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Abstract Background Patient adherence is a key factor in achieving orthodontic success. While in recent years there have been changes in orthodontic healthcare, no recent comprehensive reviews regarding adherence in orthodontics are available. Therefore, the aim of this planned scoping review is to systematically map the available literature regarding patient adherence in orthodontics to identify factors associated with patient adherence and to investigate if there are knowledge gaps in the available literature. Methods/design This protocol was drafted according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) statement and the PRISMA extension for Scoping Reviews (PRISMA-ScR). For the methods Arksey and O’Malley’s framework and the Reviewer’s Manual of the Joanna Briggs Institute for conducting scoping reviews were consulted. The inclusion criteria for this scoping review are studies of all designs assessing any form of adherence in orthodontics, published in English from 2006 onwards. The exclusion criteria are studies investigating adherence in the following patients: those with an intellectual or physical disability that could affect their ability to coincide with their therapist’s recommendations and advice, those with oral cleft and craniofacial conditions, and those solely treated for obstructive sleep apnoea. Case reports and studies published in non peer reviewed journals will also be excluded. The following electronic databases will be searched: Embase, PubMed, and Web of Science Core Collection. The following key terms will be used in the search strategies: ‘treatment adherence and compliance’, and ‘orthodontics’. Multiple reviewers will independently screen the results and perform the data charting process. A narrative description will be provided for the analysis of the included studies. The results will be categorized into multiple topics based on recommendations by previous studies into patient adherence. Identified knowledge gaps will be reported and recommendations for future research will be suggested. Discussion No systematic review has previously assessed this exact topic. Because of the broad-spectrum research questions and the expected widely scattered literature a scoping review approach was chosen over a systematic review approach. The Academic Centre for Dentistry Amsterdam (ACTA) has been conducting research in patient adherence in orthodontics up to 2006 and therefore only studies published from 2006 onwards will be researched in this review. Identifying knowledge gaps and summarizing and disseminating research findings on this topic is important for every dental professional performing orthodontic treatment. This protocol is registered in the Open Science Framework: https://osf.io/ec6qd

Among the various repositories of soil spectral data, the Brazilian Soil Spectral Library (BSSL, https://bibliotecaespectral.wixsite.com/english), created and maintained by the GeoCiS research group, is representative of the pedodiversity of the region, since it combines soil spectra from agricultural and environmental research. The BSSL database contains 16,084 observations with soil-harmonized surface layer physicochemical and spectral data in the visible, near-infrared, short-wave infrared (Vis-NIR-SWIR, 350–2,500 nm) and mid-infrared (MIR, 4,000–600 cm-¹) ranges from all 26 Brazilian states and the Federal District. The idea of creating the BSSL was born in 1995, completed in 2019 and opened to users in 2023. This database is currently available online at https://zenodo.org/records/8361419. During oppening process, data filtering was performed to ensure reliable and valuable information provided to society. Then consistency and quality assessments were executed using Pearson's correlation and the Cubist algorithm in the R environment. Modeling analysis revealed the robust predictive power of the spectral database, facilitating the modeling of key soil attributes. An open-access BSSL will help researchers validate their results by comparing measured data with predicted data, enabling the development of new models or the improvement of existing ones. The BSSL is a globally significant spectral library due to its broad coverage and representation of different tropical soil classes. Soil spectral data can help governments and corporations by providing information to decision-makers regarding the conservation or exploitation of natural resources to monitor soil health.

Abstract Background Automated dispensing systems (ADSs) for radiopharmaceuticals have been developed to reduce the radiation exposure of personnel, to improve the accuracy of the dispensed dose and to limit the microbiological contamination. However, before implementing such systems, validation according to various applicable guidelines is necessary to ensure safety and quality. Here we present the selection, validation and implementation of the PT459R2 from manufacturer Lynax s.r.o. as a guidance protocol for validation according to GMP and GRPP guidelines. Validation included linearity accuracy and precision of the internal scintillation detector for different isotopes and microbiological validation for aseptic procedures. Results The ADS can dispense accurate doses in the following linear range: 1000–10,000 MBq for lutetium-177, 20–74 MBq for zirconium-89, 100–1000 MBq for gallium-68 and 100–2000 MBq for fluorine-18. The maximum bias is 2.35% and the maximum coefficient of variation is 3.03% which meets the acceptance criteria of

