Patternize: An R Package For Quantifying Color Pattern Variation

The use of image data to quantify, study and compare variation in the colors and patterns of organisms requires the alignment of images to establish homology, followed by color-based segmentation of images. Here we describe an R package for image alignment and segmentation that has applications to quantify color patterns in a wide range of organisms. patternize is an R package that quantifies variation in color patterns obtained from image data. patternize first defines homology between pattern positions across specimens either through manually placed homologous landmarks or automated image registration. Pattern identification is performed by categorizing the distribution of colors using an RGB threshold, k-means clustering or watershed transformation. We demonstrate that patternize can be used for quantification of the color patterns in a variety of organisms by analyzing image data for butterflies, guppies, spiders and salamanders. Image data can be compared between sets of specimens, visualized as heatmaps and analyzed using principal component analysis (PCA). patternize has potential applications for fine scale quantification of color pattern phenotypes in population comparisons, genetic association studies and investigating the basis of color pattern variation across a wide range of organisms.NSF grant DEB-1257839 NIH grant 5P20GM103475-1

Do distribution volumes and clearances relate to tissue volumes and blood flows? A computer simulation

BACKGROUND: Kinetics of inhaled agents are often described by physiological models. However, many pharmacokinetic concepts, such as context-sensitive half-times, have been developed for drugs described by classical compartmental models. We derived classical compartmental models that describe the course of the alveolar concentrations (F(A)) generated by the physiological uptake and distribution models used by the Gas Man(® )program, and describe how distribution volumes and clearances relate to tissue volumes and blood flows. METHODS: Gas Man(® )was used to generate F(A )vs. time curves during the wash-in and wash-out period of 115 min each with a high fresh gas flow (8 L.min(-1)), a constant alveolar minute ventilation (4 L.min(-1)), and a constant inspired concentration (F(I)) of halothane (0.75%), isoflurane (1.15%), sevoflurane (2%), or desflurane (6%). With each of these F(I), simulations were ran for a 70 kg patient with 5 different cardiac outputs (CO) (2, 3, 5, 8 and 10 L.min(-1)) and for 5 patients with different weights (40, 55, 70, 85, and 100 kg) but the same CO (5 L.min(-1)). Two and three compartmental models were fitted to F(A )of the individual 9 runs using NONMEM. After testing for parsimony, goodness of fit was evaluated using median prediction error (MDPE) and median absolute prediction error (MDAPE). The model was tested prospectively for a virtual 62 kg patient with a cardiac output of 4.5 L.min(-1 )for three different durations (wash-in and wash-out period of 10, 60, and 180 min each) with an F(I )of 1.5% halothane, 1.5% isoflurane, sevoflurane 4%, or desflurane 12%. RESULTS: A three-compartment model fitted the data best (MDPE = 0% and MDAPE ≤ 0.074%) and performed equally well when tested prospectively (MDPE ≤ 0.51% and MDAPE ≤ 1.51%). The relationship between CO and body weight and the distribution volumes and clearances is complex. CONCLUSION: The kinetics of anesthetic gases can be adequately described e by a mammilary compartmental model. Therefore, concepts that are traditionally thought of as being applicable to the kinetics of intravenous agents can be equally well applied to anesthetic gases. Distribution volumes and clearances cannot be equated to tissue volumes and blood flows respectively

Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers : a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial

Background: Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital‐acquired pressure ulcers (PUs). Objectives: Determine if silicone foam dressings in addition to standard prevention reduce PU incidence category 2 or worse compared to standard prevention alone. Methods: Multicentre, randomised controlled, medical device trial conducted in eight Belgian hospitals. At risk adult patients were centrally randomised (n=1633) to study groups based on a 1:1:1 allocation: experimental group 1 (n=542) and 2 (n=545) ‐ pooled as the treatment group ‐ and the control group (n=546). Experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on these body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU category 2 or worse at these body sites. Results: In the intention‐to‐treat population (n=1605); 4.0% of patients developed PUs category 2 or worse in the treatment group and 6.3% in the control group (RR=0.64, 95% CI 0.41 to 0.99, P=0.04). Sacral PUs were observed in 2.8% and 4.8% of the patients in the treatment group and the control group, respectively (RR=0.59, 95% CI 0.35 to 0.98, P=0.04). Heel PUs occurred in 1.4% and 1.9% of patients in the treatment and control group respectively (RR=0.76, 95% CI 0.34 to 1.68, P=0.49). Conclusions: Silicone foam dressings reduce the incidence of PUs category 2 or worse in hospitalised at‐risk patients when used in addition to standard of care. Results show a decrease for sacrum, but no statistical difference for heel/trochanter areas

The hydrology of the humid tropics

Hydrological processes in the humid tropics differ from other regions in having greater energy inputs and faster rates of change, including human-induced change. Human influences on population growth, land use and climate change will profoundly influence tropical hydrology, yet understanding of key hydrological interactions is limited. We propose that efforts to collect tropical data should explicitly emphasize characterizing moisture and energy fluxes from below the ground surface into the atmosphere. Research needs to chiefly involve field-based characterizations and modelling of moisture cycling and catchment processes, as well as long-term data acquisition and organization

Loss of synaptic Zn²⁺ transporter function increases risk of febrile seizures

Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn(2+) into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn(2+) increases the risk of FS and more broadly support the idea that impaired synaptic Zn(2+) homeostasis can contribute to neuronal hyperexcitability

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the

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