Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review

Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses

Use of the Meganuclease I-SceI of Saccharomyces cerevisiae to select for gene deletions in actinomycetes

The search for new natural products is leading to the isolation of novel actinomycete species, many of which will ultimately require genetic analysis. Some of these isolates will likely exhibit low intrinsic frequencies of homologous recombination and fail to sporulate under laboratory conditions, exacerbating the construction of targeted gene deletions and replacements in genetically uncharacterised strains. To facilitate the genetic manipulation of such species, we have developed an efficient method to generate gene or gene cluster deletions in actinomycetes by homologous recombination that does not introduce any other changes to the targeted organism's genome. We have synthesised a codon optimised I-SceI gene for expression in actinomycetes that results in the production of the yeast I-SceI homing endonuclease which produces double strand breaks at a unique introduced 18 base pair recognition sequence. Only those genomes that undergo homologous recombination survive, providing a powerful selection for recombinants, approximately half of which possess the desired mutant genotype. To demonstrate the efficacy and efficiency of the system, we deleted part of the gene cluster for the red-pigmented undecylprodiginine complex of compounds in Streptomyces coelicolor M1141. We believe that the system we have developed will be broadly applicable across a wide range of actinomycetes

Competition and parasitism in the native White Clawed Crayfish Austropotamobius pallipes and the invasive Signal Crayfish Pacifastacus leniusculus in the UK

Many crayfish species have been introduced to novel habitats worldwide, often threatening extinction of native species. Here we investigate competitive interactions and parasite infections in the native Austropotamobius pallipes and the invasive Pacifastacus leniusculus from single and mixed species populations in theUK. We found A. pallipes individuals to be significantly smaller in mixed compared to single species populations; conversely P. leniusculus individuals were larger in mixed than in single species populations. Our data provide no support for reproductive interference as a mechanism of competitive displacement and instead suggest competitive exclusion of A. pallipes from refuges by P. leniusculus leading to differential predation. We screened 52 P. leniusculus and 12 A. pallipes for microsporidian infection using PCR. We present the first molecular confirmation of Thelohania contejeani in the native A. pallipes; in addition, we provide the first evidence for T. contejeani in the invasive P. leniusculus. Three novel parasite sequenceswere also isolated fromP. leniusculus with an overall prevalence of microsporidian infection of 38% within this species; we discuss the identity of and the similarity between these three novel sequences. We also screened a subset of fifteen P. leniusculus and three A. pallipes for Aphanomyces astaci, the causative agent of crayfish plague and for the protistan crayfish parasite Psorospermium haeckeli. We found no evidence for infection by either agent in any of the crayfish screened. The high prevalence of microsporidian parasites and occurrence of shared T. contejeani infection lead us to propose that future studies should consider the impact of these parasites on native and invasive host fitness and their potential effects upon the dynamics of native-invader systems

Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus

Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

Spatial Distribution of Cryptic Species Diversity in European Freshwater Amphipods (Gammarus fossarum) as Revealed by Pyrosequencing

In order to understand and protect ecosystems, local gene pools need to be evaluated with respect to their uniqueness. Cryptic species present a challenge in this context because their presence, if unrecognized, may lead to serious misjudgement of the distribution of evolutionarily distinct genetic entities. In this study, we describe the current geographical distribution of cryptic species of the ecologically important stream amphipod Gammarus fossarum (types A, B and C). We use a novel pyrosequencing assay for molecular species identification and survey 62 populations in Switzerland, plus several populations in Germany and eastern France. In addition, we compile data from previous publications (mainly Germany). A clear transition is observed from type A in the east (Danube and Po drainages) to types B and, more rarely, C in the west (Meuse, Rhone, and four smaller French river systems). Within the Rhine drainage, the cryptic species meet in a contact zone which spans the entire G. fossarum distribution range from north to south. This large-scale geographical sorting indicates that types A and B persisted in separate refugia during Pleistocene glaciations. Within the contact zone, the species rarely co-occur at the same site, suggesting that ecological processes may preclude long-term coexistence. The clear phylogeographical signal observed in this study implies that, in many parts of Europe, only one of the cryptic species is present

Short-term acclimation in adults does not predict offspring acclimation potential to hypoxia

Abstract The prevalence of hypoxic areas in coastal waters is predicted to increase and lead to reduced biodiversity. While the adult stages of many estuarine invertebrates can cope with short periods of hypoxia, it remains unclear whether that ability is present if animals are bred and reared under chronic hypoxia. We firstly investigated the effect of moderate, short-term environmental hypoxia (40% air saturation for one week) on metabolic performance in adults of an estuarine amphipod, and the fitness consequences of prolonged exposure. We then reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their oxyregulatory ability under declining oxygen tensions as juveniles and adults. Adults from the parental generation were able to acclimate their metabolism to hypoxia after one week, employing mechanisms typically associated with prolonged exposure. Their progeny, however, did not develop the adult pattern of respiratory regulation when reared under chronic hypoxia, but instead exhibited a poorer oxyregulatory ability than their parents. We conclude that species apparently hypoxia-tolerant when tested in short-term experiments, could be physiologically compromised as adults if they develop under hypoxia. Consequently, we propose that the increased prevalence of hypoxia in coastal regions will have marked effects in some species currently considered hypoxia tolerant

Gravity of human impacts mediates coral reef conservation gains

Coral reefs provide ecosystem goods and services for millions of people in the tropics, but reef conditions are declining worldwide. Effective solutions to the crisis facing coral reefs depend in part on understanding the context under which different types of conservation benefits can be maximized. Our global analysis of nearly 1,800 tropical reefs reveals how the intensity of human impacts in the surrounding seascape, measured as a function of human population size and accessibility to reefs (“gravity”), diminishes the effectiveness of marine reserves at sustaining reef fish biomass and the presence of top predators, even where compliance with reserve rules is high. Critically, fish biomass in high-compliance marine reserves located where human impacts were intensive tended to be less than a quarter that of reserves where human impacts were low. Similarly, the probability of encountering top predators on reefs with high human impacts was close to zero, even in high-compliance marine reserves. However, we find that the relative difference between openly fished sites and reserves (what we refer to as conservation gains) are highest for fish biomass (excluding predators) where human impacts are moderate and for top predators where human impacts are low. Our results illustrate critical ecological trade-offs in meeting key conservation objectives: reserves placed where there are moderate-to-high human impacts can provide substantial conservation gains for fish biomass, yet they are unlikely to support key ecosystem functions like higher-order predation, which is more prevalent in reserve locations with low human impacts

Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily

Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP-seq with in vitro biochemistry to characterize a putative NsrR homologue in the model organism Streptomyces venezuelae. ChIP seq analysis revealed that rather than regulating the nitrosative stress response like NsrR, Sven6563 binds to a different, much larger regulon of genes with a diverse range of functions, including a range of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activity in vitro. To our knowledge, both the sensing domain and the target gene regulon are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR for Redox sensitive response Regulator

Meeting fisheries, ecosystem function, and biodiversity goals in a human-dominated world

The worldwide decline of coral reefs necessitates targeting management solutions that can sustain reefs and the livelihoods of the people who depend on them. However, little is known about the context in which different reef management tools can help to achieve multiple social and ecological goals. Because of nonlinearities in the likelihood of achieving combined fisheries, ecological function, and biodiversity goals along a gradient of human pressure, relatively small changes in the context in which management is implemented could have substantial impacts on whether these goals are likely to be met. Critically, management can provide substantial conservation benefits to most reefs for fisheries and ecological function, but not biodiversity goals, given their degraded state and the levels of human pressure they face