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Chronic musculoskeletal pain is associated with neurobiological, physiological, and cellular measures. Importantly, we have previously demonstrated that a biobehavioral and psychosocial resilience index appears to have a protective relationship on the same biomarkers. Less is known regarding the relationships between chronic musculoskeletal pain, protective factors, and brain aging. This study investigates the relationships between clinical pain, a resilience index, and brain age. We hypothesized that higher reported chronic pain would correlate with older appearing brains, and the resilience index will attenuate the strength of the relationship between chronic pain and brain age.
Participants and Methods:
Participants were drawn from an ongoing observational multisite study and included adults with chronic pain who also reported knee pain (N = 135; age = 58.3 ± 8.1; 64% female; 49% non-Hispanic Black, 51% non-Hispanic White; education Mdn = some college; income level Mdn = $30,000 - $40,000; MoCA M = 24.27 ± 3.49). Measures included the Graded Chronic Pain Scale (GCPS), characteristic pain intensity (CPI) and disability, total pain body sites; and a cognitive screening (MoCA). The resilience index consisted of validated biobehavioral (e.g., smoking, waist/hip ratio, and active coping) and psychosocial measures (e.g., optimism, positive affect, negative affect, perceived stress, and social support). T1-weighted MRI data were obtained. Surface area metrics were calculated in FreeSurfer using the Human Connectome Project's multi-modal cortical parcellation scheme. We calculated brain age in R using previously validated and trained machine learning models. Chronological age was subtracted from predicted brain age to generate a brain age gap (BAG). With higher scores of BAG indicating predicated age is older than chronological age. Three parallel hierarchical regression models (each containing one of three pain measures) with three blocks were performed to assess the relationships between chronic pain and the resilience index in relation to BAG, adjusting for covariates. For each model, Block 1 entered the covariates, Block 2 entered a pain score, and Block 3 entered the resilience index.
Results:
GCPS CPI (R2 change = .033, p = .027) and GCPS disability (R2 change = 0.038, p = 0.017) significantly predicted BAG beyond the effects of the covariates, but total pain sites (p = 0.865) did not. The resilience index was negatively correlated and a significant predictor of BAG in all three models (p < .05). With the resilience index added in Block 3, both GCPS CPI (p = .067) and GCPS disability (p = .066) measures were no longer significant in their respective models. Additionally, higher education/income (p = 0.016) and study site (p = 0.031) were also significant predictors of BAG.
Conclusions:
In this sample, higher reported chronic pain correlated with older appearing brains, and higher resilience attenuated this relationship. The biobehavioral and psychosocial resilience index was associated with younger appearing brains. While our data is cross-sectional, findings are encouraging that interventions targeting both chronic pain and biobehavioral and psychosocial factors (e.g., coping strategies, positive and negative affect, smoking, and social support) might buffer brain aging. Future directions include assessing if chronic pain and resilience factors can predict brain aging over time.
To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.
Methods
Participants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]).
Results
Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.
Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008).
Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001).
62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.
Conclusion
This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.
Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.
We assessed the feasibility of implementing psychological counseling services (PCS) for mothers of children with autism spectrum disorders (ASD) integrated within special education settings in urban Bangladesh.
Method
In two special education schools for ASD in Dhaka City, trained female psychologists screened mothers using the Patient Health Questionnaire (PHQ-9). PCS was administered to all the mothers irrespective of a diagnosis of depression. Mothers with a PHQ-9 score >4 who met criteria for a major depressive episode (MDE) based on the DSM-IV Structured Interview Axis I Disorders (SCID-I) were also administered skill-building training through monthly home visits to support ASD care. The level of depression was assessed by the Depression Measurement Scale (DMS), and quality of life (QoL) was measured by Visual Analogue Scale (VAS) of EQ5D5L scale before and after PCS.
Result
Among 188 mothers enrolled in the study, 81 (43%) received PCS, and 27.1% (22) had MDE. In the first month, 73 sessions were scheduled and 60 completed (85%). In the last month, 53 sessions were scheduled and 52 completed (98%). The mean DMS score decreased from 79.5 ± 23 to 60 ± 20 (p = 0.004), and DMS scores were significantly higher among mothers with MDE (97.8 ± 12.1 v. 69.9 ± 22.1; p < 0.001) compared to those without MDE (72.7 ± 22.6 v. 56.1 ± 18.1; p = 0.003). The mean VAS score improved from 70.3 ± 14.1 to 80.2 ± 13.3 (p = 0.001) between the first and the last session. Changes in DMS were negatively correlated with changes in VAS scores (β: −0.213, 95% CI 0.370 to −0.056).
Conclusion
Within special education schools for ASD in urban Bangladesh, it was feasible to administer an integrated program of PCS for mothers of children with ASD by trained psychologists who were able to screen and intervene to reduce their level of depression and improve their quality of life.
In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Reproducing the planes of co-orbiting satellites observed in the MW and M31 so far has represented a challenge for cosmological simulations. We have developed a new method to search for kinematically-coherent groups of satellites and applied it to 2 different cosmological hydro-simulations of disc galaxies. In each simulation we have found such a group, that represents roughly half of the total satellite population and is distributed on a fairly thin plane that persists in time. These results are compatible with the MW and M31 observed planes.
We derive an effective macroscale description for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effective macroscale description, which incorporates dependence on the microscale structure and dynamics. In particular, the resulting description admits both interstitial growth and active cell motion. This model comprises Darcy flow, and differential equations for the volume fraction of cells within the scaffold and the concentration of nutrient, required for growth. These are coupled with Stokes-type cell problems on the microscale, incorporating dependence on active cell motion and pore scale structure. The cell problems provide the permeability tensors with which the macroscale flow is parameterised. A subset of solutions is illustrated by numerical simulations.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
The work of historians in providing new editions of primary documents, and other aids to research, has tended to go largely unsung, yet is crucial to scholarship, as providing the very foundations on which further enquiry can be based. The essays in this volume, conversely, celebrate the achievements in this field by a whole generation of medievalists, of whom the honoree, David Smith, is one of the most distinguished. They demonstrate the importance of such editions to a proper understanding and elucidation of a number of problems in medieval ecclesiastical history, ranging from thirteenth-century forgery to diocesan administration, from the church courts to the cloisters, and from the English parish clergy to the papacy. Contributors: CHRISTOPHER BROOKE, C.C. WEBB, JULIA BARROW, NICHOLAS BENNETT, JANET BURTON, CHARLES FONGE, CHRISTOPHER HARPER-BILL, R.H. HELMHOLZ, PHILIPPA HOSKIN, BRIAN KEMP, F. DONALD LOGAN, ALISON MCHARDY
The Holocene portion of the Siple Dome (Antarctica) ice core was dated by interpreting the electrical, visual and chemical properties of the core. The data were interpreted manually and with a computer algorithm. The algorithm interpretation was adjusted to be consistent with atmospheric methane stratigraphic ties to the GISP2 (Greenland Ice Sheet Project 2) ice core, 10Be stratigraphic ties to the dendrochronology 14 C record and the dated volcanic stratigraphy. The algorithm interpretation is more consistent and better quantified than the tedious and subjective manual interpretation.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.