572 research outputs found
Narcissus in Queer Time
Queer temporality has been studied in relation to the Middle Ages as a means of questioning the prevailing historiography for other modes of connection to the past, such as embodied or affective. Conversely, the other branch of queer temporality has been primarily interested in how queer lifestyles today disrupt the heteronormative plan laid out by society. Joining these modes, Gower’s revision of Narcissus questions our notions of historiography through showing us an example of a queer, transgender character and his struggles with heteronormative expectations—demonstrating that the medieval is not so disconnected from the modern
Neprilysin Deficiency-Dependent Impairment of Cognitive Functions in a Mouse Model of Amyloidosis
Alzheimer's disease, responsible for the vast majority of dementia cases in the elderly population, is caused by accumulation of toxic levels of amyloid β peptide (Aβ) in the brain. Neprilysin is a major enzyme responsible for the degradation of Aβ invivo. We have previously shown that elevation of neprilysin levels in the brain delays the deposition of Aβ -plaques in a mouse model of amyloidosis and that lack of neprilysin leads to increased Aβ generation and to signs of incipient neurodegeneration in mouse brains. This study was designed to test whether low brain levels of neprilysin affect the amyloid pathology or perturb the learning and memory performance of mice. Double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein (APP), exhibited a reinforced amyloid pathology in comparison with their APP transgenic littermates. Moreover, in contrast to their parental lines, these mice were impaired in the Morris water maze learning and memory paradigm and showed facilitated extinction in the conditioned taste aversion test. These data suggest that even a partial neprilysin deficiency, as is found during aging, exacerbates amyloid pathology and may impair cognitive function
The potential benefit of an advanced integrated utility system
The applicability of an advanced integrated utility system based on 1980 technology was investigated. An example of such a system, which provides electricity, heating and air conditioning, solid waste disposal, and water treatment in a single integrated plant, is illustrated for a hypothetical apartment complex. The system requires approximately 50 percent of the energy and approximately 55 percent of the water that would be required by a typical current conventional system
Design techniques for modular integrated utility systems
Features basic to the integrated utility system, such as solid waste incineration, heat recovery and usage, and water recycling/treatment, are compared in terms of cost, fuel conservation, and efficiency to conventional utility systems in the same mean-climatic area of Washington, D. C. The larger of the two apartment complexes selected for the test showed the more favorable results in the three areas of comparison. Restrictions concerning the sole use of currently available technology are hypothetically removed to consider the introduction and possible advantages of certain advanced techniques in an integrated utility system; recommendations are made and costs are estimated for each type of system
Accuracy of 1,2-o-Dilauryl-rac-glycero-3-glutaric Acid-(6'-methylresorufin) Ester (DGGR)-Lipase to Predict Canine Pancreas-Specific Lipase (cPL) and Diagnostic Accuracy of Both Tests for Canine Acute Pancreatitis.
