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The Journal of Pain Apr 2024Biopsychosocial factors are associated with pain, but they can be difficult to compare. One way of comparing them is to use standardized mean differences. Previously,...
Biopsychosocial factors are associated with pain, but they can be difficult to compare. One way of comparing them is to use standardized mean differences. Previously, these effects sizes have been termed as small, medium, or large, if they are bigger than or equal to, respectively, .2, .5, or .8. These cut-offs are arbitrary and recent evidence showed that they need to be reconsidered. We argue it is necessary to determine cut-offs for each biopsychosocial factor. To achieve this, we propose 3 potential approaches: 1) examining, for each factor, how the effect size differs depending upon disease severity; 2) using an existing minimum clinically important difference to anchor the large effect size; and 3) define cut-offs by comparing data from people with and without pain. This is important for pain research, as exploring these methodologies has potential to improve comparability of biopsychosocial factors and lead to more directed treatments. We note assumptions and limitations of these methods that should also be considered. PERSPECTIVE: Standardized mean differences can estimate effect sizes between groups and could theoretically allow for comparison of biopsychosocial factors. However, common thresholds to define effect sizes are arbitrary and likely differ based on outcome. We propose methods that could overcome this and be used to derive biopsychosocial outcome-specific effect sizes.
Topics: Humans; Pain Measurement; Chronic Pain; Recovery of Function
PubMed: 37871685
DOI: 10.1016/j.jpain.2023.10.014 -
Science & Justice : Journal of the... Jan 2024In recent years, numerous studies have examined the chemical compounds of petrol and petrol data for forensic research. Standard quantitative methods often assume that...
In recent years, numerous studies have examined the chemical compounds of petrol and petrol data for forensic research. Standard quantitative methods often assume that the variables or compounds do not have compositional constraints or are not part of a constrained whole, operating within an Euclidean vector space. However, chemical compounds are typically part of a whole, and the appropriate vector space for their analysis is the simplex. Biased and arbitrary results result when statistical analysis are applied on such data without proper pre-processing of such data. Compositional analysis of data has not yet been considered in forensic science. Therefore, we compare classical statistical analysis as applied in forensic research and the new proposed paradigm of compositional data analysis (CoDa). It is demonstrated how such analysis improves the analysis in petrol and forensic science. Our study shows how principal component analysis (PCA) and classification results are affected by the preprocessing steps performed on the raw data. Our results indicate that results from a log ratio analysis provides a better separation between subgroups of the data and leads to an easier interpretation of the results. In addition, with a compositional analysis a higher classification accuracy is obtained. Even a non-linear classification method - in our case a random forest - was shown to perform poorly when applied without using compositional methods. Moreover, normalization of samples due to laboratory/unit-of-measurement effects is no longer necessary, since the composition of an observation is in compositional thinking equivalent to a multiple of it, because the used (log) ratios on raw and log ratio transformed data are equal. Petrol data from different petrol stations in Brazil are used for the demonstration. This data is highly susceptible to counterfeit petrol. Forensic analysis of its chemical elements requires non-biased statistical analysis designed for compositional data to detect fraud. Based on these results, we recommend the use of compositional data methods for gasoline and petrol chemical element analysis and gasoline product characterization, authentication and fraud detection in forensic sciences.
PubMed: 38182317
DOI: 10.1016/j.scijus.2023.11.003 -
Probiotics and Antimicrobial Proteins Feb 2024This study evaluated the effects of simulated gastrointestinal conditions (SGIC) on combined potentially probiotic Limosilactobacillus fermentum 296 (~ 10 log CFU/mL),...
Effects of Simulated Gastrointestinal Conditions on Combined Potentially Probiotic Limosilactobacillus fermentum 296, Quercetin, and/or Resveratrol as Bioactive Components of Novel Nutraceuticals.
This study evaluated the effects of simulated gastrointestinal conditions (SGIC) on combined potentially probiotic Limosilactobacillus fermentum 296 (~ 10 log CFU/mL), quercetin (QUE, 160 mg), and/or resveratrol (RES, 150 mg) as the bioactive components of novel nutraceuticals. Four different nutraceuticals were evaluated during exposure to SGIC and analyzed the plate counts and physiological status of L. fermentum 296, contents and bioaccessibility of QUE and RES, and antioxidant capacity. Nutraceuticals with QUE and RES had the highest plate counts (4.94 ± 0.32 log CFU/mL) and sizes of live cell subpopulations (28.40 ± 0.28%) of L. fermentum 296 after SGIC exposure. An index of injured cells (Gmean index, arbitrary unit defined as above 0.5) indicated that part of L. fermentum 296 cells could be entered the viable but nonculturable state when the nutraceuticals were exposed to gastric and intestinal conditions while maintaining vitality. The nutraceuticals maintained high contents (QUE ~ 29.17 ± 0.62 and RES ~ 23.05 mg/100 g) and bioaccessibility (QUE ~ 41.0 ± 0.09% and RES ~ 67.4 ± 0.17%) of QUE and RES, as well as high antioxidant capacity (ABTS assay ~ 88.18 ± 1.16% and DPPH assay 75.54 ± 0.65%) during SGIC exposure, which could be linked to the protective effects on L. fermentum 296 cells. The developed nutraceuticals could cross along the gastrointestinal tract with high concentrations of functioning potentially probiotic cells and bioavailable phenolic compounds to exert their beneficial impacts on consumer health, being an innovative strategy for the co-ingestion of these bioactive components.
