Assessing the Completeness of Reporting in Preclinical Oncolytic Virus Therapy Studies

Irreproducibility of preclinical findings could be a significant barrier to the “bench-to-bedside” development of oncolytic viruses (OVs). A contributing factor is the incomplete and non-transparent reporting of study methodology and design. Using the NIH Principles and Guidelines for Reporting Preclinical Research, a core set of seven recommendations, we evaluated the completeness of reporting of preclinical OV studies. We also developed an evidence map identifying the current trends in OV research. A systematic search of MEDLINE and Embase identified all relevant articles published over an 18 month period. We screened 1,554 articles, and 236 met our a priori-defined inclusion criteria. Adenovirus (43%) was the most commonly used viral platform. Frequently investigated cancers included colorectal (14%), skin (12%), and breast (11%). Xenograft implantation (61%) in mice (96%) was the most common animal model. The use of preclinical reporting guidelines was listed in 0.4% of articles. Biological and technical replicates were completely reported in 1% of studies, statistics in 49%, randomization in 1%, blinding in 2%, sample size estimation in 0%, and inclusion/exclusion criteria in 0%. Overall, completeness of reporting in the preclinical OV therapy literature is poor. This may hinder efforts to interpret, replicate, and ultimately translate promising preclinical OV findings

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Fine sediment reduces vertical migrations of Gammarus pulex (Crustacea: Amphipoda) in response to surface water loss

Surface and subsurface sediments in river ecosystems are recognized as refuges that may promote invertebrate survival during disturbances such as floods and streambed drying. Refuge use is spatiotemporally variable, with environmental factors including substrate composition, in particular the proportion of fine sediment (FS), affecting the ability of organisms to move through interstitial spaces. We conducted a laboratory experiment to examine the effects of FS on the movement of Gammarus pulex Linnaeus (Crustacea: Amphipoda) into subsurface sediments in response to surface water loss. We hypothesized that increasing volumes of FS would impede and ultimately prevent individuals from migrating into the sediments. To test this hypothesis, the proportion of FS (1–2 mm diameter) present within an open gravel matrix (4–16 mm diameter) was varied from 10 to 20% by volume in 2.5% increments. Under control conditions (0% FS), 93% of individuals moved into subsurface sediments as the water level was reduced. The proportion of individuals moving into the subsurface decreased to 74% at 10% FS, and at 20% FS no individuals entered the sediments, supporting our hypothesis. These results demonstrate the importance of reducing FS inputs into river ecosystems and restoring FS-clogged riverbeds, to promote refuge use during increasingly common instream disturbances

Persistence of phylogeographic footprints helps to understand cryptic diversity detected in two marine amphipods widespread in the Mediterranean basin

Amphipods of the genus Gammarus are a vital component of macrozoobenthic communities in European inland and coastal, marine and brackish waters of the Mediterranean and the Black Sea. Exceptional levels of cryptic diversity have been revealed for several widespread freshwater Gammarus species in Europe. No comprehensive assessment has yet been made for brackishwater counterparts, such as Gammarus aequicauda and G. insensibilis, which are among the most widely dispersed members of the so-called “G. locusta group” in the Mediterranean and in the Black Sea. Here we probe the diversity of these morphospecies examining the partitioning of mtDNA and nDNA across multiple populations along their distribution range and discuss it within the regional paleogeographic framework. We gathered molecular data from a collection of 166 individuals of G. aequicauda and G. insensibilis from 47 locations along their distribution range in the Mediterranean including the Black Sea. They were amplified for both mitochondrial COI and 16S rRNA as well as the nuclear 28S rRNA. All five MOTU delimitation methods (ABGD, BIN, bPTP, GMYC single and multiple threshold models) applied revealed deep divergence between Black Sea and Mediterranean populations in both G. aequicauda and G. insensibilis. There were eight distinct MOTUs delimited for G. aequicauda (6–18% K2P) and 4 MOTUs for G. insensibilis (4–14% K2P). No sympatric MOTUs were detected throughout their distribution range. Multimarker time-calibrated phylogeny indicated that divergence of both G. aequicauda and G. insensibilis species complexes started already in the late Oligocene/early Miocene with the split between clades inhabiting eastern and western part of the Mediterranean occurring in both species at the similar time. Our results indicate a high cryptic diversity within Mediterranean brackishwater Gammarus, similar to that observed for freshwater counterparts. Moreover, the phylogenetic history combined with the current geographic distribution indicate that the evolution of botThis work was supported by Polish National Science Center (projects no. 2014/15/B/NZ8/00266 and 2015/17/N/NZ8/01628) and partially by the statutory funds of the Department of Invertebrate Zoology and Hydrobiology of University of Lodz. F. Costa and the University of Minho contribution was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Predicting the ecological impacts of a new freshwater invader: functional responses and prey selectivity of the ‘killer shrimp’, Dikerogammarus villosus, compared to the native Gammarus pulex

The ability to predict the likely ecological impacts of invasive species in fresh waters is a pressing research requirement. Whilst comparisons of species traits and considerations of invasion history have some efficacy in this respect, we require robust methods that can compare the effects of native and invasive species. Here, we utilise comparative functional responses and prey selectivity experiments to understand and predict the ecological impact of an invader as compared to a native.We compared the predatory functional responses of an emerging invasive species in Europe, the ‘killer shrimp’, Dikerogammarus villosus, and an analogous native species, Gammarus pulex, towards three representative prey species: Asellus aquaticus, Daphnia magna and Chironomus sp. Furthermore, as ecological impact may be greater for invasive species with more indiscriminate feeding habits, we compared the selectivity for the three prey types between the invasive and native species.In both the presence and absence of experimental habitats, large D. villosus, and those matched for body size with G. pulex, generally showed higher (Type II) functional responses than G. pulex, with the invasive species exhibiting higher maximum feeding rates. Further, D. villosus exhibited significantly more indiscriminate prey selection compared with G. pulex, a trait that became more evident as the invader increased in size. Differences in functional responses and prey selectivity were prey species specific, with higher to lower predicted impacts in the order A. aquaticus, D. magna and Chironomus sp. This is in accord with the impact of this invasive species on macroinvertebrates in the field.We thus provide understanding of the known ecological impact of D. villosus and discuss the utility of the phenomenological use of comparative functional responses and resource use as a tool through which the potential ecological impacts of invasive species may be identified

