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As earlier research results suggest that many mathematics teaching students criticize a missing relevance in their studies, we explore explanations and interrelationships of their relevance assessments. We aim at finding out how one could support the students in attributing relevance to their study programs. A two-fold model for relevance assessments in mathematics teacher education is proposed, consisting of relevance content and relevance reasons. We investigate students' relevance perceptions of mathematical topics and of topics' complexities, as well as their rating of individual and societal/ vocational relevance reasons, all in relation to their perception of the relevance of their overall program of study. Contrary to earlier research findings, our results suggest that mathematics teaching students already do attribute relevance to many content areas and that a preparation for the teaching profession is not the only reason for them to assign relevance. There also seem to be many students who would attribute relevance if they could develop as individuals and pursue their interests. We suggest that giving students opportunities to set individual priorities in their studies could hence support their relevance assessments. As low relevance assessments seem to be connected to students' motivational problems, students might profit from motivational support, as well.

PURPOSE: Alcohol use and handgun carrying are more prevalent among youth in rural than urban areas and their association may be stronger among rural adolescents. Alcohol use may be modifiable with implications for reducing handgun carrying and firearm-related harm. We examined the association between lagged alcohol use and subsequent handgun carrying in rural areas and examined variation in the association by developmental stages, hypothesizing that it would be stronger among adolescents than youth adults. METHODS: We used a longitudinal sample of 2,002 adolescents from ages 12 to 26 growing up in 12 rural communities in 7 states with surveys collected from 2004 to 2019. We estimated the association of lagged past-month alcohol use on handgun carrying in the subsequent 12 months using population-average generalized estimating equations with logistic regression on multiply imputed data. FINDINGS: During adolescence (ages 12-18), those who drank heavily had 1.43 times the odds (95% CI = [1.01, 2.03]) of subsequent handgun carrying compared to those who did not drink alcohol, and those who consumed alcohol but did not drink heavily had 1.30 times the odds of subsequent handgun carrying compared to those who did not drink (95% CI = [0.98, 1.71]). During young adulthood (ages 19-26), associations of alcohol use (OR = 1.28; 95% CI = [0.94, 1.63]) and heavy drinking (OR = 1.38; 95% CI = [1.08, 1.68]) were similar to adolescence. CONCLUSIONS: Alcohol use and subsequent handgun carrying were positively associated during adolescence and young adulthood among individuals who grew up in rural areas, similar to findings in urban areas. Reducing alcohol use may be an important strategy to prevent handgun carrying and firearm-related harm among young people in rural areas.

Abstract Benthic organisms typically possess a planktonic propagule stage in the form of larvae or spores, which enables them to spread over large distances before settlement, and promotes tight pelago-benthic coupling. However, factors driving dispersal and epibenthos recruitment in shallow hard-bottom Arctic communities are poorly known. We therefore conducted a year-round in situ colonization experiment in Isfjorden (Svalbard), and found out that variation in early-stage epibenthic assemblages was explained by the combination of: abiotic (45.9%) and biotic variables (23.9%), and their interactions (30.2%). The upward-facing experimental plates were dominated by coralline algae, and this is the first study showing that at high latitudes coralline algae Lithothamnion sp. settle in high numbers on available substrates during the polar night in winter. The downward-facing plates, which had much less exposure to light, contained more diverse organisms, with a predominance of polychaetas and bryozoans. However, in summer, the barnacle Semibalanus balanoides outcompeted all the other recruits, as a result of massive occurrence of meroplanktonic Cirripedia larvae, triggered by the phytoplankton bloom. In conclusion, the rate and success of epibenthic settlements were dependent mostly on light availability and temperature, suggesting that larval settlement will be impacted by global warming with some taxa benefitting, while others losing.

Abstract A pattern of increasing species richness from the poles to the equator is frequently observed in many animal taxa. Ecological limits, determined by the abiotic conditions and biotic interactions within an environment, are one of the major factors influencing the geographical distribution of species diversity. Energy availability is often considered a crucial limiting factor, with temperature and productivity serving as empirical measures. However, these measures may not fully explain the observed species richness, particularly in marine ecosystems. Here, through a global comparative approach and standardised methodologies, such as Autonomous Reef Monitoring Structures (ARMS) and DNA metabarcoding, we show that the seasonality of primary production explains sessile animal richness comparatively or better than surface temperature or primary productivity alone. A Hierarchical Generalised Additive Model (HGAM) is validated, after a model selection procedure, and the prediction error is compared, following a cross-validation approach, with HGAMs including environmental variables commonly used to explain animal richness. Moreover, the linear effect of production magnitude on species richness becomes apparent only when considered jointly with seasonality, and, by identifying world coastal areas characterized by extreme values of both, we postulate that this effect may result in a positive relationship in environments with lower seasonality.

