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.

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.

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.

Automated planning of stereotactic spine re-irradiation using cumulative dose limits.

Background and Purpose: The lack of dedicated tools in commercial planning systems currently restricts efficient review and planning for re-irradiation. The aim of this study was to develop an automated re-irradiation planning framework based on cumulative doses. Materials and Methods: We performed a retrospective study of 14 patients who received spine SBRT re-irradiation near a previously irradiated treatment site. A fully-automated workflow, DART (Dose Accumulation-based Re-irradiation Tool), was implemented within Eclipse by leveraging a combination of a dose accumulation script and a proprietary automated optimization algorithm. First, we converted the prior treatment dose into equivalent dose in 2 Gy fractions (EQD2) and mapped it to the current anatomy, utilizing deformable image registration. Subsequently, the intersection of EQD2 isodose lines with relevant organs at risk defines a series of optimization structures. During plan optimization, the residual allowable dose at a specified tissue tolerance was treated as a hard constraint. Results: All DART plans met institutional physical and cumulative constraints and passed plan checks by qualified medical physicists. DART demonstrated significant improvements in target coverage over clinical plans, with an average increase in PTV D99% and V100% of 2.3 Gy [range -0.3-7.7 Gy] and 3.4 % [range -0.4 %-7.6 %] (p < 0.01, paired t-test), respectively. Moreover, high-dose spillage (>105 %) outside the PTV was reduced by up to 7 cm3. The homogeneity index for DART plans was improved by 19 % (p < 0.001). Conclusions: DART provides a powerful framework to achieve more tailored re-irradiation plans by accounting for dose distributions from the previous treatments. The superior plan quality could improve the therapeutic ratio for re-irradiation patients.

Creating patient-specific digital phantoms with a longitudinal atlas for evaluating deformable CT-CBCT registration in adaptive lung radiotherapy.

BACKGROUND: Quality assurance of deformable image registration (DIR) is challenging because the ground truth is often unavailable. In addition, current approaches that rely on artificial transformations do not adequately resemble clinical scenarios encountered in adaptive radiotherapy. PURPOSE: We developed an atlas-based method to create a variety of patient-specific serial digital phantoms with CBCT-like image quality to assess the DIR performance for longitudinal CBCT imaging data in adaptive lung radiotherapy. METHODS: A library of deformations was created by extracting the longitudinal changes observed between a planning CT and weekly CBCT from an atlas of lung radiotherapy patients. The planning CT of an inquiry patient was first deformed by mapping the deformation pattern from a matched atlas patient, and subsequently appended with CBCT artifacts to imitate a weekly CBCT. Finally, a group of digital phantoms around an inquiry patient was produced to simulate a series of possible evolutions of tumor and adjacent normal structures. We validated the generated deformation vector fields (DVFs) to ensure numerically and physiologically realistic transformations. The proposed framework was applied to evaluate the performance of the DIR algorithm implemented in the commercial Eclipse treatment planning system in a retrospective study of eight inquiry patients. RESULTS: The generated DVFs were inverse consistent within less than 3 mm and did not exhibit unrealistic folding. The deformation patterns adequately mimicked the observed longitudinal anatomical changes of the matched atlas patients. Worse Eclipse DVF accuracy was observed in regions of low image contrast or artifacts. The structure volumes exhibiting a DVF error magnitude of equal or more than 2 mm ranged from 24.5% (spinal cord) to 69.2% (heart) and the maximum DVF error exceeded 5 mm for all structures except the spinal cord. Contour-based evaluations showed a high degree of alignment with dice similarity coefficients above 0.8 in all cases, which underestimated the overall DVF accuracy within the structures. CONCLUSIONS: It is feasible to create and augment digital phantoms based on a particular patient of interest using multiple series of deformation patterns from matched patients in an atlas. This can provide a semi-automated procedure to complement the quality assurance of CT-CBCT DIR and facilitate the clinical implementation of image-guided and adaptive radiotherapy that involve longitudinal CBCT imaging studies.

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.

Development of a Bioreactor-Coupled Flow-Cell Setup for 3D In Situ Nanotomography of Mg Alloy Biodegradation.

Functional materials feature hierarchical microstructures that define their unique set of properties. The prediction and tailoring of these require a multiscale knowledge of the mechanistic interaction of microstructure and property. An important material in this respect is biodegradable magnesium alloys used for implant applications. To correlate the relationship between the microstructure and the nonlinear degradation process, high-resolution in situ three-dimensional (3D) imaging experiments must be performed. For this purpose, a novel experimental flow cell is presented which allows for the in situ 3D-nano imaging of the biodegradation process of materials with nominal resolutions below 100 nm using nanofocused hard X-ray radiation from a synchrotron source. The flow cell setup can operate under adjustable physiological and hydrodynamic conditions. As a model material, the biodegradation of thin Mg-4Ag wires in simulated body fluid under physiological conditions and a flow rate of 1 mL/min is studied. The use of two full-field nanotomographic imaging techniques, namely transmission X-ray microscopy and near-field holotomography, is compared, revealing holotomography as the superior imaging technique for this purpose. Additionally, the importance of maintaining physiological conditions is highlighted by the preliminary results. Supporting measurements using electron microscopy to investigate the chemical composition of the samples after degradation are performed.

