Time-optimized high-resolution readout-segmented diffusion tensor imaging

Readout-segmented echo planar imaging with 2D navigator-based reacquisition is an uprising technique enabling the sampling of high-resolution diffusion images with reduced susceptibility artifacts. However, low signal from the small voxels and long scan times hamper the clinical applicability. Therefore, we introduce a regularization algorithm based on total variation that is applied directly on the entire diffusion tensor. The spatially varying regularization parameter is determined automatically dependent on spatial variations in signal-to-noise ratio thus, avoiding over- or under-regularization. Information about the noise distribution in the diffusion tensor is extracted from the diffusion weighted images by means of complex independent component analysis. Moreover, the combination of those features enables processing of the diffusion data absolutely user independent. Tractography from in vivo data and from a software phantom demonstrate the advantage of the spatially varying regularization compared to un-regularized data with respect to parameters relevant for fiber-tracking such as Mean Fiber Length, Track Count, Volume and Voxel Count. Specifically, for in vivo data findings suggest that tractography results from the regularized diffusion tensor based on one measurement (16 min) generates results comparable to the un-regularized data with three averages (48 min). This significant reduction in scan time renders high resolution (1×1×2.5 mm3) diffusion tensor imaging of the entire brain applicable in a clinical context

Recruitment of a critically endangered sawfish into a riverine nursery depends on natural flow regimes

The freshwater sawfish (Pristis pristis) was recently listed as the most Evolutionarily Distinct and Globally Endangered (EDGE) animal. The Fitzroy River in the remote Kimberley region of north-western Australia represents a significant stronghold for the species, which uses the freshwater reaches of the river as a nursery. There is also mounting pressure to develop the water resources of the region for agriculture that may substantially affect life history dynamics of sawfish in this system. However, the relationship between hydrology and population dynamics of freshwater sawfish was unknown. We used standardized catch data collected over 17 years to determine how wet season volume influences recruitment of freshwater sawfish into their riverine nursery. Negligible recruitment occurred in years with few days of high flood levels (above 98th percentile of cease-to-flow stage height), and relatively high recruitment occurred in years with 14 or more days of high flood levels. This relationship is indicative of a distinct boom-or-bust cycle, whereby freshwater sawfish rely almost entirely on the few years with large wet season floods, and the brief periods of highest water levels within these years, to replenish juvenile populations in the Fitzroy River nursery. This has direct implications for sustainable water resource management for the Fitzroy River basin in order to preserve one of the last known intact nursery habitats for this globally threatened species

Disentangling the Evolution of Electrons and Holes in photoexcited ZnO nanoparticles

The evolution of charge carriers in photoexcited room temperature ZnO nanoparticles in solution is investigated using ultrafast ultraviolet photoluminescence spectroscopy, ultrafast Zn K-edge absorption spectroscopy and ab-initio molecular dynamics (MD) simulations. The photoluminescence is excited at 4.66 eV, well above the band edge, and shows that electron cooling in the conduction band and exciton formation occur in <500 fs, in excellent agreement with theoretical predictions. The X-ray absorption measurements, obtained upon excitation close to the band edge at 3.49 eV, are sensitive to the migration and trapping of holes. They reveal that the 2 ps transient largely reproduces the previously reported transient obtained at 100 ps time delay in synchrotron studies. In addition, the X-ray absorption signal is found to rise in ~1.4 ps, which we attribute to the diffusion of holes through the lattice prior to their trapping at singly-charged oxygen vacancies. Indeed, the MD simulations show that impulsive trapping of holes induces an ultrafast expansion of the cage of Zn atoms in <200 fs, followed by an oscillatory response at a frequency of ~100 cm-1, which corresponds to a phonon mode of the system involving the Zn sub-lattice

Pebbled places preferred by people and pipefish in a World Heritage protected area

Although the ecological impacts of recreational activities in clear tropical streams are occasionally acknowledged and addressed, frequently they remain unmanaged, despite the fact that such streams are highly sought-after destinations for leisure pursuits. Here, we provide a case study on the ecological characteristics of the Indo-Pacific freshwater pipefish Microphis leiaspis Bleeker, 1854, which is a habitat specialist with little available information aside from its reproductive biology and the downstream migration patterns of its larvae. Drawing from our collective experiences, we describe the distribution and habitat of Microphis leiaspis and examine the potential impacts of various small-scale human activities on its livelihood, including those occur- ring within protected areas. In particular, we document incidental observations of human disturbances to adult Microphis leiaspis habitat in clear freshwater streams located within the Australian Wet Tropics (AWT) World Heritage Area. Using these observations as a foundation, we conceptualize human interactions with this species in the AWT streams and more broadly across the tropical Indo-Pacific Ocean. Microphis leiaspis occurs in the lower-mid course of short-steep-coastal-streams, in association with pebble fields, where it feeds on microscop- ic benthic invertebrates. We observed three distinct human behaviours in the pipefish habitat within the AWT, including stone-stacking, the construction of boulder-cobble dams, and stone-skimming. Additionally, we report on other small-scale human activities that may potentially impact this pipefish species in streams across Pacific Island nations and select coastal regions of continents. Our recommendation is to promote a ‘leave no trace’ approach to the public, which can be effectively communicated by key individuals such as indigenous custodi- ans, national park managers, locals, and tourism operators. This approach aims to minimize rock movement by people, thereby aiding in the protection of diadromous pipefish and other aquatic species residing in short-steepcoastal-streams

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

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