Abstract Background Chronic pain often clusters in families, where parents and their offspring both experience chronic pain conditions. Young children of parents with irritable bowel syndrome (IBS) represent an at-risk group for the development of abdominal pain, disability, and excess health care visits in later childhood. Parental solicitous responses to children’s expressions of discomfort and maternal modeling of their own illness behavior contribute to a greater focus on somatic sensations, leading to illness behaviors in children. This randomized controlled trial will test the effectiveness of an early preventive web-based psychosocial intervention (REACH)[TM] vs. an educational web-based safety comparison condition delivered to parents with IBS to alter parental responses and lead to improved child health and decreased health care costs. Methods Parents with IBS who have children ages 4–7 years are recruited via community-based approaches (e.g., social media advertisements, school electronic distribution, research networks) and health care providers. The target sample is 460 parents randomized to REACH, a web-based social learning and cognitive behavior therapy (SLCBT) intervention or an educational web-based safety comparison condition (EC). Participants will be assessed at baseline, 6-week (immediate post-intervention), 6-month, 12-month, and 18-month follow-up periods (months post-completion of intervention). The primary outcome is change in parental solicitous/protective behaviors. Secondary outcomes include parent risk and protective factors, child health and symptom outcomes, and health care utilization and cost savings. Discussion This study adapts a validated, parent-delivered intervention to treat chronic pain in children to a web-based application designed to prevent the development of chronic pain in very young, high-risk children. If successful, this strategy can both prevent adverse sequelae of this condition from developing as well as be widely accessible. Furthermore, the availability of a prevention model for parent training could result in significant short- and long-term health benefits across a broad spectrum of conditions. Trial registration ClinicalTrials.gov NCT05730491. Registered on February 15, 2023.

In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received front-line anti-PD-1 or therapy against programmed cell death 1 ligand 1 and whose tumors progressed was tested in comparison with CTLA-4 blockade alone. Ninety-two eligible patients were randomly assigned in a 3:1 ratio to receive the combination of ipilimumab and nivolumab, or ipilimumab alone. The primary endpoint was progression-free survival. Secondary endpoints included the difference in CD8 T cell infiltrate among responding and nonresponding tumors, objective response rate, overall survival and toxicity. The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in progression-free survival over ipilimumab (hazard ratio = 0.63, 90% confidence interval (CI) = 0.41-0.97, one-sided P = 0.04). Objective response rates were 28% (90% CI = 19-38%) and 9% (90% CI = 2-25%), respectively (one-sided P = 0.05). Grade 3 or higher treatment-related adverse events occurred in 57% and 35% of patients, respectively, which is consistent with the known toxicity profile of these regimens. The change in intratumoral CD8 T cell density observed in the present analysis did not reach statistical significance to support the formal hypothesis tested as a secondary endpoint. In conclusion, primary resistance to PD-1 blockade therapy can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade. Clinicaltrials.gov identifier: NCT03033576 .

Abstract Study goal We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) “donna”. Methods We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. Results We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p

BackgroundA clinical dashboard is a data-driven clinical decision support tool visualizing multiple key performance indicators in a single report while minimizing time and effort for data gathering. Studies have shown that including patient-reported outcome measures (PROMs) in clinical dashboards supports the clinician’s understanding of how treatments impact patients’ health status, helps identify changes in health-related quality of life at an early stage, and strengthens patient-physician communication. ObjectiveThis study aims to determine design components for clinical dashboards incorporating PROMs to inform software producers and users (ie, physicians). MethodsWe conducted interviews with software producers and users to test preselected design components. Furthermore, the interviews allowed us to derive additional components that are not outlined in existing literature. Finally, we used inductive and deductive coding to derive a guide on which design components need to be considered when building a clinical dashboard incorporating PROMs. ResultsA total of 25 design components were identified, of which 16 were already surfaced during the literature search. Furthermore, 9 additional components were derived inductively during our interviews. The design components are clustered in a generic dashboard, PROM-related, adjacent information, and requirements for adoption components. Both software producers and users agreed on the primary purpose of a clinical dashboard incorporating PROMs to enhance patient communication in outpatient settings. Dashboard benefits include enhanced data visualization and improved workflow efficiency, while interoperability and data collection were named as adoption challenges. Consistency in dashboard design components is preferred across different episodes of care, with adaptations only for disease-specific PROMs. ConclusionsClinical dashboards have the potential to facilitate informed treatment decisions if certain design components are followed. This study establishes a comprehensive framework of design components to guide the development of effective clinical dashboards incorporating PROMs in health care practice.

