The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness.

OBJECTIVE: To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients. STUDY DESIGN: The institutional cardiopulmonary exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA. RESULTS: A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI. CONCLUSION: In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.

Plant diversity and community age stabilize ecosystem multifunctionality.

It is well known that biodiversity positively affects ecosystem functioning, leading to enhanced ecosystem stability. However, this knowledge is mainly based on analyses using single ecosystem functions, while studies focusing on the stability of ecosystem multifunctionality (EMF) are rare. Taking advantage of a long-term grassland biodiversity experiment, we studied the effect of plant diversity (1-60 species) on EMF over 5 years, its temporal stability, as well as multifunctional resistance and resilience to a 2-year drought event. Using split-plot treatments, we further tested whether a shared history of plants and soil influences the studied relationships. We calculated EMF based on functions related to plants and higher-trophic levels. Plant diversity enhanced EMF in all studied years, and this effect strengthened over the study period. Moreover, plant diversity increased the temporal stability of EMF and fostered resistance to reoccurring drought events. Old plant communities with shared plant and soil history showed a stronger plant diversity-multifunctionality relationship and higher temporal stability of EMF than younger communities without shared histories. Our results highlight the importance of old and biodiverse plant communities for EMF and its stability to extreme climate events in a world increasingly threatened by global change.

Spectral performance evaluation of a second-generation spectral detector CT.

PURPOSE: The aim of this study was to characterize a second-generation wide-detector dual-layer spectral computed tomography (CT) system for material quantification accuracy, acquisition parameter and patient size dependencies, and tissue characterization capabilities. METHODS: A phantom with multiple tissue-mimicking and material-specific inserts was scanned with a dual-layer spectral detector CT using different tube voltages, collimation widths, radiation dose levels, and size configurations. Accuracy of iodine density maps and virtual monoenergetic images (MonoE) were investigated. Additionally, differences between conventional and MonoE 70 keV images were calculated to evaluate acquisition parameter and patient size dependencies. To demonstrate material quantification and differentiation, liver-mimicking inserts with adipose and iron were analyzed with a two-base decomposition utilizing MonoE 50 and 150 keV, and root mean square error (RMSE) for adipose and iron content was reported. RESULTS: Measured inserts exhibited quantitative accuracy across a wide range of MonoE levels. MonoE 70 keV images demonstrated reduced dependence compared to conventional images for phantom size (1 vs. 27 HU) and acquisition parameters, particularly tube voltage (4 vs. 37 HU). Iodine density quantification was successful with errors ranging from -0.58 to 0.44 mg/mL. Similarly, inserts with different amounts of adipose and iron were differentiated, and the small deviation in values within inserts corresponded to a RMSE of 3.49 ± 1.76% and 1.67 ± 0.84 mg/mL for adipose and iron content, respectively. CONCLUSION: The second-generation dual-layer CT enables acquisition of quantitatively accurate spectral data without compromises from differences in patient size and acquisition parameters.

A zero-inflated endemic-epidemic model with an application to measles time series in Germany.

Count data with an excess of zeros are often encountered when modeling infectious disease occurrence. The degree of zero inflation can vary over time due to nonepidemic periods as well as by age group or region. A well-established approach to analyze multivariate incidence time series is the endemic-epidemic modeling framework, also known as the HHH approach. However, it assumes Poisson or negative binomial distributions and is thus not tailored to surveillance data with excess zeros. Here, we propose a multivariate zero-inflated endemic-epidemic model with random effects that extends HHH. Parameters of both the zero-inflation probability and the HHH part of this mixture model can be estimated jointly and efficiently via (penalized) maximum likelihood inference using analytical derivatives. We found proper convergence and good coverage of confidence intervals in simulation studies. An application to measles counts in the 16 German states, 2005-2018, showed that zero inflation is more pronounced in the Eastern states characterized by a higher vaccination coverage. Probabilistic forecasts of measles cases improved when accounting for zero inflation. We anticipate zero-inflated HHH models to be a useful extension also for other applications and provide an implementation in an R package.

Factors associated with low levels of HIV testing among young men who have sex with men (MSM) participating in EMIS-2017 in Spain.