Introduction “Cluster suicides,” also known as “suicide clusters,” refer to a phenomenon in which a series of suicides occur within a specific community, group, or geographic area within a relatively short period of time. These suicides often appear to be interconnected, either through imitation or contagion, and may involve individuals who have some form of social or emotional connection to each other. Objectives - Understanding the definition and characteristics of cluster suicides. - Analyzing common risk factors and triggers in cluster suicide cases. - Evaluating prevention and support strategies for affected individuals and communities. Methods We conduct an analysis of this concept based on a sample of suicides that occurred in a Spanish region over an 8-year period (2015-2022). We will Analyzethe following aspects: - Definition and characteristics of cluster suicides. - Risk factors contributing to the occurrence of cluster suicides. - Examples of real cases or case studies illustrating this phenomenon. - The role of imitation and contagion in cluster suicides. - Prevention and support strategies, including education on warning signs and access to mental health services. - The impact of media coverage and how it can amplify the contagion effect. - Measures to reduce access to lethal means of suicide. Results We will discuss about the results found: - Definition and characteristics of cluster suicides. - Risk factors contributing to the occurrence of cluster suicides. - Examples of real cases or case studies illustrating this phenomenon. - The role of imitation and contagion in cluster suicides. - Prevention and support strategies, including education on warning signs and access to mental health services. - The impact of media coverage and how it can amplify the contagion effect. - Measures to reduce access to lethal means of suicide. Conclusions The main conclusions of our presentation are : - The importance of recognizing cluster suicides as a real and concerning phenomenon. - The need to address specific risk factors and triggers in affected communities. - The effectiveness of prevention and support strategies in reducing cluster suicide cases. - The importance of promoting media responsibility in suicide coverage. BIBLIOGRAPHY 1. Cluster Suicides: A Critical Review and Theoretical Framework” (2019) - Este estudio proporciona una revisión crítica de la literatura sobre cluster suicides y presenta un marco teórico para comprender mejor este fenómeno 2. “Clusters of Suicides and Suicide Attempts: Identification, Prediction, and Prevention” (2016) - Aunque este estudio no se centra exclusivamente en España, ofrece información sobre la identificación y prevención de clusters de suicidio que puede ser relevante. 3. “Epidemiology of Suicide in Spain, 1981–2008” (2012) - Proporciona una visión general de la epidemiología del suicidio en España, lo que podría ayudar a contextualizar los estudios específicos sobre clusters. Disclosure of Interest None Declared

Surface-level ozone (O3) is a secondary air pollutant that has adverse effects on human health. In the troposphere, O3 is produced in complex cycles of photochemical reactions involving nitrogen oxides (NOx) and volatile organic compounds (VOCs). Determining if O3 levels will be decreased by lowering NOx emissions (“NOx-sensitive”), VOC emissions (“VOC-sensitive”), or both (“the transition zone”) can be done by using the formaldehyde (HCHO; a VOC species) to nitrogen dioxide (NO2; a component of NOx) concentration ratio (HCHO/NO2; “FNR”). Generally, lower FNR values indicate VOC sensitivity, while higher values indicate NOx sensitivity. Despite being a highly populated region with coastal O3 air quality issues, the Lake Michigan region in the United States, including the Chicago, Illinois, metropolitan area (CMA), remains relatively understudied, especially from the satellite perspective. In this work, we present the first study that utilizes TROPOspheric Monitoring Instrument (TROPOMI) satellite data over the Lake Michigan region from 2019–2021 to assess changes in O3 precursor levels and the inferred O3 chemistry sensitivity between (1) O3 season days and CMA O3 exceedance days and (2) weekdays and weekends. Higher NO2 vertical column densities (VCDs), HCHO VCDs, and FNR values are seen throughout the study domain on exceedance days, indicating generally more NOx-sensitive O3 chemistry. The largest change occurs in the areal extent of the transition zone, which decreases by 40 % during exceedance days. Major urban cores in the domain (e.g., Chicago, Illinois; Gary, Indiana; and Milwaukee, Wisconsin) remain VOC-sensitive on exceedance days as the higher NO2 VCDs in these areas counterbalance the regionally higher HCHO VCDs. Utilizing 10 m wind analysis data, we show that the lake breeze circulation is stronger on exceedance days. The strengthening of the lake breeze causes stronger convergence of the wind field along the southwestern Lake Michigan coastline, which can concentrate NO2 emissions originating in this area. This finding provides a possible explanation for the higher TROPOMI NO2 VCDs over the urban core of Chicago on exceedance days. Investigation of 2 m air temperature analysis data reveals that temperatures are higher on exceedance days, which explains the stronger lake breeze circulation and provides a possible cause for the higher TROPOMI HCHO VCDs over the entire region (due to increased temperature-dependent biogenic VOC emissions). Comparing weekdays and weekends, higher FNR values throughout much of the region indicate increasingly NOx-sensitive O3 chemistry on weekends. These changes are driven by lower NO2 VCDs in urban areas, particularly in Chicago, and higher HCHO VCDs in the southern part of the domain on weekends. Overall, our analyses suggest that VOC emissions controls in major urban areas and NOx emissions controls throughout the entire domain are necessary to decrease O3 levels in the Lake Michigan region.