Direct observations of the effect of fine sediment deposition on the vertical movement of Gammarus pulex (Amphipoda: Gammaridae) during substratum drying

Benthic macroinvertebrates inhabit the streambed sediments of temporary streams during drying events. Fine sediment (< 2 mm in diameter) deposition and clogging of interstitial pathways reduces the connectivity between benthic and subsurface habitats, potentially inhibiting macroinvertebrate vertical movements. Direct observations within subsurface sediments are, however, inherently difficult. As a result, confirmation of macroinvertebrate vertical movement, and the effect of fine sediment, is limited. We used laboratory mesocosms containing transparent gravel sized particles (10–15 mm) to facilitate the direct observation and tracking of vertical movements by Gammarus pulex in response to water level reduction and sedimentation. Seven sediment treatments comprised two fine sediment fractions (small: 0.125–0.5 mm, coarse sand: 0.5–1 mm) deposited onto the surface of the substrate, and a control treatment where no fine sediment was applied. We found that G. pulex moved into the subsurface gravel sediments in response to drying, but their ability to remain submerged during water level reduction was impeded by fine sediment deposition. In particular deposition of the coarser sand fraction clogged the sediment surface, limiting vertical movements. Our results highlight the potential effect of sedimentation on G. pulex resistance to drying events in streams

Coral reef ecology in the Anthropocene

We are in the Anthropocene—an epoch where humans are the dominant force of planetary change. Ecosystems increasingly reflect rapid human-induced, socioeconomic and cultural selection rather than being a product of their surrounding natural biophysical setting. This poses the intriguing question: To what extent do existing ecological paradigms capture and explain the current ecological patterns and processes we observe? We argue that, although biophysical drivers still influence ecosystem structure and function at particular scales, their ability to offer predictive capacity over coupled social–ecological systems is increasingly compromised as we move further into the Anthropocene. Traditionally, the dynamics of coral reefs have been studied in response to their proximate drivers of change rather than their underlying socioeconomic and cultural drivers. We hypothesise this is limiting our ability to accurately predict spatial and temporal changes in coral reef ecosystem structure and function. We propose “social–ecological macroecology” as a novel approach within the field of coral reef ecology to a) identify the interactive effects of biophysical and socioeconomic and cultural drivers of coral reef ecosystems across spatial and temporal scales; b) test the robustness of existing coral reef paradigms; c) explore whether existing paradigms can be adapted to capture the dynamics of contemporary coral reefs; and d) if they cannot, develop novel coral reef social–ecological paradigms, where human dynamics are part of the paradigms rather than the drivers of them. Human socioeconomic and cultural processes must become embedded in coral reef ecological theory and practice as much as biophysical processes are today if we are to predict and manage these systems successfully in this era of rapid change. This necessary shift in our approach to coral reef ecology will be challenging and will require truly interdisciplinary collaborations between the natural and social sciences. A plain language summary is available for this article

Biosecurity and Vector Behaviour: Evaluating the Potential Threat Posed by Anglers and Canoeists as Pathways for the Spread of Invasive Non-Native Species and Pathogens

Invasive non-native species (INNS) endanger native biodiversity and are a major economic problem. The management of pathways to prevent their introduction and establishment is a key target in the Convention on Biological Diversity's Aichi biodiversity targets for 2020. Freshwater environments are particularly susceptible to invasions as they are exposed to multiple introduction pathways, including non-native fish stocking and the release of boat ballast water. Since many freshwater INNS and aquatic pathogens can survive for several days in damp environments, there is potential for transport between water catchments on the equipment used by recreational anglers and canoeists. To quantify this biosecurity risk, we conducted an online questionnaire with 960 anglers and 599 canoeists to investigate their locations of activity, equipment used, and how frequently equipment was cleaned and/or dried after use. Anglers were also asked about their use and disposal of live bait. Our results indicate that 64% of anglers and 78.5% of canoeists use their equipment/boat in more than one catchment within a fortnight, the survival time of many of the INNS and pathogens considered in this study and that 12% of anglers and 50% of canoeists do so without either cleaning or drying their kit between uses. Furthermore, 8% of anglers and 28% of canoeists had used their equipment overseas without cleaning or drying it after each use which could facilitate both the introduction and secondary spread of INNS in the UK. Our results provide a baseline against which to evaluate the effectiveness of future biosecurity awareness campaigns, and identify groups to target with biosecurity awareness information. Our results also indicate that the biosecurity practices of these groups must improve to reduce the likelihood of inadvertently spreading INNS and pathogens through these activities

Isolating the impact of antipsychotic medication on metabolic health : secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first‐episode psychosis (the STAGES study)

Background Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids. Methods This study utilized data from a triple-blind randomized placebo-controlled trial comparing two groups of antipsychotic-naïve young people with a FEP who were randomized to receive a second-generation antipsychotic medication (FEP-medication group) or placebo (FEP-placebo group) for 6 months. Twenty-seven control participants were also recruited. Results Eighty-one participants commenced the trial; 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP-placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants (t = 0.76, p = .45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP-placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant (t = 0.8, p = .44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months. Conclusions While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP