Substantial Heterogeneity Research Articles

Genetic and brain similarity independently predict childhood anthropometrics and neighborhood socioeconomic conditions

Linking the developing brain with individual differences in clinical and demographic traits is challenging due to the substantial interindividual heterogeneity of brain anatomy and organization. Here we employ an integrative approach that parses individual differences in both cortical thickness and common genetic variants, and assess their effects on a wide set of childhood traits. The approach uses a linear mixed model framework to obtain the unique effects of each type of similarity, as well as their covariance. We employ this approach in a sample of 7760 unrelated children in the ABCD cohort baseline sample (mean age 9.9, 46.8% female). In general, associations between cortical thickness similarity and traits were limited to anthropometrics such as height, weight, and birth weight, as well as a marker of neighborhood socioeconomic conditions. Common genetic variants explained significant proportions of variance across nearly all included outcomes, although estimates were somewhat lower than previous reports. No significant covariance of the effects of genetic and cortical thickness similarity was found. The present findings highlight the connection between anthropometrics as well as neighborhood socioeconomic conditions and the developing brain, which appear to be independent from individual differences in common genetic variants in this population-based sample.

The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies.

The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach. PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs). A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity. Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

EEG epilepsy seizure prediction: the post-processing stage as a chronology

Almost one-third of epileptic patients fail to achieve seizure control through anti-epileptic drug administration. In the scarcity of completely controlling a patient’s epilepsy, seizure prediction plays a significant role in clinical management and providing new therapeutic options such as warning or intervention devices. Seizure prediction algorithms aim to identify the preictal period that Electroencephalogram (EEG) signals can capture. However, this period is associated with substantial heterogeneity, varying among patients or even between seizures from the same patient. The present work proposes a patient-specific seizure prediction algorithm using post-processing techniques to explore the existence of a set of chronological events of brain activity that precedes epileptic seizures. The study was conducted with 37 patients with Temporal Lobe Epilepsy (TLE) from the EPILEPSIAE database. The designed methodology combines univariate linear features with a classifier based on Support Vector Machines (SVM) and two post-processing techniques to handle pre-seizure temporality in an easily explainable way, employing knowledge from network theory. In the Chronological Firing Power approach, we considered the preictal as a sequence of three brain activity events separated in time. In the Cumulative Firing Power approach, we assumed the preictal period as a sequence of three overlapping events. These methodologies were compared with a control approach based on the typical machine learning pipeline. We considered a Seizure Prediction horizon (SPH) of 5 mins and analyzed several values for the Seizure Occurrence Period (SOP) duration, between 10 and 55 mins. Our results showed that the Cumulative Firing Power approach may improve the seizure prediction performance. This new strategy performed above chance for 62% of patients, whereas the control approach only validated 49% of its models.

Customer Preferences for Delivery Service Attributes in Attended Home Delivery

Retailers face increasing competitive pressure to determine how best to deliver products purchased online to the end customer. Grocery retailers often require attended home delivery where the customer must be present to receive the delivery. For attended home delivery to function, the retailer and customer must agree on a delivery time slot that works for both parties. Using online data from a grocery retailer, we observe customer preferences for three delivery service attributes associated with each time slot: speed, precision, and timing. We define speed as the expected time between the placement of an order and its delivery, precision as the duration of the offered time slot, and timing as the availability of choices across times of the day and days of the week. We show that customers not only value speed as an attribute of delivery service but that precision and timing are also key drivers of the customer’s time slot selection process. We also observe substantial customer heterogeneity in the willingness of customers to pay for time slots. Customers that differ in their loyalty to the retailer, basket value, basket size, and basket composition exhibit distinct differences in their willingness to pay. We show that retailers with the capability to tailor their time slot offerings to specific customer segments have the potential to generate approximately 9% more shipping revenue than those who cannot. Our findings inform practitioners seeking to design competitive fulfillment strategies and academics modeling customer behavior in the attended home delivery context. This paper was accepted by Vishal Gaur, operations management. Funding: This work was supported by the Fundação para a Ciência e a Tecnologia [PTDC/EME-SIS/31908/2017]. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2020.01274 .

Immune checkpoint inhibitors for patients with microsatellite instability-high colorectal cancer: protocol of a pooled analysis of clinical trials.

Colorectal cancer (CRC) is the third most common cause of cancer and the second leading cause of cancer-related deaths worldwide. Microsatellite instability-high (MSI-H) is a distinct molecular subtype of CRC that occurs in approximately 15% of all cases. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic approach for patients with MSI-H colorectal cancer, exhibiting higher response rates than standard chemotherapies. To assess the effectiveness and safety of ICIs for the treatment of patients with MSI-H CRC, we propose a comprehensive pooled analysis of clinical trial data. A systematic search of multiple electronic databases, including PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov, will be conducted from their inception until September, 2023 to identify eligible randomized controlled trials (RCTs) and non-randomized studies. Inclusion criteria comprise studies of adult patients with histologically confirmed MSI-H CRC treated with immune checkpoint inhibitors, with a comparison to a control group receiving conventional therapies. Outcomes of interest will be overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse events (AEs). The Cochrane Risk of Bias tool and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool will be employed to evaluate the methodological quality of included studies. A random-effects model using the DerSimonian and Laird method will be applied for pooling the effect estimates, calculating hazard ratios (HRs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Heterogeneity will be assessed using I² statistics, and subgroup analysis and meta-regression will be performed to explore potential effect modifiers in case of substantial heterogeneity. Publication bias will be evaluated with funnel plots and Egger's test. Sensitivity analysis will be conducted to assess the robustness of the results. This meta-analysis will synthesize available evidence from clinical trials on immune checkpoint inhibitors in treating MSI-H colorectal cancer. The findings will offer valuable information about the effectiveness and safety of ICIs in this patient population, contributing to the refinement of clinical guidelines and enhancing the decision-making process for healthcare providers, policy-makers, and patients. The comprehensive analysis of subgroups and sensitivity allows for an in-depth understanding of potential effect modification, providing essential directions for future research. This study will involve the use of published data; hence, ethical approval is not required. The results of the study will be disseminated through publications in peer-reviewed journals and presentations at relevant conferences. The findings will potentially impact clinical decision-making and contribute to the development of evidence-based treatment recommendations for patients with MSI-H colorectal cancer. Open Science Framework identifier, 10.17605/OSF.IO/ZHJ85.

Different electrophysiological profiles of genetically labelled dopaminergic neurons in the mouse midbrain and olfactory bulb.

Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta [SNC] and Ventral Tegmental Area [VTA]) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Compelling evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain bulbar DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential (AP) firing across midbrain and forebrain bulbar DA subtypes. We found that each DA subgroup within midbrain and OB was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single "dopaminergic" neuronal phenotype.

La calidad higiénica de la leche cruda destinada al consumo humano en Argelia: Metaanálisis

The main goal of this article was to conduct a meta–analysis, to estimate the hygienic quality of the raw milk intended for human consumption and subsequently relative risk factors that may impact milk quality in Algeria. Weighted random–effects meta–analysis models were employed to analyze the data in this study. A total of 4,685 sampling results from 61 included studies, investigating the bacterial quality of raw milk across 35/48 Provinces in Algeria, from 2009 to 2022. In this meta–analysis, the average level of contamination by Total Aerobic Mesophilic Bacteria (TAMB) was 5.84 log10 CFU·mL-1. 95% CI [5.55–6.13]. The P–value was 0.001. The I2 test indicates the presence of substantial statistical heterogeneity across studies; (I2=86.26%, P<0,001). No significant publication bias was observed using the funnel plots and Egger’s test (P=0.885). In this article TAMB values did not differ significantly among species (P>0.05).The average contamination level TAMB was lower in milk samples collected from individual milking and farm tank milk (4.57 log10 CFU·mL-1 and 5.89 log10 CFU·mL-1), compared to those recorded in milk samples collected from the collector, dairy, and sales (6.59 log10 CFU·mL-1, 6.60 log10 CFU·mL-1, and 6.74 log10 CFU·mL-1, respectively). The contamination level of milk by TAMB was higher during summer and spring (6.80 log10 CFU·mL-1 and 6.70 log10 CFU·mL-1), compared to winter and autumn (4.27 log10 CFU·mL-1 and 5.64 log10 CFU·mL-1).