Abstract Background Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with ‘best supportive care’. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. Methods A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the ‘Trial within cohorts’ (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with ‘best supportive care’ and ‘best supportive care’ only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. Discussion The PANCOSAR trial studies the added value of SBRT as compared to ‘best supportive care’ in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. Trial registration Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Abstract Background It is challenging to reliably assess the language comprehension of children with severe motor and speech impairments using traditional assessment tools. The Computer Based instrument for Low motor Language Testing (C-BiLLT) aims to reduce barriers to evidence-based assessment for this population by allowing children to access the test using non-traditional methods such as eye gaze so they can independently respond to test items. The purpose of this study is to develop a contextualized understanding of the factors that influenced clinicians’ implementation of the C-BILLT in practice in the Netherlands and Norway. Materials and methods A qualitative approach including semi-structured individual interviews with 15 clinicians (speech-language pathologists, neuropsychologists, and one teacher, counsellor, and vision specialist) was used. Data analysis was conducted in two rounds. First, a deductive approach including a codebook was used to code data within the COM-B components describing clinicians’ capability, opportunity, and motivation for behaviour change. Then, an abductive approach applying thematic analysis was used to identify meaningful patterns within the COM-B components. Results Several meaningful barriers and facilitators were identified across the data. Clinicians used the C-BiLLT with two distinct groups of clients: (1) the population it was originally developed for, and (2) clients that could have also been assessed using a traditional language test. Clinicians working with the first group experienced more, and more complex barriers across all COM-B components, to successful C-BiLLT use than the latter. Conclusion This study provides timely insights into the capability, opportunity, and motivation factors important for creating and sustaining assessment behaviour change in clinicians who used or attempted to use the C-BiLLT. Potential tailored intervention strategies aimed at improving implementation of novel assessment tools are discussed and may be helpful for others working to improve service delivery for children with complex needs.

Abstract A grand challenge in microbial ecology is disentangling the traits of individual populations within complex communities. Various cultivation-independent approaches have been used to infer traits based on the presence of marker genes. However, marker genes are not linked to traits with complete fidelity, nor do they capture important attributes, such as the timing of gene expression or coordination among traits. To address this, we present an approach for assessing the trait landscape of microbial communities by statistically defining a trait attribute as a shared transcriptional pattern across multiple organisms. Leveraging the KEGG pathway database as a trait library and the Enhanced Biological Phosphorus Removal (EBPR) model microbial ecosystem, we demonstrate that a majority (65%) of traits present in 10 or more genomes have niche-differentiating expression attributes. For example, while many genomes containing high-affinity phosphorus transporter pstABCS display a canonical attribute (e.g. up-regulation under phosphorus starvation), we identified another attribute shared by many genomes where transcription was highest under high phosphorus conditions. Taken together, we provide a novel framework for unravelling the functional dynamics of uncultivated microorganisms by assigning trait-attributes through genome-resolved time-series metatranscriptomics.

Abstract Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.

Current screens to assess tumour drug resistance require a large amount of material, normally not available from patients. Here the authors report CombiSeq, a scalable microfluidic workflow to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout.

Abstract Background Discussing patients with cancer in a multidisciplinary team meeting (MDTM) is customary in cancer care worldwide and requires a significant investment in terms of funding and time. Efficient collaboration and communication between healthcare providers in all the specialisms involved is therefore crucial. However, evidence-based criteria that can guarantee high-quality functioning on the part of MDTMs are lacking. In this systematic review, we examine the factors influencing the MDTMs’ efficiency, functioning and quality, and offer recommendations for improvement. Methods Relevant studies were identified by searching Medline, EMBASE, and PsycINFO databases (01–01-1990 to 09–11-2021), using different descriptions of ‘MDTM’ and ‘neoplasm’ as search terms. Inclusion criteria were: quality of MDTM, functioning of MDTM, framework and execution of MDTM, decision-making process, education, patient advocacy, patient involvement and evaluation tools. Full text assessment was performed by two individual authors and checked by a third author. Results Seventy-four articles met the inclusion criteria and five themes were identified: 1) MDTM characteristics and logistics, 2) team culture, 3) decision making, 4) education, and 5) evaluation and data collection. The quality of MDTMs improves when the meeting is scheduled, structured, prepared and attended by all core members, guided by a qualified chairperson and supported by an administrator. An appropriate amount of time per case needs to be established and streamlining of cases (i.e. discussing a predefined selection of cases rather than discussing every case) might be a way to achieve this. Patient centeredness contributes to correct diagnosis and decision making. While physicians are cautious about patients participating in their own MDTM, the majority of patients report feeling better informed without experiencing increased anxiety. Attendance at MDTMs results in closer working relationships between physicians and provides some medico-legal protection. To ensure well-functioning MDTMs in the future, junior physicians should play a prominent role in the decision-making process. Several evaluation tools have been developed to assess the functioning of MDTMs. Conclusions MDTMs would benefit from a more structured meeting, attendance of core members and especially the attending physician, streamlining of cases and structured evaluation. Patient centeredness, personal competences of MDTM participants and education are not given sufficient attention.