PURPOSE: The European Men who have sex with men Internet Survey looked over the characteristics and needs of men who have sex with men (MSM) across Europe. Our objective was to estimate the prevalence of HIV testing and its associated factors among MSM younger than 25 years old participating in the EMIS-2017 in Spain. METHODS: Multivariable regression model was used to compare those who had been tested for HIV within the last 12 months and those that had not. RESULTS: Of 2313 participants, 1070 (46.3%) had been tested for HIV in the past 12 months. Increased age (age 19-21 years, aOR=3.38 (95% CI 2.57 to 4.44); age 22-24 years, aOR=5.26 (4.06 to 6.92) compared with age 16-18 years); being migrant (Latin America: aOR=1.34 (0.98 to 1.84); Europe, North America and Mediterranean countries (aOR=1.56 (0.98 to 2.51) compared with those from Spain); living more openly with one's sexuality (out to some people (aOR=1.53 (1.19 to 1.96)); out to all or almost all people (aOR=2.24 (1.75 to 2.87) compared with those out to none or a few people); having had one condomless steady partners in the las year ((aOR=1.59 (1.26 to 2.02)); having had condomless non-steady partners in the last year (one: aOR=1.76 (1.35 to 2.29)); two or more partners: aOR=2.37 (1.84 to 3.04)); and having practised sex work in the past year (aOR=1.52 (1.07 to 2.13)) were associated with increased odds of HIV testing. Living in a smaller city was associated with less likelihood of HIV testing (<1 00 000 inhabitants: aOR=0.51 (95% CI 0.41 to 0.64); 100 000-500 000: aOR=0.68 (95% CI 0.54 to 0.86) compared with more than 500 000). CONCLUSION: Young MSM showed low HIV testing rate. Future programming specifically targeting this population, especially those middle adolescents, living in a medium-small city and having less 'outness', can help increase HIV testing and prevent access barriers.

Would eligible gay, bisexual and other men who have sex with men use PrEP? Awareness, knowledge, eligibility and intention to use PrEP among EMIS-2017 participants in Spain.

Pre-exposure prophylaxis (PrEP) is an efficacious strategy for reducing the incidence of HIV infection. It has been available in Spain since 2019. We aim to report on awareness, knowledge of, intention to use, and eligibility for PrEP and related factors among participants in the European Men-Who-Have-Sex-With-Men Internet Survey (EMIS-2017) in Spain. We used Spanish data from EMIS-2017, a cross-sectional study performed among gay, bisexual, and other men who have sex with mean (GBMSM) from 50 countries. We found that 65.3% of the 10,634 participants were aware of PrEP, some 30.1% of those HIV-negative and ≥ 18 years were eligible and 52.7% of those eligible intended to use it. Regarding knowledge about PrEP, only 15.4% of the participants knew 3 statement with true information about that PrEP meant. Older age, being born in Western Europe (WE) and greater outness were associated with greater awareness. Older age, being born in Latin America or Caribbean or WE, sex work, and living in a large city were associated with greater eligibility. A greater degree of outness was associated with reduced intention to use. Our study point to possible barriers in the implementation of PrEP in Spain and similar countries.

Non-pharmacological, psychosocial MAKS-s intervention for people with severe dementia in nursing homes: results of a cluster-randomised trial.

BACKGROUND: Severe dementia is one of the most challenging conditions when caring for people in nursing homes. A manualised non-pharmacological, psychosocial group intervention especially adapted to the needs of people with severe dementia (PWSDs) is currently still lacking. To close this gap, we adapted the evidence-based multicomponent non-pharmacological MAKS intervention (Motor stimulation, ADL stimulation, Cognitive [german: Kognitive] stimulation, and Social functioning in a group setting) to the special needs of PWSDs called the MAKS-s intervention, where the s stands for severe dementia. METHODS: In a prospective, multicentre, cluster-randomised trial with a waitlist control group design, 26 nursing homes comprising 152 PWSDs were randomly assigned to either the MAKS-s intervention group (IG) or control group (CG) - 121 PWSDs were still alive after the 6-month intervention period (t6) and included in the intention-to-treat (ITT) sample. The two primary outcomes, behavioural and psychological symptoms (BPSDs, measured with NPI-NH) and quality of life (QoL, measured with QUALIDEM), and the secondary outcome, activities of daily living (ADLs, measured with ADCS-ADL-sev), were assessed at baseline (t0) and at t6. Mixed ANOVAs were computed to investigate possible effects of the MAKS-s intervention on the outcomes. RESULTS: In the ITT sample, BPSDs and QoL did not change significantly over time, and group assignment did not affect them, although the IG participants had significantly better overall QoL than the CG participants. ADLs decreased significantly over time, but group assignment did not affect them. Analyses in the per protocol (PP) sample showed comparable results, with the exception that the IG participants showed a significantly greater increase in BPSDs than the CG participants did. DISCUSSION: Under the situational conditions of the Covid-19 pandemic, no beneficial effects of the MAKS-s intervention on BPSDs, QoL, or ADLs were observed. This finding also means that under 'normal circumstances' (i.e., if there had been no pandemic), we could not make any statements about the effect or non-effect of MAKS-s. In order to be able to address the hypotheses formulated here, the study will have to be repeated incorporating helpful experiences of the present study. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN15722923 (Registered prospectively, 07. August 2019).