Public preferences for the allocation of societal resources over different healthcare purposes

ObjectiveIncreasing healthcare expenditures require governments to make difficult prioritization decisions. Considering public preferences can help raise citizens’ support. Previous research has predominantly elicited preferences for the allocation of public resources towards specific treatments or patient groups and principles for resource allocation. This study contributes by examining public preferences for budget allocation over various healthcare purposes in the Netherlands. MethodsWe conducted a Participatory Value Evaluation (PVE) choice experiment in which 1408 respondents were asked to allocate a hypothetical budget over eight healthcare purposes: general practice and other easily accessible healthcare, hospital care, elderly care, disability care, mental healthcare, preventive care by encouragement, preventive care by discouragement, and new and better medicines. A default expenditure was set for each healthcare purpose, based on current expenditures. Respondents could adjust these default expenditures using sliders and were presented with the implications of their adjustments on health and well-being outcomes, the economy, and the healthcare premium. As a constraint, the maximum increase in the mandatory healthcare premium for adult citizens was €600 per year. The data were analysed using descriptive statistics and a Latent Class Cluster Analysis (LCCA). ResultsOn average, respondents preferred to increase total expenditures on all healthcare purposes, but especially on elderly care, new and better medicines, and mental healthcare. Three preference clusters were identified. The largest cluster preferred modest increases in expenditures, the second a much higher increase of expenditures, and the smallest favouring a substantial reduction of the healthcare premium by decreasing the expenditure on all healthcare purposes. The analyses also demonstrated substantial preference heterogeneity between clusters for budget allocation over different healthcare purposes. ConclusionsThe results of this choice experiment show that most citizens in the Netherlands support increasing healthcare expenditures. However, substantial heterogeneity was identified in preferences for healthcare purposes to prioritize. Considering these preferences may increase public support for prioritization decisions.

Definition and measurement of post-COVID-19 conditions in real-world practice: a global systematic literature review

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review...

Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis.

In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.

Transportation, childcare, lodging, and meals: Key for participant engagement and inclusion of historically underrepresented populations in the healthy brain and child development birth cohort.

Participant recruitment and retention (R&R) are well-documented challenges in longitudinal studies, especially those involving populations historically underrepresented in research and vulnerable groups (e.g., pregnant people or young children and their families), as is the focus of the HEALthy Brain and Child Development (HBCD) birth cohort study. Subpar access to transportation, overnight lodging, childcare, or meals can compromise R&R; yet, guidance on how to overcome these "logistical barriers" is sparse. This study's goal was to learn about the HBCD sites' plans and develop best practice recommendations for the HBCD consortium for addressing these logistical barriers. The HBCD's workgroups developed a survey asking the HBCD sites about their plans for supporting research-related transportation, lodging, childcare, and meals, and about the presence of institutional policies to guide their approach. Descriptive statistics described the quantitative survey data. Qualitative survey responses were brief, not warranting formal qualitative analysis; their content was summarized. Twenty-eight respondents, representing unique recruitment locations across the U.S., completed the survey. The results indicated substantial heterogeneity across the respondents in their approach toward supporting research-related transportation, lodging, childcare, and meals. Three respondents were aware of institutional policies guiding research-related transportation (10.7%) or childcare (10.7%). This study highlighted heterogeneity in approaches and scarcity of institutional policies regarding research-related transportation, lodging, childcare, and meals, underscoring the need for guidance in this area to ensure equitable support of participant R&R across different settings and populations, so that participants are representative of the larger community, and increase research result validity and generalizability.

