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Curcumin is a biopharmaceutical classification system (BCS) class IV substance with many potential therapeutic effects. However, like many other BCS IV active pharmaceutical ingredients, complex formulations are needed to guarantee a sufficiently high bioavailability. A not-so-well-known delivery system is a suspoemulsion (SE). SEs are emulsions with a crystalline API in continuous or dispersed phases. This study aimed to produce curcumin-loaded o/w suspoemulsions with the particle in the oil phase for, e.g., encapsulation or triggered release effects. The particles need to be smaller than the emulsion droplet size to attain high encapsulation efficiencies (EE) in the oil phase. Sonofragmentation and bead milling were tested for their ability to produce these nanocrystals in different dispersion media. It was discovered that production in miglyol was the best fit for the needed application of the crystals in SEs. Around 85% (by volume) of the particles produced with bead milling were smaller than the droplet size of about 5 µm. In contrast, only 23% of the sonofragmentated particles were below the diameter of those droplets. This oily suspension was then used to successfully produce hydrogel-based o/w suspoemulsions. In the second part of this study, we investigated different methods for determining encapsulation efficiency, but none of the methods accurately and satisfactorily resolved the encapsulation efficiency. Finally, the suspoemulsions could not be macroscopically distinguished from one another and were physically stable. In summary, we showed that stable hydrogel-based curcumin-loaded o/w suspoemulsions could be produced.

As our societies and natural systems are becoming ever more interconnected, it is critical that sustainable management can adapt to new knowledge from both the ecological and the social domains, and act on it in a timely and effective manner. This need is amplifying in the Anthropocene as we are approaching the limit for humanity's safe operating space, leading to irreversible change to ecosystem function. This urgently requires increased attention and concern regarding the information feedbacks between the silos of science, policy and society. A web of policies is in place to protect the health of people and the planet, but to ensure that they are effective we need frameworks to make sense of real-world complexities and interlinkages between multiple factors. The Drivers-Pressures-State-Impacts-Response (DPSIR) framework was created for this purpose, however, its' implicit focus on 1) analytical and 2) procedural aspects must be made explicit, to enable coordination across silos and studies. Continued creation of new DPSIR derivatives may limit its impact, while more explicit coordination between these two aspects can improve the effectiveness of DPSIR while retaining its flexibility. We thus propose five elements to support sustainable policy development and implementation using DPSIR: 1) iteration; 2) risk, uncertainty and analytical bias; 3) flexible integration; 4) use of quantitative methods, and; 5) clear and standard definitions for DPSIR. We illustrate these elements in four cases: Three highlight missing feedbacks when DPSIR elements are not made explicit and a fourth case – on per-and-polyfluorinated alkyl substances (PFAS) – showing a potential roadmap to successful policy implementation using DPSIR.

Over the last decades, an expansion of the underground network has been taking place to cope with the increasing amount of moving people and freight. As a consequence, it is of vital importance to guarantee the full functionality of the tunnel network by means of preventive maintenance and the monitoring of the tunnel lining state over time. A new method has been developed for the real-time prediction of the utilization level in tunnel segmental linings based on input monitoring data. The new concept is founded on a framework, which encompasses an offline and an online stage. In the former, the generation of feedforward neural networks is accomplished by employing synthetically produced data. Finite element simulations of the lining structure are conducted to analyze the structural response under multiple loading conditions. The scenarios are generated by assuming ranges of variation of the model input parameters to account for the uncertainty due to the not fully determined in situ conditions. Input and target quantities are identified to better assess the structural utilization of the lining. The latter phase consists in the application of the methodological framework on input monitored data, which allows for a real-time prediction of the physical quantities deployed for the estimation of the lining utilization. The approach is validated on a full-scale test of segmental lining, where the predicted quantities are compared with the actual measurements. Finally, it is investigated the influence of artificial noise added to the training data on the overall prediction performances and the benefits along with the limits of the concept are set out.

Abstract Fisheries worldwide face uncertain futures as climate change manifests in environmental effects of hitherto unseen strengths. Developing climate-ready management strategies traditionally requires a good mechanistic understanding of stock response to climate change in order to build projection models for testing different exploitation levels. Unfortunately, model-based projections of fish stocks are severely limited by large uncertainties in the recruitment process, as the required stock-recruitment relationship is usually not well represented by data. An alternative is to shift focus to improving the decision-making process, as postulated by the decision-making under deep uncertainty (DMDU) framework. Robust Decision Making (RDM), a key DMDU concept, aims at identifying management decisions that are robust to a vast range of uncertain scenarios. Here we employ RDM to investigate the capability of North Sea cod to support a sustainable and economically viable fishery under future climate change. We projected the stock under 40,000 combinations of exploitation levels, emission scenarios and stock-recruitment parameterizations and found that model uncertainties and exploitation have similar importance for model outcomes. Our study revealed that no management strategy exists that is fully robust to the uncertainty in relation to model parameterization and future climate change. We instead propose a risk assessment that accounts for the trade-offs between stock conservation and profitability under deep uncertainty.

Abstract Marine fisheries are increasingly impacted by climate change, affecting species distribution and productivity, and necessitating urgent adaptation efforts. Climate vulnerability assessments (CVA), integrating expert knowledge, are vital for identifying species that could thrive or suffer under changing environmental conditions. This study presents a first CVA for the Western Baltic Sea's fish community, a crucial fishing area for Denmark and Germany. Characterized by a unique mix of marine, brackish, and freshwater species, this coastal ecosystem faces significant changes due to the combined effects of overfishing, eutrophication and climate change. Our CVA involved a qualitative expert scoring of 22 fish species, assessing their sensitivity and exposure to climate change. Our study revealed a dichotomy in climate change vulnerability within the fish community of the Western Baltic Sea because traditional fishing targets cod and herring as well as other species with complex life histories are considered to face increased risks, whereas invasive or better adaptable species might thrive under changing conditions. Our findings hence demonstrate the complex interplay between life-history traits and climate change vulnerability in marine fish communities. Eventually, our study provides critical knowledge for the urgent development of tailored adaptation efforts addressing existing but especially future effects of climate change on fish and fisheries in the Western Baltic Sea, to navigate this endangered fisheries systems into a sustainable future.