Biodiversity increases the resistance of ecosystem productivity to climate extremes.

It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities. However, subsequent experimental tests produced mixed results. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16-32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.

Inhibiting Interleukin 36 Receptor Signaling Reduces Fibrosis in Mice With Chronic Intestinal Inflammation.

BACKGROUND & AIMS: Intestinal fibrosis is a long-term complication in inflammatory bowel diseases (IBD) that frequently results in functional damage, bowel obstruction, and surgery. Interleukin (IL) 36 is a group of cytokines in the IL1 family with inflammatory effects. We studied the expression of IL36 and its receptor, interleukin 1 receptor like 2 (IL1RL2 or IL36R) in the development of intestinal fibrosis in human tissues and mice. METHODS: We obtained intestinal tissues from 92 patients with Crohn's disease (CD), 48 patients with ulcerative colitis, and 26 patients without inflammatory bowel diseases (control individuals). Tissues were analyzed by histology to detect fibrosis and by immunohistochemistry to determine the distribution of fibroblasts and levels of IL36R ligands. Human and mouse fibroblasts were incubated with IL36 or control medium, and transcriptome-wide RNA sequences were analyzed. Mice were given neutralizing antibodies against IL36R, and we studied intestinal tissues from Il1rl2-/- mice; colitis and fibrosis were induced in mice by repetitive administration of DSS or TNBS. Bone marrow cells were transplanted from Il1rl2-/- to irradiated wild-type mice and intestinal tissues were analyzed. Antibodies against IL36R were applied to mice with established chronic colitis and fibrosis and intestinal tissues were studied. RESULTS: Mucosal and submucosal tissue from patients with CD or ulcerative colitis had higher levels of collagens, including type VI collagen, compared with tissue from control individuals. In tissues from patients with fibrostenotic CD, significantly higher levels of IL36A were noted, which correlated with high numbers of activated fibroblasts that expressed α-smooth muscle actin. IL36R activation of mouse and human fibroblasts resulted in expression of genes that regulate fibrosis and tissue remodeling, as well as expression of collagen type VI. Il1rl2-/- mice and mice given injections of an antibody against IL36R developed less severe colitis and fibrosis after administration of DSS or TNBS, but bone marrow cells from Il1rl2-/- mice did not prevent induction of colitis and fibrosis. Injection of antibodies against IL36R significantly reduced established fibrosis in mice with chronic intestinal inflammation. CONCLUSION: We found higher levels of IL36A in fibrotic intestinal tissues from patients with IBD compared with control individuals. IL36 induced expression of genes that regulate fibrogenesis in fibroblasts. Inhibition or knockout of the IL36R gene in mice reduces chronic colitis and intestinal fibrosis. Agents designed to block IL36R signaling could be developed for prevention and treatment of intestinal fibrosis in patients with IBD.

Discovery of Magnetic Single- and Triple-q States in Mn/Re(0001).

We experimentally verify the existence of two model-type magnetic ground states that were previously predicted but so far unobserved. We find them in Mn monolayers on the Re(0001) surface using spin-polarized scanning tunneling microscopy. For fcc stacking of Mn the collinear row-wise antiferromagnetic state occurs, whereas for hcp Mn a three-dimensional spin structure appears, which is a superposition of three row-wise antiferromagnetic states known as the triple-q state. Density-functional theory calculations elucidate the subtle interplay of different magnetic interactions to form these spin structures and provide insight into the role played by relativistic effects.

