Revising ethical guidance for the evaluation of programmes and interventions not initiated by researchers

Public health and service delivery programmes, interventions and policies (collectively, “programmes)” are typically developed and implemented for the primary purpose of effecting change rather than generating knowledge. Nonetheless, evaluations of these programmes may produce valuable learning that helps to determine effectiveness and costs as well as informing design and implementation of future programmes. Such studies might be termed “opportunistic evaluations”, since they are responsive to emergent opportunities rather than being studies of interventions that are initiated or designed by researchers. However, current ethical guidance and registration procedures make little allowance for scenarios where researchers have played no role in the development or implementation of a programme, but nevertheless plan to conduct a prospective evaluation. We explore the limitations of the guidance and procedures with respect to opportunistic evaluations, providing a number of examples. We propose that the key missing distinction in current guidance is that moral responsibility: researchers can only be held accountable for those aspects of a study over which they have control. We argue that requiring researchers to justify an intervention, programme or policy that would occur regardless of their involvement prevents or hinders research in the public interest without providing any further protections to research participants. We recommend that trial consent and ethics procedures allow for a clear separation of responsibilities for the intervention and the evaluation.SIW and RJL are funded by the NIHR Global Health Research Unit on Improving Health in Slums. CT, PJC and RJL are also supported by the National Institute for Health Research (NIHR) Collaboration for Leadership for Applied Health Research Care (CLAHRC) West Midlands initiative. EBW and ELD are employed by Partners In Health. MD-W is supported by the Health Foundation’s grant to the University of Cambridge for The Healthcare Improvement Studies (THIS) Institute. THIS Institute is supported by the Health Foundation - an independent charity committed to bringing about better health and health care for people in the UK. This work was also supported by MDW’s Wellcome Trust Investigator award WT09789. MDW is a National Institute for Health Research (NIHR) Senior Investigator. This paper presents independent research and the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Healt

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Managing Relationship Decay Network, Gender, and Contextual Effects

Relationships are central to human life strategies and have crucial fitness consequences. Yet, at the same time, they incur significant maintenance costs that are rarely considered in either social psychological or evolutionary studies. Although many social psychological studies have explored their dynamics, these studies have typically focused on a small number of emotionally intense ties, whereas social networks in fact consist of a large number of ties that serve a variety of different functions. In this study, we examined how entire active personal networks changed over 18 months across a major life transition. Family relationships and friendships differed strikingly in this respect. The decline in friendship quality was mitigated by increased effort invested in the relationship, but with a striking gender difference: relationship decline was prevented most by increased contact frequency (talking together) for females but by doing more activities together in the case of males

Interspecific Communicative and Coordinated Hunting between Groupers and Giant Moray Eels in the Red Sea

Intraspecific group hunting has received considerable attention because of the close links between cooperative behaviour and its cognitive demands. Accordingly, comparisons between species have focused on behaviours that can potentially distinguish between the different levels of cognitive complexity involved, such as “intentional” communication between partners in order to initiate a joint hunt, the adoption of different roles during a joint hunt (whether consistently or alternately), and the level of food sharing following a successful hunt. Here we report field observations from the Red Sea on the highly coordinated and communicative interspecific hunting between the grouper, Plectropomus pessuliferus, and the giant moray eel, Gymnothorax javanicus. We provide evidence of the following: (1) associations are nonrandom, (2) groupers signal to moray eels in order to initiate joint searching and recruit moray eels to prey hiding places, (3) signalling is dependent on grouper hunger level, and (4) both partners benefit from the association. The benefits of joint hunting appear to be due to complementary hunting skills, reflecting the evolved strategies of each species, rather than individual role specialisation during joint hunts. In addition, the partner species that catches a prey item swallows it whole immediately, making aggressive monopolisation of a carcass impossible. We propose that the potential for monopolisation of carcasses by one partner species represents the main constraint on the evolution of interspecific cooperative hunting for most potentially suitable predator combinations

Radiocarbon constraint on relict organic carbon contributions to Ross Sea sediments

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 7 (2006): Q04012, doi:10.1029/2005GC001097.We estimate the relative contribution of relict organic matter to the acid-insoluble organic carbon (AIOC) fraction of surface sediments from Ross Sea, Antarctica, on the basis of 14C abundance. The bulk isotopic characteristics of AIOC can largely be explained by simple two-source models of modern and relict organic carbon, when samples are grouped according to two geographical regions, namely, southwestern and south central Ross Sea. This spatial variability in relict organic carbon could be controlled by proximity to the edge of the Ross Ice Shelf and ice drainage areas. Radiocarbon abundance in the AIOC is potentially an excellent tool to estimate the contribution of relict organic carbon in the Antarctic margin sediments.This work was partly supported by a grant from Japan Society for the Promotion of Science to N.O

Endoscopic Imaging in Barrett's Oesophagus: Applications in Routine Clinical Practice and Future Outlook

The practice for endoscopic surveillance of Barrett's oesophagus has evolved from "blind" or random 4 quadrant biopsies (Seattle protocol) to a more "intelligent" targeted biopsy approach. This evolution has been possible due to the rapid advances in endoscopic imaging technology and expertise in the last decade. Previous endoscopes had relatively poor image resolution that often did not allow the subtle mucosal changes associated with dysplastic Barrett's mucosa to be identified. Newer endoscopic imaging techniques available today may allow endoscopists to identify areas of dysplasia or malignancy and target biopsies accordingly. These modalities which include narrow band imaging, chromoendoscopy, autofluorescence imaging, and confocal endomicroscopy as well as a few novel imaging modalities on the horizon will be discussed further

Molecular characterisation of Giardia duodenalis from human and companion animal sources in the United Kingdom using an improved triosephosphate isomerase molecular marker

Giardia duodenalis is a protozoan parasite known for its ability to cause gastrointestinal disease in human and non-human mammals. In the UK, the full impact of this parasite has yet to be fully explored, due to the limited testing which has been undertaken in humans and the low-resolution assemblage-typing methods currently available. Rather than being primarily a travel-associated condition, a recent study has highlighted that an endemic Giardia cycle is present in the UK, although the source of human disease is unclear in the majority of cases. This study focussed on the improvement of one of the commonly used assemblage-typing assays, a nested topoisomerase phosphate (tpi) PCR, to increase the amplification success rate across both human and companion animal samples. After comparing published primers to full Giardia reference genomes, this marker protocol was optimised and then deployed to test a substantial number of human (n ​= ​79) and companion animal (n ​= ​174) samples to gain an insight into the molecular epidemiology of Giardia in the UK. One assemblage A1 and eleven assemblage A2 genotypes were detected in humans, along with and 25 assemblage B genotypes. Assemblage A1 genotypes, known to be human-infective, were found in three feline and one canine sample, while one feline sample contained assemblage A2. Additionally, four feline samples contained assemblage B, which is recognised as potentially human-infective. This study demonstrates the presence of potentially human-infective Giardia genotypes circulating in the companion animal population, notably with 17.4% (8/46) of feline-derived Giardia strains being potentially zoonotic. Using a modified tpi-based genotyping assay, this work highlights the potential for domestic pets to be involved in the endemic transmission of giardiasis in the UK and underlines the need for appropriate hygiene measures to be observed when interacting with both symptomatic and asymptomatic animals. It also serves to underline the requirement for further studies to assess the zoonotic risk of Giardia associated with companion animals in high-income countries

Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer

Review of the articleMitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio