In pursuit of knowledge: Addressing barriers to effective conservation evaluation

Evaluation, the process of assessing the effectiveness of programs and activities, has gained increasing attention in the conservation sector as programs seek to account for investments, measure their impacts, and adapt interventions to improve future outcomes. We conducted a country-wide evaluation of terrestrial-based conservation programs in Samoa. Though rarely applied, the benefit of evaluating multiple projects at once is that it highlights factors which are persistent and influential across the entire conservation sector. We found mixed success in achieving goals among conservation programs; yet this result is surrounded by uncertainty because of the quality of existing evidence on project outcomes. We explore the role of different components of the conservation management system, i.e., context, planning, inputs, processes, and outputs, in facilitating and/or constraining collection of data on project outcomes, and thereby assessment of whether projects were successful. Our study identified a number of direct and indirect barriers that affected the capacity of projects to carry out informative evaluations and generate knowledge on conservation progress in Samoa. These attributes and mechanisms include: the availability and management of data, design and planning of projects, and systems for reporting among donors and proponents. To overcome these barriers to evaluation, we believe that a shift in institutional approaches to reporting outcomes is needed, from a reflective way of thinking to a more prospective outlook

The introduction and refinement of the assessment of digitally recorded audio presentations

This case study critically evaluates benefits and challenges of a form of assessment included in a final year undergraduate Religious Studies Open University module, which combines a written essay task with a digital audio recording of a short oral presentation. Based on the analysis of student and tutor feedback and sample assignments, this study critically examines how teaching and learning practices linked to this novel form of assessment have been iteratively developed in light of the project findings over a period of two years. It concludes that while this form of assessment poses a number of challenges, it can create valuable opportunities for the development of transferable twenty-first-century graduate employability skills as well as deep, effective learning experiences, particularly – though not exclusively – in distance learning settings

Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104-week extension to a 52-week randomized, phase 3 study and liver fat MRI substudy

Aim: To report the results of a 104-week extension to a 52-week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin. Materials and methods: This extension to a 52-week global, multicentre, parallel-group, active-controlled, double-blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5\ua0mg) plus placebo, or GLIM (1-6\ua0mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.5-91.3 mmol/mol [7.5%-10.5%]), and a body mass index of 20.0 to 45.0\ua0kg/m2, and were receiving metformin (MET; ≥1500 mg/d). Key outcomes were: requirement for treatment intensification, based on HbA1c ≥53 mmol/mol (7%); achieving therapeutic glycaemic response; and changes in adipose tissue and liver fat on magnetic resonance imaging in a substudy. Results: Overall, 382 participants entered and 338 completed the 104-week extension period (MRI substudy, n\ua0=\ua082). The need for treatment intensification during the 156-week period was lower for DAPA+SAXA+MET (37.0%) than GLIM+MET (55.6%; hazard ratio 0.52, 95% confidence interval [CI] 0.39-0.68; P < 0.001). At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23-3.42; P\ua0=\ua00.006). DAPA+SAXA+MET led to greater adjusted mean reductions from baseline in liver fat and visceral and subcutaneous adipose tissue volumes versus GLIM+MET at week 122 (least-squares mean difference from GLIM+MET −4.89%, −0.41 L and −0.44 L, respectively; nominal P values ≤ 0.008). Safety was consistent with that of the monocomponents. Conclusions: Overall, glycaemic control, metabolic benefits and efficacy were better maintained with DAPA+SAXA+MET than with GLIM+MET in T2D

TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling

Myelodysplastic syndrome (MDS) is a hematological malignancy characterized by blood cytopenias and predisposition to acute myeloid leukemia (AML). Therapies for MDS are lacking, particularly those that have an impact in the early stages of disease. We developed a model of MDS in zebrafish with knockout of Rps14, the primary mediator of the anemia associated with del(5q) MDS. These mutant animals display dose- and age-dependent abnormalities in hematopoiesis, culminating in bone marrow failure with dysplastic features. We used Rps14 knockdown to undertake an in vivo small-molecule screening, to identify compounds that ameliorate the MDS phenotype, and we identified imiquimod, an agonist of Toll-like receptor-7 (TLR7) and TLR8. Imiquimod alleviates anemia by promoting hematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation and Myd88. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature, indicating cross talk via TLR7 between proinflammatory pathways endogenous to Rps14 loss and the NF-κB pathway. Finally, in highly purified human bone marrow samples from anemic patients, imiquimod led to an increase in erythroid output from myeloerythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del(5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anemia

A decision support system-based procedure for evaluation and monitoring of protected areas sustainability for the Mediterranean region

