An investigation of the shortcomings of the CONSORT 2010 statement for the reporting of group sequential randomised controlled trials: a methodological systematic review

Background It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design. Methods We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported. Results Of the 284 screened trials, 68(24%) were eligible. Most trials were published in “high impact” peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments. Discussion and Conclusions There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.

Parents' verbal communication and childhood anxiety: a systematic review

Parents’ verbal communication to their child, particularly the expression of fear-relevant information (e.g., attributions of threat to the environment), is considered to play a key role in children’s fears and anxiety. This review considers the extent to which parental verbal communication is associated with child anxiety by examining research that has employed objective observational methods. Using a systematic search strategy, we identified 15 studies that addressed this question. These studies provided some evidence that particular fear-relevant features of parental verbal communication are associated with child anxiety under certain conditions. However, the scope for drawing reliable, general conclusions was limited by extensive methodological variation between studies, particularly in terms of the features of parental verbal communication examined and the context in which communication took place, how child anxiety was measured, and inconsistent consideration of factors that may moderate the verbal communication–child anxiety relationship. We discuss ways in which future research can contribute to this developing evidence base and reduce further methodological inconsistency so as to inform interventions for children with anxiety problems.

Systematic and random errors between collocated satellite ice water path observations

There remains large disagreement between ice-water path (IWP) in observational data sets, largely because the sensors observe different parts of the ice particle size distribution. A detailed comparison of retrieved IWP from satellite observations in the Tropics (!30 " latitude) in 2007 was made using collocated measurements. The radio detection and ranging(radar)/light detection and ranging (lidar) (DARDAR) IWP data set, based on combined radar/lidar measurements, is used as a reference because it provides arguably the best estimate of the total column IWP. For each data set, usable IWP dynamic ranges are inferred from this comparison. IWP retrievals based on solar reflectance measurements, in the moderate resolution imaging spectroradiometer (MODIS), advanced very high resolution radiometer–based Climate Monitoring Satellite Applications Facility (CMSAF), and Pathfinder Atmospheres-Extended (PATMOS-x) datasets, were found to be correlated with DARDAR over a large IWP range (~20–7000 g m -2 ). The random errors of the collocated data sets have a close to lognormal distribution, and the combined random error of MODIS and DARDAR is less than a factor of 2, which also sets the upper limit for MODIS alone. In the same way, the upper limit for the random error of all considered data sets is determined. Data sets based on passive microwave measurements, microwave surface and precipitation products system (MSPPS), microwave integrated retrieval system (MiRS), and collocated microwave only (CMO), are largely correlated with DARDAR for IWP values larger than approximately 700 g m -2 . The combined uncertainty between these data sets and DARDAR in this range is slightly less MODIS-DARDAR, but the systematic bias is nearly an order of magnitude.

Higher PUFA and omega-3 PUFA, CLA, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses

Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI −1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI −122, −20) % and 93 (95 % CI −116, −70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.

Composition differences between organic and conventional meat: a systematic literature review and meta-analysis

Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.

Implementing systematic review techniques in chemical risk assessment: challenges, opportunities and recommendations

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.

A systematic method of parameterisation estimation using data assimilation

In numerical weather prediction, parameterisations are used to simulate missing physics in the model. These can be due to a lack of scientific understanding or a lack of computing power available to address all the known physical processes. Parameterisations are sources of large uncertainty in a model as parameter values used in these parameterisations cannot be measured directly and hence are often not well known; and the parameterisations themselves are also approximations of the processes present in the true atmosphere. Whilst there are many efficient and effective methods for combined state/parameter estimation in data assimilation (DA), such as state augmentation, these are not effective at estimating the structure of parameterisations. A new method of parameterisation estimation is proposed that uses sequential DA methods to estimate errors in the numerical models at each space-time point for each model equation. These errors are then fitted to pre-determined functional forms of missing physics or parameterisations that are based upon prior information. We applied the method to a one-dimensional advection model with additive model error, and it is shown that the method can accurately estimate parameterisations, with consistent error estimates. Furthermore, it is shown how the method depends on the quality of the DA results. The results indicate that this new method is a powerful tool in systematic model improvement.

Hydrodynamics with spin angular momentum from systematic coarse graining: a tutorial example

The derivation of time evolution equations for slow collective variables starting from a micro- scopic model system is demonstrated for the tutorial example of the classical, two-dimensional XY model. Projection operator techniques are used within a nonequilibrium thermodynamics framework together with molecular simulations in order to establish the building blocks of the hydrodynamics equations: Poisson brackets that determine the deterministic drift, the driving forces from the macroscopic free energy and the friction matrix. The approach is rather general and can be applied for deriving the equations of slow variables for a broad variety of systems.

Alcantarea (Bromeliaceae) leaf anatomical characterization and its systematic implications

Alcantarea (Bromeliaceae) has 26 species that are endemic to eastern Brazil, occurring mainly on gneiss-granitic rock outcrops (`inselbergs`). Alcantarea has great ornamental potential and several species are cultivated in gardens. Limited data is available in the literature regarding the leaf anatomical features of the genus, though it has been shown that it may provide valuable information for characterizing of Bromeliaceae taxa. In the present work, we employed leaf anatomy to better characterize the genus and understand its radiation into harsh environments, such as inselbergs. We also searched for characteristics potentially useful in phylogenetic analyses and in delimiting Alcantarea and Vriesea. The anatomical features of the leaves, observed for various Alcantarea species, are in accordance with the general pattern shown by other Bromeliaceae members. However, some features are notable for their importance for sustaining life on rock outcrops, such as: small epidermal thick-walled cells, uneven sinuous epidermal walls, hypodermis often differentiated into lignified layers with thick-walled cells, aquiferous hypodermis bearing collapsible cells, and the presence of well developed epicuticular stratum. Alcantarea leaves tend to show different shapes in the spongy parenchyma, and have chlorenchymatous palisade parenchyma arranged in more well-defined arches, when compared to Vriesea species from the same habitat.

A systematic revision of Goniosomatinae (Arachnida : Opiliones : Gonyleptidae), with a cladistic analysis and biogeographical notes

Goniosomatine harvestmen have strongly armed pedipalps, generally large bodies and, commonly, very long legs (sometimes more than 20 cm), and are distributed in the Brazilian Atlantic forest, from southern Bahia to Santa Catarina. Since they are conspicuous animals and individuals of some species tend to concentrate in caves (and also under rock boulders), they have been (and still are) the target of several studies, especially those focusing on reproductive and defensive behavior, population ecology, physiology, chromosomes, etc. In spite of their importance for biological studies (some species constitute important and frequently used models for these studies), the taxonomy of Goniosomatinae has faced some problems, including misidentification, a large number of undescribed species and the lack of a phylogenetic hypothesis for the relationships among its species (which would allow evolutionary studies to be made). The last taxonomic changes in the subfamily were made 60 years ago. Considering a taxonomic revision and cladistic analysis of the subfamily to be of paramount importance, the main scope of the present paper is to provide a cladistic analysis and taxonomic revision of the species of Goniosomatinae and a new arrangement of genera (and species). The main taxonomic changes are given as follows. Six genera are recognised within the subfamily: Goniosoma; the newly described genus Pyatan; the reestablished genera Serracutisoma, Heteromitobates and Mitogoniella; and Acutisoma. New generic synonyms include: Glyptogoniosoma = Goniosomella = Lyogoniosoma = Metalyogoniosoma = Xulapona = Goniosoma, Acutisomelloides = Pygosomoides = Spelaeosoma = Serracutisoma; and Acutisomella = Heteromitobates. Newly described species include: Goniosoma capixaba; G. apoain; Pyatan insperatum DaSilva, Stefanini-Jim & Gnaspini; Serracutisoma pseudovarium; S. fritzmuelleri; S. guaricana; Heteromitobates anarchus; H. harlequin; H. alienus; Mitogoniella taquara; M. unicornis; and Acutisoma coriaceum. New combinations include: Goniosoma macracanthum (Mello-Leitao, 1922); G. unicolor (Mello-Leitao, 1932); G. carum (Mello-Leitao, 1936); Serracutisoma proximum (Mello-Leitao, 1922); S. banhadoae (Soares & Soares, 1947); S. molle (Mello-Leitao, 1933); S. thalassinum (Simon, 1879); S. catarina (Machado, Pinto-da-Rocha & Ramires, 2002); S. inerme (Mello-Leitao, 1927); S. spelaeum (MelloLeitao, 1933); Heteromitobates inscriptus (Mello-Leitao, 1922); H. albiscriptus (Mello-Leitao, 1932); Mitogoniella modesta (Perty, 1833); and M. badia (Koch, 1839). Reestablished combinations include: Mitogoniella indistincta MelloLeitao, 1936 and Acutisoma longipes Roewer, 1913. New speci. c synonyms include: Acutisomella cryptoleuca = Acutisomella intermedia = Goniosoma junceum = Goniosoma patruele = Goniosoma xanthophthalmum = Metalyogoniosoma unum = Goniosoma varium, Goniosoma geniculatum = Goniosoma venustum; Goniosomella perlata = Progoniosoma minense = Goniosoma vatrax, Glyptogoniosoma perditum = Progoniosoma cruciferum = Progoniosoma tijuca = Goniosoma dentipes; Leitaoius iguapensis = Leitaoius viridifrons = Serracutisoma proximum; Acutisoma marumbicola = Acutisoma patens = Serracutisoma thalassinum; Progoniosoma tetrasetae = Serracutisoma inerme; and Acutisoma monticola = Leitaoius nitidissimus = Leitaoius xanthomus = Mitogoniella mutila = Acutisoma longipes. The following species are considered species inquirenda: Goniosoma lepidum Gervais, 1844; G. monacanthum Gervais, 1844; G. obscurum Perty, 1833; G. versicolor Perty, 1833; and Mitogoniella badia (Koch, 1839). The monotpic genus Goniosomoides Mello-Leitao, 1932 (and its species, G. viridans Mello-Leitao, 1932) is removed from Goniosomatinae and considered incertae sedis.

