Satellite tagging and flipper tag recoveries reveal migration patterns and foraging distribution of loggerhead sea turtles (Caretta caretta) from eastern Australia

Marine turtles encounter different threats during various life-history stages. Therefore, understanding their movements and spatial distribution is crucial for effectively managing these long-lived migratory organisms. This study combines satellite telemetry data with long-term capture-mark-recapture data derived from flipper tag studies to determine distribution patterns of endangered loggerhead turtles (Caretta caretta) during post-nesting migrations from different eastern Australian nesting sites. Individuals from the K’gari-Fraser Island and Great Barrier Reef island rookeries typically migrated northward, whereas individuals from mainland rookeries migrated equally northward and southward. Despite this difference in foraging distribution, loggerheads from the different rookeries did not differ substantially in their migration duration or distance travelled. The foraging distribution identified from successful satellite tag deployments represented 50% of the foraging distribution identified from a large long-term flipper tag recovery database. However, these satellite telemetry results have identified new migration and foraging habitats not previously recognised for loggerhead turtles nesting in eastern Australia. Additionally, they support the conclusion from a past study using flipper tag recovery data that the mainland nesting turtles migrate to different foraging grounds than the turtles nesting on Great Barrier Reef islands. Collectively, the two data sources provide valuable data on the migration route, habitat distribution and ecological range for a threatened genetic stock of loggerhead turtles

Prevalence and Types of Drugs Used Among Hepatitis A Patients During Outbreaks Associated with Person-to-Person Transmission, Kentucky, Michigan, and West Virginia, 2016–2019

Background: People who use drugs are at increased risk for hepatitis A virus infection. Since 1996, the Advisory Committee on Immunization Practices has recommended hepatitis A vaccination for people who use drugs. Since 2016, the U.S. has experienced widespread hepatitis A outbreaks associated with person-to-person transmission. Purpose: To describe the prevalence of drug use, route of use, and drugs used among hepatitis A outbreak-associated patients. Methods: State outbreak and medical records were reviewed to describe the prevalence, type, and route of drug use among a random sample of 812 adult outbreak-associated hepatitis A patients from Kentucky, Michigan, and West Virginia during 2016–2019. Differences in drug-use status were analyzed by demographic and risk-factor characteristics using the χ2 test. Results: Among all patients, residents of Kentucky (55.6%), Michigan (51.1%), and West Virginia (60.1%) reported any drug use, respectively. Among patients that reported any drug use, methamphetamine was the most frequently reported drug used in Kentucky (42.3%) and West Virginia (42.1%); however, opioids were the most frequently reported drug used in Michigan (46.8%). Hepatitis A patients with documented drug use were more likely (p\u3c0.05) to be experiencing homelessness/unstable housing, have been currently or recently incarcerated, and be aged 18–39 years compared to those patients without documented drug use. Implications: Drug use was prevalent among person-to-person hepatitis A outbreak-associated patients, and more likely among younger patients and patients experiencing homelessness or incarceration. Increased hepatitis A vaccination coverage is critical to prevent similar outbreaks in the future

Cluster Control in Oligouranyl Complexes of p-t-Butylcalix[8]arene

Formation of uranyl ion complexes of p-t-butylcalix[8]arene by reaction of the calixarene with [UO2(dmso)5]2+ in the presence of various bases leads to the crystallisation of solids with interestingly different stoichiometry, involving both di- and tri-uranate oligomers bound to the calixarene in anionic species. In all, the calixarene hexa-anion is present in a virtually identical conformation, suggesting that conformational preferences of the ligand must be a major factor controlling the form of the bound oxo-metal complex. Hydrogen bonding to the anions does not appear to be prominent even in the presence of protonated amines and this may explain the formation of some remarkable cation/solvent/simple anion clusters found within the lattices

Fostering effective and sustainable scientific collaboration and knowledge exchange: a workshop-based approach to establish a national ecological observatory network (NEON) domain-specific user group