Abstract Background Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine. Methods A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea. Results A total of 746 patients were included. Median age was 64 years (interquartile range 57–71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54–7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85–5.87) were the only risk factors for severe diarrhea. Conclusions Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.

Abstract Background Physiologically based pharmacokinetic (PBPK) models combine drug-specific information with prior knowledge on the physiology and biology at the organism level. Whole-body PBPK models contain an explicit representation of the organs and tissue and are a tool to predict pharmacokinetic behavior of drugs. The aim of this study was to develop a PBPK model to describe organ distribution of 68Ga-DOTATATE in a population of patients without detectable neuroendocrine tumors (NETs). Methods Clinical 68Ga-DOTATATE PET/CT data from 41 patients without any detectable somatostatin receptor (SSTR) overexpressing tumors were included. Scans were performed at 45 min (range 30–60 min) after intravenous bolus injection of 68Ga-DOTATATE. Organ (spleen, liver, thyroid) and blood activity levels were derived from PET scans, and corresponding DOTATATE concentrations were calculated. A whole-body PBPK model was developed, including an internalization reaction, receptor recycling, enzymatic reaction for intracellular degradation and renal clearance. SSTR2 expression was added for several organs. Input parameters were fixed or estimated using a built-in Monte Carlo algorithm for parameter identification. Results 68Ga-DOTATATE was administered with a median peptide amount of 12.3 µg (range 8.05–16.9 µg) labeled with 92.7 MBq (range 43.4–129.9 MBq). SSTR2 amounts for spleen, liver and thyroid were estimated at 4.40, 7.80 and 0.0108 nmol, respectively. Variability in observed organ concentrations was best described by variability in SSTR2 expression and differences in administered peptide amounts. Conclusions To conclude, biodistribution of 68Ga-DOTATATE was described with a whole-body PBPK model, where tissue distribution was mainly determined by variability in SSTR2 organ expression and differences in administered peptide amounts.

Normative studies are needed to obtain norms for comparing individuals with the reference population on relevant clinical or educational measures. Norms can be obtained in an efficient way by regressing the test score on relevant predictors, such as age and sex. When several measures are normed with the same sample, a multivariate regression-based approach must be adopted for at least two reasons: (1) to take into account the correlations between the measures of the same subject, in order to test certain scientific hypotheses and to reduce misclassification of subjects in clinical practice, and (2) to reduce the number of significance tests involved in selecting predictors for the purpose of norming, thus preventing the inflation of the type I error rate. A new multivariate regression-based approach is proposed that combines all measures for an individual through the Mahalanobis distance, thus providing an indicator of the individual's overall performance. Furthermore, optimal designs for the normative study are derived under five multivariate polynomial regression models, assuming multivariate normality and homoscedasticity of the residuals, and efficient robust designs are presented in case of uncertainty about the correct model for the analysis of the normative sample. Sample size calculation formulas are provided for the new Mahalanobis distance-based approach. The results are illustrated with data from the Maastricht Aging Study (MAAS).

In foreign language learning, it is important that learners become autonomous and learn how to self-regulate their learning to continue language development. This article presents a self-evaluation procedure designed to promote self-regulation in speaking skills in a foreign language. This self-evaluation procedure was tested in a quasi-experimental study among 329 secondary school students in the Netherlands to investigate to what extent changes occurred in students' self-regulation of their speaking skills and to what extent students perceived the self-evaluation procedure as motivating and adaptive to their needs. The results showed that shifts were found in the focus of students' diagnoses and improvement plans for their own speaking performances. It was also found that the perceived need for teachers' assistance decreased. Moreover, students found support to be adaptive and appreciated the activities in the self-evaluation procedure--especially producing and executing an improvement plan. In conclusion, this study contributes to the development of knowledge about guiding students' self-regulation of speaking skills by adding concrete design principles to realize such a learning process.

