Investigation of Factors Limiting Pelagic Phytoplankton Abundance and Composition in the Ancient Malili Lakes of Indonesia

Factors regulating composition and relative abundance in phytoplankton communities were investigated in an ancient lake with a highly endemic food web. Lake Matano has genera diversity (21) similar to tropical lakes, but low phytoplankton biomass (0.0162 ug/L). Vertical mixing physically limits primary production (42% Zeu:Zm); phytoplankton are moved below the euphotic zone. Macronutrient concentrations (0.30 umol/L N, 0.13 umol/L P) are low. Nutrient bioassays used N and P (30-320 umol/L individually, 60:5-1920:160 umol/L N:P combined). After 16 days, no significant (p \u3e 0.05) changes in relative abundance and no biologically significant changes in phytoplankton biomass occurred. CHU-10 growth media cultivation, however, significantly increased chl-a. Analysis identified Cr (0.14 umol/L) above a threshold to restrict algal growth (0.12 umol/L) and Mo (0.0005 umol/L) below requirements by most aquatic life (0.008 umol/L). Therefore, physical (mixing) and chemical (toxicity, micronutrient) factors are concluded to limit composition and relative abundance of phytoplankton in Matano

THE COUNTER-COLONIAL TRAVEL WRITING OF FANNY PARKES AND E.M. FORSTER

During the colonial period in India, British travelers wrote various forms of travel writing texts, such as letters, diaries, travelogues, scientific or geographical exposés, and novels. Usually those texts reflected an attitude of racial superiority and were often forms of propaganda that perpetuated British imperial expansion. This paper discusses the works of two British travelers who were influenced by their experiences in India and wrote texts that did not reflect racism or approval of colonialism. Fanny Parkes and E.M. Forster traveled to India in different centuries and for different reasons. Although they both demonstrated an imperialist perspective upon arriving in India, they eventually grew to love and appreciate India's culture and people. In order to understand the significant ways Parkes and Forster deviated from their contemporaries, the general travel writing trends and theories of the late eighteenth century through the middle of the twentieth century will be discussed, drawing heavily from the travel writing discourse of Mary Louise Pratt and Edward Said, as well as Sinan Akilli, Chinua Achebe, William Dalrymple and others. Representative texts from the various eras, modes, and conventions of the genre will be given and analyzed.  Parkes's published journal, Begums, Thugs, and Englishmen, The Journals of Fanny Parkes (2002), was originally published in 1850 and is vastly different than the journals and letters written by other British travelers to India. Her text will be compared to several others, particularly Emily Eden's, Miss Eden's Letters (1919). In his novel, A Passage to India (1936), Forster's depiction of Indians and Britons is one which includes the full spectrum of humanity, thus deconstructing the colonial proclivity to dehumanize Indians. His novel will be contrasted with Joseph Conrad's Heart of Darkness (1918). There are benefits of identifying and studying travel writers who deconstructed the colonial perspective in India. Those benefits will be discussed in the context of comments from scholars and writers in the field, such as Colin Thubron, Debbie Lisle, James Duncan, and Derek Gregory.  M.A

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

THE COUNTER-COLONIAL TRAVEL WRITING OF FANNY PARKES AND E.M. FORSTER

THE COUNTER-COLONIAL TRAVEL WRITING OF FANNY PARKES AND E.M. FORSTER  by  Amy Lynn Snook  June, 2010  Chair: Dr. Richard Taylor  Major Department: English   During the colonial period in India, British travelers wrote various forms of travel writing texts, such as letters, diaries, travelogues, scientific or geographical exposes, and novels. Usually those texts reflected an attitude of racial superiority and were often forms of propaganda that perpetuated British imperial expansion. This paper discusses the works of two British travelers who were influenced by their experiences in India and wrote texts that did not reflect racism or approval of colonialism. Fanny Parkes and E.M. Forster traveled to India in different centuries and for different reason. Although they both demonstrate an imperialist perspective upon arriving in India, they eventually grew to love and appreciate India's culture and people.    In order to understand the significant ways Parkes and Forster deviated from their contemporaries, the general travel writing trends and theories of the late eighteenth century through the middle of the twentieth century will be discussed, drawing heavily from the travel writing discourse of Mary Louise Pratt and Edward Said, as well as Sinan Akilli, Chinua Achebe, William Dalrymple and others. Representative texts from the various eras, modes, and conventions of the genre will be given and analyzed.   Parkes's published journal, Begums, Thugs, and Englishmen, The Journals of Fanny Parkes (2002), was originally published in 1850 and is vastly different than the journals and letters written by other British travelers to India. Her text will be compared to several others, particularly Emily Eden's, Miss Eden's Letters (1919). In his novel, A Passage to India (1936), Forster's depiction of Indians and Britons is one which includes the full spectrum of humanity, thus deconstructing the colonial proclivity to dehumanize Indians. His novel will be contrasted with Joseph Conrad's Heart of Darkness (1918).    There are benefits of identifying and studying travel writers who deconstructed the colonial perspective in India. Those benefits will be discussed in the context of comments from scholars and writers in the field, such as: Colin Thubron, Debbie Lisle, James Duncan, and Derek Gregory. 

Notice of Retraction and Replacement. Snook et al. Change in percentages of adults with overweight or obesity trying to lose weight, 1988-2014. JAMA. 2017;317(9):971-973

Work published in Journal of the American Medical Association