Topics: Humans; Quercetin; Limosilactobacillus fermentum; Resveratrol; Antioxidants; Probiotics; Gastrointestinal Diseases
PubMed: 36708461
DOI: 10.1007/s12602-023-10046-w -
The Lancet. Child & Adolescent Health Apr 2024Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief.
METHODS
Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611).
FINDINGS
Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study.
INTERPRETATION
Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management.
FUNDING
Wellcome Trust and Bliss.
Topics: Humans; Infant, Newborn; Pain; Pain, Procedural; Tachycardia; Touch; United Kingdom
PubMed: 38373429
DOI: 10.1016/S2352-4642(23)00340-1 -
MedRxiv : the Preprint Server For... Jul 2023Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of...
Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of which have similar statistical significance. While statistical fine-mapping in individuals of European ancestries has made important discoveries, cross-population fine-mapping has the potential to improve power and resolution by capitalizing on the genomic diversity across ancestries. Here we present SuSiEx, an accurate and computationally efficient method for cross-population fine-mapping, which builds on the single-population fine-mapping framework, Sum of Single Effects (SuSiE). SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and LD patterns, accounts for multiple causal variants in a genomic region, and can be applied to GWAS summary statistics. We comprehensively evaluated SuSiEx using simulations, a range of quantitative traits measured in both UK Biobank and Taiwan Biobank, and schizophrenia GWAS across East Asian and European ancestries. In all evaluations, SuSiEx fine-mapped more association signals, produced smaller credible sets and higher posterior inclusion probability (PIP) for putative causal variants, and captured population-specific causal variants.
PubMed: 36711496
DOI: 10.1101/2023.01.07.23284293 -
Scandinavian Journal of Medicine &... Jan 2024Delayed onset muscle soreness (DOMS) develops after performing unaccustomed eccentric exercises. Animal studies have shown that DOMS is mechanical hyperalgesia through...
Delayed onset muscle soreness (DOMS) develops after performing unaccustomed eccentric exercises. Animal studies have shown that DOMS is mechanical hyperalgesia through nociceptor sensitization induced by nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) upregulated by cyclooxygenase-2 (COX-2). However, no previous study has investigated these in relation to DOMS in humans. This study compared the first and second bouts of one-leg eccentric cycling (ECC) for changes in NGF, GDNF, and COX-2 mRNA in the vastus lateralis (VL). Seven healthy adults (18-40 years) performed two bouts of ECC (10 sets of 50 contractions) with 80% maximal voluntary concentric peak torque separated by 2 weeks (ECC1, ECC2). Muscle soreness that was assessed by a visual analog scale and maximal voluntary isometric contraction (MVC) torque of the knee extensors were measured before, immediately after (MVC only), 24 and 48 h post-exercise. Muscle biopsy was taken from the VL before the first bout from nonexercised leg (control) and 24 h after each bout from the exercised leg, and analyzed for NGF, GDNF, and COX-2 mRNA. Peak DOMS was more than two times greater and MVC torque at 48 h post-exercise was approximately 20% smaller after ECC1 than ECC2 (p < 0.05), suggesting the repeated bout effect. NGF mRNA level was higher (p < 0.05) post-ECC1 (0.79 ± 0.68 arbitrary unit) than control (0.06 ± 0.07) and post-ECC2 (0.08 ± 0.10). GDNF and COX-2 mRNA did not show significant differences between control, post-ECC1, and post-ECC2. These results suggest that an increase in NGF is associated with the development of DOMS in humans.
Topics: Adult; Humans; Quadriceps Muscle; Muscle, Skeletal; Myalgia; Glial Cell Line-Derived Neurotrophic Factor; Leg; Cyclooxygenase 2; Nerve Growth Factor; Isometric Contraction; RNA, Messenger; Muscle Contraction
PubMed: 37724768
DOI: 10.1111/sms.14497 -
The Journal of Infectious Diseases Apr 2024Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for...
BACKGROUND
Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase.
METHODS
This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1,899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions.
RESULTS
Compared with the <2,500 arbitrary unit (AU)/mL category, the 2,500-5,000, 5,000-10,000, and ≥10,000 AU/mL categories had adjusted RRs (95% CI) of 0.81 (0.61-1.08), 0.51 (0.36-0.72), and 0.41 (0.31-0.54), respectively. The spline function showed a non-linear relationship between antibody titer and risk.
CONCLUSIONS
Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future vaccination.
PubMed: 38656998
DOI: 10.1093/infdis/jiae207 -
BJGP Open Apr 2024Research has indicated that providing women with information about menopause can improve their attitudes towards it and symptom experience. Nevertheless, information...