Abstract Background Several evidence-based psychotherapeutic treatment options are available for depression, but the treatment results could be improved. The D*Phase study directly compares short-term psychodynamic supportive psychotherapy (SPSP) and cognitive behavioural therapy (CBT) for Major Depressive Disorder (MDD). The objectives are 1. to investigate if, from a group level perspective, SPSP is not inferior to CBT in the treatment of major depressive disorder, 2. to build a model that may help predict the optimal type of treatment for a specific individual; and 3. to determine whether a change of therapist or a change of therapist and treatment method are effective strategies to deal with non-response. Furthermore (4.), the effect of the therapeutic alliance, treatment integrity and therapist allegiance on treatment outcome will be investigated. Method In this pragmatic randomised controlled trial, 308 patients with a primary diagnosis of MDD are being recruited from a specialised mental health care institution in the Netherlands. In the first phase, patients are randomised 1:1 to either SPSP or CBT. In case of treatment non-response, a second phase follows in which non-responders from treatment phase one are randomised 1:1:1 to one of three groups: continuing the initial treatment with the same therapist, continuing the initial treatment with another therapist or continuing the other type of treatment with another therapist. In both treatment phases, patients are offered sixteen twice-weekly psychotherapy sessions. The primary outcome is an improvement in depressive symptoms. Process variables, working alliance and depressive symptoms, are frequently measured. Comprehensive assessments take place before the start of the first phase (at baseline), in week one, two and four during the treatment, and directly after the treatment (week eight). Discussion While the naturalistic setting of the study involves several challenges, we expect, by focusing on a large and diverse number of research variables, to generate important knowledge that may help enhance the effect of psychotherapeutic treatment for MDD. Trial registration The study was registered on 26 August 2016 with the Netherlands Trial Register, part of the Dutch Cochrane Centre (NL5753), https://www.trialregister.nl/trial/5753

Abstract Rationale Salivary glands are highly perfused and express the prostate-specific membrane antigen (PSMA) receptor as well as the sodium—iodide symporter. As a consequence, treatment with 177Lu/225Ac-PSMA for prostate cancer or 131I for thyroid cancer leads to a high radiation dose in the salivary glands, and patients can be confronted with persistent xerostomia and reduced quality of life. Salivation can be inhibited using an antimuscarinic pharmaceutical, such as glycopyrronium bromide (GPB), which may also reduce perfusion. The primary objective of this work was to determine if inhibition with GPB could provide a considerable (> 30%) reduction in the accumulation of administered 123I or 68Ga-PSMA-11 in salivary glands. Methods Ten patients who already received a whole-body 68Ga-PSMA-11 PET/CT scan for (re)staging of prostate cancer underwent a repeat PET/CT scan with tracer administration at 90 min after intravenous injection of 0.2 mg GPB. Four patients in follow-up after thyroid cancer, who had been treated with one round of ablative 131I therapy with curative intent and had no signs of recurrence, received 123I planar scintigraphy at 4 h after tracer administration without GPB and a repeated scan at least one week later, with tracer administration at 30 min after intramuscular injection of 0.4 mg GPB. Tracer uptake in the salivary glands was quantified on PET and scintigraphy, respectively, and values with and without GPB were compared. Results No significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SULmean parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SULmean submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased 123I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46). Conclusion Muscarinic inhibition of salivation with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in salivary glands, and can be dismissed as a potential strategy to reduce toxicity from radionuclide therapies.

Efectos de los perros domésticos (Canis familiaris) en la vida silvestre en dos puntos críticos del Brasil e implicaciones para la conservación. Las especies exóticas son una de las principales amenazas para la biodiversidad en todo el mundo. Los perros domésticos (Canis familiaris) se encuentran entre los depredadores invasores más comunes del mundo, ya que interactúan con la vida silvestre de muchas maneras. Presentamos datos ecológicos obtenidos mediante cámaras de trampeo y observaciones ocasionales de perros domésticos criados en libertad de localidades situadas dentro de los puntos críticos del bosque atlántico y el Cerrado brasileños. Canis familiaris fue la segunda especie de mamífero más abundante y el carnívoro más abundante. Los perros interactuaron con al menos 26 especies nativas persiguiéndolas, matándolas o compitiendo con ellas. No consumieron ninguno de los animales muertos, lo que, junto con los registros predominantes de individuos solitarios en actividad diurna, indica que se trata principalmente de perros criados en libertad que dependen de los humanos para alimentarse y refugiarse. La elevada abundancia de perros y la gran variedad de presas sugieren que la vida silvestre podría verse muy afectada por los perros domésticos, especialmente en zonas muy amenazadas por actividades humanas, como los puntos críticos de biodiversidad. Destacamos algunas medidas (por ejemplo, la erradicación o eliminación de perros de áreas naturales) que representan una posibilidad de reducir los daños ambientales causados por perros domésticos en la región.