Abstract Manifestations of climate change in the Arctic include an increase in water temperatures and massive loss of sea ice enabling more light penetration. Yet to understand tempo and scale of these parameters change over time, constant monitoring is needed. We present 16-yr long-term datasets of sea water temperature and relative light intensity at two depth strata (8 and 14 ± 1 m) of two hard-bottom sites in southern Isfjorden proper (Spitsbergen, 78°N). The high temporal resolution of the datasets (every 30 min, between 2006–2022) makes them suitable for studying changes at a local scale, correlating environmental variability with observed processes in benthic assemblages, and serving as ground-truth for comparison with, for example, remotely sensed or mooring data. These datasets serve as baseline for long-term investigations in the shallows of a high-Arctic fjord undergoing severe environmental changes.

Abstract Background As patient-reported outcomes (PROs) gain prominence in hip and knee arthroplasty (HA and KA), studies indicate PRO variations between genders. Research on the specific health domains particularly impacted is lacking. Hence, we aim to quantify the gender health gap in PROs for HA/KA patients, differentiating between general health, health-related quality of life (HrQoL), physical functioning, pain, fatigue, and depression. Methods The study included 3,693 HA patients (1,627 men, 2,066 women) and 3,110 KA patients (1,430 men, 1,680 women) receiving surgery between 2020 to 2021 in nine German hospitals, followed up until March 2022. Questionnaires used were: EQ-VAS, EQ-5D-5L, HOOS-PS, KOOS-PS, PROMIS-F-SF, PROMIS-D-SF, and a joint-specific numeric pain scale. PROs at admission, discharge, 12-months post-surgery, and the change from admission to 12-months (PRO-improvement) were compared by gender, tested for differences, and assessed using multivariate linear regressions. To enable comparability, PROs were transformed into z-scores (standard deviations from the mean). Results Observed differences between genders were small in all health domains and differences reduced over time. Men reported significantly better health versus women pre-HA (KA), with a difference of 0.252 (0.224) standard deviations from the mean for pain, 0.353 (0.243) for fatigue (PROMIS-F-SF), 0.327 (0.310) for depression (PROMIS-D-SF), 0.336 (0.273) for functionality (H/KOOS-PS), 0.177 (0.186) for general health (EQ-VAS) and 0.266 (0.196) for HrQoL (EQ-5D-5L). At discharge, the gender health gap reduced and even disappeared for some health dimensions since women improved in health to a greater extent than men. No gender health gap was observed in most PRO-improvements and at month 12. Conclusions Men experiencing slightly better health than women in all health dimensions before surgery while experiencing similar health benefits 12-months post-surgery, might be an indicator of men receiving surgery inappropriately early, women unnecessarily late or both. As studies often investigate the PRO-improvement, they miss pre-surgery gender differences, which could be an important target for improvement initiatives in patient-centric care. Moreover, future research on cutoffs for meaningful between-group PRO differences per measurement time would aid the interpretation of gender health disparities. Trial registration German Register for Clinical Trials, DRKS00019916, 26 November 2019.

Abstract Background The self-perceived health status of patients undergoing total hip and knee arthroplasty (THA and TKA) might differ post-operatively due to gender, age, or comorbidities. Patient-reported outcome measures (PROMs) such as the EQ-5D-5L measure the self-perceived health status. This study investigates whether the index score of the EQ-5D-5L is a valid tool for interpreting gender differences in outcomes for patients undergoing THA and TKA. Methods Routine and PROM-data of elective primary THA or TKA patients in two German hospitals between 2016 and 2018 were analyzed. Univariate analysis with Pearson’s chi-square was conducted to identify control variables for gender. To quantify the association between gender and the EQ-5D-5L dimensions, a cumulative odds ordinal logistic regression with proportional odds was conducted. Results Two thousand three hundred sixty-eight​​ THA patients (m = 978; f = 1390) and 1629 TKA patients (m = 715; f = 914) were considered. The regression analysis of the individual EQ-5D-5L dimensions showed that female gender was significantly associated with better self-care (THA and TKA) and better post-operative mobility (THA). In contrast, male gender was significantly associated with less pain/discomfort (TKA) and less anxiety/depression (THA) pre-surgery and 3-months post-surgery. Conclusion Our results confirmed that the self-perceived health status improved after surgery. However, due to the different associations of gender to the individual dimensions of the EQ-5D-5L, the weighted index score clouds the comparability between patients with different gender undergoing THA or TKA. Therefore, we argue to use the individual five dimensions for health status analysis, to reveal relevant additional information.

PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (r s ); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation r s = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (r s = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (r s = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (r s from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

This study examines the cost effectiveness of two interventions for disruptive behavior problems: First Step Next (FSN), a school-based intervention, and a multicomponent intervention that combined FSN with a home-based intervention, homeBase (hB). Analyses were based on findings from a large-scale comparative efficacy trial in the United States (Frey et al., 2022). Intervention costs were estimated using an activities-based ingredients method (Levin & McEwan, 2001). For each disruptive behavior examined (attention-deficit/hyperactivity disorder [ADHD], conduct disorder [CD], and comorbid ADHD and CD), we defined intervention response as movement from the clinical range into the borderline or normative range or from the borderline range into the normative range at post-intervention. Comparative cost-effectiveness analyses involved calculating incremental cost-effectiveness ratios (ICERs), which showed that the combined intervention was always more cost effective. Improvement in comorbid ADHD and CD was the costliest to achieve, followed by CD, and then ADHD. Sensitivity analyses showed that FSN + hB had a high probability of being cost effective across a range of estimates, indicating stakeholder willingness to pay to reduce disruptive behavior problems. This study expands the literature by estimating the costs of implementing a school-based intervention alone or alongside a home-based intervention with elementary students and comparing their cost effectiveness.

Histoplasmosis is the most common endemic fungal infection in the USA. The majority of cases are asymptomatic and have clear exposure to endemic regions. In contrast, we present an adolescent immunocompromised patient with systemic and relatively non-specific symptoms including abdominal pain, weight loss, lower extremity edema, and scabbing skin lesions, without known exposure to endemic areas for histoplasmosis. Histologic analysis of gastrointestinal and skin biopsies eventually revealed a diagnosis of disseminated histoplasmosis; the patient was successfully treated with amphotericin B followed by itraconazole maintenance therapy. Ultimately, a high bar of suspicion for fungal disease must be maintained in immunosuppressed individuals even without apparent exposure history to endemic areas. This case report serves as a valuable reference for practitioners evaluating differential diagnosis of infections in immunocompromised patients.

Abstract Background Between 2008 and 2018, the share of robotic-assisted surgeries (RAS) for radical prostatectomies (RPEs) has increased from 3 to 46% in Germany. Firstly, we investigate if this diffusion of RAS has contributed to RPE treatment centralization. Secondly, we analyze if a hospital’s use of an RAS system influenced patients’ hospital choice. Methods To analyze RPE treatment centralization, we use (bi-) annual hospital data from 2006 to 2018 for all German hospitals in a panel-data fixed effect model. For investigating RAS systems’ influence on patients’ hospital choice, we use patient level data of 4614 RPE patients treated in 2015. Employing a random utility choice model, we estimate the influence of RAS as well as specialization and quality on patients’ marginal utilities and their according willingness to travel. Results Despite a slight decrease in RPEs between 2006 and 2018, hospitals that invested in an RAS system could increase their case volumes significantly (+ 82% compared to hospitals that did not invest) contributing to treatment centralization. Moreover, patients are willing to travel longer for hospitals offering RAS (+ 22% than average travel time) and for specialization (+ 13% for certified prostate cancer treatment centers, + 9% for higher procedure volume). The influence of outcome quality and service quality on patients’ hospital choice is insignificant or negligible. Conclusions In conclusion, centralization is partly driven by (very) high-volume hospitals’ investment in RAS systems and patient preferences. While outcome quality might improve due to centralization and according specialization, evidence for a direct positive influence of RAS on RPE outcomes still is ambiguous. Patients have been voting with their feet, but research yet has to catch up.

PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (rs); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation rs = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (rs = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (rs = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (rs from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

Embedded pragmatic clinical trials (ePCTs) and quality improvement (QI) activities often occur simultaneously within healthcare systems (HCSs). Embedded PCTs within HCSs are conducted to test interventions and provide evidence that may impact public health, health system operations, and quality of care. They are larger and more broadly generalizable than QI initiatives, and may generate what is considered high-quality evidence for potential use in care and clinical practice guidelines. QI initiatives often co-occur with ePCTs and address the same high-impact health questions, and this co-occurrence may dilute or confound the ability to detect change as a result of the ePCT intervention. During the design, pilot, and conduct phases of the large-scale NIH Collaboratory Demonstration ePCTs, many QI initiatives occurred at the same time within the HCSs. Although the challenges varied across the projects, some common, generalizable strategies and solutions emerged, and we share these as case studies. KEY LESSONS: Study teams often need to monitor, adapt, and respond to QI during design and the course of the trial. Routine collaboration between ePCT researchers and health systems stakeholders throughout the trial can help ensure research and QI are optimally aligned to support high-quality patient-centered care.

PURPOSE: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study. METHODS: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmers test with anesthesia were also evaluated. RESULTS: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3. CONCLUSION: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.

PurposeOmega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study.MethodsBlood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated.ResultsThere was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3.ConclusionPrevious studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.