Habitat Use by the Eastern Sand Darter, Ammocrypta pellucida, in Two Lake Champlain Tributaries

The Eastern Sand Darter (Ammocrypta pellucida) is endangered or threatened throughout much of its range, which includes the St. Lawrence-Lake Ontario drainage of southern Ontario and Quebec and several Vermont tributaries of Lake Champlain. The species is known for its tendency to burrow, and field observations have suggested that habitat use may depend on substrate particle size. To determine whether Eastern Sand Darter densities were correlated with substrate particle size, fish and substrates were sampled in 156 plots in two Vermont rivers during the summers of 2001 and 2002. The Eastern Sand Darter occurred mainly in areas in which substrate composition was over 45% fine to medium sand (0.24-0.54 mm); they were much less abundant in areas in which substrate composition exceeded 25% particles greater than 1.9 mm. Substrate preference was tested by allowing 49 fish kept in aquaria to choose among four different substrates. The fish showed a significant preference (P < 0.005) for the finer substrate categories (0.24-0.54 mm, 0.55-1.0 mm), and mostly avoided the coarser substrates (1.0-1.9 mm, 2.0-4.1 mm). This suggests that the Eastern Sand Darter is selective regarding substrate composition, and therefore might be affected by fluctuations or changes in substrate composition within its habitat, such as those caused by changes in flow

The Evolution of AIFA Registries to Support Managed Entry Agreements for Orphan Medicinal Products in Italy

Italy has a well-established prominent system of national registries to support managed entry agreements (MEAs), monitoring innovative medicinal products (MPs) with clinical as well as economic uncertainties to ensure appropriate use and best value for money. The technological architecture of the registries is funded by pharmaceutical companies, but fully governed by the national medicines agency (AIFA). A desktop analysis was undertaken of data over a 15-year timeframe of all AIFA indication-based registries and associated EMA information. The characteristics of registries were evaluated, comparing orphan MPs vs. all MPs exploring cancer and non-cancer indications. OMP (orphan medicinal product) registries’ type vs. AIFA innovation status and EMA approval was reviewed. Of the 283 registries, 182 are appropriateness registries (35.2% relate to OMPs, with an almost equal split of cancer vs. non-cancer for OMPs and MPs), 35 include financial-based agreements [20% OMPs (2 non-cancer, 5 cancer)], and 60 registries are payment by result agreements [23.3% OMPs (4 non-cancer, 10 cancer)]. Most OMPs (53/88) came through the normal regulatory route. With the strengthening of the system for evaluation of innovation, fewer outcomes-based registries have been instigated. AIFA has overcome many of the challenges experienced with MEA through developing an integrated national web-based data collection system: the challenge that remains for AIFA is to move from using the system for individual patient decisions about treatment to reviewing the wealth of data it now holds to optimize healthcare

Technological and Implementation Issues in Moodle-Based Digital Badge System

Digital badges, touted as a gamification tool that can potentially influence learner motivation, engagement and participation, are being used increasingly in a variety of educational domains to facilitate and motivate learning. Using a badge system design implemented in the Moodle learning management platform, data was collected from four experiments from 2015 to 2017 to examine the effects of gamification with the use of digital badges on introductory programming students' intrinsic motivation. This paper provides an in-depth examination of seldomly discussed technological and implementation issues we encountered in implementing our Moodle-based badge system, worthy of exploration to support future gamification studies in this area. Our gamified implementation is analyzed according to five main factors primarily adopted from an IT implementation framework: (1) assessment of needs, (2) choice of technology, (3) technological infrastructure, (4) system and environmental factors and (5) evaluation. The findings highlight enabling and challenging factors associated with the technology and badge implementation. Our experience shows that badge systems may be influenced by contextual factors such as cost and scale of implementation. We provide recommendations to guide educational stakeholders, particularly those considering Moodle as their badge implementation platform

Technological and Implementation Issues in Moodle-Based Digital Badge System

Digital badges, touted as a gamification tool that can potentially influence learner motivation, engagement and participation, are being used increasingly in a variety of educational domains to facilitate and motivate learning. Using a badge system design implemented in the Moodle learning management platform, data was collected from four experiments from 2015 to 2017 to examine the effects of gamification with the use of digital badges on introductory programming students' intrinsic motivation. This paper provides an in-depth examination of seldomly discussed technological and implementation issues we encountered in implementing our Moodle-based badge system, worthy of exploration to support future gamification studies in this area. Our gamified implementation is analyzed according to five main factors primarily adopted from an IT implementation framework: (1) assessment of needs, (2) choice of technology, (3) technological infrastructure, (4) system and environmental factors and (5) evaluation. The findings highlight enabling and challenging factors associated with the technology and badge implementation. Our experience shows that badge systems may be influenced by contextual factors such as cost and scale of implementation. We provide recommendations to guide educational stakeholders, particularly those considering Moodle as their badge implementation platform

The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer.

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications andisomiRs that are predicted to target theALDH1,CD166,BMI1,LRIG1, andLGR5SC genes.miR-23bandmiR-92Aare of particular interest because our previously reported studies on miRNA expressionin isolated normal versus malignant human colonic SCs showed thatmiR-23bandmiR-92aareregulators of theLGR5andLRIG1SC genes, respectively. We also identify additional miRNAs whoseexpression inversely correlated with mRNA levels of their target genes and associated with CRCpatient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulationof SC genes could provide insight into how dysregulation of miRNAs leads to the emergence ofdifferent CSC populations and SC overpopulation in CRC

Real-world evidence to support Payer/HTA decisions about highly innovative technologies in the EU-actions for stakeholders

Report of multi-stakeholder deliberations about the potential to develop robust real-world evidence that could inform health technology assessment/healthcare payer decisions; founded on the principles of collaboration and transparency. Recommended actions to support the generation, analysis, and interpretation of real-world data to inform decision making are presented for each stakeholder group. Call for stakeholders to collaborate on demonstration projects and contribute to a learning network that can develop systems to support a learning health system and improve patient outcomes through best use of real-world data

Retinoids in Treatment of Colorectal Cancer

Retinoids are vitamin A metabolites best known for their role in embryonic development. Indeed, retinoid acid (RA) signaling plays a key role in regulating the development of the embryo body-plan by controlling embryonic stem cells (SCs). Retinoids function through their ability to induce cellular differentiation. Mutations in RA signaling pathway genes occur in most human cancers. The classic example is the chromosomal translocation involving RA receptor alpha in acute promyelocytic leukemia (APL). Because all-trans retinoic acid (ATRA) is a highly effective and often curative treatment for APL patients, determining if retinoids are efficacious for other cancer types is imperative. We review the current research on retinoids in colorectal cancer (CRC) and provide bioinformatics analyses of RA signaling. Our results show that most RA pathway genes are overexpressed and often mutated in CRC. Moreover, aberrant expression of many RA signaling proteins predicts decreased CRC patient survival. We also review aldehyde dehydrogenase (ALDH) expression in CRC because ALDH is a key enzyme in RA signaling, which regulates colonic SCs. Further investigation of RA signaling mechanisms that regulate colon SCs and how dysregulation contributes to the SC overpopulation that drives CRC growth should provide insight into strategies for designing new SC-targeted therapies for CRC

Habitat complexity affects functional traits and diversity of ant assemblages in urban green spaces (Hymenoptera: Formicidae)

Habitat complexity conferred by vegetation characteristics mediates key processes that govern the assemblage of insect communities. Thus, species within the community should only persist if their functional traits are well-matched to the conditions of their environment. Here, we compared ant assemblages between habitats in terms of species richness and functional-trait distribution at the species and the assemblage level. Ants were collected from 36 sites representing different degrees of habitat complexity mediated by standing vegetation. We found fewer ant species in simpler habitats, supporting the "habitat-heterogeneity" hypothesis. We measured key functional traits of ants that reflect their foraging and dispersal strategies, such as body size, femur length, antenna scape length, and head length / width. Interactions of species traits with measured habitat complexity variables were assessed at the species and the assemblage level using a fourth-corner approach. Ant traits were closely related to environmental complexity. In wooded habitats, ants were larger and had broader heads, while ants with longer antenna scapes prevailed in habitats with a dense herb / grass layer. Our study suggests that vegetation structural complexity can act as an environmental filter, driving ant assemblages in terms of both species numbers and functional traits. Our results can be used to predict turnover patterns in ant assemblages due to changes in management practices

Multinuclear Solid-State Magnetic Resonance as a Sensitive Probe of Structural Changes upon the Occurrence of Halogen Bonding in Co-crystals

Although the understanding of intermolecular interactions, such as hydrogen bonding, is relatively well-developed, many additional weak interactions work both in tandem and competitively to stabilize a given crystal structure. Due to a wide array of potential applications, a substantial effort has been invested in understanding the halogen bond. Here, we explore the utility of multinuclear (13C, 14/15N, 19F, and 127I) solid-state magnetic resonance experiments in characterizing the electronic and structural changes which take place upon the formation of five halogen-bonded co-crystalline product materials. Single-crystal X-ray diffraction (XRD) structures of three novel co-crystals which exhibit a 1:1 stoichiometry between decamethonium diiodide (i.e., [(CH3)3N+(CH 2)10N+(CH3)3][2 I -]) and different para-dihalogen-substituted benzene moieties (i.e., p-C6X2Y4, X=Br, I; Y=H, F) are presented. 13C and 15N NMR experiments carried out on these and related systems validate sample purity, but also serve as indirect probes of the formation of a halogen bond in the co-crystal complexes in the solid state. Long-range changes in the electronic environment, which manifest through changes in the electric field gradient (EFG) tensor, are quantitatively measured using 14N NMR spectroscopy, with a systematic decrease in the 14N quadrupolar coupling constant (CQ) observed upon halogen bond formation. Attempts at 127I solid-state NMR spectroscopy experiments are presented and variable-temperature 19F NMR experiments are used to distinguish between dynamic and static disorder in selected product materials, which could not be conclusively established using solely XRD. Quantum chemical calculations using the gauge-including projector augmented-wave (GIPAW) or relativistic zeroth-order regular approximation (ZORA) density functional theory (DFT) approaches complement the experimental NMR measurements and provide theoretical corroboration for the changes in NMR parameters observed upon the formation of a halogen bond