Effect of an aluminum foil-processed diet on internal human aluminum burden.

BACKGROUND AND PURPOSE: Aluminum can be released into food by aluminum-containing food-contact materials (Al-FCM) during preparation or storage. There is considerable concern that extra aluminum intake may have negative effects on public health, especially with regard to its high background exposure and neurotoxic properties of aluminum in high exposures. Human in-vivo data on the additional aluminum load from Al-FCM, however, are lacking. As such, the objective of this study was to explore whether the consumption of a diet highly exposed to such products leads to an increased systemic Al load in real-world conditions. MATERIALS AND METHODS: An exploratory, single-arm intervention study with a partially standardized diet was designed and carried out with 11participants. The same 10-day sequence of dishes was repeated three times. Participants were exposed to Al-FCM from Days 11 to 20, whereas control-phase meals were prepared without Al-FCM during the first and last 10-day periods. Spot urine samples were collected each morning and evening and analyzed for their aluminum concentration; appropriate contamination countermeasures were taken. PRINCIPAL RESULTS: Urinary aluminum excretion showed a strong dependency on the creatinine concentration in urine and required adjustment in further analyses. The creatinine-adjusted aluminum excretion during the exposure phase (median 1.98 µg/g creatinine) was higher than in both control phases (1.78 µg/g creatinine each). Two different mixed-effects regression models showed a significant effect in the exposure phase. Considering a discrete time effect, the creatinine-adjusted mean increase in the exposure phase was estimated to be 0.19 µg/L (95% CI: 0.07-0.31; p = 0.0017). MAJOR CONCLUSIONS: This study demonstrated a measurable but fully reversible additional Al burden in humans from subacute Al-FCM exposure under real-world conditions. The estimated increase from Al-FCM corresponds to 8% of the baseline concentration. These data enable a more robust assessment of human health risks by Al-FCM.

Multi-stage image registration based on list-mode proton radiographies for small animal proton irradiation: A simulation study.

We present a multi-stage and multi-resolution deformable image registration framework for image-guidance at a small animal proton irradiation platform. The framework is based on list-mode proton radiographies acquired at different angles, which are used to deform a 3D treatment planning CT relying on normalized mutual information (NMI) or root mean square error (RMSE) in the projection domain. We utilized a mouse X-ray micro-CT expressed in relative stopping power (RSP), and obtained Monte Carlo simulations of proton images in list-mode for three different treatment sites (brain, head and neck, lung). Rigid transformations and controlled artificial deformation were applied to mimic position misalignments, weight loss and breathing changes. Results were evaluated based on the residual RMSE of RSP in the image domain including the comparison of extracted local features, i.e. between the reference micro-CT and the one transformed taking into account the calculated deformation. The residual RMSE of the RSP showed that the accuracy of the registration framework is promising for compensating rigid (>97% accuracy) and non-rigid (∼95% accuracy) transformations with respect to a conventional 3D-3D registration. Results showed that the registration accuracy is degraded when considering the realistic detector performance and NMI as a metric, whereas the RMSE in projection domain is rather insensitive. This work demonstrates the pre-clinical feasibility of the registration framework on different treatment sites and its use for small animal imaging with a realistic detector. Further computational optimization of the framework is required to enable the use of this tool for online estimation of the deformation.

Convolutional neural network-based single-shot speckle tracking for x-ray phase-contrast imaging.

X-ray phase-contrast imaging offers enhanced sensitivity for weakly-attenuating materials, such as breast and brain tissue, but has yet to be widely implemented clinically due to high coherence requirements and expensive x-ray optics. Speckle-based phase contrast imaging has been proposed as an affordable and simple alternative; however, obtaining high-quality phase-contrast images requires accurate tracking of sample-induced speckle pattern modulations. This study introduced a convolutional neural network to accurately retrieve sub-pixel displacement fields from pairs of reference (i.e., without sample) and sample images for speckle tracking. Speckle patterns were generated utilizing an in-house wave-optical simulation tool. These images were then randomly deformed and attenuated to generate training and testing datasets. The performance of the model was evaluated and compared against conventional speckle tracking algorithms: zero-normalized cross-correlation and unified modulated pattern analysis. We demonstrate improved accuracy (1.7 times better than conventional speckle tracking), bias (2.6 times), and spatial resolution (2.3 times), as well as noise robustness, window size independence, and computational efficiency. In addition, the model was validated with a simulated geometric phantom. Thus, in this study, we propose a novel convolutional-neural-network-based speckle-tracking method with enhanced performance and robustness that offers improved alternative tracking while further expanding the potential applications of speckle-based phase contrast imaging.

