Nevin Manimala

NMR Biomed. 2023 Aug 29:e5026. doi: 10.1002/nbm.5026. Online ahead of print.

ABSTRACT

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is one of the most used imaging techniques to map brain activity or to obtain clinical information about human cortical vasculature, in both healthy and disease conditions. Nevertheless, BOLD fMRI is an indirect measurement of brain functioning triggered by neurovascular coupling. The origin of the BOLD signal is quite complex, and the signal formation thus depends, among other factors, on the topology of the cortical vasculature and the associated hemodynamic changes. To understand the hemodynamic evolution of the BOLD signal response in humans, it is beneficial to have a computational framework available that virtually resembles the human cortical vasculature, and simulates hemodynamic changes and corresponding MRI signal changes via interactions of intrinsic biophysical and magnetic properties of the tissues. To this end, we have developed a mechanistic computational framework that simulates the hemodynamic fingerprint of the BOLD signal based on a statistically defined, three-dimensional, vascular model that approaches the human cortical vascular architecture. The microvasculature is approximated through a Voronoi tessellation method and the macrovasculature is adapted from two-photon microscopy mice data. Using this computational framework, we simulated hemodynamic changes-cerebral blood flow, cerebral blood volume, and blood oxygen saturation-induced by virtual arterial dilation. Then we computed local magnetic field disturbances generated by the vascular topology and the corresponding blood oxygen saturation changes. This mechanistic computational framework also considers the intrinsic biophysical and magnetic properties of nearby tissue, such as water diffusion and relaxation properties, resulting in a dynamic BOLD signal response. The proposed mechanistic computational framework provides an integrated biophysical model that can offer better insights regarding the spatial and temporal properties of the BOLD signal changes.

PMID:37643645 | DOI:10.1002/nbm.5026

J R Soc Interface. 2023 Aug;20(205):20230310. doi: 10.1098/rsif.2023.0310. Epub 2023 Aug 30.

ABSTRACT

Despite widespread claims of power laws across the natural and social sciences, evidence in data is often equivocal. Modern data and statistical methods reject even classic power laws such as Pareto’s law of wealth and the Gutenberg-Richter law for earthquake magnitudes. We show that the maximum-likelihood estimators and Kolmogorov-Smirnov (K-S) statistics in widespread use are unexpectedly sensitive to ubiquitous errors in data such as measurement noise, quantization noise, heaping and censorship of small values. This sensitivity causes spurious rejection of power laws and biases parameter estimates even in arbitrarily large samples, which explains inconsistencies between theory and data. We show that logarithmic binning by powers of λ > 1 attenuates these errors in a manner analogous to noise averaging in normal statistics and that λ thereby tunes a trade-off between accuracy and precision in estimation. Binning also removes potentially misleading within-scale information while preserving information about the shape of a distribution over powers of λ, and we show that some amount of binning can improve sensitivity and specificity of K-S tests without any cost, while more extreme binning tunes a trade-off between sensitivity and specificity. We therefore advocate logarithmic binning as a simple essential step in power-law inference.

PMID:37643642 | DOI:10.1098/rsif.2023.0310

Pain Med. 2023 Aug 29:pnad119. doi: 10.1093/pm/pnad119. Online ahead of print.

ABSTRACT

BACKGROUND: Orthopedic patients report pain as their main symptom complaint. Subjective pain experience is correlated with self-reported psychological state such as distress.

PURPOSE: This study tests whether scores from a measure of mindful attention are associated with subjective pain levels and if psychological distress scores function as a mediation path.

METHODS: During routine visits to a single orthopedic clinic in East Los Angeles, 525 patients were recruited to participate in the study. Participants reported on measures of pain (Universal Pain Assessment Tool, UPAT), mindful attention (Five-Facet Mindfulness Questionnaire, FFMQ) and psychological distress (Depression, Anxiety, and Stress Scale, DASS). We used Pearson correlation to examine relationships between FFMQ and UPAT scores, and mediation analyses to test indirect effects of DASS scores as a mediation path.