Abstract Background Forensic psychiatric patients often suffer from a multitude of severe psychiatric and social problems. Meanwhile multimodal evidence-based interventions are scarce and treatment effectiveness is in need of improvement. The main goal of forensic psychiatric treatment is to address psychiatric and social factors and thereby mitigate criminal behaviour. Notably, a supportive social network is an important protective factor for criminal behaviour. As such, improving a poor social network may decrease the risk of criminal recidivism. This study aims to examine the effectiveness of the addition of an informal social network intervention (FNC) to treatment as usual (TAU) among forensic psychiatric outpatients. Methods In a mono-center randomized controlled clinical trial with two parallel groups, forensic psychiatric outpatients with social network-related problems (N = 105) will be allocated to either TAU + FNC or TAU alone. The informal social network intervention consists of a 12-month coaching intervention, performed by the forensic network coach (a volunteer trained by an informal care institute). Assessments will be conducted at baseline and 3 months, 6 months, 9 months, 12 months, and 18 months after baseline. The primary outcome variable is mental wellbeing. Psychiatric functioning, criminal recidivism, substance abuse, quality of life, social network, social support, loneliness and self-sufficiency are included as secondary outcomes. A variety of potential mediators and moderators of effectiveness will be explored. Additionally, a qualitative evaluation of effectiveness will be performed. Discussion This study will contribute to the existing literature of forensic treatment effectiveness as it is the first RCT examining the effectiveness of adding a social network intervention in a forensic outpatient population. If effectiveness is shown, forensic mental health care could be optimized by collaborating with informal care or community initiatives aimed at improving a positive social network. In addition, results will provide insight regarding mediators and moderators of treatment effectiveness. Trial registration This study is registered at the Netherlands Trial Register ( NTR7163 ). Date of registration: 16 april 2018.

Abstract Background Pathophysiology of life-threatening acute metabolic decompensations (AMD) in propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is insufficiently understood. Here, we study the metabolomes of PA and MMA patients over time, to improve insight in which biochemical processes are at play during AMD. Methods Longitudinal data from clinical chemistry analyses and metabolic assays over the life-course of 11 PA and 13 MMA patients were studied retrospectively. Direct-infusion high-resolution mass spectrometry was performed on 234 and 154 remnant dried blood spot and plasma samples of PA and MMA patients, respectively. In addition, a systematic literature search was performed on reported biomarkers. All results were integrated in an assessment of biochemical processes at play during AMD. Results We confirmed many of the metabolite alterations reported in literature, including increases of plasma valine and isoleucine during AMD in PA patients. We revealed that plasma leucine and phenylalanine, and urinary pyruvic acid were increased during AMD in PA patients. 3-hydroxyisovaleric acid correlated positively with plasma ammonia. We found that known diagnostic biomarkers were not significantly further increased, while intermediates of the branched-chain amino acid (BCAA) degradation pathway were significantly increased during AMD. Conclusions We revealed that during AMD in PA and MMA, BCAA and BCAA intermediates accumulate, while known diagnostic biomarkers remain essentially unaltered. This implies that these acidic BCAA intermediates are responsible for metabolic acidosis. Based on this, we suggest to measure plasma 3-hydroxyisovaleric acid and urinary ketones or 3-hydroxybutyric acid for the biochemical follow-up of a patient’s metabolic stability.

STEM teacher shortage remains a serious problem in secondary education in many European countries, despite many interventions and many research studies over the last decades. The observation that past interventions and research outcomes have not significantly contributed to reduce teacher shortage implies that places to effectively intervene in the teacher education system have not been found yet. In this article, a systems thinking approach is presented to evaluate the fundamental and structural problems of an academic teacher education system regarding STEM student entry. A thorough understanding of the systemic structure of a teacher education system is essential to identify leverage points for STEM teacher recruitment. Based on systems thinking principles and theoretical frameworks, a stepwise research framework was defined, which was tested in the Dutch academic teacher education system. First, potential factors of concern were identified based on the collection of many data such as existing public information, reports and long-term student entry data. These potential factors of concern were subsequently investigated by student surveys and structured interviews with stakeholders from science faculties and teacher training institutes. Synthesis of the results led to the identification of three leverage points for increasing STEM student entry in teacher training, which were all found at the organizational and structural level of the academic teacher education system. The systems thinking research framework presented in this article provides a valuable framework to address persistent problems in education and enables the identification of novel and potentially more effective interventions.