Electrical Detection of Domain Walls and Skyrmions in Co Films Using Noncollinear Magnetoresistance.

A large noncollinear magnetoresistance (NCMR) is observed for Rh/Co atomic bilayers on Ir(111) using scanning tunneling microscopy and spectroscopy. The effect is 20% at the Fermi energy and large in a broad energy range. The NCMR can be used to electrically detect nanometer-scale domain walls and skyrmions directly in the tunnel current without the need for a differential measurement. The NCMR results from changes in the density of states of noncollinear spin textures with respect to the ferromagnetic state. Density functional theory calculations reveal that they originate from spin mixing between majority d_{xz} and minority p_{z} states.

Towards a novel small animal proton irradiation platform: the SIRMIO project.

Background: Precision small animal radiotherapy research is a young emerging field aiming to provide new experimental insights into tumor and normal tissue models in different microenvironments, to unravel complex mechanisms of radiation damage in target and non-target tissues and assess efficacy of novel therapeutic strategies. For photon therapy, modern small animal radiotherapy research platforms have been developed over the last years and are meanwhile commercially available. Conversely, for proton therapy, which holds potential for an even superior outcome than photon therapy, no commercial system exists yet. Material and methods: The project SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology) aims at realizing and demonstrating an innovative portable prototype system for precision image-guided small animal proton irradiation, suitable for installation at existing clinical treatment facilities. The proposed design combines precise dose application with in situ multi-modal anatomical image guidance and in vivo verification of the actual treatment delivery. Results and conclusions: This manuscript describes the status of the different components under development, featuring a dedicated beamline for degradation and focusing of clinical proton beams, along with novel detector systems for in situimaging and range verification. The foreseen workflow includes pre-treatment proton transmission imaging, complemented by ultrasonic tumor localization, for treatment planning and position verification, followed by image-guided delivery with on site range verification by means of ionoacoustics (for pulsed beams) and positron-emission-tomography (PET, for continuous beams). The proposed compact and cost-effective system promises to open a new era in small animal proton therapy research, contributing to the basic understanding of in vivo radiation action to identify areas of potential breakthroughs for future translation into innovative clinical strategies.

Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure.

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9 h under real-life conditions (2 mg/cm2 body surface area; double re-application; corresponding to 3.8 g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray-ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525 µg/g and 213 µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8 h after first application. First-phase terminal half-lives were 8-9 h. For 5OH-EHS, a second-phase terminal half-life could be determined (87 h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24 h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24 h reached up to 334 µg EHS and 124 µg of 5OH-EHS. Simulated real-life sunscreen use for 1 day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.

Incorporating social contact data in spatio-temporal models for infectious disease spread.

Routine public health surveillance of notifiable infectious diseases gives rise to weekly counts of reported cases-possibly stratified by region and/or age group. We investigate how an age-structured social contact matrix can be incorporated into a spatio-temporal endemic-epidemic model for infectious disease counts. To illustrate the approach, we analyze the spread of norovirus gastroenteritis over six age groups within the 12 districts of Berlin, 2011-2015, using contact data from the POLYMOD study. The proposed age-structured model outperforms alternative scenarios with homogeneous or no mixing between age groups. An extended contact model suggests a power transformation of the survey-based contact matrix toward more within-group transmission.

Competition of Dzyaloshinskii-Moriya and Higher-Order Exchange Interactions in Rh/Fe Atomic Bilayers on Ir(111).

Using spin-polarized scanning tunneling microscopy and density functional theory we demonstrate the occurrence of a novel type of noncollinear spin structure in Rh/Fe atomic bilayers on Ir(111). We find that higher-order exchange interactions depend sensitively on the stacking sequence. For fcc-Rh/Fe/Ir(111), frustrated exchange interactions are dominant and lead to the formation of a spin spiral ground state with a period of about 1.5 nm. For hcp-Rh/Fe/Ir(111), higher-order exchange interactions favor an up-up-down-down (↑↑↓↓) state. However, the Dzyaloshinskii-Moriya interaction at the Fe/Ir interface leads to a small angle of about 4° between adjacent magnetic moments resulting in a canted ↑↑↓↓ ground state.

Children with autism spectrum disorder have unstable neural responses to sound.

Autism spectrum disorder (ASD) is diverse, manifesting in a wide array of phenotypes. However, a consistent theme is reduced communicative and social abilities. Auditory processing deficits have been shown in individuals with ASD-these deficits may play a role in the communication difficulties ASD individuals experience. Specifically, children with ASD have delayed neural timing and poorer tracking of a changing pitch relative to their typically developing peers. Given that accurate processing of sound requires highly coordinated and consistent neural activity, we hypothesized that these auditory processing deficits stem from a failure to respond to sound in a consistent manner. Therefore, we predicted that individuals with ASD have reduced neural stability in response to sound. We recorded the frequency-following response (FFR), an evoked response that mirrors the acoustic features of its stimulus, of high-functioning children with ASD age 7-13 years. Evident across multiple speech stimuli, children with ASD have less stable FFRs to speech sounds relative to their typically developing peers. This reduced auditory stability could contribute to the language and communication profiles observed in individuals with ASD.

The Erlangen test of activities of daily living in persons with mild dementia or mild cognitive impairment (ETAM) - an extended validation.

BACKGROUND: The ability to perform activities of daily living (ADLs) is a central marker in the diagnosis and progression of the dementia syndrome. ADLs can be identified as basic ADLs (BADLs), which are fairly easy to perform, or instrumental ADLs (IADLs), which involve more complex activities. Presently, the only performance-based assessment of IADL capabilities in persons with cognitive impairment is the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM). The aim of the present study was to revalidate the ETAM in persons with mild cognitive impairment (MCI) or mild dementia and to analyze its application to persons with moderate dementia. METHODS: We used baseline data from a cluster randomized controlled trial involving a sample of 443 users of 34 day-care centers in Germany. We analyzed groups of persons with MCI, mild dementia, and moderate dementia, categorized on the basis of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). An item analysis was performed, and new discriminant validities were calculated. We computed a confirmatory factor analysis (CFA) to examine the postulated theoretical model of the ETAM with all six items loading on a single IADL factor. This was the first time that the ETAM's sensitivity to change was analyzed after a time period of 6 months. RESULTS: The overall sample scored on average 17.3 points (SD = 7.2) on the ETAM (range: 0-30 points). Persons with MCI scored on average 23.2 points, persons with mild dementia scored 18.4 points, and persons with moderate dementia scored 12.9 points, p < .001 (ANOVA). The item analysis yielded good difficulty indices and discrimination powers. The CFA indicated a good fit between the model and the observed data. After 6 months, both the ETAM score at baseline and the change in MMSE score (t0-t1) were significant predictors of the ETAM score at t1. CONCLUSIONS: The ETAM is a valid and reliable instrument for assessing IADL capabilities in persons with MCI or mild dementia. It is sensitive to changes in cognitive abilities. The test parameters confirm its application to persons with moderate dementia. TRIAL REGISTRATION: Identifier: ISRCTN16412551 (Registration date: 30 July 2014, registered retrospectively).

Probabilistic forecasting in infectious disease epidemiology: the 13th Armitage lecture.

Routine surveillance of notifiable infectious diseases gives rise to daily or weekly counts of reported cases stratified by region and age group. From a public health perspective, forecasts of infectious disease spread are of central importance. We argue that such forecasts need to properly incorporate the attached uncertainty, so they should be probabilistic in nature. However, forecasts also need to take into account temporal dependencies inherent to communicable diseases, spatial dynamics through human travel and social contact patterns between age groups. We describe a multivariate time series model for weekly surveillance counts on norovirus gastroenteritis from the 12 city districts of Berlin, in six age groups, from week 2011/27 to week 2015/26. The following year (2015/27 to 2016/26) is used to assess the quality of the predictions. Probabilistic forecasts of the total number of cases can be derived through Monte Carlo simulation, but first and second moments are also available analytically. Final size forecasts as well as multivariate forecasts of the total number of cases by age group, by district and by week are compared across different models of varying complexity. This leads to a more general discussion of issues regarding modelling, prediction and evaluation of public health surveillance data. Copyright © 2017 John Wiley & Sons, Ltd.