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University-based boundary organisations provide academics with an environment where they can interact with a wide variety of societal partners to produce knowledge and work on research projects, often of a transdisciplinary nature. This environment, however, implies that their researchers may be confronted with multiple and sometimes conflicting demands coming from various stakeholders. In this study, we focus on one such case, a Real-world Laboratory (RwL), set up by the Karlsruhe Institute of Technology. This RwL focuses on urban sustainable development challenges. Drawing on boundary work literature, we analyse the boundary work strategies employed by the lab's leading researchers to manage such demands as part of a RwL research project. We observe that the managing researchers buffer several types of boundaries in order not to compromise the transdisciplinary nature of the RwL. They appear to utilise four types of boundary devices when managing boundaries: language, people, objects, and spaces. We conclude that, to reduce tensions, the managing researchers should acknowledge the presence of boundaries early on in their RwL research project, that is, during its conception phase.

Abstract Objectives Total tumor volume (TTV) is associated with overall and recurrence-free survival in patients with colorectal cancer liver metastases (CRLM). However, the labor-intensive nature of such manual assessments has hampered the clinical adoption of TTV as an imaging biomarker. This study aimed to develop and externally evaluate a CRLM auto-segmentation model on CT scans, to facilitate the clinical adoption of TTV. Methods We developed an auto-segmentation model to segment CRLM using 783 contrast-enhanced portal venous phase CTs (CT-PVP) of 373 patients. We used a self-learning setup whereby we first trained a teacher model on 99 manually segmented CT-PVPs from three radiologists. The teacher model was then used to segment CRLM in the remaining 663 CT-PVPs for training the student model. We used the DICE score and the intraclass correlation coefficient (ICC) to compare the student model’s segmentations and the TTV obtained from these segmentations to those obtained from the merged segmentations. We evaluated the student model in an external test set of 50 CT-PVPs from 35 patients from the Oslo University Hospital and an internal test set of 21 CT-PVPs from 10 patients from the Amsterdam University Medical Centers. Results The model reached a mean DICE score of 0.85 (IQR: 0.05) and 0.83 (IQR: 0.10) on the internal and external test sets, respectively. The ICC between the segmented volumes from the student model and from the merged segmentations was 0.97 on both test sets. Conclusion The developed colorectal cancer liver metastases auto-segmentation model achieved a high DICE score and near-perfect agreement for assessing TTV. Critical relevance statement AI model segments colorectal liver metastases on CT with high performance on two test sets. Accurate segmentation of colorectal liver metastases could facilitate the clinical adoption of total tumor volume as an imaging biomarker for prognosis and treatment response monitoring. Key Points Developed colorectal liver metastases segmentation model to facilitate total tumor volume assessment. Model achieved high performance on internal and external test sets. Model can improve prognostic stratification and treatment planning for colorectal liver metastases. Graphical Abstract

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Background and Context: In order to fully include learners with visual impairments in early programming education, it is necessary to gain insight into specificities regarding their experience of and approach to abstract computational concepts. Objective: In this study, we use the model of the layers of abstraction to explore how learners with visual impairments approach the computational concept of abstraction, working with the Bee-bot and Blue-bot. Method: Six blind and three low vision learners from the elementary school level were observed while completing programming assignments. Findings: The model of the layers of abstraction, can overall be generalized to learners with visual impairments, who engage in patterns that reflect iterative actions of redesigning and debugging. Especially our blind learners use specific tactile and physical behaviors to engage in these actions. Implications: Ultimately, understanding such specificities can contribute to inclusive tailored educational instruction and support.

University-based living labs serve as open innovation platforms that foster collaborative research and experimentation across various disciplines. These labs bring together academics, citizens, community organisations, companies, and other entities to collectively address complex contemporary issues. The labs' managers are expected to adopt flexible, agile management approaches to support the openness of their lab to stakeholders. Flexible management approaches create various challenges, as the labs are often expected also to comply with traditional project management principles of deadlines, project deliverables, budget restrictions, and quality conditions as set by their project sponsors and host organisation. The combination of prescriptive and agile project management approaches in such open innovation settings has been relatively underexplored in higher education research. Drawing on the theoretical literature on boundary work and project management, we analyse how the managers of a Dutch university-based living lab execute flexible project management styles in a setting that is dominated by prescriptive project management traditions. Based on information from 20 interviews and document analysis we identify five areas of tension between agile and prescriptive project management. Living lab managers, supported by researchers, buffer these tensions through boundary work that shapes the openness of the projects in rather unexpected ways.

The study examined what factors determine the use of educational innovations by teachers in higher education. Three sort of factors were compared: teachers' motivation for the enhancement of education, their contact with or exposure to dissemination of educational innovations and institutional factors, that is, support provided by higher education institutions. Further, teachers were classified regarding their use of educational innovations. The study used survey data collected among academic staff at public Norwegian higher education institutions. Results of the multinominal logistic regression models showed that intrinsic motivation was an important factor for teachers' innovation behaviour in this context. Dissemination and institutional factors exerted little or no significant impact. The assumptions currently underlying research on educational innovations and the design of national and institutional support programmes are discussed against the background of these results.

This study examined whether and how moral judgment components (moral reasoning and moral value evaluation) combined with self-serving cognitive distortions are related to peer bullying (including associated participant roles) among adolescents. A total of 522 adolescents (49% males) from grades 1 to 4 of three public secondary schools in Spain (M[subscript age] = 14.6 years, range 12-18 years) completed questionnaires on moral judgment, self-serving cognitive distortions, and bullying. Bullies and bully-victims showed the lowest levels of moral judgment and the highest levels of self-serving cognitive distortions. In contrast, moral judgment was highest and self-serving cognitive distortions lowest for defenders and bystanders. Self-serving cognitive distortions mediated completely the relationship between moral reasoning and bullying, and partially between moral evaluation and bullying. Multigroup analyses indicated that the strength of the relationships between the moral judgment components and self-serving cognitive distortions varied across adolescents' role. Anti-bullying intervention programs should include the facilitation of moral reasoning and valuing as well as the reduction of self-serving cognitive distortions.

Las relaciones filioparentales en familias de origen chino apenas han sido investigadas en España desde el punto de vista del desarrollo psicológico. Mediante entrevistas individuales con 18 adolescentes y adultos emergentes de origen familiar chino (de 2.ª generación y generación 1.5), se exploraron sus experiencias en el ámbito laboral familiar, su tiempo de ocio, sus percepciones acerca de la relación con sus progenitores, el apoyo parental recibido, su orientación cultural, así como el modo en que estos aspectos afectan a su bienestar psicológico. Los resultados muestran que varios de estos aspectos, algunos de ellos normativos, afectan al bienestar de los entrevistados y a la calidad de la relación con sus figuras parentales. Estos jóvenes se sentían obligados/as, de forma directa o indirecta, a contribuir al negocio familiar o a apoyarlo a través de tareas domésticas o administrativas. Su propio desarrollo les permite reinterpretar esas experiencias pasadas viendo su necesidad en el sistema familiar, y percibiéndolas no solo como obstáculo a su bienestar psicológico en relación con su falta de autonomía, sino también como motor de su desarrollo. Indican que tienen una identidad bicultural y discrepan de las expectativas parentales sobre el cumplimiento de normas relativas al respeto a los progenitores (piedad filial). Como principales dificultades en la relación señalan la limitación impuesta de tiempo libre y autonomía y la falta de calidez de sus padres.

Abstract Background Several research groups have explored the potential of scandium radionuclides for theragnostic applications due to their longer half-lives and equal or similar coordination chemistry between their diagnostic and therapeutic counterparts, as well as lutetium-177 and terbium-161, respectively. Unlike the gallium-68/lutetium-177 pair, which may show different in-vivo uptake patterns, the use of scandium radioisotopes promises consistent behaviour between diagnostic and therapeutic radiopeptides. An advantage of scandium’s longer half-life over gallium-68 is the ability to study radiopeptide uptake over extended periods and its suitability for centralized production and distribution. However, concerns arise from scandium-44’s decay characteristics and scandium-43’s high production costs. This study aimed to evaluate the dosimetric implications of using scandium radioisotopes with somatostatin analogues against gallium-68 for PET imaging of neuroendocrine tumours. Methods Absorbed dose per injected activity (AD/IA) from the generated time-integrated activity curve (TIAC) were estimated using the radiopeptides [43/44/44mSc]Sc- and [68Ga]Ga-DOTATATE. The kidneys, liver, spleen, and red bone marrow (RBM) were selected for dose estimation studies. The EGSnrc and MCNP6.1 Monte Carlo (MC) codes were used with female (AF) and male (AM) ICRP phantoms. The results were compared to Olinda/EXM software, and the effective dose concentrations assessed, varying composition between the scandium radioisotopes. Results Our findings showed good agreement between the MC codes, with − 3 ± 8% mean difference. Kidneys, liver, and spleen showed differences between the MC codes (min and max) in a range of − 4% to 8%. This was observed for both phantoms for all radiopeptides used in the study. Compared to Olinda/EXM the largest observed difference was for the RBM, of 21% for the AF and 16% for the AM for scandium- and gallium-based radiopeptides. Despite the differences, our findings showed a higher absorbed dose on [43/44Sc]Sc-DOTATATE compared to its 68Ga-based counterpart. Conclusion This study found that [43/44Sc]Sc-DOTATATE delivers a higher absorbed dose to organs at risk compared to [68Ga]Ga-DOTATATE, assuming equal distribution. This is due to the longer half-life of scandium radioisotopes compared to gallium-68. However, calculated doses are within acceptable ranges, making scandium radioisotopes a feasible replacement for gallium-68 in PET imaging, potentially offering enhanced diagnostic potential with later timepoint imaging.

Abstract Background Technology improves accessibility of psychological interventions for youth. An ecological momentary intervention (EMI) is a digital intervention geared toward intervening in daily life to enhance the generalizability and ecological validity, and to be able to intervene in moments most needed. Identifying working mechanisms of the use of ecological momentary interventions might generate insights to improve interventions. Methods The present study investigates the working mechanisms of the use and acceptability of an ecological momentary intervention, named SELFIE, targeting self-esteem in youth exposed to childhood trauma, and evaluates under what circumstances these mechanisms of use and acceptability do or do not come into play. A realist evaluation approach was used for developing initial program theories (data: expert interviews and a stakeholders focus group), and subsequently testing (data: 15 interviews with participants, a focus group with therapists, debriefing questionnaire), and refining them. Results The SELFIE intervention is offered through a smartphone application enabling constant availability of the intervention and thereby increasing accessibility and feasibility. When the intervention was offered on their personal smartphone, this enhanced a sense of privacy and less hesitance in engaging with the app, leading to increased disclosure and active participation. Further, the smartphone application facilitates the practice of skills in daily life, supporting the repeated practice of exercises in different situations leading to the generalizability of the effect. Buffering against technical malfunction seemed important to decrease its possible negative effects. Conclusions This study enhanced our understanding of possible working mechanisms in EMIs, such as the constant availability supporting increased accessibility and feasibility, for which the use of the personal smartphone was experienced as a facilitating context. Hereby, the current study contributes to relatively limited research in this field. For the field to move forward, mechanisms of use, and acceptability of EMIs need to be understood. It is strongly recommended that alongside efficacy trials of an EMI on specific target mechanisms, a process evaluation is conducted investigating the working mechanisms of use. Trial registration The current paper reports on a realist evaluation within the SELFIE trial (Netherlands Trial Register NL7129 (NTR7475)).

Abstract Background Intensive Care Unit (ICU) capacity management is essential to provide high-quality healthcare for critically ill patients. Yet, consensus on the most favorable ICU design is lacking, especially whether ICUs should deliver dedicated or non-dedicated care. The decision for dedicated or non-dedicated ICU design considers a trade-off in the degree of specialization for individual patient care and efficient use of resources for society. We aim to share insights of a model simulating capacity effects for different ICU designs. Upon request, this simulation model is available for other ICUs. Methods A discrete event simulation model was developed and used, to study the hypothetical performance of a large University Hospital ICU on occupancy, rejection, and rescheduling rates for a dedicated and non-dedicated ICU design in four different scenarios. These scenarios either simulate the base-case situation of the local ICU, varying bed capacity levels, potential effects of reduced length of stay for a dedicated design and unexpected increased inflow of unplanned patients. Results The simulation model provided insights to foresee effects of capacity choices that should be made. The non-dedicated ICU design outperformed the dedicated ICU design in terms of efficient use of scarce resources. Conclusions The choice to use dedicated ICUs does not only affect the clinical outcome, but also rejection- rescheduling and occupancy rates. Our analysis of a large university hospital demonstrates how such a model can support decision making on ICU design, in conjunction with other operation characteristics such as staffing and quality management.

Background and objective: Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26). Methods: Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo. Key findings and limitations: Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval [CI] 96–97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75–78), with a median EPIC-26 incontinence domain score of 100 (interquartile range [IQR] 86–100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63–68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39–45%), with a median EPIC-26 score of 76 (IQR 61–100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a “moderate or big problem” with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43–92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50–54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14–20%), without medication in 6% (37/630; 95% CI 4–8%) and needing medication in 11% (68/630; 95% CI 9–13%); the median EPIC-26 domain score was 26 (IQR 13–57). Conclusions and clinical implications: Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year. Patient summary: At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections.

Artificial intelligence (AI) has recently become a vital technology affecting several sectors, including hospitality. The expanding use of AI robots in functions previously performed by humans raises important issues — which are currently unknown — regarding how AI robotics may affect personnel and guests. This study examined guests’ and staff’s experiences with service robots in a 4-star southern Dutch hotel. The report offers the hospitality industry AI robot implementation advice. In-depth staff interviews and 4-star hotel guest surveys were completed. Data from customers and staff showed a need for service robots at the front office. This demand highlights the need for service robots at the front desk to serve leisure and business clients and to aid staff. However, both quantitative and qualitative studies imply that a tangible human welcome is still necessary, especially for leisure tourists. This study found that customers and personnel at the front office want service robots, with leisure and business guests preferring something different. These demographics perceive human connections as essential for a good visitor experience, emphasising the complexities of AI in hospitality.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body This selection of highlights provides commentary on 24 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

Background: Limited treatment options with a rapid onset of action are available to treat off episodes in Parkinson’s disease (PD) patients. Therefore, the development of rapid onset formulations, for instance with levodopa, is warranted, which was the reason to investigate an inhalable formulation of levodopa. Objectives: The primary objective was to determine the duration until maximum effect is reached of inhaled levodopa on the improvement of motor function of PD patients. The secondary objective was to compare the time until maximal effect and the maximal effect of inhaled levodopa versus oral levodopa. Design: Open-label randomized two-way one-period crossover trial. Methods: Nine PD patients in the ‘off state’ received one dose of inhaled levodopa (90 mg) from Cyclops® and one dose of levodopa orodispersible tablet (100 mg) on two consecutive days in a randomized order. A timed tapping test, Timed Up and Go test (TUG test) and Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III score were performed pre-dose and on set time points up to 90 min post-dose as measure for motor function. In addition, blood samples were taken for a pharmacokinetic evaluation ( T max , C max and area under the concentration time curve (AUC) 0–3 h). Results: The maximal effect of inhaled levodopa was reached at 30 min (tapping test), at 75 min (TUG test) and at 60 min (UPDRS III). The positive effect on the UPDRS was statistically significant within 20 min after inhalation. After oral administration, C max and AUC 0–3 h were found to be significant higher ( p = 0.028 and p = 0.028, respectively) than after pulmonary administration. T max was achieved significantly ( p = 0.028) faster after inhalation. The motor function examinations showed a similar maximum clinical improvement after pulmonary and oral administration and although not significant, inhaled levodopa results in a shorter median duration to maximum clinical effect for the TUG and timed finger-tapping test compared with oral administration (TUG: inhalation 55.0 and oral 67.5 min, timed finger-tapping test: inhalation 35.0 and oral 57.5 min). After the levodopa inhalation, there were no adverse events observed and no significant differences found in long-function parameters. Conclusion: Inhaled levodopa from Cyclops ® shows promising data as a rescue therapy for PD patients with off episodes, not responsive to the current oral therapies. Trial registration: The study protocol was approved by the local ethics board ‘Regionale toetsingscommissie patiëntgebonden onderzoek’ (RTPO) in Leeuwarden, The Netherlands (approval number RTPO1019). The study was registered in in the Dutch trial register (LTR) with identification number NL6876. From 5 March 2024 on, the research data on onderzoekmetmensen.nl are known as ‘Overview of Medical Research in the Netherlands’ (OMON). This means the use of the name LTR has thus been dropped. Now, it is registered in the OMON with the same identification number (NL6876, Effectiveness of inhaled levodopa in PD | Research with human participants (onderzoekmetmensen.nl)). All patients provided written informed consent.

The interest in terbium radionuclides, which can be used in nuclear medicine, has increased tremendously over the last decade. Several research studies have shown the potential of four terbium radionuclides 149,152,155,161Tb both for cancer diagnosis as well as therapy. The comparison of 161Tb and 177Lu showed 161Tb as the preferred candidate not only for standard radiotherapy, but also for the treatment of minimal residual disease. Nevertheless, among the terbium sisters, currently, only 161Tb has an established production protocol where its no-carrier-added form is obtained via neutron irradiation of enriched 160Gd targets. The other terbium radioisotopes face challenges related to production capacity and production yield, which currently restricts their use in nuclear medicine. The purpose of this review is to report on recent research on the production and separation of terbium sisters and to assess the prospects for upscaling their production for nuclear medicine applications.

Objective To investigate whether accuracy of a risk model for colorectal cancer (CRC) patients undergoing emergency surgery, including patient and tumour characteristics from disease-specific data, was improved by inclusion of physiological and surgical measures from linked treatment-specific data. Approach Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. Results 846 of 10,578 (8.0%) patients died within 90 days of surgery. The selected model included seven pre-operative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the ten patient and tumour characteristics in the basic model (year of surgery, age, sex, ASA grade, cancer site, number of comorbidities, emergency admission, TNM T stage, N stage and M stage). The selected model had considerably better discrimination than the basic model (C-statistic: 0.824 versus 0.783, respectively). Conclusion Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improved the accuracy of predictions. Implications Our new accurate and relatively simple risk prediction model for patients undergoing emergency CRC surgery will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

The utility of nonsurgical, mechanical compression-based joint injury models to study osteoarthritis pathogenesis and treatments is increasing. Joint injury may be induced via cyclic compression loading or acute overloading to induce anterior cruciate ligament rupture. Models utilizing mechanical testing systems are highly repeatable, require little expertise, and result in a predictable onset of osteoarthritis-like pathology on a rapidly progressing timeline. In this chapter, we describe the procedures and equipment needed to perform mechanical compression-induced initiation of osteoarthritis in mice and rats.