Characterization of Kinetics-Controlled Morphologies in the Growth of Silver Crystals from a Primary Lead Melt

Silver, a precious metal, can be recovered as a by-product of the processing of non-ferrous metals such as lead. In this work, silver crystals grown from the controlled cooling of a 10% silver–90% lead melt have been examined to quantify crystal morphologies developed under industrial conditions. X-ray tomography (XCT) is adapted to quantify the size and morphology of silver crystal structures grown from the Ag-Pb melt. The examination utilized high X-ray energies and small sample sizes to mitigate attenuation and enhance image quality. Examination of single crystal dendrites under high magnification demonstrates that silver crystals, even those grown under commercial conditions, yield a Face-Centered Cubic (FCC) crystalline lattice, which could be important for the practical extension of this work to the commercial production of Ag nano-crystals and crystalline supra-molecular structures. The crystals observed are composed of multiple twinned euhedral grains in a variety of dendritic to acicular arrangements, yielding a substantial heterogeneity of crystalline forms. XCT data were used to generate size and shape descriptors for the individual crystals. The results were compared to an equivalent set of descriptors generated from laser sizing examination of a sample of unconsolidated crystals from the same experimental run. The correspondence to within 9% of the crystal equivalent diameters determined independently by the XCT and laser sizing demonstrates a favorable outcome in particle sizing as achieved by visual inspection of XCT results. XCT examination of crystal assemblages identifies small octahedral crystals and larger triangular platelets. The structures expected for FCC crystals grown at thermodynamically controlled conditions are not observed in our systems, suggesting the possibility of the first crystal nuclei form at such conditions, but their growth transition to kinetically controlled mechanisms occurs as their size increases above a threshold cutoff. Based on literature observations, this size threshold is much smaller than the resolution of the XCT instrumentation employed herein. Our characterization data are in fact consistent with thermodynamics/kinetics—and then kinetics-controlled mechanisms—as the crystal size increases. This observation is important because the systems considered here are representative of commercial processes. As such, this work extends prior crystal growth concepts, which were explored in aqueous systems often probed by electrodeposition.

Novel Prevention Approaches of Breast Cancer Surgery Related Complications: Systematic Review and Network Meta-Analysis.

Breast cancer surgery related complications are a complex condition influenced by interactions among nerve pathways and the physiological responses to breast surgery. The intensity of this complications displays substantial heterogeneity, dependent on individual patient characteristics, the extent of the surgical procedure performed, and various contributing factors. A comprehensive search of electronic databases was conducted to identify relevant randomized controlled trials (RCTs) investigating interventions for post-mastectomy pain syndrome (PMPS). A network meta-analysis was performed to integrate direct and indirect evidence, enabling comparisons of multiple interventions across different outcome measures. The systematic search yielded a total of 26 RCTs investigating 4 groups of different interventions for PMPS. The interventions included pharmacological agents, nerve blocks, physical therapy, and anesthesia regimens. Nerve blocks (OR: 0.34; 95% CrI: 0.24-0.46) and anesthesia (OR: 0.39; 95% CrI: 0.26-0.56) demonstrated improvements in functional outcomes and quality of life. This systematic review and network meta-analysis provide a comprehensive evaluation of interventions for PMPS, highlighting their varying efficacy in alleviating pain and improving functional outcomes and quality of life. However, further research with large-scale, well-designed RCTs is warranted to strengthen the evidence base and validate the effectiveness of these interventions in managing PMPS effectively.

The impact of austerity on children: Uncovering effect heterogeneity by political, economic, and family factors in low- and middle-income countries

Which children are most vulnerable when their government imposes austerity? Research tends to focus on either the political-economic level or the family level. Using a sample of nearly two million children in 67 countries, this study synthesizes theories from family sociology and political science to examine the heterogeneous effects on child poverty of economic shocks following the implementation of an International Monetary Fund (IMF) program. To discover effect heterogeneity, we apply machine learning to policy evaluation. We find that children's average probability of falling into poverty increases by 14 percentage points. We find substantial effect heterogeneity, with family wealth and governments' education spending as the two most important moderators. In contrast to studies that emphasize the vulnerability of low-income families, we find that middle-class children face an equally high risk of poverty. Our results show that synthesizing family and political factors yield deeper knowledge of how economic shocks affect children.

Bias-Adjusted Predictions of County-Level Vaccination Coverage from the COVID-19 Trends and Impact Survey.