Curcumin is a biopharmaceutical classification system (BCS) class IV substance with many potential therapeutic effects. However, like many other BCS IV active pharmaceutical ingredients, complex formulations are needed to guarantee a sufficiently high bioavailability. A not-so-well-known delivery system is a suspoemulsion (SE). SEs are emulsions with a crystalline API in continuous or dispersed phases. This study aimed to produce curcumin-loaded o/w suspoemulsions with the particle in the oil phase for, e.g., encapsulation or triggered release effects. The particles need to be smaller than the emulsion droplet size to attain high encapsulation efficiencies (EE) in the oil phase. Sonofragmentation and bead milling were tested for their ability to produce these nanocrystals in different dispersion media. It was discovered that production in miglyol was the best fit for the needed application of the crystals in SEs. Around 85% (by volume) of the particles produced with bead milling were smaller than the droplet size of about 5 µm. In contrast, only 23% of the sonofragmentated particles were below the diameter of those droplets. This oily suspension was then used to successfully produce hydrogel-based o/w suspoemulsions. In the second part of this study, we investigated different methods for determining encapsulation efficiency, but none of the methods accurately and satisfactorily resolved the encapsulation efficiency. Finally, the suspoemulsions could not be macroscopically distinguished from one another and were physically stable. In summary, we showed that stable hydrogel-based curcumin-loaded o/w suspoemulsions could be produced. [ABSTRACT FROM AUTHOR]

IntroductionThe ABLE Exoskeleton has been tested to be safe and feasible for persons with spinal cord injury (SCI) to complete basic skills in clinical settings but has not been tested for use in home and community environments. A user-centered design process was employed to test the feasibility of the current ABLE Exoskeleton (designed for clinical use) for persons with SCI to perform the basic and advanced skills required for home and community environments, to gain crucial feedback for the development of a novel personal-use exoskeleton.MethodsIn this prospective pretest-posttest quasi-experimental study across two SCI centers (Germany, Spain), in-and outpatients with SCI were included into a 22-session training and assessment protocol, utilizing the ABLE Exoskeleton. Feasibility and usability measures [level of assistance (LoA) for basic and advanced skills, donning/doffing-time and LoA] were recorded together with safety outcomes, and participant and therapist satisfaction with the device.Results10 participants (44.4 ± 24 years), with SCI from C5 to T11, (American Spinal Injury Association Impairment Scale A–D) completed the study. In 209 sessions, six device-related adverse events (pain and skin lesions) were reported. Average total time for don and doff was 10:23 ± 3:30 min. Eight participants were able to complete don and doff with minimal assistance or less. Independence to carry out all skills in the device increased significantly for all participants (p

Abstract Background The prevalence of sacroiliac joint pain (SIJP) is estimated to be 10–30% in patients with chronic low back pain. Numerous conservative and surgical treatment modalities for SIJP have been described with limited evidence regarding long-term pain relief. Spinal cord stimulation (SCS) is a well-established technique to treat patients with chronic low back pain. However, the effect on patients with SIJP is not consistent. Therefore, peripheral nerve stimulation (PNS) for chronic SIJP was implemented in experimental trials. Clinical data on PNS for SIJP is still lacking. The authors present a case series and a protocol for a prospective, multicenter study to determine the effect of PNS in patients with chronic intractable SIJP. Method A multicenter, prospective randomized controlled trial was designed. Patients with chronic intractable SIJP will be recruited and randomized in a 4:3 ratio to either the peripheral nerve stimulation group or to the best medical treatment group. A total of 90 patients are planned to be enrolled (52 in the PNS group and 38 in the BMT group). Patients in the intervention group receive a percutaneous implantation of a unilateral or bilateral lead which is externalized for a trial phase for 3–14 days. After trial phase only patients with at least 50% reduction of pain receive an impulse generator for permanent stimulation. Regular visits for participants are planned on day 0, after 3 months (± 30 days), 6 months (± 30 days), and 12 months (± 60 days). The primary outcome measurements is the difference in Numeric Pain Rating Scale (NRS) between baseline and after 6 months. Secondary outcomes is improvement of pain associated disability (ODI) and improvement of health-related quality of life after 6 and 12 months. Discussion We have described the protocol for a prospective, multicenter, randomized trial evaluating the influence of PNS on patients with chronic sacroiliac joint syndrome. We believe that PNS on patients with chronic sacroiliac joint syndrome will show promising results regarding pain relief and quality of life in comparison to BMT after 12 months. The design of this trial promises high evidence in comparison to the data to date. Trial registration ClinicalTrials.gov, NCT05357300. Registered on April 26, 2022.

Background: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. Objective: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called “Microburst VNS” (μVNS). μVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. Methods: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of μVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. Results: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of μVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%–83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%–77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%–56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). Conclusion: Overall, μVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

Abstract Background Coronary heart diseases (CHDs) have experienced the largest increase worldwide as a cause of death, accounting for 16% of all deaths. In Saxony-Anhalt, a federal state in Germany, both CHD morbidity and acute myocardial infarction mortality rates are particularly high. Several risk factors associated with CHDs have been studied in Saxony-Anhalt, but sex differences in service use and medication have not been investigated. This study therefore aimed to investigate sex differences in the quality and quantity of cardiological care provided to adults with CHD. Methods This study used health claims data from 2018 to 2020 to analyse the utilisation of healthcare services and adherence to medication-related guideline recommendations in primary and specialist care. The sample included 133,661 individuals with CHD from a major statutory health insurance company (Germany). Results Almost all CHD patients (> 99%) received continuous primary care. Continuous cardiologist utilisation was lower for females than for males, with 15.0% and 22.2%, respectively, and sporadic utilisation showed greater differences, with 33.5% of females and 43.4% of males seeking sporadic cardiologist consultations. Additionally, 43.1% of the identified CHD patients participated in disease management programmes (DMPs). The study also examined the impact of DMP participation and cardiologist care on medication uptake and revealed that sex differences in medication uptake, except for statin use, were mitigated by these factors. Statins were prescribed to 42.9% of the CHD patients eligible for statin prescription in accordance with the QiSA indicator for statin prescription eligibility. However, there were significant sex differences in statin utilisation. Female CHD patients were less likely to use statins (35.2%) than male CHD patients were (50.1%). The difference in statin utilisation persisted after adjustment for DMP participation and cardiologist consultation. Conclusions This study highlights sex differences in the utilisation of cardiological healthcare services for patients with CHD in the Saxony-Anhalt cohort. These findings underscore the continuing need for interventions to reduce sex inequalities in accessing healthcare and providing health care for patients with CHD. Factors at the health care system, patient, and physician levels should be further investigated to eventually improve statin prescription in people with CHD, especially women.

Abstract Importance Contact tracing is the process of identifying people who have recently been in contact with someone diagnosed with an infectious disease. During an outbreak, data collected from contact tracing can inform interventions to reduce the spread of infectious diseases. Understanding factors associated with completion rates of contact tracing surveys can help design improved interview protocols for ongoing and future programs. Objective To identify factors associated with completion rates of COVID-19 contact tracing surveys in New York City (NYC) and evaluate the utility of a predictive model to improve completion rates, we analyze laboratory-confirmed and probable COVID-19 cases and their self-reported contacts in NYC from October 1st 2020 to May 10th 2021. Methods We analyzed 742,807 case investigation calls made during the study period. Using a log-binomial regression model, we examined the impact of age, time of day of phone call, and zip code-level demographic and socioeconomic factors on interview completion rates. We further developed a random forest model to predict the best phone call time and performed a counterfactual analysis to evaluate the change of completion rates if the predicative model were used. Results The percentage of contact tracing surveys that were completed was 79.4%, with substantial variations across ZIP code areas. Using a log-binomial regression model, we found that the age of index case (an individual who has tested positive through PCR or antigen testing and is thus subjected to a case investigation) had a significant effect on the completion of case investigation – compared with young adults (the reference group,24 years old 65 years old) were lower by 12.1% (95%CI: 11.1% – 13.3%), and the completion rate for youth group (age