The decision to establish a network of researchers centers on identifying shared research goals. Ecologically specific regions, such as the USA’s National Ecological Observatory Network’s (NEON’s) eco-climatic domains, are ideal locations by which to assemble researchers with a diverse range of expertise but focused on the same set of ecological challenges. The recently established Great Lakes User Group (GLUG) is NEON’s first domain specific ensemble of researchers, whose goal is to address scientific and technical issues specific to the Great Lakes Domain 5 (D05) by using NEON data to enable advancement of ecosystem science. Here, we report on GLUG’s kick off workshop, which comprised lightning talks, keynote presentations, breakout brainstorming sessions and field site visits. Together, these activities created an environment to foster and strengthen GLUG and NEON user engagement. The tangible outcomes of the workshop exceeded initial expectations and include plans for (i) two journal articles (in addition to this one), (ii) two potential funding proposals, (iii) an assignable assets request and (iv) development of classroom activities using NEON datasets. The success of this 2.5-day event was due to a combination of factors, including establishment of clear objectives, adopting engaging activities and providing opportunities for active participation and inclusive collaboration with diverse participants. Given the success of this approach we encourage others, wanting to organize similar groups of researchers, to adopt the workshop framework presented here which will strengthen existing collaborations and foster new ones, together with raising greater awareness and promotion of use of NEON datasets. Establishing domain specific user groups will help bridge the scale gap between site level data collection and addressing regional and larger ecological challenges

The Novel Deacetylase Inhibitor AR-42 Demonstrates Pre-Clinical Activity in B-Cell Malignancies In Vitro and In Vivo

While deacetylase (DAC) inhibitors show promise for the treatment of B-cell malignancies, those introduced to date are weak inhibitors of class I and II DACs or potent inhibitors of class I DAC only, and have shown suboptimal activity or unacceptable toxicities. We therefore investigated the novel DAC inhibitor AR-42 to determine its efficacy in B-cell malignancies.In mantle cell lymphoma (JeKo-1), Burkitt's lymphoma (Raji), and acute lymphoblastic leukemia (697) cell lines, the 48-hr IC(50) (50% growth inhibitory concentration) of AR-42 is 0.61 microM or less. In chronic lymphocytic leukemia (CLL) patient cells, the 48-hr LC(50) (concentration lethal to 50%) of AR-42 is 0.76 microM. AR-42 produces dose- and time-dependent acetylation both of histones and tubulin, and induces caspase-dependent apoptosis that is not reduced in the presence of stromal cells. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. AR-42 significantly reduced leukocyte counts and/or prolonged survival in three separate mouse models of B-cell malignancy without evidence of toxicity.Together, these data demonstrate that AR-42 has in vitro and in vivo efficacy at tolerable doses. These results strongly support upcoming phase I testing of AR-42 in B-cell malignancies

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

An Economic Evaluation of the Syncope: Pacing or Recording in the Later Years (SPRITELY) Trial

The Syncope: Pacing or Recording In ThE Later Years (SPRITELY) trial tests the hypothesis that pacemaker insertion in patients with syncope, bifascicular block, and age greater than 50 years prevents syncope recurrences and major clinical events more effectively than therapy guided by monitoring with an implantable loop recorder. Equipoise or uncertainty reflected in guidelines and recommendations for both strategies may contribute to variation in management and inefficient resource use. Clinical analysis of the SPRITELY trial is complemented with an economic evaluation. The goal of this thesis was to establish the relative cost-effectiveness of the implantable loop recorder and the pacemaker in patients with bifascicular block, unexplained syncope, and age greater than 50 years. An economic evaluation of the SPRITELY trial was conducted to match the prespecified time horizon of two years for the clinical analysis (Chapter 3), and a decision analytic model was built to extend the time horizon to three years to match clinical practice (Chapter 4). In Chapter 5, the effect of taking three different national perspectives for the SPRITELY trial evaluation was explored. This thesis ends with a discussion and conclusions in Chapter 6