Truly form-factor-free industrially scalable system integration for electronic textile architectures with multifunctional fiber devices.

An integrated textile electronic system is reported here, enabling a truly free form factor system via textile manufacturing integration of fiber-based electronic components. Intelligent and smart systems require freedom of form factor, unrestricted design, and unlimited scale. Initial attempts to develop conductive fibers and textile electronics failed to achieve reliable integration and performance required for industrial-scale manufacturing of technical textiles by standard weaving technologies. Here, we present a textile electronic system with functional one-dimensional devices, including fiber photodetectors (as an input device), fiber supercapacitors (as an energy storage device), fiber field-effect transistors (as an electronic driving device), and fiber quantum dot light-emitting diodes (as an output device). As a proof of concept applicable to smart homes, a textile electronic system composed of multiple functional fiber components is demonstrated, enabling luminance modulation and letter indication depending on sunlight intensity.

Phantom-based quantification of the spectral accuracy in dual-layer spectral CT for pediatric imaging at 100 kVp.

Background: To determine the spectral accuracy in detector-based dual-energy CT (DECT) at 100 kVp and wide (8 cm) collimation width for dose levels and object sizes relevant to pediatric imaging. Methods: A spectral CT phantom containing tissue-equivalent materials and iodine inserts of varying concentrations was scanned on the latest generation detector-based DECT system. Two 3D-printed extension rings were used to mimic varying pediatric patient sizes. Scans were performed at 100 and 120 kVp, 4 and 8 cm collimation widths, and progressively reduced radiation dose levels, down to 0.9 mGy CTDIvol. Virtual mono-energetic, iodine density, effective atomic number, and electron density results were quantified and compared to their expected values for all acquisition settings and phantom sizes. Results: DECT scans at 100 kVp provided highly accurate spectral results; however, a size dependence was observed for iodine quantification. For the medium phantom configuration (15 cm diameter), measurement errors in iodine density, effective atomic number, and electron density (ED) were below 0.3 mg/mL, 0.2 and 1.8 %EDwater, respectively. The average accuracy was slightly different from scans at 120 kVp; however, not statistically significant for all configurations. Collimation width had no substantial impact. Spectral results were accurate and reliable for radiation exposures down to 0.9 mGy CTDIvol. Conclusions: Detector-based DECT at 100 kVp can provide on-demand or retrospective spectral information with high accuracy even at extremely low doses, thereby making it an attractive solution for pediatric imaging.

Biodiversity-stability relationships strengthen over time in a long-term grassland experiment.

Numerous studies have demonstrated that biodiversity drives ecosystem functioning, yet how biodiversity loss alters ecosystems functioning and stability in the long-term lacks experimental evidence. We report temporal effects of species richness on community productivity, stability, species asynchrony, and complementarity, and how the relationships among them change over 17 years in a grassland biodiversity experiment. Productivity declined more rapidly in less diverse communities resulting in temporally strengthening positive effects of richness on productivity, complementarity, and stability. In later years asynchrony played a more important role in increasing community stability as the negative effect of richness on population stability diminished. Only during later years did species complementarity relate to species asynchrony. These results show that species complementarity and asynchrony can take more than a decade to develop strong stabilizing effects on ecosystem functioning in diverse plant communities. Thus, the mechanisms stabilizing ecosystem functioning change with community age.

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).

An endemic-epidemic beta model for time series of infectious disease proportions.

Time series of proportions of infected patients or positive specimens are frequently encountered in disease control and prevention. Since proportions are bounded and often asymmetrically distributed, conventional Gaussian time series models only apply to suitably transformed proportions. Here we borrow both from beta regression and from the well-established HHH model for infectious disease counts to propose an endemic-epidemic beta model for proportion time series. It accommodates the asymmetric shape and heteroskedasticity of proportion distributions and is consistent for complementary proportions. Coefficients can be interpreted in terms of odds ratios. A multivariate formulation with spatial power-law weights enables the joint estimation of model parameters from multiple regions. In our application to a flu activity index in the USA, we find that the endemic-epidemic beta model provides a better fit than a seasonal ARIMA model for the logit-transformed proportions. Furthermore, a multivariate approach can improve regional forecasts and reduce model complexity in comparison to univariate beta models stratified by region.

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.