With the fact that the main operational parameters of the construction process in mechanized tunneling are currently selected based on monitoring data and engineering experience without exploiting the advantages of computer methods, the focus of this work is to develop a simulation-based real-time assistant system to support the selection of operational parameters. The choice of an appropriate set of these parameters (i.e., the face support pressure, the grouting pressure, and the advance speed) during the operation of tunnel boring machines (TBM) is determined by evaluating different tunneling-induced soil-structure interactions such as the surface settlement, the associated risks on existing structures and the tunnel lining behavior. To evaluate soil-structure behavior, an advanced process-oriented numerical simulation model based on the finite cell method is utilized. To enable the real-time prediction capability of the simulation model for a practical application during the advancement of TBMs, surrogate models based on the Proper Orthogonal Decomposition and Radial Basis Functions (POD-RBF) are adopted. The proposed approach is demonstrated through several synthetic numerical examples inspired by the data of real tunnel projects. The developed methods are integrated into a user-friendly application called SMART to serve as a support platform for tunnel engineers at construction sites. Corresponding to each user adjustment of the input parameters, i.e., each TBM driving scenario, approximately two million outputs of soil-structure interactions are quickly predicted and visualized in seconds, which can provide the site engineers with a rough estimation of the impacts of the chosen scenario on structural responses of the tunnel and above ground structures.

Abstract Background Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associated TGase 2, and targeted covalent inhibitors appear to be particularly attractive as vector molecules. Such an inhibitor, equipped with a radionuclide suitable for noninvasive imaging, would be supportive for answering the general question on the possibility for functional characterization of tumor-associated TGase 2. For this purpose, the recently developed 18F-labeled N ε-acryloyllysine piperazide [ 18 F]7b, which is a potent and selective irreversible inhibitor of TGase 2, was subject to a detailed radiopharmacological characterization herein. Results An alternative radiosynthesis of [ 18 F]7b is presented, which demands less than 300 µg of the respective trimethylammonio precursor per synthesis and provides [ 18 F]7b in good radiochemical yields (17 ± 7%) and high (radio)chemical purities (≥ 99%). Ex vivo biodistribution studies in healthy mice at 5 and 60 min p.i. revealed no permanent enrichment of 18F-activity in tissues with the exception of the bone tissue. In vivo pretreatment with ketoconazole and in vitro murine liver microsome studies complemented by mass spectrometric analysis demonstrated that bone uptake originates from metabolically released [18F]fluoride. Further metabolic transformations of [ 18 F]7b include mono-hydroxylation and glucuronidation. Based on blood sampling data and liver microsome experiments, pharmacokinetic parameters such as plasma and intrinsic clearance were derived, which substantiated the apparently rapid distribution of [ 18 F]7b in and elimination from the organisms. A TGase 2-mediated uptake of [ 18 F]7b in different tumor cell lines could not be proven. Moreover, evaluation of [ 18 F]7b in melanoma tumor xenograft models based on A375-hS100A4 (TGase 2 +) and MeWo (TGase 2 −) cells by ex vivo biodistribution and PET imaging studies were not indicative for a specific targeting. Conclusion [ 18 F]7b is a valuable radiometric tool to study TGase 2 in vitro under various conditions. However, its suitability for targeting tumor-associated TGase 2 is strongly limited due its unfavorable pharmacokinetic properties as demonstrated in rodents. Consequently, from a radiochemical perspective [ 18 F]7b requires appropriate structural modifications to overcome these limitations.

This paper deals with double-pulse laser-induced breakdown spectroscopy (LIBS) underwater, which is a promising analytical method for elemental analysis in the deep sea up to a water depth of 6000 m. A double-pulse laser with a wavelength of 1064 nm is used, which provides a pulse energy of up to 266 mJ for each laser pulse (in single pulse mode), a pulse width of 5–7 ns and a pulse delay in the range of 0.5 to 20 µs. In the double-pulse LIBS method, the first laser pulse creates a cavity on the material surface, and then the second laser pulse forms the plasma in this cavity. It is expected that the plasma is affected by the cavity’s size and lifetime. For this reason, the influence of focus position, pulse energy and pulse delay on the cavity and plasma formation at shallow water depth has been investigated.

Modeling forms the basis for optimal control of complex technical processes in the context of industry 4.0 development and, hence, for high product quality as well as efficient production. For the mechanical joining process of self-pierce riveting with 11 input and 5 output variables, two modeling approaches based on (1) experimental data and (2) FEM computer simulation are outlined and performed. A physical modeling approach is ruled out due to the high problem dimensionality and complex nonlinear dynamic relationships between input and output variables. Alternatively, data-based approaches lead to Artificial Intelligence (AI) model designs. The experimental approach is cost- and resource-consuming; therefore, only a relatively small data set can be collected. Here, we present results from experimental trials that serve as representatives and are generalized by a description with high-dimensional parametric membership functions (fuzzification). The fuzzification procedure is also applied to the FEM computer simulation results. In principle, it can provide an arbitrarily large database. However, consequently, time- and computational effort increase considerably. Both data sets form the basis for parallel model building using the AI method of local fuzzy pattern models, which can be used to describe highly nonlinear input-output relationships by error-minimizing partitioning. Finally, the comparison of the results of the two modeling approaches is outlined. Finally, a coupled modeling strategy and future model adaptation are proposed. [ABSTRACT FROM AUTHOR]

Background Hypertension is the leading risk factor for cardiovascular disease worldwide. Patients with blood pressure (BP) response to dietary sodium reduction are referred to as “salt sensitive.” Salt sensitivity (SS) might be due to differences in sodium storage capacity and the erythrocyte SS examines this capacity of the red blood cells. This study aimed to test the effect of a self‐performed sodium reduced diet on BP in patients with essential hypertension and examine whether erythrocyte SS predicts SS. Methods and Results Seventy‐two patients with hypertension were included and randomized 2:1 to either sodium reduction or a control group for 4 weeks. Blood samples, 24‐hour BP measurement, and 24‐hour urine collection were performed before and after. The intervention group received advice on how to lower sodium intake. Urinary sodium excretion decreased 66 mmol (95% CI, −96 to −37 mmol) in the intervention group compared with the control group. Systolic 24‐hour BP decreased 9 mm Hg after low‐sodium diet compared with the control group (95% CI, −13 to −4 mm Hg). Similarly, the difference in reduction in diastolic BP between the groups was 5 mm Hg (95% CI, −8 to −1 mm Hg). We found no correlation between erythrocyte SS at baseline and decrease in 24‐hour BP, neither systolic nor diastolic (P=0.66 and P = 0.84). Conclusions Self‐performed sodium reduction was feasible and led to decrease in 24‐hour BP of 9/5 mm Hg compared with a control group. The erythrocyte SS did not correlate to the change in BP after lowering sodium intake. Registration URL: https://clinicaltrials.gov; Unique Identifier: NCT05165823.

BackgroundSodium-glucose-cotransporter 2 inhibitors (SGLT2is) have revolutionized the treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), reducing the risk of cardiovascular and renal end points by up to 40%. The underlying mechanisms are not fully understood. ObjectiveThe study aims to examine the effects of empagliflozin versus placebo on renal hemodynamics, sodium balance, vascular function, and markers of the innate immune system in patients with DM2, DM2 and CKD, and nondiabetic CKD. MethodsWe conducted 3 double-blind, crossover, randomized controlled trials, each with identical study protocols but different study populations. We included patients with DM2 and preserved kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m2), DM2 and CKD, and nondiabetic CKD (both with estimated glomerular filtration rate 20-60 mL/min/1.73 m2). Each participant was randomly assigned to 4 weeks of treatment with either 10 mg of empagliflozin once daily or a matching placebo. After a wash-out period of at least 2 weeks, participants were crossed over to the opposite treatment. End points were measured at the end of each treatment period. The primary end point was renal blood flow measured with 82Rubidium positron emission tomography–computed tomography (82Rb-PET/CT). Secondary end points include glomerular filtration rate measured with 99mTechnetium-diethylene-triamine-pentaacetate (99mTc-DTPA) clearance, vascular function assessed by forearm venous occlusion strain gauge plethysmography, measurements of the nitric oxide (NO) system, water and sodium excretion, body composition measurements, and markers of the complement immune system. ResultsRecruitment began in April 2021 and was completed in September 2022. Examinations were completed by December 2022. In total, 49 participants completed the project: 16 participants in the DM2 and preserved kidney function study, 17 participants in the DM2 and CKD study, and 16 participants in the nondiabetic CKD study. Data analysis is ongoing. Results are yet to be published. ConclusionsThis paper describes the rationale, design, and methods used in a project consisting of 3 double-blind, crossover, randomized controlled trials examining the effects of empagliflozin versus placebo in patients with DM2 with and without CKD and patients with nondiabetic CKD, respectively. Trial RegistrationEU Clinical Trials Register 2019-004303-12; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004303-12, EU Clinical Trials Register 2019-004447-80; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004447-80, EU Clinical Trials Register 2019-004467-50; https://www.clinicaltrialsregister.eu/ctr-search/search?query=and+2019-004467-50 International Registered Report Identifier (IRRID)DERR1-10.2196/56067

Introduction Upper limb (UL) dysfunctions are highly prevalent in people after breast cancer and have a great impact on performing activities in daily living. To improve care, a more comprehensive understanding of the development and persistence of UL dysfunctions is needed. Therefore, the UPLIFT-BC study will primarily examine the prognostic value of different factors at the body functions and structures, environmental and personal level of the International Classification of Functioning, Disability and Health (ICF) framework at 1-month post-surgery for persisting UL dysfunctions at 6 months after finishing cancer treatment.Methods and analysis A prospective longitudinal cohort study, running from 1-week pre-surgery to 6 months post-local cancer treatment, is performed in a cohort of 250 women diagnosed with primary breast cancer. Different potentially prognostic factors to UL dysfunctions, covering body functions and structures, environmental and personal factors of the ICF, are assessed pre-surgically and at different time points post-surgery. The primary aim is to investigate the prognostic value of these factors at 1-month post-surgery for subjective UL function (ie, QuickDASH) at 6 months post-cancer treatment, that is, 6 months post-radiotherapy or post-surgery (T3), depending on the individuals’ cancer treatment trajectory. In this, factors with relevant prognostic value pre-surgery are considered as well. Similar analyses are performed with an objective measure for UL function (ie, accelerometry) and a composite score of the combination of subjective and objective UL function. Second, in the subgroup of participants who receive radiotherapy, the prognostic value of the same factors is explored at 1-month post-radiotherapy and 6 months post-surgery. A forward stepwise selection strategy is used to obtain these multivariable prognostic models.Ethics and dissemination The study protocol was approved by the Ethics Committee of UZ/KU Leuven (reference number s66248). The results of this study will be published in peer-reviewed journals and will be presented at several research conferences.Trial registration number NCT05297591.

Introduction Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema.Methods and analysis A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient’s own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased.Ethics and dissemination The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations.Trial registration number NCT05064176

Raw observations (carrier-phase and code observations) from the Global Navigation Satellite System (GNSS) can now be accessed from Android mobile phones (Version 7.0 onwards). This paves the way for GNSS data to be utilized for low-cost precise positioning or in ionospheric or tropospheric applications. This paper presents results from data collection campaigns using the CAMALIOT mobile app. In the first campaign, 116.3 billion measurements from 11,828 mobile devices were collected from all continents. Although participation decreased during the second campaign, data are still being collected globally. In this contribution, we demonstrate the potential of volunteered geographic information (VGI) from mobile phones to fill data gaps in geodetic station networks that collect GNSS data, e.g. in Brazil, but also how the data can provide a denser set of observations than current networks in countries across Europe. We also show that mobile phones capable of dual-frequency reception, which is an emerging technology that can provide a richer source of GNSS data, are contributing in a substantial way. Finally, we present the results from a survey of participants to indicate that participation is diverse in terms of backgrounds and geography, where the dominant motivation for participation is to contribute to scientific research.

Abstract Background Understanding community transmission of SARS-CoV-2 variants of concern (VOCs) is critical for disease control in the post pandemic era. The Delta variant (B.1.617.2) emerged in late 2020 and became the dominant VOC globally in the summer of 2021. While the epidemiological features of the Delta variant have been extensively studied, how those characteristics shaped community transmission in urban settings remains poorly understood. Methods Using high-resolution contact tracing data and testing records, we analyze the transmission of SARS-CoV-2 during the Delta wave within New York City (NYC) from May 2021 to October 2021. We reconstruct transmission networks at the individual level and across 177 ZIP code areas, examine network structure and spatial spread patterns, and use statistical analysis to estimate the effects of factors associated with COVID-19 spread. Results We find considerable individual variations in reported contacts and secondary infections, consistent with the pre-Delta period. Compared with earlier waves, Delta-period has more frequent long-range transmission events across ZIP codes. Using socioeconomic, mobility and COVID-19 surveillance data at the ZIP code level, we find that a larger number of cumulative cases in a ZIP code area is associated with reduced within- and cross-ZIP code transmission and the number of visitors to each ZIP code is positively associated with the number of non-household infections identified through contact tracing and testing. Conclusions The Delta variant produced greater long-range spatial transmission across NYC ZIP code areas, likely caused by its increased transmissibility and elevated human mobility during the study period. Our findings highlight the potential role of population immunity in reducing transmission of VOCs. Quantifying variability of immunity is critical for identifying subpopulations susceptible to future VOCs. In addition, non-pharmaceutical interventions limiting human mobility likely reduced SARS-CoV-2 spread over successive pandemic waves and should be encouraged for reducing transmission of future VOCs.

RESUMO A partir da trajetória pessoal e intelectual de Raúl Prebisch - de um jovem neoclássico a serviço da oligarquia argentina a um crítico do desenvolvimento latino-americano - este artigo fornece uma análise detalhada e uma avaliação crítica de sua contribuição final ao capitalismo periférico. Em conclusão, pretende-se afirmar que sua busca por uma abordagem alternativa ao capitalismo latino-americano não conseguiu quebrar as fronteiras da economia política burguesa.

Abstract Objective Topoisomerase I (topo I) is a highly conserved enzyme which is known to reduce torsional stress at double-stranded (ds) DNA. Torsional stress induced by supercoiling of dsDNA requires either very long dsDNA existing in genomic DNA or circulation as presented in plasmid DNA. To enable DNA relaxation, topo I induce a transient single-strand break followed by stress-relieving rotation of the released DNA strand. Our group found by serendipity that the topo I inhibitor irinotecan is able to suppress murine systemic lupus erythematosus (SLE), an autoimmune disease which is characterized by the existence of pathogenic anti-dsDNA antibodies (abs). As a possible mechanism we demonstrated in the absence of immunosuppression an increased binding of anti-dsDNA abs to long genomic or circulated plasmid dsDNA modified with topo I. Results Here we show that this effect requires active site tyrosine of topo I which is known to facilitate DNA relaxation activity. Moreover, topo I enhanced anti-dsDNA abs binding to short linear oligonucleotides down to a size of 42 bp. Since oligonucleotides of such length are devoid of torsional stress and relaxation respectively, our results suggest a new and unknown function for the enzyme topo I.

Abstract Neuronal ceroid lipofuscinosis 6 (CLN6) is a rare and fatal autosomal recessive disease primarily affecting the nervous system in children. It is caused by a pathogenic mutation in the CLN6 gene for which no therapy is available. Employing an untargeted metabolomics approach, we analyzed the metabolic changes in CLN6 subjects to see if this system could potentially yield biomarkers for diagnosis and monitoring disease progression. Neuronal-like cells were derived from human fibroblast lines from CLN6-affected subjects (n = 3) and controls (wild type, n = 3). These were used to assess the potential of a neuronal-like cell-based metabolomics approach to identify CLN6 distinctive and specific biomarkers. The most impacted metabolic profile is associated with sphingolipids, glycerophospholipids metabolism, and calcium signaling. Over 2700 spectral features were screened, and fifteen metabolites were identified that differed significantly between both groups, including the sphingolipids C16 GlcCer, C24 GlcCer, C24:1 GlcCer and glycerophospholipids PG 40:6 and PG 40:7. Of note, these fifteen metabolites were downregulated in the CLN6 disease group. This study is the first to analyze the metabolome of neuronal-like cells with a pathogenic mutation in the CLN6 gene and to provide insights into their metabolomic alterations. This could allow for the development of novel biomarkers for monitoring CLN6 disease.

Cellulose microspheres have a wide range of applications due to their unique properties and versatility. Various preparation methods have been explored to tailor these microspheres for specific applications. Among these methods, the acetate method using cellulose acetate is well known. However, replacement of the acetate group through the butyrate group significantly extends the variety of morphological properties. In the present work, microspheres based on cellulose acetate butyrate are being developed with modified characteristics in terms of particle size, porosity, surface morphology and the inner structure of the microspheres. While the inner structure of cellulose acetate microspheres is predominantly porous, microspheres prepared from cellulose acetate butyrate are mainly filled or contain several smaller microspheres. Carbon materials from cellulose acetate butyrate microspheres exhibit a high specific surface area of 567 m2 g−1, even without further activation. Activation processes can further increase the specific surface area, accompanied by an adaptation of the pore structure. The prepared carbons show promising results in symmetrical supercapacitors with aqueous 6 M KOH electrolytes. Activated carbons derived from cellulose acetate butyrate microspheres demonstrate an energy density of 12 Wh kg−1 at a power density of 0.9 kW kg−1.

Objective To provide an overview of existing instruments measuring patient-perceived quality of nursing care and to develop and psychometrically evaluate a new multidimensional scale applicable to the German acute care sector.Design We conducted a scale development and validation study involving the following phases: (1) performing a structured literature search to identify existing scales, (2) generating an initial pool of items using the results of the literature search and expert interviews, (3) coding/categorising the item pool, (4) organising a peer researcher workshop to select relevant items, (5) drafting the survey questionnaire and conducting cognitive pretesting, (6) pilot testing the survey questionnaire, (7) administering the survey to a large sample of hospital patients and (8) conducting a psychometric evaluation comprising exploratory factor analysis using the survey results, followed by confirmatory factor analysis and reliability and validity assessment of the resulting draft scale.Survey participants 17 859 recently hospitalised patients discharged from non-intensive care in non-paediatric and non-psychiatric hospital units in Germany between May and October 2019.Results We identified 32 instruments comprising 635 items on nursing care quality. Alongside 135 indicators derived from expert interviews, these formed our initial item pool, which we coded into 15 categories. From this pool, 36 items were selected in the peer researcher workshop for pretesting and psychometric evaluation. Based on the results of our exploratory and confirmatory factor analyses, we propose a second-order scale to measure Patients’ Experience of Nursing Quality in Acute Hospitals (PENQuAH), including the two higher-order dimensions ‘patients’ perception of direct nursing care activities’ and ‘patients’ perception of guidance provided by nurses’. The results of various tests suggest the scale has sufficient goodness of fit, reliability and validity.Conclusions The PENQuAH scale is promising in terms of its psychometric properties, the plausibility and meaningfulness of its dimensions, and its ease of use.

Background: Even though Thailand has launched multiple migrant health policies, migrants still face various barriers in accessing health care. To some extent, these barriers may be reduced by health microinsurance. The M-FUND is a low-cost, not-for-profit health protection scheme for migrant workers in Thailand, created by Dreamlopments Social Enterprise and Foundation to support sustainable access to quality healthcare services for migrants. We aimed to investigate the impact of the M-FUND on utilization of health services. Methods: Over a period of three months, we conducted quantitative face-to-face interviews with 408 M-FUND members, and 452 age, sex and location matched non-member controls in Tak Province, Thailand. We compared utilization of health services between members and non-members using logistic regression controlling for a number of socio-demographic variables and variables related to migration such as years in Thailand, legal status, etc. Findings: M-FUND members were more likely to have utilized outpatient services (adjusted odds ratio: 1·74, 95 % confidence interval: 1·24–2·44), inpatient services (2·96, 1.11–7·92), and emergency care (1·89, 0·78–4·56), although the latter was not statistically significant. Members were more likely not to have purchased medicines over-the-counter (1·67, 1·22–2·27) than non-members. Members were also more likely to have utilized any additional specific service during a consultation (2·31, 1·49–3·58) including any type of imaging method (2·62, 1·29–5·29) and blood tests (1·64, 0·99–2·71). There were some differences between men and women, but most were not statistically significant. Interpretation: The M-FUND health microinsurance was positively associated with the utilization of all major types of health services among migrant workers and their dependents in Thailand. For migrants, particularly vulnerable migrant workers and their dependents, the M-FUND appears to be a good approach to reducing barriers to health care. This study of the impact of health microinsurance for migrants provides important information for policy and program planners in the field of migrant health. However, more research is needed on health microinsurance schemes for migrants in different settings and for other underserved communities as well as the sex-specific impact on health service utilization.

The creation of crop type maps from satellite data has proven challenging and is often impeded by a lack of accurate in situ data. Street-level imagery represents a new potential source of in situ data that may aid crop type mapping, but it requires automated algorithms to recognize the features of interest. This paper aims to demonstrate a method for crop type (i.e., maize, wheat and others) recognition from street-level imagery based on a convolutional neural network using a bottom-up approach. We trained the model with a highly accurate dataset of crowdsourced labelled street-level imagery using the Picture Pile application. The classification results achieved an AUC of 0.87 for wheat, 0.85 for maize and 0.73 for others. Given that wheat and maize are two of the most common food crops grown globally, combined with an ever-increasing amount of available street-level imagery, this approach could help address the need for improved global crop type monitoring. Challenges remain in addressing the noise aspect of street-level imagery (i.e., buildings, hedgerows, automobiles, etc.) and uncertainties due to differences in the time of day and location. Such an approach could also be applied to developing other in situ data sets from street-level imagery, e.g., for land use mapping or socioeconomic indicators.

Abstract Background Cambodia is undergoing a series of reforms with the objective of reaching universal health coverage. Information on the causes of inefficiencies in health facilities could pave the way for a better utilization of limited resources available to ensure the best possible health care for the population. Objectives The purpose of this study is to evaluate the technical efficiency of health centers and the determinants for inefficiencies. Methods This cross-sectional study used secondary data from a costing study on 43 health centers in six Cambodian provinces (2016–2017). Firstly, the Data Envelopment Analysis method with output-orientation was applied to calculate efficiency scores by selecting multiple input and output variables. Secondly, a tobit regression was performed to analyze potential explanatory variables that could influence the inefficiency of health centers. Results Study findings showed that 18 (43%) health centers were operating inefficiently with reference to the variable returns to scale efficiency frontier and had a mean pure technical efficiency score of 0.87. Overall, 22 (51%) revealed deficits in producing outputs at an optimal scale size. Distance to the next referral hospital, size and quality performance of the health centers were significantly correlated with health center inefficiencies. Conclusion Differences in efficiency exist among health centers in Cambodia. Inefficient health centers can improve their technical efficiency by increasing the utilization and quality of health services, even if it involves higher costs. Technical efficiency should be continuously monitored to observe changes in health center performance over time.

Abstract Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.

The purpose of this study was to explore the effects of the integration of machine learning into daily radiological diagnostics, using the example of the machine learning software mdbrain® (Mediaire GmbH, Germany) in the diagnostic MRI workflow of patients with multiple sclerosis at the University Medicine Greifswald. The data were assessed through expert interviews, a comparison of analysis times with and without the machine learning software, as well as a process analysis of MRI workflows. Our results indicate a reduction in the screen-reading workload, improved decision-making regarding contrast administration, an optimized workflow, reduced examination times, and facilitated report communication with colleagues and patients. Our results call for a broader and quantitative analysis.

Abstract Background Medical research is increasingly interdisciplinary. However, not all projects are successful and cooperation is not always sustained beyond the end of funding. This study empirically assesses the effect of control and trust on the sustainability of interdisciplinary medical research in terms of its performance and satisfaction. Methods The sample consists of 100 German publicly funded medical research collaborations with scientists from medicine, natural and social sciences (N = 364). We develop a system model to analyze the influence of trust and control on performance and satisfaction of the cooperation. Findings Both control and trust are important prerequisites for sustainability, control mainly for the performance of the collaboration, and trust primarily for its satisfaction. While the level of interdisciplinarity is a positive moderator for performance, expectation of continuity is a negative intervening variable for the effect of trust and control on satisfaction. Moreover, trust principally adds to the positive impact of control on sustainability. Conclusions Interdisciplinary medical research requires a participative but systematic management of the respective consortium.

Abstract Background Robotic lower-limb exoskeletons have the potential to provide additional clinical benefits for persons with spinal cord injury (SCI). However, high variability between protocols does not allow the comparison of study results on safety and feasibility between different exoskeletons. We therefore incorporated key aspects from previous studies into our study protocol and accordingly conducted a multicentre study investigating the safety, feasibility and usability of the ABLE Exoskeleton in clinical settings. Methods In this prospective pretest-posttest quasi-experimental study across two SCI centres in Germany and Spain, in- and outpatients with SCI were recruited into a 12-session training and assessment protocol, utilising the ABLE Exoskeleton. A follow-up visit after 4 weeks was included to assess after-training outcomes. Safety outcomes (device-related adverse events (AEs), number of drop-outs), feasibility and usability measures (level of assistance, donning/doffing-time) were recorded at every session together with changes in gait parameters and function. Patient-reported outcome measures including the rate of perceived exertion (RPE) and the psychosocial impact of the device were performed. Satisfaction with the device was evaluated in both participants and therapists. Results All 24 participants (45 ± 12 years), with mainly subacute SCI (

Abstract Understanding individual growth in commercially exploited fish populations is key to successful stock assessment and informed ecosystem‐based fisheries management. Traditionally, growth rates in marine fish are estimated using otolith age‐readings in combination with age‐length relationships from field samples, or tag‐recapture field experiments. However, for some species, otolith‐based approaches have been proven unreliable and tag‐recapture experiments suffer from high working effort and costs as well as low recapture rates. An important alternative approach for estimating fish growth is represented by bioenergetic modelling which in addition to pure growth estimation can provide valuable insights into the processes leading to temporal growth changes resulting from environmental and related behavioural changes. We here developed an individual‐based bioenergetic model for Western Baltic cod (Gadus morhua), traditionally a commercially important fish species that however collapsed recently and likely suffers from climate change effects. Western Baltic cod is an ideal case study for bioenergetic modelling because of recently gained in‐situ process knowledge on spatial distribution and feeding behaviour based on highly resolved data on stomachs and fish distribution. Additionally, physiological processes such as gastric evacuation, consumption, net‐conversion efficiency and metabolic rates have been well studied for cod in laboratory experiments. Our model reliably reproduced seasonal growth patterns observed in the field. Importantly, our bioenergetic modelling approach implementing depth‐use patterns and food intake allowed us to explain the potentially detrimental effect summer heat periods have on the growth of Western Baltic cod that likely will increasingly occur in the future. Hence, our model simulations highlighted a potential mechanism on how warming due to climate change affects the growth of a key species that may apply for similar environments elsewhere.

Abstract Background Low T3-(/T4-) syndrome, also known as non-thyroidal Illness Syndrome (NTIS) describes a decrease in free serum thyroid hormones without a concomitant increase in TSH, frequently observed in critically ill patients. However, whether NTIS is only a metabolic adaption to stress in critically ill or plays a crucial role as an independent risk factor for ICU mortality, remains unknown. Our study aimed to evaluate NTIS as an independent risk factor for increased ICU mortality. Methods All patients admitted to the interdisciplinary intensive care unit (ICU) at the University Hospital of Leipzig between 2008 and 2014 were retrospectively analyzed for thyroidal function. Baseline data, information on additional thyroid function tests, disease progression, hospital and ICU length of stay (LOS) and patient outcome were retrospectively analyzed from the hospitals digital information system. For statistical evaluation, univariate analysis, matched pairs analysis and multivariate logistic regression were conducted. Results One thousand, seven hundred ninety patients were enrolled in the study, of which 665 showed NTIS. Univariate analysis revealed a positive association of NTIS with ICU- and hospital-LOS, need for mechanical ventilation, incidence of sepsis, acute respiratory distress syndrome, acute liver failure and increased ICU mortality. Results of matched pair analysis confirmed these findings. In multivariate logistic regression, NTIS was associated with an increased ICU-LOS, increased duration of mechanical ventilation, acute kidney injury and liver failure, but showed no independent association with increased ICU-mortality. Conclusion Duration of mechanical ventilation as well as incidence of acute kidney injury, sepsis and acute liver failure were detected as independent predictors of mortality in patients with NTIS. NTIS itself was no independent predictor of increased ICU-mortality.

Abstract Background The first wave of the COVID-19 pandemic reached Germany between March and May 2020. In order to contain the spread of the virus and particularly protect vulnerable people, the government imposed a lockdown in March 2020. In addition to infection control measures, such as hygiene and social distancing requirements, a general ban on access to nursing homes for relatives and external service providers was issued. Methods To investigate the challenges and consequences of the enacted infection prevention measures and specific strategies for nursing homes in Germany, a multicentre cross-sectional qualitative interview study with nursing home managers and ward managers was conducted. Recorded audio data were transcribed, analysed using thematic framework analysis and reflected in peer debriefings. Results Seventy-eight interviews with 40 nursing home managers and 38 ward managers from 43 German nursing homes were conducted. At organisational level, the following six themes were identified: Appointing a multi-professional crisis task force, reorganizing the use of building and spatial structures, continuous adaption and implementation of hygiene plans, adapting staff deployment to dynamically changing demands, managing additional communicative demands and relying on and resorting to informal networks. To deal with the pandemic challenges also six themes can be described for the direct care level: Changed routines, taking over non-nursing tasks, increased medical responsibility, increased documentation demands, promoting social participation and increased communication demands. Also various negative consequences were identified (four themes): Psychological stress, negative emotional consequences, permanent feeling of responsibility and increased potential for conflicts. Positive emotional consequences were also reported (two themes): resources for the challenges and positive emotional consequences for home managers and staff. Conclusions The results of the described challenges, strategies and consequences allow recommendations as basis for possible approaches and successful adaptation processes in nursing home care in the future. In particular, there is a need for local networks to act in a coordinated way and a need for quantitative and qualitative support for nurses, such as staff support as well as advanced nursing practice, to cope with the challenges of the pandemic.

Abstract The intensive global plastic production, use and associated plastic pollution have caused concern for the potential risks to human health and the environment. This has led to the adoption of numerous regulatory initiatives aiming to combat plastic pollution. Despite the considerable regulatory activity in the field of plastic, it appears that there is still debate about the actual risks of plastic to humans and the environment. This raises the question of to what extent the current plastic regulation is evidence-based, a declared ambition in the European Union. Therefore, the aim of this study was to investigate to what extent key policy initiatives targeting plastic pollution are based on scientific evidence. Selection of initiatives was based on expert elicitation accounting for the opinions of persons involved in the development of the policy initiatives, and a thorough assessment of the historical development of plastic pollution regulation, with focus on their importance both with respect to regulation of plastics as well as their historical importance as drivers for societal actions on plastic pollution. We find that scientific evidence appears to be generally present in the scientific foundation for the policy initiatives analysed in this study. All the initiatives are supported by scientific articles and reports about among others plastic sources, ecological impacts of plastic production and consumption patterns. Marine litter monitoring data was found to contribute to the evidence base for 4 out of the 6 policy initiatives and thereby appears to be one of the central scientific drivers behind the societal actions on plastic pollution. Other scientific tools applied when shaping the policy initiatives include risk assessment, impact assessment and life cycle assessment. Despite the prevalent consideration and application of scientific evidence, there seems to be a broad recognition in the preparatory work of the initiatives that there is still a lot of uncertainty related to determining the harm of plastic pollution. In these cases, taking precautionary actions seems however to be justified, recalling not least the precautionary principle. As the issue of plastic pollution is complex and still subject to uncertainty, it seems important both that policy initiatives allow for flexibility and continuing adjustment to the on-going knowledge generation and that the scientific community provides the needed research to continue the science-informed policy development.

The global spatial extent of croplands is a crucial input to global and regional agricultural monitoring and modeling systems. Although many new remotely-sensed products are now appearing due to recent advances in the spatial and temporal resolution of satellite sensors, there are still issues with these products that are related to the definition of cropland used and the accuracies of these maps, particularly when examined spatially. To address the needs of the agricultural monitoring community, here we have created a hybrid map of global cropland extent at a 500 m resolution by fusing two of the latest high resolution remotely-sensed cropland products: the European Space Agency’s WorldCereal and the cropland layer from the University of Maryland. We aggregated the two products to a common resolution of 500 m to produce percentage cropland and compared them spatially, calculating two kinds of disagreement: density disagreement, where the two maps differ by more than 80%, and absence-presence of cropland disagreement, where one map indicates the presence of cropland while the other does not. Based on these disagreements, we selected continuous areas of disagreement, referred to in the paper as hotspots of disagreement, for manual correction by experts using the Geo-Wiki land cover application. The hybrid map was then validated using a stratified random sample based on the disagreement layer, where the sample was visually interpreted by a different set of experts using Geo-Wiki. The results show that the hybrid product improves upon the overall accuracy statistics in the areas where the underlying cropland layer from the University of Maryland was improved with the WorldCereal product, but more importantly, it represents an improved spatially explicit cropland mask for early warning and food security assessment purposes.