RESULTS: The average age of the sample was 54 years (range 18-98), 61% were male, and 64% were non-Hispanic White individuals. The locations of injury were shoulder (72%), elbow (21%) and clavicle or wrist (7%). 91% reported mild or greater pain in the past two weeks (M = 4.2 ± 2.5, range 0-10) and 49% reported mild or more severe distress symptoms (DASS: 13.0 ± 11.5). FFMQ scores inversely predicted UPAT scores (β = 0.-22, p < 0.01) mediated through DASS scores. DASS subscale scores for depression (β=-0.10, p = 0.02) and stress (β=-0.08, p = 0.04) but not anxiety (β=-0.03, p = 0.33) produced significant indirect effects. FFMQ acting-with-awareness and non-judging subscales had the largest effect on depression and stress DASS subscale scores.

CONCLUSIONS: We find statistical support to suggest distress-particularly depressed mood and stress-mediates the association between mindful attention and pain intensity among orthopedic patients. A disposition of mindful attention may counter distress ailments that exacerbate subjective pain, and this has possible implications for mindfulness training interventions offered to orthopedic patients.

PMID:37643631 | DOI:10.1093/pm/pnad119

Stat Med. 2023 Aug 29. doi: 10.1002/sim.9887. Online ahead of print.

ABSTRACT

Response-dependent sampling is routinely used as an enrichment strategy in the design of family studies investigating the heritable nature of disease. In addition to the response of primary interest, investigators often wish to investigate the association between biomarkers and secondary responses related to possible comorbidities. Statistical analysis regarding genetic biomarkers and their association with the secondary outcome must address the biased sampling scheme involving the primary response. In this article, we develop composite likelihoods and two-stage estimation procedures for such secondary analyses in which the within-family dependence structure for the primary and secondary outcomes is modeled via a Gaussian copula. The dependence among responses within family members is modeled based on kinship coefficients. Auxiliary data from independent individuals are exploited by augmenting the composite likelihoods to increase precision of marginal parameter estimates and enhance the efficiency of estimators of the dependence parameters. Simulation studies are carried out to evaluate the finite sample performance of the proposed method, and an application to a motivating family study in psoriatic arthritis is given for illustration.

PMID:37643587 | DOI:10.1002/sim.9887

Clin Biomech (Bristol, Avon). 2023 Aug 23;109:106077. doi: 10.1016/j.clinbiomech.2023.106077. Online ahead of print.

ABSTRACT

BACKGROUND: Observational gait analysis is frequently used by clinicians to subjectively assess straight walking but is not often used to examine turning. Interlimb comparisons of phase- specific turning biomechanics in people with unilateral lower limb amputation has not previously been documented.

METHODS: A retrospective examination of gait kinematics and kinetics from five participants with unilateral transtibial amputation was performed. Data were collected during 90° step and spin turns capturing three distinct turning steps. Gait metrics of interest included: total turn time, stance time, peak knee flexion angle during Pre-Swing and Initial Swing gait phases, peak hip flexion and extension, ground reaction impulse, and whole body angular momentum. Statistical comparisons were made based on turn type between sound and prosthetic limbs.

FINDINGS: During the three turn steps (approach, apex, depart), participants spent significantly more time (P < 0.01) on their sound limb compared to their prosthetic limb regardless of turn type. Additionally, the prosthetic limb hip and knee exhibited more flexion (P < 0.05) during the apex step of turns, and whole body angular momentum was higher when the sound limb was used during the apex step of a turn (P < 0.05).

INTERPRETATION: This descriptive study offers the first phase-specific quantification of turning biomechanics in people with lower limb amputation. Results indicate that people with unilateral transtibial amputation spend more time on and experience higher impulses through their sound compared to their prosthetic limb during 90° turns, and that the prosthetic limb is performing differently than the sound limb, potentially increasing risks of injury or falls.

