Epidemiology and reporting characteristics of preclinical systematic reviews

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common—along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE’s] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015–2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

A cross sectional study of a sample of recent preclinical systematic reviews reveals deficiencies in reporting and provides the justification and evidence to inform the development of specific guidelines for conducting and reporting preclinical systematic reviews.     

Polymorphism of transferrin and esterase in Alaskan wolves: evidence of close molecular homology with the dog

By the use of isoelectric focusing in polyacrylamide gels serum samples from 146 Alaskan wolves were studied with regard to transferrin (Tf) and esterase (ArE) polymorphism, comparing the phenotypic band patterns with those of selected Norwegian dogs. The study revealed Tf and ArE polymorphisms in the wolf with phenotypic band patterns being indistinguishable from the corresponding ones in dogs. This suggests the occurrence of the same two common Tf alleles in the wolf as in the dog. In the ArE system the results are consistent with the occurrence of three alleles which also occur in dogs whereas a fourth allele, so far not seen in dogs, is seen in Alaskan wolves.     

The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. There is increasing attention for responsible research practices and implementation of reporting guidelines, but whether these efforts have improved the methodological quality of RCTs (e.g., lower risk of bias) is unknown. We, therefore, mapped risk-of-bias trends over time in RCT publications in relation to journal and author characteristics. Meta-information of 176,620 RCTs published between 1966 and 2018 was extracted. The risk-of-bias probability (random sequence generation, allocation concealment, blinding of patients/personnel, and blinding of outcome assessment) was assessed using a risk-of-bias machine learning tool. This tool was simultaneously validated using 63,327 human risk-of-bias assessments obtained from 17,394 RCTs evaluated in the Cochrane Database of Systematic Reviews (CDSR). Moreover, RCT registration and CONSORT Statement reporting were assessed using automated searches. Publication characteristics included the number of authors, journal impact factor (JIF), and medical discipline. The annual number of published RCTs substantially increased over 4 decades, accompanied by increases in authors (5.2 to 7.8) and institutions (2.9 to 4.8). The risk of bias remained present in most RCTs but decreased over time for allocation concealment (63% to 51%), random sequence generation (57% to 36%), and blinding of outcome assessment (58% to 52%). Trial registration (37% to 47%) and the use of the CONSORT Statement (1% to 20%) also rapidly increased. In journals with a higher impact factor (>10), the risk of bias was consistently lower with higher levels of RCT registration and the use of the CONSORT Statement. Automated risk-of-bias predictions had accuracies above 70% for allocation concealment (70.7%), random sequence generation (72.1%), and blinding of patients/personnel (79.8%), but not for blinding of outcome assessment (62.7%). In conclusion, the likelihood of bias in RCTs has generally decreased over the last decades. This optimistic trend may be driven by increased knowledge augmented by mandatory trial registration and more stringent reporting guidelines and journal requirements. Nevertheless, relatively high probabilities of bias remain, particularly in journals with lower impact factors. This emphasizes that further improvement of RCT registration, conduct, and reporting is still urgently needed.

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. Analysis of 176,620 RCTs published between 1966 and 2018 reveals that the risk of bias in RCTs generally decreased. Nevertheless, relatively high probabilities of bias remain, showing that further improvement of RCT registration, conduct, and reporting is still urgently needed.     

Xylem Hydraulic Characteristics, Water Relations and Wood Anatomy of the Resurrection PlantMyrothamnus flabellifoliusWelw.

Myrothamnus flabellifoliusWelw. is a desiccation-tolerant (‘resurrection’)plant with a woody stem. Xylem vessels are narrow (14 µmmean diameter) and perforation plates are reticulate. This leadsto specific and leaf specific hydraulic conductivities thatare amongst the lowest recorded for angiosperms (k_s0.87 kg m^-1MPa^-1s^-1;k_l3.28x10^-5kg m^-1MPa^-1s^-1, stem diameter 3 mm). Hydraulic conductivitiesdecrease with increasing pressure gradient. Transpiration ratesin well watered plants were moderate to low, generating xylemwater potentials of -1 to -2 MPa. Acoustic emissions indicatedextensive cavitation events that were initiated at xylem waterpotentials of -2 to -3 MPa. The desiccation-tolerant natureof the tissue permits this species to survive this interruptionof the water supply. On rewatering the roots pressures thatwere developed were low (2.4 kPa). However capillary forceswere demonstrated to be adequate to account for the refillingof xylem vessels and re-establishment of hydraulic continuityeven when water was under a tension of -8 kPa. During dehydrationand rehydration cycles stems showed considerable shrinking andswelling. Unusual knob-like structures of unknown chemical compositionwere observed on the outer surface of xylem vessels. These maybe related to the ability of the stem to withstand the mechanicalstresses associated with this shrinkage and swelling.Copyright1998 Annals of Botany Company cavitation, desiccation, hydraulic conductivity, refilling, resurrection plant, root pressure, xylem anatomy,Myrothamnus flabellifolius     

Incorporating equity,diversity, and inclusiveness into the Hong Kong Principles

In this response to Labib and Evans, authors of the Hong Kong Principles look forward to collaborating with those from the broad research integrity community to ensure that issues of equity, diversity and inclusion will become part of the ecosystem of research integrity.

We thank Ms. Labib and Dr. Evans for their work on the Hong Kong Principles (HKPs) [1]. Your letter raises important points and gives us an opportunity to respond and clarify our perspective. As you indicate in your letter, equity, diversity, and inclusion (EDI) are important topics that require attention in the assessment of researchers. We did not address them specifically in the HKPs because our main focus was on rewarding responsible research practices that improve the transparency and validity of research. As a clarification (and not to be interpreted as defensive on our part), EDI also wasn’t mentioned prominently in our breakout discussions with more than 100 participants of the 6th World Conference on Research Integrity, where the draft HKPs were discussed and finalized.In our paper [2], Principle 5 (recognize essential other tasks like peer review and mentoring) provides a useful example that illustrates that the essence of the Labib and Evans comments about EDI are in alignment with our views—“Macquarie University, Sydney, Australia, has some exciting initiatives in their new academic promotion policy, which includes five pillars, one of which is in leadership and citizenship. Here, researchers can show their alignment with the university’s values and broader contribution to the university and its community [87]. Since this policy was introduced, it has been reported that the number of promotion applications increased by 50%, and the number of women promoted has also increased [88]”.We think there will be an opportunity to more forcefully address EDI in the envisioned Cape Town Statement on Fostering Research Integrity through equity, fairness, and diversity (programmed as a focus track on the 7th World Conference on Research Integrity, Cape Town, South Africa, 2022). We can imagine that the Cape Town Statement will demand fostering EDI in research, including in the assessment of researchers for hiring, promotion, or tenure. We would see this as an update of the HKPs.We are pleased that the HKPs has initiated discussion on EDI as part of the process of assessing researchers for hiring, promotion, and tenure. We look forward to collaborating with Labib and Evans and many others from the broad research integrity community to ensure that EDI will become part of the ecosystem of research integrity.