WOS: 000297078900015Despite common acknowledgement of the value of protected areas as instruments in ensuring sustainability, and their promotion for the achievement of policies on halting the loss of biodiversity, there is no common approach today for monitoring and evaluating them. This paper presents a novel integrated nature conservation management procedure developed to monitor and evaluate the sustainability of Mediterranean protected areas. This procedure was successfully implemented and formally evaluated by protected area managers in six Mediterranean countries, results of which are presented here together with an overview of the web-based Decision Support System (DSS) developed to facilitate its wide adoption. The DSS and procedure has been designed and evaluated by managers as a useful tool, which facilitates and provides needed procedural guidance for protected area monitoring whilst minimizing input requirements to do so. The procedure and DSS were developed following a review of existing protected area assessment tools and a detailed primary investigation of the needs and capacity of its intended users. Essentially, the procedure and DSS guides provide the facilities for protected area managers, in following a participatory approach to develop a context-specific sustainability monitoring strategy, for their protected area. Consequently, the procedure is, by design, participatory, context specific, holistic and relevant to protected area management and institutional procedures. The procedure was piloted and formally evaluated in Greece, Italy, Turkey, Egypt, Malta and Cyprus. Feedback collected from the pilot evaluations is also summarised herein.INTERREG III B [A.1.222 INNOVA]This research was funded under INTERREG III B Programme 'Archimed' A.1.222 INNOVA Project. The authors would like to acknowledge the contribution and input of the partners, protected area authorities, stakeholders and local communities. Special thanks to the University of Bari, the Polytechnic of Bari, Apulian Ministry of Environment, University of Lecce, Maltese Ministry of Rural Affairs and Environment, University of Malta, Agricultural Research Institute of Cyprus, Prefecture of Chania, Egyptian Desert Research Center, Palestinian Ministry of Agriculture, Palestinian National Authority, and Al Quads University

Bid chimeras indicate that most BH3-only proteins can directly activate Bak and Bax, and show no preference for Bak versus Bax

The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, we developed recombinant Bid chimeras in which the BH3 domain was replaced with that of other BH3-only proteins (Bim, Puma, Noxa, Bad, Bmf, Bik and Hrk). The chimeras were stable following purification, and each immunoprecipitated with full-length Bcl-xL according to the specificity reported for the related BH3 peptide. When tested for activation of Bak and Bax in mitochondrial permeabilization assays, Bid chimeras were ~1000-fold more effective than the related BH3 peptides. BH3 sequences from Bid and Bim were the strongest activators, followed by Puma, Hrk, Bmf and Bik, while Bad and Noxa were not activators. Notably, chimeras and peptides showed no apparent preference for activating Bak or Bax. In addition, within the BH3 domain, the h0 position recently found to be important for Bax activation, was important also for Bak activation. Together, our data with full-length proteins indicate that most BH3-only proteins can directly activate both Bak and Bax

Strong CP violation and the neutron electric dipole form factor

We calculate the neutron electric dipole form factor induced by the CP violating theta-term of QCD, within a perturbative chiral quark model which includes pion and kaon clouds. On this basis we derive the neutron electric dipole moment and the electron-neutron Schiff moment. From the existing experimental upper limits on the neutron electric dipole moment we extract constraints on the theta-parameter and compare our results with other approaches.Comment: 18 pages, 2 figures, accepted for publication in Phys. Atom. Nuc

A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown

© 2019 Elsevier Inc. Gene knockdown is an advantageous therapeutic strategy to lower dangerous genetic over-expression. However, the molecules responsible for initiating this process are unstable. Porous nanoparticles called metal-organic frameworks can encapsulate, protect, and deliver these compounds efficaciously without the need for chemical modifications—commonly done to enhance stability. By applying this platform technology, this work demonstrates the successful reduction in expression of a gene by avoiding retention and subsequent degradation in cellular compartments.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (NanoMOFdeli), ERC-2016-COG 726380, and (SUPUVIR) no. 722380. M.H.T. thanks the Gates Cambridge Trust for funding, S. Haddad for helpful discussions, and A. Li for assistance with data visualization. D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. S.B.d.Q.F., F.M.R., and D.I.J. were funded by Cancer Research UK Senior Group Leader Grant CRUK/A15678. O.K.F. gratefully acknowledges DTRA for financial support (grant HDTRA-1-14-1-0014). C.F.K. acknowledges funding from the UK Engineering and Physical Sciences Research Council (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research Council (grants MR/K015850/1 and MR/K02292X/1), and Infinitus (China) Ltd. Computational work was supported by the Cambridge High Performance Computing Cluster, Darwin

Nuclear Electric Dipole Moment of 3He

A permanent electric dipole moment (EDM) of a physical system requires time-reversal (T) and parity (P) violation. Experimental programs are currently pushing the limits on EDMs in atoms, nuclei, and the neutron to regimes of fundamental theoretical interest. Here we calculate the magnitude of the PT-violating EDM of 3He and the expected sensitivity of such a measurement to the underlying PT-violating interactions. Assuming that the coupling constants are of comparable magnitude for pi-, rho-, and omega-exchanges, we find that the pion-exchange contribution dominates. Our results suggest that a measurement of the 3He EDM is complementary to the planned neutron and deuteron experiments, and could provide a powerful constraint for the theoretical models of the pion-nucleon PT-violating interaction.Comment: 6 pages, 1 figur

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: