Independent age estimates resolve the controversy of ancient human footprints at White Sands.

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant Ruppia cirrhosa. These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated 14C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the Ruppia seeds, along with optically stimulated luminescence ages of sediments from within the human footprint-bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum.

Luminescence sediment tracing reveals the complex dynamics of colluvial wedge formation.

Paleoearthquake studies that inform seismic hazard rely on assumptions of sediment transport that remain largely untested. Here, we test a widespread conceptual model and a new numerical model on the formation of colluvial wedges, a key deposit used to constrain the timing of paleoearthquakes. We perform this test by applying luminescence, a sunlight-sensitive sediment tracer, at a field site displaying classic colluvial wedge morphostratigraphy. The model and data comparison reveals complex sediment transport processes beyond the predictions of either conceptual or numerical models, including periods of simultaneous debris and wash facies forming processes, erosion, and reworking. These processes could lead to preservation bias, such as incomplete or overinterpretable paleoearthquake records, given the right environmental conditions. Attention to the site-specific mechanics of fault zone depositional systems, such as via sediment tracing, may buffer against the possible effects of preservation bias on paleoseismic study.

Financial conflicts of interest during meetings of the cardiovascular and renal drugs advisory committee.

CONTEXT: The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) of the Food and Drug Administration (FDA) reviews safety and efficacy data for cardiovascular and renal drugs, ultimately making recommendations to the Commissioner of Food and Drugs for approval. The Open Public Hearing segment of these meetings allows for patients, advocates, healthcare professionals, clinical trialists, and members of the public to provide testimony, which often results in expressing their preference for, or against, drug approval. Prior to providing testimony, the public speakers are highly encouraged to disclose any financial conflicts of interest (FCOIs) with the sponsor or other groups. Given the potential influence of these speakers on drug approval recommendations, we investigated the industry associations disclosed by public speakers in the Open Public Hearing section of the CRDAC meetings. Previous studies, such as one done by Lurie et al. indicated that positive testimony is tied to a higher likelihood of drug approval, and because drug companies provide financial compensation for speakers to provide testimony in general, we wanted to determine the likelihood with which speakers who have an FCOI provided a positive testimony vs. those without any FCOI. OBJECTIVES: The purpose is to evaluate whether public speakers with an FCOI are more likely to provide positive testimony regarding the drug in question during the CRDAC of the FDA between February 2009 and December 2019 through the use of publicly available transcripts. METHODS: Independent researchers investigated public transcripts and minutes of the CRDAC meetings with public speakers (n=20). We identified all speakers, along with characteristics such as an FCOI, and classified statements utilizing a pilot-tested Google form. The data collected were analyzed utilizing Stata. The speaker's testimony was then compared with their FCOI. An ordered logistic regression was performed utilizing the speaker's testimony regarding the drug as the dependent variable. RESULTS: Of the 88 speakers represented in our sample, 35 (35/88, 39.8%) disclosed an FCOI, most commonly regarding travel cost. Among speakers with an FCOI, 30 (30/35, 85.7%) spoke positively. Speakers with an FCOI were 4.96 times more likely to provide positive testimony (OR=4.96, 95% CI 1.67-14.78). Speakers with the disease were also more likely to provide positive testimony (OR=13.05, 95% CI 2.84-59.93). CONCLUSIONS: Public speakers often play a role during meetings, and they may also have an FCOI, most commonly related to travel expenses. Our study shows that speakers with an FCOI are more likely to provide positive testimony. Stipulations, such as requiring disclosure of FCOI and randomizing the selection process of speakers, can help ensure the integrity of the drug approval process.

Clinical Trial Registry Use in Orthopaedic Surgery Systematic Reviews.

BACKGROUND: Results from systematic reviews and meta-analyses, which have the highest level of evidence (Level I), often drive clinical decision-making and health policy. Often, unpublished trial data are omitted from systematic reviews, raising concerns about the extent of the reliability and validity of results that have been drawn from systematic reviews. We aimed to determine the extent to which systematic review authors include searches of clinical trial registries for unpublished data when conducting systematic reviews in orthopaedic surgery. METHODS: Systematic reviews and/or meta-analyses were gathered from the top 5 orthopaedic surgery journals based on the h5-index from Google Scholar Metrics. Systematic reviews that had been published in the Cochrane Database of Systematic Reviews, which requires the inclusion of a clinical trial registry search, served as controls. For the primary outcome, each systematic review from the top 5 orthopaedic journals was screened to determine whether the authors of each study searched for unpublished data in clinical trial registries. We then compared the rate of registry searches with those in the control group. For the secondary analysis, a search of ClinicalTrials.gov was performed for unpublished trial data for 100 randomized systematic reviews. RESULTS: All 38 of the Cochrane systematic reviews (100%) included clinical trial registry searches, while the top 5 orthopaedic journals had only 31 of 480 studies (6.5%) that looked at clinical trial registries. The secondary analysis yielded 59 of 100 systematic review articles (59.0%) that could have included unpublished clinical trial data from ≥1 studies to their sample. CONCLUSIONS: Systematic reviews that have been published in the top orthopaedic surgery journals seldom included a search for unpublished clinical trial data. CLINICAL RELEVANCE: The exclusion of clinical trial registry searches potentially contributes to publication bias within the orthopaedic literature. Moving forward, systematic review authors should include clinical trial registry searches for unpublished clinical trial data to provide the most accurate representation of the available evidence for systematic reviews and meta-analyses.

An Evaluation of Reporting Guidelines and Clinical Trial Registry Requirements Among Addiction Medicine Journals.

CONTEXT: Robust methodology and ethical reporting are paramount for quality scientific research, but recently, that quality in addiction research has been questioned. Avenues to improve such research quality include adherence to reporting guidelines and proper usage of clinical trial registries. Reporting guidelines and clinical trial registries have been shown to lead researchers to more ethical and transparent methodology. OBJECTIVES: To investigate the reporting guideline and clinical trial registration policies of addiction research journals and identify areas of improvement. METHODS: We used Google Scholar Metrics' h-5 index to identify the top 20 addiction research journals. We then examined the instructions for authors from each journal to identify whether they required, recommended, or made no mention of trial registration and reporting guidelines, including the Consolidated Standards of Reporting Trials (CONSORT), Meta-Analysis of Observational Studies in Epidemiology (MOOSE), Quality of Reporting of Meta-analyses (QUOROM), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Standards for Reporting Diagnostic Accuracy Studies (STARD), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), Animal Research: Reporting of In Vivo Experiments (ARRIVE), Case Reports (CARE), Consolidated Health Economic Evaluation Reporting Standards (CHEERS), Standards for Reporting Qualitative Research (SRQR), Standards for Quality Improvement Reporting Excellence (SQUIRE), Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), Consolidated Criteria for Reporting Qualitative Research (COREQ), Transparent Reporting of a Multivariate Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the International Committee of Medical Journal Editors (ICMJE) guidelines. We performed the same analysis regarding requirements for clinical trial registration. RESULTS: Of the 20 journals included in this study, 10 journals (50%) did not require adherence to any reporting guidelines. Trial registration followed a similar trend; 15 journals (75%) did not mention any form of trial or systematic review registration, and ClinicalTrials.gov was only recommended by only 1 journal (5%). CONCLUSIONS: Among top addiction medicine journals, required adherence to reporting guidelines and clinical trial registry policies remains substandard. A step toward fulfilling the National Institute on Drug Abuses' call for improvement in transparency and reproducibility within addiction research should include all journals adopting a strict reporting guideline and clinical trial registry adherence policy.

An Evaluation of the Presence of Spin in the Abstracts of Tonsillectomy Systematic Reviews.

OBJECTIVES/HYPOTHESIS: Spin-the practice of adding or omitting information intentionally or unintentionally to make the results of a study more favorable-may influence clinical decision making, especially when present in study abstracts. Here, we quantify and characterize the presence of spin in the abstracts of systematic reviews regarding tonsillectomy. METHODS: This study is an analysis of systematic review abstracts. Searches were conducted on September 23, 2019 on PubMed and Embase using the advanced search feature to retrieve systematic reviews regarding tonsillectomies. The nine most severe forms of spin were then evaluated. Spin was classified by two investigators in parallel, with each blinded to the classifications of the other. Study characteristics were also recorded in duplicate. Consensus meetings between investigators were held to resolve disagreements. RESULTS: In the 85 included systematic reviews, at least one form of spin was present in 44.7% (38/85) of abstracts. Journals with higher impact factors were less likely to contain spin in the abstracts of systematic reviews (point biserial correlation coefficient of -0.30). No statistically significant associations were found between the presence of spin and intervention type (P = .56) or adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P = .08); however, there was a significant association between spin and funding source (P = .03). CONCLUSIONS: Spin was common in the abstracts of our sample of tonsillectomy systematic reviews. Researchers, clinicians, and peer reviewers could benefit from learning to recognize spin in medical literature. Further research is needed into the effects of spin on clinical decision making. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.

Depth-dependent soil mixing persists across climate zones.

Soil mixing over long (>102 y) timescales enhances nutrient fluxes that support soil ecology, contributes to dispersion of sediment and contaminated material, and modulates fluxes of carbon through Earth's largest terrestrial carbon reservoir. Despite its foundational importance, we lack robust understanding of the rates and patterns of soil mixing, largely due to a lack of long-timescale data. Here we demonstrate that luminescence, a light-sensitive property of minerals used for geologic dating, can be used as a long-timescale sediment tracer in soils to reveal the structure of soil mixing. We develop a probabilistic model of transport and mixing of tracer particles and associated luminescence in soils and compare with a global compilation of luminescence versus depth in various locations. The model-data comparison reveals that soil mixing rate varies over the soil depth, with this depth dependency persisting across climate and ecological zones. The depth dependency is consistent with a model in which mixing intensity decreases linearly or exponentially with depth, although our data do not resolve between these cases. Our findings support the long-suspected idea that depth-dependent mixing is a spatially and temporally persistent feature of soils. Evidence for a climate control on the patterns and intensities of soil mixing with depth remains elusive and requires the further study of soil mixing processes.

The use of systematic reviews to justify orthopaedic trauma randomized controlled trials: A cross-sectional analysis.

OBJECTIVE: Orthopaedic trauma is one of the largest surgical fields in medicine, and as such, requires the latest evidence to ensure the best standard of care. Systematic reviews are an invaluable resource that compiles an exhaustive summary of the most current evidence on a given clinical question. The primary aim of this study is to evaluate the use of systematic reviews as justification in conducting randomized controlled trials published in high impact orthopaedic trauma journals. METHODS: We analyzed randomized controlled trials published in the top three high impact orthopaedic trauma journals between 2015 and 2018. We performed data extraction blind, independent, and in duplicative manner to ensure the validity of the findings. For each trial, data was extracted by the number of systematic reviews cited in each clinical trial and whether or not the study used a systematic review as justification for conducting the trial. A subgroup of general orthopaedic clinical trials were included for comparison. RESULTS: Of 144 articles retrieved, 128 were included. Overall, 71.1% (91/128; [95% CI, 63.2-78.9]) of included orthopaedic trauma randomized controlled trials referenced a systematic review and 28.9% (37/128) of studies did not cite a systematic review. Of the 91 trials that referenced a systematic review, 33.0% (30/91; [95% CI, 23.3-42.6]) of RCTs cited a systematic review as trial justification, whether that be "verbatim" or "inferred". "Verbatim" justifications occurred in 20.0% (6/30; [95% CI, 5.7-34.3]) of included trauma RCTs that cited a systematic review as justification for conducting the trial and "inferred" justifications occurred in 80.0% (24/30; [95% CI, 65.7-94.3]). CONCLUSION: Systematic reviews are frequently cited in orthopaedic trauma RCTs but are not commonly cited as justification for conducting a clinical trial. Ideally, evidentiary uncertainty regarding a research question should be established by existing literature through a systematic review to reduce research waste.

Trial Registry Use in Surgery Systematic Reviews: A Cross-Sectional Study.

OBJECTIVE: To determine the extent to which systematic reviews published in surgery journals reported a clinical trial registry search as part of their search strategy and whether systematic reviews that omitted such searches would have located additional trials for inclusion. BACKGROUND: Systematic reviews are used by clinicians to guide clinical decision making. When conducting systematic reviews, the comprehensive search strategy is particularly critical to identify all studies-whether published or not-for producing an overall summary effect. Inclusion of only published studies may lead to overestimated and inaccurate summary effects; thus, it is important to consider unpublished studies. Here, we investigate the extent of clinical trial registry searches performed in surgical systematic reviews because trial registries may be the most viable approach to locate unpublished trial data. METHODS: We retrieved systematic reviews from the top surgery journals and the Cochrane Collaboration. Each was reviewed to determine which bibliographic databases were used and which, if any, trial registries were searched. RESULTS: Of 996 total systematic reviews, 252 (25.3%) reported having included a clinical trial registry search, with systematic reviews published in journals reporting searches of unpublished research at a rate of 6.4% (47/737). Reviews published by the Cochrane Collaboration included searches of unpublished research 79.2% of the time (205/259). CONCLUSIONS: Many systematic reviews published in surgery journals include only published research, which may contribute to publication bias. We recommend that authors maximize available information by using unpublished trial data found in clinical trial registries.

Using the CONSORT statement to evaluate the completeness of reporting of addiction randomised trials: a cross-sectional review.

OBJECTIVES: Evaluate the completeness of reporting of addiction randomised controlled trials (RCTs) using the Consolidated Standards of Reporting Trials (CONSORT) statement. SETTING: Not applicable. PARTICIPANTS: RCTs identified using a PubMed search of 15 addiction journals and a 5-year cross-section. OUTCOME MEASURES: Completeness of reporting. RESULTS: Our analysis of 394 addiction RCTs found that the mean number of CONSORT items reported was 19.2 (SD 5.2), out of a possible 31. Twelve items were reported in <50% of RCTs; similarly, 12 items were reported in >75% of RCTs. Journal endorsement of CONSORT was found to improve the number of CONSORT items reported. CONCLUSIONS: Poor reporting quality may prohibit readers from critically appraising the methodological quality of addiction trials. We recommend journal endorsement of CONSORT since our study and those previous have shown that CONSORT endorsement improves the quality of reporting.

Evaluation of spin in the abstracts of otolaryngology randomized controlled trials.

OBJECTIVE: Spin, the misrepresentation and distortion of research findings, has been shown to affect clinical decision making. Spin has been found in randomized controlled trials (RCTs) published in various fields of medicine, but no study has tested for the presence of spin in otolaryngology RCTs. The purpose of this study is to evaluate the abstracts of RCTs found in the otolaryngology literature for spin. METHODS: In this cross-sectional analysis, we analyzed the abstracts of RCTs for spin using a pilot-tested form. Double data extraction was performed by two blinded authors, and discrepancies were resolved using mutual discussion. RESULTS: Out of the 534 PubMed citations retrieved by our search string, 162 parallel-group RCTs with clearly defined primary and secondary endpoints were identified. Further analysis identified 47 trials with nonsignificant primary outcomes, which were then evaluated for spin. Spin was identified in 33 of the 47 (70%) abstracts. Spin was found in the results sections of 25 (53%) of the included abstracts and was found in the conclusion section of 27 (57%) of the abstracts. Spin was not present in the titles of any of the included studies. CONCLUSION: Spin was common in our sample of otolaryngology RCTs. Spin may potentially create false impressions about the true validity of a drug or intervention. Further research needs to test for potential clinical implications of spin in the otolaryngology literature. LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

An analysis of the literature addressing tonsillectomy knowledge gaps.

IMPORTANCE: The ability of clinical practice guidelines to improve patient outcomes depends on the quality of evidence that they are built upon. Research into tonsillectomy in children is lacking, and the gaps in evidence were identified by guideline authors. OBJECTIVE: The objective of this study is to evaluate the extent that new research is addressing the gaps identified in the AAO-HNS Tonsillectomy in Children Guideline. DESIGN: For each recommendation in the AAO-HNS guideline Tonsillectomy In Children, we created PICO (Participants, Intervention, Comparator, Outcome) questions and search strings. PubMed was searched to locate studies undertaken after the final literature search performed by the AAO-HNS work group. These studies were then extracted and analyzed. SETTING: This study is relevant to all invested in focusing otolaryngological research on questions which currently lack strong evidence. PARTICIPANTS: Trials in tonsillectomy that started after the development of the AAO-HNS clinical practice guidelines. MAIN OUTCOME MEASURES: The main outcome measures of this study is the extent to which tonsillectomy research is addressing the evidence gaps listed in the clinical practice guideline. RESULTS: Of the 2519 studies included in our sample, 276 (11%) were relevant to the 18 recommendations made within the Tonsillectomy in Pediatric Patients clinical practice guideline. All but one of the recommendations was met by at least one study. CONCLUSIONS: and Relevance: Our findings indicate that knowledge gaps within the guideline at publication may have since been addressed and a guideline update may thus be warranted. LEVEL OF EVIDENCE: NA.

Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in mice.

The purpose of the present study was to determine the effects of prolonged hyperinsulinemia on mitochondrial respiration and uncoupling in distinct adipose tissue depots. Sixteen-week-old male mice were injected daily with placebo or insulin to induce an artificial hyperinsulinemia for 28 days. Following the treatment period, mitochondrial respiration and degree of uncoupling were determined in permeabilized perirenal, inguinal, and interscapular adipose tissue. White adipose tissue (WAT) mitochondria (inguinal and perirenal) respire at substantially lower rates compared with brown adipose tissue (BAT). Insulin treatment resulted in a significant reduction in mitochondrial respiration in inguinal WAT (iWAT) and interscapular BAT (iBAT), but not in perirenal WAT (pWAT). Furthermore, these changes were accompanied by an insulin-induced reduction in UCP-1 (uncoupling protein 1) and PGC-1α in iWAT and iBAT only, but not in pWAT or skeletal muscle. Compared with adipose tissue mitochondria in placebo conditions, adipose tissue from hyperinsulinemic mice manifested a site-specific reduction in mitochondrial respiration probably as a result of reduced uncoupling. These results may help explain weight gain so commonly seen with insulin treatment in type 2 diabetes mellitus.