Abstract Background In oncology, Health Care Professionals often experience conducting Advance Care Planning (ACP) conversations as difficult and are hesitant to start them. A structured approach could help to overcome this. In the ACTION trial, a Phase III multi-center cluster-randomized clinical trial in six European countries (Belgium, Denmark, Italy, the Netherlands, Slovenia, United Kingdom), patients with advanced lung or colorectal cancer are invited to have one or two structured ACP conversations with a trained facilitator. It is unclear how trained facilitators experience conducting structured ACP conversations. This study aims to understand how facilitators experience delivering the ACTION Respecting Choices (RC) ACP conversation. Methods A qualitative study involving focus groups with RC facilitators. Focus group interviews were recorded, transcribed, anonymized, translated into English, and thematically analysed, supported by NVivo 11. The international research team was involved in data analysis from initial coding and discussion towards final themes. Results Seven focus groups were conducted, involving 28 of in total 39 trained facilitators, with different professional backgrounds from all participating countries. Alongside some cultural differences, six themes were identified. These reflect that most facilitators welcomed the opportunity to participate in the ACTION trial, seeing it as a means of learning new skills in an important area. The RC script was seen as supportive to ask questions, including those perceived as difficult to ask, but was also experienced as a barrier to a spontaneous conversation. Facilitators noticed that most patients were positive about their ACTION RC ACP conversation, which had prompted them to become aware of their wishes and to share these with others. The facilitators observed that it took patients substantial effort to have these conversations. In response, facilitators took responsibility for enabling patients to experience a conversation from which they could benefit. Facilitators emphasized the need for training, support and advanced communication skills to be able to work with the script. Conclusions Facilitators experienced benefits and challenges in conducting scripted ACP conversations. They mentioned the importance of being skilled and experienced in carrying out ACP conversations in order to be able to explore the patients’ preferences while staying attuned to patients’ needs. Trial registration International Standard Randomised Controlled Trial Number registry 63110516 (ISRCTN63110516) per 10/3/2014.

Abstract Background Aortic regurgitation (AR) and subclinical left ventricular (LV) dysfunction expressed by myocardial deformation imaging are common in patients with transposition of the great arteries after the arterial switch operation (ASO). Echocardiographic evaluation is often hampered by reduced acoustic window settings. Cardiovascular magnetic resonance (CMR) imaging provides a robust alternative as it allows for comprehensive assessment of degree of AR and LV function. The purpose of this study is to validate CMR based 4-dimensional flow quantification (4D flow) for degree of AR and feature tracking strain measurements for LV deformation assessment in ASO patients. Methods A total of 81 ASO patients (median 20.6 years, IQR 13.5–28.4) underwent CMR for 4D and 2D flow analysis. CMR global longitudinal strain (GLS) feature tracking was compared to echocardiographic (echo) speckle tracking. Agreements between and within tests were expressed as intra-class correlation coefficients (ICC). Results Eleven ASO patients (13.6%) showed AR > 5% by 4D flow, with good correlation to 2D flow assessment (ICC = 0.85). 4D flow stroke volume of the aortic valve demonstrated good agreement to 2D stroke volume over the mitral valve (internal validation, ICC = 0.85) and multi-slice planimetric LV stroke volume (external validation, ICC = 0.95). 2D flow stroke volume showed slightly less, though still good agreement with 4D flow (ICC = 0.78) and planimetric LV stroke volume (ICC = 0.87). GLS by CMR was normal (− 18.8 ± 4.4%) and demonstrated good agreement with GLS and segmental analysis by echocardiographic speckle tracking (GLS = − 17.3 ± 3.1%, ICC of 0.80). Conclusions Aortic 4D flow and CMR feature tracking GLS analysis demonstrate good to excellent agreement with 2D flow assessment and echocardiographic speckle tracking, respectively, and can therefore reliably be used for an integrated and comprehensive CMR analysis of aortic valve competence and LV deformation analysis in ASO patients.

Abstract Background The objective of this study is to investigate the role and experience of early stage non-small cell lung cancer (NSCLC) patient in decision making process concerning treatment selection in the current clinical practice. Methods Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68) were included in this prospective study and completed a questionnaire that explored: (1) perceived patient knowledge of the advantages and disadvantages of the treatment options, (2) experience with current clinical decision making, and (3) the information that the patient reported to have received from their treating physician. This was assessed by multiple-choice, 1–5 Likert Scale, and open questions. The Decisional Conflict Scale was used to assess the decisional conflict. Health related quality of life (HRQoL) was measured with SF-36 questionnaire. Results In 19% of patients, there was self-reported perceived lack of knowledge about the advantages and disadvantages of the treatment options. Seventy-four percent of patients felt that they were sufficiently involved in decision-making by their physician, and 81% found it important to be involved in decision making. Forty percent experienced decisional conflict, and one-in-five patients to such an extent that it made them feel unsure about the decision. Subscores with regard to feeling uninformed and on uncertainty, contributed the most to decisional conflict, as 36% felt uninformed and 17% of patients were not satisfied with their decision. HRQoL was not influenced by patient experience with decision-making or patient preferences for shared decision making. Conclusions Dutch early-stage NSCLC patients find it important to be involved in treatment decision making. Yet a substantial proportion experiences decisional conflict and feels uninformed. Better patient information and/or involvement in treatment-decision-making is needed in order to improve patient knowledge and hopefully reduce decisional conflict.