ABC triblock terpolymers are promising soft templates for organic/inorganic hybrids because of their ability to form nanostructures with complex shapes, multiple compartments, and precisely localized chemistry. Exemplified on multicompartment nanofibers (MCNFs) of triblock terpolymers, it is demonstrated that microdomains can be selectively loaded, thereby giving access to nanoscale multimetallic hybrid materials. MCNFs with micrometer length, homogenous diameter (90 nm), and a helix‐on‐cylinder morphology are formed from polystyrene‐block‐polybutadiene‐block‐poly(tert‐butyl methacrylate) (PS‐b‐PB‐b‐PT). After postmodification (cross‐linking/hydrolysis), selective loading with FeCl3, PdCl2, H2PtCl6, AgNO3, CuCl2, or ZnCl2 leads to a variety of hybrid MCNFs analyzed by transmission electron microscopy, scanning transmission electron microscopy, electron tomography, energy‐dispersive X‐ray spectroscopy, and atomic force microscopy. Mild sulfonation of the PS shell to polystyrene sulfonate renders the MNCFs water‐dispersible and allows the formation of mixed‐bimetallic Pt/Pd/Pt@MCNFs and trimetallic Pt/Pd/Ag@MCNFs. It is demonstrated that the order of loading is key to successfully create multimetallic nanostructures. These and other structures can become useful for energy applications as well as in photo‐ and electrocatalysis.

Abstract Background Despite the current undersupply of cochlear implants (CIs) with simultaneously increasing indication, CI implantation numbers in Germany still are at a relatively low level. Methods As there are hardly any solid forecasts available in the literature, we develop a System Dynamics model that forecasts the number and costs of CI implantations in adults for 40 years from a social health insurance (SHI) perspective. Results CI demand will grow marginally by demographic changes causing average annual costs of about 538 million €. Medical-technical progress with following relaxed indication criteria and patients’ increasing willingness for implantation will increase implantation numbers significantly with average annual costs of 765 million €. Conclusion CI demand by adults will increase in the future, thus will the costs for CI supply. Continuous research and development in CI technology and supply is crucial to ensure long-term financing of the growing CI demand through cost-reducing innovations.

Abstract Background Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system that often leads to premature incapacity for work. Therefore, the MSnetWork project implements a new form of care and pursues the goal of maintaining or even improving the state of health of MS patients and having a positive influence on their ability to work as well as their participation in social life. A network of neurologists, occupational health and rehabilitation physicians, psychologists, and social insurance suppliers provide patients with targeted services that have not previously been part of standard care. According to the patient’s needs treatment options will be identified and initiated. Methods The MSnetWork study is designed as a multicenter randomized controlled trial, with two parallel groups (randomization at the patient level with 1:1 allocation ratio, planned N = 950, duration of study participation 24 months). After 12 months, the patients in the control group will also receive the interventions. The primary outcome is the number of sick leave days. Secondary outcomes are health-related quality of life, physical, affective and cognitive status, fatigue, costs of incapacity to work, treatment costs, out-of-pocket costs, self-efficacy, and patient satisfaction with therapy. Intervention effects are analyzed by a parallel-group comparison between the intervention and the control group. Furthermore, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group, before and after receiving the intervention in MSnetWork, will be performed. Discussion Due to the multiple approaches to patient-centered, multidisciplinary MS care, MSnetWork can be considered a complex intervention. The study design and linkage of comprehensive, patient-specific primary and secondary data in an outpatient setting enable the evaluation of this complex intervention, both on a qualitative and quantitative level. The basic assumption is a positive effect on the prevention or reduction of incapacity for work as well as on the patients’ quality of life. If the project proves to be a success, MSnetWork could be adapted for the treatment of other chronic diseases with an impact on the ability to work and quality of life. Trial registration The trial MSnetWork has been retrospectively registered in the German Clinical Trials Register (DRKS) since 08.07.2022 with the ID DRKS00025451 .

In this study, the authors analyse contact tracing records for ~650,000 suspected or confirmed COVID-19 cases in New York City during the second epidemic wave. They reconstruct transmission networks and find that vaccination and zone-based control policies likely contributed to control of the epidemic.

Measurement(s) land cover Technology Type(s) visual interpretation of satellite imagery Sample Characteristic - Location Indonesia

Abstract Background Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN. Methods This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition. Discussion The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER. Trial registration The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 .

Abstract Background Person-centred care (PCC) has been suggested as the preferred model of dementia care in all settings. The EPCentCare study showed that an adapted PCC approach was difficult to implement and had no effect on prescription of antipsychotics in nursing home residents in Germany. This paper reports the qualitative process evaluation to identify facilitators and barriers of the implementation of PCC in German nursing homes from the perspective of participating practice development champions. Methods Five individual and 14 group interviews were conducted with 66 participants (staff and managers) from 18 nursing homes. The analysis was based on inductive coding to identify factors influencing the PCC implementation process. Identified factors were systematised and structured by mapping them to the four constructs (coherence, cognitive participation, collective action, reflexive monitoring) of the Normalization Process Theory (NPT) as a framework that explains implementation processes. Results Facilitating implementation factors included among others broadening of the care perspective (coherence), tolerance development within the care team regarding challenging behaviour (cognitive participation), testing new approaches to solutions as a multi-professional team (collective action), and perception of effects of PCC measures (reflexive monitoring). Among the facilitating factors reported in all the NPT constructs, thus affecting the entire implementation process, were the involvement of relatives, multi-professional teamwork and effective collaboration with physicians. Barriers implied uncertainties about the implementation and expectation of a higher workload (coherence), concerns about the feasibility of PCC implementation in terms of human resources (cognitive participation), lack of a person-centred attitude by colleagues or the institution (collective action), and doubts about the effects of PCC (reflexive monitoring). Barriers influencing the entire implementation process comprised insufficient time resources, lack of support, lack of involvement of the multi-professional team, and difficulties regarding communication with the attending physicians. Conclusions The findings provide a comprehensive and detailed overview of facilitators and barriers structured along the implementation process. Thus, our findings may assist both researchers and clinicians to develop and reflect more efficiently on PCC implementation processes in nursing homes. Trial registration ClinicalTrials.gov identifier: NCT02295462 ; November 20, 2014.

Abstract In 2009, the Democratic Republic of Congo (DRC) started its journey towards achieving Universal Health Coverage (UHC). This study examines the evolution of financial risk protection and health outcomes indicators in the context of the commitment of DRC to UHC. To measure the effects of such a commitment on financial risk protection and health outcomes indicators, we analyse whether changes have occurred over the last two decades and, if applicable, when these changes happened. Using five variables as indicators for the measurement of the financial risk protection component, there as well retained three indicators to measure health outcomes. To identify time-related effects, we applied the parametric approach of breakpoint regression to detect whether the UHC journey has brought change and when exactly the change has occurred. Although there is a slight improvement in the financial risk protection indicators, we found that the adopted strategies have fostered access to healthcare for the wealthiest quantile of the population while neglecting the majority of the poorest. The government did not thrive persistently over the past decade to meet its commitment to allocate adequate funds to health expenditures. In addition, the support from donors appears to be unstable, unpredictable and unsustainable. We found a slight improvement in health outcomes attributable to direct investment in building health centres by the private sector and international organizations. Overall, our findings reveal that the prevention of catastrophic health expenditure is still not sufficiently prioritized by the country, and mostly for the majority of the poorest. Therefore, our work suggests that DRC’s UHC journey has slightly contributed to improve the financial risk protection and health outcomes indicators but much effort should be undertaken.