PMID:37643570 | DOI:10.1016/j.clinbiomech.2023.106077

Vet Parasitol. 2023 Aug 25;322:110008. doi: 10.1016/j.vetpar.2023.110008. Online ahead of print.

ABSTRACT

Parasitic diseases are considered to be a cause of oxidative stress which leads to oxidative damage of various molecules including DNA. This can result in mutations, replication errors, and genome instability. Therefore, aim of this study was to measure DNA damage induced by Dirofilaria immitis in the single cells such as dogs’ leukocytes using the comet assay. Also, we monitored the effects of antiparasitic treatment on mitigation of sensitivity to DNA damage in leukocytes treated with H₂O₂ using the in vivo and ex vivo comet assay. The whole blood samples from 34 dogs from Serbia were used, both males and females, from one to 13 years old, both pure and mixed-breeds. A rapid immunochromatographic test (Antigen Rapid Heartworm Ag 2.0 Test Kit, Bionote, Minnesota, USA) was used for the detection of D. immitis antigens. The modified Knott’s test and PCR were used in the aim of detecting D. immitis microfilariae in dogs’ blood, and evaluating the number of circulating microfilariae during the treatment. The genotoxicity evaluation showed that D. immitis infection resulted in DNA damage in naturally infected dogs, with the highest DNA damage occurring in the group of dogs with severe clinical signs. Treatment with ivermectin and doxycycline decreased DNA damage in leukocytes of dogs in all groups, as the intensity of infection decreased due to applied therapy. Ex vivo comet assay results showed that leukocytes exhibited decreased sensitivity to H₂O₂-induced DNA damage during treatment. The results of the modified Knott’s test and PCR in our study showed that treatment with ivermectin and doxycycline was successful in decreasing the average number of microfilariae during the time and at the end eliminating them from the dogs’ blood.

PMID:37643566 | DOI:10.1016/j.vetpar.2023.110008

J Clin Oncol. 2023 Sep 1;41(25):4065-4076. doi: 10.1200/JCO.22.02765.

ABSTRACT

PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy.

MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication.

RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with ≤ 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months-an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant.

CONCLUSION: During the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.

PMID:37643543 | DOI:10.1200/JCO.22.02765

J Clin Oncol. 2023 Sep 1;41(25):4077-4083. doi: 10.1200/JCO.22.02766.

ABSTRACT

Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population.Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m² plus a 24-hour infusion of paclitaxel 135 mg/m² (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m² over 3 hours (arm II).Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02).Conclusion: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.

PMID:37643542 | DOI:10.1200/JCO.22.02766

Waste Manag. 2023 Aug 27;171:32-42. doi: 10.1016/j.wasman.2023.08.021. Online ahead of print.

ABSTRACT

Although there have been many research results on the chemical activation of fly ash (FA) as a supplementary cementitious material (SCM) in cementitious materials. However, there is a lack of research on the use of CO₂ foaming agent (sodium bicarbonate and potassium aluminum sulfate) to activate fly ash. In this experiment, the effects of CO₂ foaming agent, sodium bicarbonate, and potassium aluminum sulfate on the activity of FA mixed paste were investigated. The mechanism of FA activation by activator was revealed by selective acid dissolution, QXRD, BSE-EDS statistical analysis, and quantitative analysis of TGA. The results showed that the remaining fly ash amounts of MG, SBG, and PASG after 28 days were 17.5%, 25.9%, and 43.3% lower than those of the control group, respectively. In addition, potassium aluminium sulphate promoted hydration to generate more CH to activate the FA. Sodium bicarbonate promoted hydration and produces more CH to activate FA by generating nano-CaCO₃. The mixture of sodium bicarbonate and potassium aluminum sulfate took advantage of both nano-CaCO₃ and potassium aluminum sulfate to promote silicate hydration to provide CH. As a result, the two synergistically activate FA. The above results show that CO₂ foaming agents can be used not only as foaming agents to prepare lightweight materials, but also as chemical activators to activate solid waste. This will have a high practical application value.

PMID:37643482 | DOI:10.1016/j.wasman.2023.08.021