Abstract Background While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues. Methods Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival. Results The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (

Abstract In idiopathic pulmonary fibrosis (IPF), home monitoring experiences are limited, not yet real-time available nor implemented in daily care. We evaluated feasibility and potential barriers of a new home monitoring program with real-time wireless home spirometry in IPF. Ten patients with IPF were asked to test this home monitoring program, including daily home spirometry, for four weeks. Measurements of home and hospital spirometry showed good agreement. All patients considered real-time wireless spirometry useful and highly feasible. Both patients and researchers suggested relatively easy solutions for the identified potential barriers regarding real-time home monitoring in IPF.

Abstract In this paper we test the complex Langevin algorithm for numerical simulations of a random matrix model of QCD with a first order phase transition to a phase of finite baryon density. We observe that a naive implementation of the algorithm leads to phase quenched results, which were also derived analytically in this article. We test several fixes for the convergence issues of the algorithm, in particular the method of gauge cooling, the shifted representation, the deformation technique and reweighted complex Langevin, but only the latter method reproduces the correct analytical results in the region where the quark mass is inside the domain of the eigenvalues. In order to shed more light on the issues of the methods we also apply them to a similar random matrix model with a milder sign problem and no phase transition, and in that case gauge cooling solves the convergence problems as was shown before in the literature.

Abstract Background The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10–12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these “blind” systematic biopsies with reliable imaging-based targeted biopsies. Methods/design In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols. Discussion This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification. Trial registration The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

Slope deformation is one of the typical geohazards that causes an extensive economic damage in mountainous regions. As such, they are usually intensively monitored by means of modern expertise commonly by national geological or emergency services. Resulting landslide susceptibility maps, or landslide inventories, offer an overview of areas affected by previously activated landslides as well as slopes known to be unstable currently. Current slope instabilities easily transform into a landslide after various triggering factors, such as an intensive rainfall or a melting snow cover. In these inventories, the majority of the existing landslide-affected slopes are marked as either stable or active, after a continuous investigative work of the experts in geology. In this paper we demonstrate the applicability of Sentinel-1A satellite SAR interferometry (InSAR) to assist by identifying slope movement activity and use the information to update national landslide inventories. This can be done reliably in cases of semi-arid regions or low vegetated slopes. We perform several analyses based on multitemporal InSAR techniques of Sentinel-1A data over selected areas prone to landslides.

Acknowledgement of the limited learning outcomes in our first-year physics lab course, strikingly similar to the observed and reported issues in literature, incited renewal of the course with a focus on developing students' ability to engage in experimental physics research. The "procedural and conceptual knowledge (PACKS) model"--addressing different types of knowledge required for scientific investigation--was used as a "guide" in the transformation of the course. This educational design research study--distinguishing three stages--describes our approach in transforming the course and provides theoretical insights and practical solutions through the combined study of both the process of learning and the means that support that process. The merits and trade-offs of our approach and the effectiveness of the course transformation are evaluated through surveys, interviews, and assessment of students' inquiry skills. The findings provide insights into the application of the PACKS model and its effectiveness in facilitating students' development of physics inquiry abilities. The results reveal an alignment between perceived, attained and intended learning goals. The self-conceived experiment at the end of the course showcases students' successful integration of the targeted knowledge types, previously addressed in isolated "preparatory" activities. We argue that the PACKS-model and the design principles are useful attributes when transforming a traditional lab activity, but also specify the limitations.

Assessment and monitoring of safety in special education schools is imperative to establish and maintain a safe environment in which students can develop academic and social-emotional skills. The present study describes the development of a student self-report measure, the Safe at School questionnaire. Factorial validity, reliability and concurrent validity was examined in a construction sample of 280 students (68.6% male, age M = 13.29, SD = 2.52) and a validation sample of 1572 students (77.4% male; age M = 14.33, SD = 2.04), representing 233 classes from 20 schools for special education in the Netherlands. Multilevel confirmatory factor analysis was used to examine the factor structure of the Safe at School questionnaire. A model with three correlating factors at the within- and between-group level (Rules and Social Norms, Perceived Own Safety and Perceived Safety of Other Students) showed a satisfactory fit to the data. Reliabilities of the scales were good. Also, measurement invariance for gender was demonstrated, indicating no differences in latent means between boys and girls. Implications for practice and future research are discussed.