Involving research participants in a pan-European research initiative: the EPAD participant panel experience

Abstract: Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations

Distribution and abundance of western gray whales during a seismic survey near Sakhalin Island, Russia

Exxon Neftegas Limited, operator of the Sakhalin-1 consortium, is developing oil and gas reserves on the continental shelf off northeast Sakhalin Island, Russia. DalMorNefteGeofizika (DMNG), on behalf of the Sakhalin-1 consortium, conducted a 3-D seismic survey of the Odoptu license area during 17 August-September 2001. A portion of the primary known feeding area of the endangered western gray whale (Eschrichtius robustus) is located adjacent to the seismic block. The data presented here were collected as part of daily monitoring to determine if there was any measurable effect of the seismic survey on the distribution and abundance of western gray whales. Mitigation and monitoring program included aerial surveys conducted between 19 July and 19 November using the methodology outlined by the Southern California High Energy Seismic Survey team (HESS). These surveys provided documentation of the distribution, abundance and bottom feeding activity of western gray whales in relation to seismic survey sounds. From an operations perspective, the aerial surveys provided near real-time data on the location of whales in and outside the feeding area, and documented whether whales were displaced out of an area normally used as feeding habitat. The objectives of this study were to assess (a) temporal changes in the distribution and abundance of gray whales in relation to seismic survey, and (b) the influence of seismic survey, environmental factors, and other variables on the distribution and abundance of gray whales within their preferred feeding area adjacent to Piltun Bay. Multiple regression analysis revealed a limited redistribution of gray whales southward within the Piltun feeding area when the seismic survey was fully operational. A total of five environmental and other variables unrelated to seismic survey (date and proxies of depth, sea state and visibility) and one seismic survey-related variable (seg3d, i.e., received sound energy accumulated over 3 days) had statistically significant effects on the distribution and abundance of gray whales. The distribution of two to four gray whales observed on the surface (i.e., about five to ten whales in total) has likely been affected by the seismic survey. However, the total number of gray whales observed within the Piltun feeding area remained stable during the seismic survey

Measurements on the reality of the wavefunction

Quantum mechanics is an outstandingly successful description of nature, underpinning fields from biology through chemistry to physics. At its heart is the quantum wavefunction, the central tool for describing quantum systems. Yet it is still unclear what the wavefunction actually is: does it merely represent our limited knowledge of a system, or is it an element of reality? Recent no-go theorems argued that if there was any underlying reality to start with, the wavefunction must be real. However, that conclusion relied on debatable assumptions, without which a partial knowledge interpretation can be maintained to some extent. A different approach is to impose bounds on the degree to which knowledge interpretations can explain quantum phenomena, such as why we cannot perfectly distinguish non-orthogonal quantum states. Here we experimentally test this approach with single photons. We find that no knowledge interpretation can fully explain the indistinguishability of non-orthogonal quantum states in three and four dimensions. Assuming that some underlying reality exists, our results strengthen the view that the entire wavefunction should be real. The only alternative is to adopt more unorthodox concepts such as backwards-in-time causation, or to completely abandon any notion of objective reality.Comment: 7 pages, 4 figure

Herpes Simplex Virus Type 2, Genital Ulcers and HIV-1 Disease Progression in Postpartum Women

Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2

Distribution and abundance of western gray whales off northeastern Sakhalin Island, Russia, 2001’003

In 2001’003, >60,000 km of aerial surveys and 7,700 km of vessel surveys were conducted during June to November when critically endangered Korean–Okhotsk or western gray whales (Eschrichtius robustus) were present off the northeast coast of Sakhalin Island, Russia. Results of surveys in all years indicated gray whales occurred in predominantly two areas, (1) adjacent to Piltun Bay, and (2) offshore from Chayvo Bay, hereafter referred to as the Piltun and offshore feeding areas. In the Piltun feeding area, the majority of whales were observed in waters shallower than 20 m and were distributed from several hundred meters to ∼ 5 km from the shoreline. In the offshore feeding area during all years, the distribution of gray whales extended from southwest to northeast in waters 30’5 m in depth. During all years, the distribution and abundance of whales changed in both the Piltun and offshore feeding areas, and both north–south and inshore–offshore movements were documented within and between feeding seasons. The discovery of a significant number of whales feeding in the offshore area each year was a substantial finding of this study and raises questions regarding western gray whale abundance and population levels, feeding behavior and ecology, and individual site-fidelity. Fluctuations in the number of whales observed within the Piltun and offshore feeding areas and few sightings outside of these two areas indicate that gray whales move between the Piltun and offshore feeding areas during their summer–fall feeding season. Seasonal shifts in the distribution and abundance of gray whales between and within both the Piltun and offshore feeding areas are thought, in part, to be a response to seasonal changes in the distribution and abundance of prey. However, the mechanism driving the movements of whales along the northeast coast of Sakhalin Island is likely very complex and influenced by a multitude of factors

Role of Conserved Non-Coding Regulatory Elements in LMW Glutenin Gene Expression

Transcriptional regulation of LMW glutenin genes were investigated in-silico, using publicly available gene sequences and expression data. Genes were grouped into different LMW glutenin types and their promoter profiles were determined using cis-acting regulatory elements databases and published results. The various cis-acting elements belong to some conserved non-coding regulatory regions (CREs) and might act in two different ways. There are elements, such as GCN4 motifs found in the long endosperm box that could serve as key factors in tissue-specific expression. Some other elements, such as the AACA/TA motifs or the individual prolamin box variants, might modulate the level of expression. Based on the promoter sequences and expression characteristic LMW glutenin genes might be transcribed following two different mechanisms. Most of the s- and i-type genes show a continuously increasing expression pattern. The m-type genes, however, demonstrate normal distribution in their expression profiles. Differences observed in their expression could be related to the differences found in their promoter sequences. Polymorphisms in the number and combination of cis-acting elements in their promoter regions can be of crucial importance in the diverse levels of production of single LMW glutenin gene types

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe