Characteristics of retracted publications related to pain research:a systematic review

Retraction is a mechanism for correcting the scientific record and alerts readers when a study contains unreliable or flawed data. Such data may arise from error or research misconduct. Studies examining the landscape of retracted publications provide insight into the extent of unreliable data and its effect on a medical discipline. We aimed to explore the extent and characteristics of retracted publications in pain research. We searched the EMBASE, PubMed, CINAHL, PsycINFO, and Retraction Watch databases to December 31, 2022. We included retracted articles that (1) investigated mechanisms of painful conditions, (2) tested treatments that aimed to reduce pain, or (3) measured pain as an outcome. Descriptive statistics were used to summarise the included data. We included 389 pain articles published between 1993 and 2022 and retracted between 1996 and 2022. There was a significant upward trend in the number of retracted pain articles over time. Sixty-six percent of articles were retracted for reasons relating to misconduct. The median (interquartile range) time from article publication to retraction was 2 years (0.7-4.3). The time to retraction differed by reason for retraction, with data problems, comprising data falsification, duplication, and plagiarism, resulting in the longest interval (3 [1.2-5.2] years). Further investigations of retracted pain articles, including exploration of their fate postretraction, are necessary to determine the impact of unreliable data on pain research.</p

Characteristics of retracted publications related to pain research:a systematic review

Retraction is a mechanism for correcting the scientific record and alerts readers when a study contains unreliable or flawed data. Such data may arise from error or research misconduct. Studies examining the landscape of retracted publications provide insight into the extent of unreliable data and its effect on a medical discipline. We aimed to explore the extent and characteristics of retracted publications in pain research. We searched the EMBASE, PubMed, CINAHL, PsycINFO, and Retraction Watch databases to December 31, 2022. We included retracted articles that (1) investigated mechanisms of painful conditions, (2) tested treatments that aimed to reduce pain, or (3) measured pain as an outcome. Descriptive statistics were used to summarise the included data. We included 389 pain articles published between 1993 and 2022 and retracted between 1996 and 2022. There was a significant upward trend in the number of retracted pain articles over time. Sixty-six percent of articles were retracted for reasons relating to misconduct. The median (interquartile range) time from article publication to retraction was 2 years (0.7-4.3). The time to retraction differed by reason for retraction, with data problems, comprising data falsification, duplication, and plagiarism, resulting in the longest interval (3 [1.2-5.2] years). Further investigations of retracted pain articles, including exploration of their fate postretraction, are necessary to determine the impact of unreliable data on pain research.</p

Efficacy and Safety of Medicines Targeting Neurotrophic Factors in the Management of Low Back Pain: Protocol for a Systematic Review and Meta-Analysis (Preprint)

BACKGROUND Low back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions. OBJECTIVE The aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica. METHODS In this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively. RESULTS The protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records. CONCLUSIONS This systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica. CLINICALTRIAL Open Science Framework; https://osf.io/b8adn/ INTERNATIONAL REGISTERED REPORT DERR1-10.2196/22905 </sec

IR Surface Brightness Fluctuations of Magellanic Star Clusters

We present surface brightness fluctuations (SBFs) in the near--IR for 191 Magellanic star clusters available in the Second Incremental and All Sky Data releases of the Two Micron All Sky Survey (2MASS), and compare them with SBFs of Fornax Cluster galaxies and with predictions from stellar population models. Our goals are twofold. First, to provide an empirical calibration of near--IR SBFs, given that existing stellar population synthesis models are particularly discrepant in the near--IR. Second, whereas most previous SBF studies have focused on old, metal rich populations, this is the first application to a system with such a wide range of ages (~ 10^6 to more than 10^10 yr, i.e., 4 orders of magnitude), at the same time that the clusters have a very narrow range of metallicities (Z ~ 0.0006 -- 0.01, ie., 1 order of magnitude only). Since stellar population synthesis models predict a more complex sensitivity of SBFs to metallicity and age in the near--IR than in the optical, this analysis offers a unique way of disentangling the effects of age and metallicity. We find a satisfactory agreement between models and data. We also confirm that near--IR fluctuations and fluctuation colors are mostly driven by age in the Magellanic cluster populations, and that in this respect they constitute a sequence in which the Fornax Cluster galaxies fit adequately. Moreover, fluctuation colors display a tendency to redden with age that can be fit by a straight line. Finally, we use for the first time a Poissonian approach to establish the error bars of the fluctuation measurements, instead of the customary Monte Carlo simulations.Comment: 54 pages, 12 figures, accepted by Ap

The First Detection of Blue Straggler Stars in the Milky Way Bulge

We report the first detections of Blue Straggler Stars (BSS) in the bulge of the Milky Way galaxy. Proper motions from extensive space-based observations along a single sight-line allow us to separate a sufficiently clean and well-characterized bulge sample that we are able to detect a small population of bulge objects in the region of the color-magnitude diagram commonly occupied young objects and blue strgglers. However, variability measurements of these objects clearly establish that a fraction of them are blue stragglers. Out of the 42 objects found in this region of the color-magnitude diagram, we estimate that at least 18 are genuine BSS. We normalize the BSS population by our estimate of the number of horizontal branch stars in the bulge in order to compare the bulge to other stellar systems. The BSS fraction is clearly discrepant from that found in stellar clusters. The blue straggler population of dwarf spheroidals remains a subject of debate; some authors claim an anticorrelation between the normalised blue straggler fraction and integrated light. If this trend is real, then the bulge may extend it by three orders of magnitude in mass. Conversely, we find that the genuinely young (~5Gy or younger) population in the bulge, must be at most 3.4% under the most conservative scenario for the BSS population.Comment: ApJ in press; 25 pages, 6 figures, 2 table

Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain : systematic review and meta-analysis

Abstract: Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection: Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis: Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results: 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions: Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/

Image-Subtraction Photometry of the Globular Cluster M3: identification of new double-mode RR Lyrae stars

We have applied the image subtraction method to the M3 dataset previously analyzed by Corwin & Carney (2001; CC01). The new analysis produced light curves and periods for 15 variables, bringing to 222 the total number of RR Lyrae stars in CC01 M3 dataset. We have identified three new candidate double-mode (RRd) variables (V13, V200, and V251) in M3. Of the newly discovered RRd's V13 is unusual in that it has the fundamental as the dominant pulsation mode. Two of the new candidate RRd's (V13 and V200) have period ratios as low as 0.738-0.739. They lie separated from all previously known RRd's in the Petersen diagram, in positions implying a large spread in mass and/or, less likely, in heavy element mass fraction, among the M3 horizontal branch (HB) stars. We explore mass transfer and helium enhancement as possible explanations for the apparent spread in HB masses. We also note that the masses derived from the RRd analyses now favor little mass loss on the red giant branch. V200 has changed its dominant pulsation mode from fundamental to first overtone, while V251 has changed its dominant mode from first overtone to fundamental in the interval 1992 to 1993. Together with M3-V166 this is the first time that RRd variables are observed to switch their dominant pulsation modes while remaining RRd's. The phenomenon is found to occur in a one year time-span thus suggesting that these stars are undergoing a rapid evolutionary phase, and that both redward and blueward evolution may take place among the HB stars in M3. The unusual behavior of the M3 RRd's is discussed and compared to that of the RRd's identified so far in globular clusters and in the field of our and other Local Group galaxies. We find lack of correlation between the presence of RRd variables and any of the cluster structural parameters.Comment: 38 pages, 16 figures, AJ in pres

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

A Spectroscopic Analysis of Blue Stragglers, Horizontal Branch and Turn-Off Stars in Four Globular Clusters

We present a spectroscopic analysis of HST/STIS and FOS low- and intermediate-resolution spectroscopy of 55 stars (turn-off stars, horizontal branch stars and blue stragglers) in four globular clusters (47 Tucanae, M3, NGC6752, and NGC6397). Stars were analyzed with non-Local Thermodynamic Equilibrium model atmospheres, and values for their effective temperatures and gravities and some rotation rates were obtained. Using photometric fluxes, we also obtained radii, luminosities and spectroscopic masses.Comment: 71 pages, 28 figures. Electronic figures only in the published versio

Plasma proteomic signature predicts myeloid neoplasm risk

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development. EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard regression was used to test for an association between plasma protein levels and MN risk. RESULTS: We identified 115 proteins associated with MN risk, of which 30% (N = 34) were also associated with CH. These were enriched for known regulators of the innate and adaptive immune system. Plasma proteomics improved the prediction of MN risk (AUC = 0.85; P = 5×10-9) beyond clinical factors and CH (AUC = 0.80). In an independent group (N = 381,485), we used inherited polygenic risk scores (PRS) for plasma protein levels to validate the relevance of these proteins toMNdevelopment. PRS analyses suggest that most MN-associated proteins we identified are not directly causally linked toMN risk, but rather represent downstream markers of pathways regulating the progression of CH to MN. CONCLUSIONS: These data highlight the role of immune cell regulation in the progression of CH to MN and the promise of leveraging multi-omic characterization of CH to improveMN risk stratification. See related commentary by Bhalgat and Taylor, p. 3095