination under anaesthetic and imaging of the neck (fig 1). Fig 1 Computed tomogram of the neck

As Richard Lerner has pointed out in a 1980 article in Practicing Anthropology, the preamble of the National Historic Preservation Act of 1966 expresses Congressional concern for the protection of the sociocultural environment as a whole, including both its tangible and intangible aspects. It speaks of "the historical and cultural foundations of the Nation," which "should be preserved as a living part of our community life and development."

Chile is a long narrow strip of land lying between the summits of the Andes and the Pacific Ocean. It extends from the tropic of Capricorn to Cape Horn, or from 24 deg. to 56 deg. south latitude—a distance of 2000 miles, while its average breadth is under 100 miles. Its length, therefore, exceeds its breadth about 20 times. In a tract of country extending over 32 degrees of latitude in the temperate zone we may expect to find great diversity of climate. North Chile is a sandy desert, South Chile is a rainy forest; in the former cotton grows to perfection, in the latter glaciers descend even to the sea. The central provinces enjoy a climate resembling that of Italy; from the spring to the autumn equinox no rain falls, while the rest of the year is rainy. In South Chile there are innumerable rivers and lesser streams, but, as we go northwards, the country gets drier, the streams fewer and smaller, until at last we reach a region in the north where the river beds have no water in them. The one I intend to speak of to-night is at Carrizal, in the province of Atacama, 28 deg. south latitude, or 300 miles north of Valparaiso. One cannot say exactly where the desert begins. The last considerable river north of Valparaiso is the Aconcagua, beyond it being a few smaller ones, but all the country north of Coquimbo may be called desert. From this point to the north This 250-word extract was created in the absence of an abstract

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Summary 1 The medial epicondyle and adjacent bone (diaphysis) were deliberately excised in 16 patients with ulnar neuritis and for other causes including irritation in the groove, cubitus valgus and varus, as a preliminary step for arthroplasty of the elbow, for repair of ruptured triceps; for ununited fracture of the olecranon and also when the ulnar nerve had to be sutured at the wrist and there was a three inch gap to be bridged. Skiagrams of five illustrative cases are shown. 2 The results have been satisfactory. The minor neurological changes cleared up and where there were gross signs there was either improvement or no further progress of nerve degeneration and pain disappeared. 3 This simple operation appears to avoid the danger of fibro-cicatrical contracture, which occasionally occurs when the nerve is embedded in the flexor muscles and, perhaps, minimizes the danger of pressure upon it by external objects as can take place if the nerve is transposed anteriorly and subcutaneously.

Transient severe hyperammonaemia developed in the absence of serious liver dysfunction in three patients being treated for acute leukaemia. The onset of the biochemical disturbance was abrupt and led rapidly to acute encephalopathy, fatal in two cases. In the third patient, prompt initiation of aggressive haemodialysis and intravenous sodium benzoate and sodium phenylacetate infusion successfully controlled plasma ammonium levels until they spontaneously resolved. The cause of the disorder remains to be determined, but urinary nitrogen partition studies suggest temporary impairment of ureagenesis in a catabolic setting as a major pathophysiological feature of this disorder. The absence of liver disease, the normal mitochondrial ultrastructure seen in two cases, and the plasma aminoacid profiles observed serve to distinguish this disorder from others such as Reye's syndrome.

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