Different lipase assays have variable reported diagnostic accuracies for acute pancreatitis (AP) in dogs. The aims of this retrospective study were to evaluate optimal cutoffs for 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR)-lipase to predict diagnostic cutoffs of canine pancreas-specific lipase (cPL; IDEXX). DGGR-lipase activity and cPL from the same blood draw in 301 dogs with a variety of diseases were compared using Spearman's rank correlation, Cohen's kappa agreement, and receiver operating characteristic (ROC) curves. Activity of DGGR-lipase (10-15,616 U/L) and cPL concentrations (8.1-≥2000 µg/L) were highly correlated (rs = 0.91). Areas under the ROC curves (AUCs) to predict cPL >200 and ≥400 µg/L with DGGR-lipase were 0.97 and 0.99, with optimal cutoffs of 143 U/L (sensitivity (Se) 91.7%; specificity (Sp) 95.3%) and 205 U/L (Se 97.5%; Sp 96.4%), and Cohen's kappa agreements of 0.87 and 0.92, respectively. AUCs for a clinical diagnosis of AP, assigned to 87/301 dogs, with DGGR-lipase (0.75) and cPL (0.76) did not differ significantly (p = 0.48); optimal cutoffs were 161 U/L for DGGR (Se 67%; Sp 81%) and 235 µg/L for cPL (Se 68%; Sp 84%). To conclude, DGGR-lipase is a highly accurate predictor of cPL with a comparable performance when used to diagnose AP in dogs
Cognition in Rodents
Cognition is a loosely defined term with divergent meanings in different disciplines and species. In human psychology, ‘cognition’ is often used in reference to concepts such as ‘mind’ or ‘higher mental functions’. However, in more general terms, ‘cognition’ is regularly used to refer to all manner of information organization by the brain: from collection, to processing, to storage and recognition or recall. Whereas ‘cognition’ would seem to permeate all mental functions, including subjective perception and innate responses, ‘cognitive ability’ has a slightly more specific connotation – something more akin to intelligence or information-processing ability. Thus, ‘cognition’ deals with mental process structure and ‘cognitive abilities’ with natural variations impinging upon functioning at the higher end of that structure. Although the term ‘cognition’ sometimes subsumes or substitutes ‘cognitive ability’ in the literature, understanding this methodological distinction allows us to read across the two fields without the misunderstandings that classical cognitive psychologists have sometimes shown for cognitive ability research
Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy.
Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease.
In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2-5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above.
Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05).
Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various subgroups of interest, including patients with HER2-negative and triple-negative disease
Profiling inflammatory markers in patients with pneumonia on intensive care
Clinical investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for a panel of inflammatory mediators to aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27 with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory mediators, including cytokines and oxylipins, were measured in patients’ serum using flow cytometry and mass spectrometry. The mediators could separate patients admitted to ICU with pneumonia compared to brain injury with an area under the receiver operating characteristic curve (AUROC) 0.75 (0.61–0.90). Changes in inflammatory mediators were similar in both groups over the course of ICU stay with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing over time and interleukin-6 decreasing. However, brain injured patients who developed VAP maintained inflammatory profiles similar to those at admission. A multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9-dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6, and interleukin-8, could differentiate patients with VAP from brain injured patients without infection (AUROC 0.94 (0.80–1.00)). The use of a selected group of markers showed promise to aid the diagnosis of VAP especially when combined with clinical data
Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network.
The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches.
This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d'Oncologie including 101 members of various oncological specialties. Participants' demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals.
Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4-7) for ovarian, 5/10 (IQR 3-7) for colorectal, and 3/10 (IQR 1-3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6-10).
Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities
Feasibility and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Carcinomatosis: A Retrospective Cohort Study.
Background. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced as a novel repeatable treatment for peritoneal carcinomatosis. The available evidence from the pioneer center suggests good tolerance and high response rates, but independent confirmation is needed. A single-center cohort was analyzed one year after implementation for feasibility and safety. Methods. PIPAC was started in January 2015, and every patient was entered into a prospective database. This retrospective analysis included all consecutive patients operated until April 2016 with emphasis on surgical feasibility and early postoperative outcomes. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59-73) years) with 91 PIPAC procedures in total (4×: 1, 3×: 17, 2×: 12, and 1×: 12) were analyzed. Abdominal accessibility rate was 95% (42/44); laparoscopic access was not feasible in 2 patients with previous HIPEC. Median initial peritoneal carcinomatosis index (PCI) was 10 (IQR 5-17). Median operation time was 94 min (89-108) with no learning curve observed. One PIPAC application was postponed due to intraoperative intestinal lesion. Overall morbidity was 9% with 7 minor complications (Clavien I-II) and one PIPAC-unrelated postoperative mortality. Median postoperative hospital stay was 3 days (2-3). Conclusion. Repetitive PIPAC is feasible in most patients with refractory carcinomatosis of various origins. Intraoperative complications and postoperative morbidity rates were low. This encourages prospective studies assessing oncological efficacy
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