The potential for selection bias in nonrepresentative, large-scale, low-cost survey data can limit their utility for population health measurement and public health decision making. We developed an approach to bias adjust county-level COVID-19 vaccination coverage predictions from the large-scale US COVID-19 Trends and Impact Survey. We developed a multistep regression framework to adjust for selection bias in predicted county-level vaccination coverage plateaus. Our approach included poststratification to the American Community Survey, adjusting for differences in observed covariates, and secondary normalization to an unbiased reference indicator. As a case study, we prospectively applied this framework to predict county-level long-run vaccination coverage among children ages 5 to 11 y. We evaluated our approach against an interim observed measure of 3-mo coverage for children ages 5 to 11 y and used long-term coverage estimates to monitor equity in the pace of vaccination scale up. Our predictions suggested a low ceiling on long-term national vaccination coverage (46%), detected substantial geographic heterogeneity (ranging from 11% to 91% across counties in the United States), and highlighted widespread disparities in the pace of scale up in the 3 mo following Emergency Use Authorization of COVID-19 vaccination for 5- to 11-y-olds. We relied on historical relationships between vaccination hesitancy and observed coverage, which may not capture rapid changes in the COVID-19 policy and epidemiologic landscape. Our analysis demonstrates an approach to leverage differing strengths of multiple sources of information to produce estimates on the time scale and geographic scale necessary for proactive decision making. Designing integrated health measurement systems that combine sources with different advantages across the spectrum of timeliness, spatial resolution, and representativeness can maximize the benefits of data collection relative to costs. The COVID-19 pandemic catalyzed massive survey data collection efforts that prioritized timeliness and sample size over population representativeness.The potential for selection bias in these large-scale, low-cost, nonrepresentative data has led to questions about their utility for population health measurement.We developed a multistep regression framework to bias adjust county-level vaccination coverage predictions from the largest public health survey conducted in the United States to date: the US COVID-19 Trends and Impact Survey.Our study demonstrates the value of leveraging differing strengths of multiple data sources to generate estimates on the time scale and geographic scale necessary for proactive public health decision making.

Efficacy and safety of steroids for chronic subdural hematoma: A systematic review and meta-analysis

Background: Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain’s arachnoid and dura mater coverings. While steroids have been explored as a potential treatment option, their efficacy and safety remain uncertain. This meta-analysis and systematic review aimed to assess the impact of steroids on CSDH management, including mortality, recurrence, complications, and functional outcomes. Methods: We conducted a comprehensive literature search in major electronic databases up to June 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Handbook for Systematic Reviews and Interventions. Inclusion criteria encompassed adult patients with CSDH, the use of steroids as monotherapy or adjuvant therapy, and clearly defined outcomes. Randomized controlled trials and cohort studies meeting these criteria were included in the study. Results: The initial search yielded 4315 articles, with 12 studies meeting the inclusion criteria. Our findings indicate a non-significant trend toward reduced mortality with steroids in combination with standard care (Odds ratios [OR] = 0.66, 95% confidence interval [CI] 0.20–2.18). However, substantial heterogeneity was observed (I2 = 70%). Sensitivity analysis, excluding influential studies, suggested a potential increased mortality risk associated with steroids (OR = 1.47, 95% CI 0.87–2.48). Steroids showed a possible benefit in reducing the recurrence of CSDH (OR = 0.58, 95% CI 0.20–1.67), but with significant heterogeneity (I2 = 89%). No clear advantage of steroids was observed in terms of functional outcomes at three months (modified Rankin scale scores). Furthermore, steroids were associated with a significantly higher incidence of adverse effects and complications (OR = 2.17, 95% CI 1.48–3.17). Conclusion: Steroids may have a potential role in reducing CSDH recurrence but do not appear to confer significant advantages in terms of mortality or functional outcomes. However, their use is associated with a higher risk of adverse effects and complications. Given the limitations of existing studies, further research is needed to refine the role of steroids in CSDH management, considering patient-specific factors and treatment protocols.