Croton laceratoglandulosus (Euphorbiaceae s.s.), a new glandular-stipulate species from Brazil and Bolivia, and its systematic position based on molecular analysis

Croton laceratoglandulosus, a new species from the dry forests of the Brazilian states of Piaui, Ceara, Bahia and Minas Gerais, and the Bolivian department of Santa Cruz, is described and illustrated here. Molecular sequence data demonstrate that it is most closely related to the taxa of Croton section Cascarilla, and not to sections Medea or Barhamia, which also have glandular calyces and laciniate stipules. (C) 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 158, 493-498.

Systematic revision and cladistic analysis of the Brazilian subfamily Sodreaninae (Opiliones: Gonyleptidae)

Sodreaninae is reviewed and all ten species are combined under its type genus, Sodreana Mello-Leitao, 1922, according to a cladistic analysis of morphological characters, which revealed a pectinate pattern of clades. The subfamily is endemic to the Brazilian Atlantic rainforest from Santa Catarina state to Rio de Janeiro state. Sodreana is herein considered a senior synonym of Stygnobates Mello-Leitao, 1927, Zortalia Mello-Leitao, 1936, Gertia B. Soares & H. Soares, 1946 and Annampheres H. Soares, 1979. The following new combinations are proposed: Sodreana barbiellinii (Mello-Leitao, 1927), Sodreana hatschbachi (B. Soares & H. Soares, 1946), Sodreana inscripta (Mello-Leitao, 1939), Sodreana leprevosti (B. Soares & H. Soares, 1947b), Sodreana bicalcarata (Mello-Leitao, 1936). Sodreana granulata (Mello-Leitao, 1937) is revalidated from the synonymy of Sodreana sodreana Mello-Leitao, 1922. Three new species are described: Sodreana glaucoi from Ilhabela and Boraceia, Sao Paulo state; S. curupira from Parque Nacional da Serra dos Orgaos, Rio de Janeiro state, and S. caipora from Ubatuba, Sao Paulo state. Sodreaninae species are restricted to forested areas and most occur in the southern part of the coastal Atlantic rainforest, one species occurs in interior Atlantic rainforest. The biogeographical analysis (Brooks Parsimony Analysis) resulted in a single and fully resolved most parsimonious tree with three main: components: northern (Bahia and Serra do Espinhaco), southern (Santa Catarina, Parana, Serra do Mar of Sao Paulo), and central (Espirito Santo, Serra da Bocaina, southern state of Rio de Janeiro, Serra dos Orgaos, Serra da Mantiqueira, Serra do Mar of Sao Paulo).

NMR Chemical Shielding and Spin-Spin Coupling Constants of Liquid NH(3): A Systematic Investigation using the Sequential QM/MM Method

The NMR spin coupling parameters, (1)J(N,H) and (2)J(H,H), and the chemical shielding, sigma((15)N), of liquid ammonia are studied from a combined and sequential QM/MM methodology. Monte Carlo simulations are performed to generate statistically uncorrelated configurations that are submitted to density functional theory calculations. Two different Lennard-Jones potentials are used in the liquid simulations. Electronic polarization is included in these two potentials via an iterative procedure with and without geometry relaxation, and the influence on the calculated properties are analyzed. B3LYP/aug-cc-pVTZ-J calculations were used to compute the V(N,H) constants in the interval of -67.8 to -63.9 Hz, depending on the theoretical model used. These can be compared with the experimental results of -61.6 Hz. For the (2)J(H,H) coupling the theoretical results vary between -10.6 to -13.01 Hz. The indirect experimental result derived from partially deuterated liquid is -11.1 Hz. Inclusion of explicit hydrogen bonded molecules gives a small but important contribution. The vapor-to-liquid shifts are also considered. This shift is calculated to be negligible for (1)J(N,H) in agreement with experiment. This is rationalized as a cancellation of the geometry relaxation and pure solvent effects. For the chemical shielding, U(15 N) Calculations at the B3LYP/aug-pcS-3 show that the vapor-to-liquid chemical shift requires the explicit use of solvent molecules. Considering only one ammonia molecule in an electrostatic embedding gives a wrong sign for the chemical shift that is corrected only with the use of explicit additional molecules. The best result calculated for the vapor to liquid chemical shift Delta sigma((15)N) is -25.2 ppm, in good agreement with the experimental value of -22.6 ppm.