BACKGROUND
Research has indicated that providing women with information about menopause can improve their attitudes towards it and symptom experience. Nevertheless, information shared on the menopause is often arbitrary.
AIM
To examine women's information needs about menopause, and understand if, when, and from whom they want information.
DESIGN & SETTING
A cross-sectional study was undertaken. A questionnaire survey was distributed to women in the waiting room of 54 general practice clinics in South-Eastern Norway in autumn 2022.
METHOD
Medical students recruited women in the clinic waiting rooms. A 1-page study-specific questionnaire was used, focusing on need for information about menopause. A multinominal logistic regression model was used to analyse the association between the desire for information and education level, country of birth, and menopausal status.
RESULTS
A total of 625 women were included, with a mean age of 44.4 years (standard deviation [SD] 8.7). In all, 59% answered that they wanted information about menopause, and 81% of these wanted their GP to inform them, from a median age of 45 years. According to the women, only 10% of GPs had initiated a discussion on the menopause. Higher education was a predictor for wanting information. A main driver of information needs was to help oneself in the present and in the future. In all, 33% did not want information. The main reasons were that they already possessed sufficient information, would take menopause as it comes, were too young, or were already postmenopausal. The sex of the GP did not influence the results.
CONCLUSION
Most women wanted information about menopause from their GP. The study emphasises the need for GPs to consider prioritising this discussion, and to keep up to date on recommendations and treatment options.
PubMed: 37669803
DOI: 10.3399/BJGPO.2023.0127 -
Biometrics Sep 2023We develop sensitivity analyses for the sample average treatment effect in matched observational studies while allowing unit-level treatment effects to vary. The methods...
We develop sensitivity analyses for the sample average treatment effect in matched observational studies while allowing unit-level treatment effects to vary. The methods may be applied to studies using any optimal without-replacement matching algorithm. In contrast to randomized experiments and to paired observational studies, we show for general matched designs that over a large class of test statistics, any procedure bounding the worst-case expectation while allowing for arbitrary effect heterogeneity must be unnecessarily conservative if treatment effects are actually constant across individuals. We present a sensitivity analysis which bounds the worst-case expectation while allowing for effect heterogeneity, and illustrate why it is generally conservative if effects are constant. An alternative procedure is presented that is asymptotically sharp if treatment effects are constant, and that is valid for testing the sample average effect under additional restrictions which may be deemed benign by practitioners. Simulations demonstrate that this alternative procedure results in a valid sensitivity analysis for the weak null hypothesis under a host of reasonable data-generating processes. The procedures allow practitioners to assess robustness of estimated sample average treatment effects to hidden bias while allowing for effect heterogeneity in matched observational studies.
Topics: Humans; Bias; Observational Studies as Topic; Research Design
PubMed: 35980014
DOI: 10.1111/biom.13741 -
Gynecologic Oncology Jan 2024We evaluated usability of single base substitution signature 3 (Sig3) as a biomarker for homologous recombination deficiency (HRD) in tubo-ovarian high-grade serous... (Clinical Trial)
Clinical Trial Observational Study
OBJECTIVES
We evaluated usability of single base substitution signature 3 (Sig3) as a biomarker for homologous recombination deficiency (HRD) in tubo-ovarian high-grade serous carcinoma (HGSC).
MATERIALS AND METHODS
This prospective observational trial includes 165 patients with advanced HGSC. Fresh tissue samples (n = 456) from multiple intra-abdominal areas at diagnosis and after neoadjuvant chemotherapy (NACT) were collected for whole-genome sequencing. Sig3 was assessed by fitting samples independently with COSMIC v3.2 reference signatures. An HR scar assay was applied for comparison. Progression-free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier and Cox regression analysis.
RESULTS
Sig3 has a bimodal distribution, eliminating the need for an arbitrary cutoff typical in HR scar tests. Sig3 could be assessed from samples with low (10%) cancer cell proportion and was consistent between multiple samples and stable during NACT. At diagnosis, 74 (45%) patients were HRD (Sig3+), while 91 (55%) were HR proficient (HRP, Sig3-). Sig3+ patients had longer PFS and OS than Sig3- patients (22 vs. 13 months and 51 vs. 34 months respectively, both p < 0.001). Sig3 successfully distinguished the poor prognostic HRP group among BRCAwt patients (PFS 19 months for Sig3+ and 13 months for Sig3- patients, p < 0.001). However, Sig3 at diagnosis did not predict chemoresponse anymore in the first relapse. The patient-level concordance between Sig3 and HR scar assay was 87%, and patients with HRD according to both tests had the longest median PFS.
CONCLUSIONS
Sig3 is a prognostic marker in advanced HGSC and useful tool in patient stratification for HRD.
Topics: Female; Humans; Cicatrix; Cystadenocarcinoma, Serous; Ovarian Neoplasms; Prognosis; Progression-Free Survival
PubMed: 38061276
DOI: 10.1016/j.ygyno.2023.11.027