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment

Introduction: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. Methods: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. Results: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3–4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R² _N = 0.64). Conclusion: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

Orthodontic tooth movement through regenerative sites: A 25-year systematic review

This systematic review aimed to investigate the efficacy of orthodontic tooth movement (OTM) through bone regenerated with osteoconductive grafts, together with the risk of root resorption (RR), in relation to the material and the timing of force initiation. Following PRISMA-ScR guidelines, three major electronic databases were searched (PubMed, EMBASE, and Cochrane). Only studies which reported on the primary outcome (OTM rate) were included. Investigations with fewer than 3 participants/groups and an absence of controls were excluded. The final sample consisted of 16 randomized and controlled clinical trials. Among them, 9 reported on RR (the secondary outcome). The articles showed substantial heterogeneity and low-moderate quality. Most studied OTM through alloplasts (7) and xenografts (8), 3 addressed allografts, 3 autografts and 6 analyzed 2 grafts. Timing for force initiation varied from 0 to 13 weeks post-grafting. Based on limited evidence, it can be cautiously concluded that most graft materials have either no impact or slightly impair OTM, with no significant increase in RR. Xenografts might impede OTM and increase RR risk. The optimal timing for force application depends on the state of bone healing. Future studies are mandatory for deciding on the ideal graft and timing for optimal OTM in each clinical setup.

Quantifying economic impacts of trade agreements with heterogeneous trade elasticities

AbstractBilateral trade relationships between countries vary across products. Such heterogeneity poses challenges when assessing the economic impacts of trade agreements. This paper estimates bilateral trade elasticities at the product level and explores these impacts using a hypothetical no‐deal Brexit as an example. Our findings indicate that the European Union's demand for the United Kingdom products is often less elastic compared to products from other trading partners. We also observed substantial heterogeneity in the elasticities across products and a negative correlation between these elasticities and tariffs. These factors mitigate extent of trade welfare losses compared to a scenario using homogeneous elasticities.

Rod Angulation Relationship with Thoracic Kyphosis after Adolescent Idiopathic Scoliosis Posterior Instrumentation.

Surgery to correct spinal deformities in scoliosis involves the use of contoured rods to reshape the spine and correct its curvatures. It is crucial to bend these rods appropriately to achieve the best possible correction. However, there is limited research on how the rod bending process relates to spinal shape in adolescent idiopathic scoliosis surgery. A retrospective study was conducted using a prospective multicenter scoliosis database. This study included adolescent idiopathic scoliosis patients from the database who underwent surgery with posterior instrumentation covering the T4 to T12 segments. Standing global spine X-rays were used in the analysis. The sagittal Cobb angles between T5 and T11 were measured on the spine. Additionally, the curvature of the rods between T5 and T11 was measured using the tangent method. To assess the relationship between these measurements, the difference between the dorsal kyphosis (TK) and the rod kyphosis (RK) was calculated (ΔK = TK - RK). This study aimed to analyze the correlation between ΔK and various patient characteristics. Both descriptive and statistical analyses were performed to achieve this goal. This study encompassed a cohort of 99 patients, resulting in a total of 198 ΔK measurements for analysis. A linear regression analysis was conducted, revealing a statistically significant positive correlation between the kyphosis of the rods and that of the spine (r = 0.77, p = 0.0001). On average, the disparity between spinal and rod kyphosis averaged 5.5°. However, it is noteworthy that despite this modest mean difference, there was considerable variability among the patients. In particular, in 84% of cases, the concave rod exhibited less kyphosis than the spine, whereas the convex rod displayed greater kyphosis than the spine in 64% of cases. It was determined that the primary factor contributing to the flattening of the left rod was the magnitude of the coronal Cobb angle, both before and after the surgical procedure. These findings emphasize the importance of considering individual patient characteristics when performing rod bending procedures, aiming to achieve the most favorable outcomes in corrective surgery. Although there is a notable and consistent correlation between the curvature of the spine and the curvature of the rods, it is important to acknowledge the substantial heterogeneity observed in this study. This heterogeneity suggests that individual patient factors play a significant role in shaping the outcome of spinal corrective surgery. Furthermore, this study highlights that more severe spinal curvatures in the frontal plane have an adverse impact on the shape of the rods in the sagittal plane. In other words, when the scoliosis curve is more pronounced in the frontal plane, it tends to influence the way the rods are shaped in the sagittal plane. This underscores the complexity of spinal deformities and the need for a tailored approach in surgical interventions to account for these variations among patients.