BackgroundHigh throughput sequencing has enabled the interrogation of the transcriptomic landscape of glucagon-secreting alpha cells, insulin-secreting beta cells, and somatostatin-secreting delta cells. These approaches have furthered our understanding of expression patterns that define healthy or diseased islet cell types and helped explicate some of the intricacies between major islet cell crosstalk and glucose regulation. All three endocrine cell types derive from a common pancreatic progenitor, yet alpha and beta cells have partially opposing functions, and delta cells modulate and control insulin and glucagon release. While gene expression signatures that define and maintain cellular identity have been widely explored, the underlying epigenetic components are incompletely characterized and understood. However, chromatin accessibility and remodeling is a dynamic attribute that plays a critical role to determine and maintain cellular identity.ResultsHere, we compare and contrast the chromatin landscape between mouse alpha, beta, and delta cells using ATAC-Seq to evaluate the significant differences in chromatin accessibility. The similarities and differences in chromatin accessibility between these related islet endocrine cells help define their fate in support of their distinct functional roles. We identify patterns that suggest that both alpha and delta cells are poised, but repressed, from becoming beta-like. We also identify patterns in differentially enriched chromatin that have transcription factor motifs preferentially associated with different regions of the genome. Finally, we not only confirm and visualize previously discovered common endocrine- and cell specific- enhancer regions across differentially enriched chromatin, but identify novel regions as well. We compiled our chromatin accessibility data in a freely accessible database of common endocrine- and cell specific-enhancer regions that can be navigated with minimal bioinformatics expertise.ConclusionsBoth alpha and delta cells appear poised, but repressed, from becoming beta cells in murine pancreatic islets. These data broadly support earlier findings on the plasticity in identity of non-beta cells under certain circumstances. Furthermore, differential chromatin accessibility shows preferentially enriched distal-intergenic regions in beta cells, when compared to either alpha or delta cells.

Abstract Background The National Health Service in England pledged >£365 million to improve access to mental healthcare services via Community Perinatal Mental Health Teams (CPMHTs) and reduce the rate of perinatal relapse in women with severe mental illness. This study aimed to explore changes in service use patterns following the implementation of CPMHTs in pregnant women with a history of specialist mental healthcare in England, and conduct a cost-analysis on these changes. Methods This study used a longitudinal cohort design based on existing routine administrative data. The study population was all women residing in England with an onset of pregnancy on or after 1st April 2016 and who gave birth on or before 31st March 2018 with pre-existing mental illness (N = 70,323). Resource use and costs were compared before and after the implementation of CPMHTs. The economic perspective was limited to secondary mental health services, and the time horizon was the perinatal period (from the start of pregnancy to 1-year post-birth, ~ 21 months). Results The percentage of women using community mental healthcare services over the perinatal period was higher for areas with CPMHTs (30.96%, n=9,653) compared to areas without CPMHTs (24.72%, n=9,615). The overall percentage of women using acute care services (inpatient and crisis resolution teams) over the perinatal period was lower for areas with CPMHTs (4.94%, n=1,540 vs. 5.58%, n=2,171), comprising reduced crisis resolution team contacts (4.41%, n=1,375 vs. 5.23%, n=2,035) but increased psychiatric admissions (1.43%, n=445 vs. 1.13%, n=441). Total mental healthcare costs over the perinatal period were significantly higher for areas with CPMHTs (fully adjusted incremental cost £111, 95% CI £29 to £192, p-value 0.008). Conclusions Following implementation of CPMHTs, the percentage of women using acute care decreased while the percentage of women using community care increased. However, the greater use of inpatient admissions alongside greater use of community care resulted in a significantly higher mean cost of secondary mental health service use for women in the CPMHT group compared with no CPMHT. Increased costs must be considered with caution as no data was available on relevant outcomes such as quality of life or satisfaction with services.

Abstract Ovarian cancer is the most lethal gynecologic malignancy, mainly due to late-stage diagnosis, frequent recurrences, and eventually therapy resistance. To identify potentially actionable genetic variants, sequencing data of 351 Belgian ovarian cancer patients were retrospectively captured from electronic health records. The cohort included 286 (81%) patients with high-grade serous ovarian cancer, 17 (5%) with low-grade serous ovarian cancer, and 48 (14%) with other histotypes. Firstly, an overview of the prevalence and spectrum of the BRCA1/2 variants highlighted germline variants in 4% (11/250) and somatic variants in 11% (37/348) of patients. Secondly, application of a multi-gene panel in 168 tumors revealed a total of 214 variants in 28 genes beyond BRCA1/2 with a median of 1 (IQR, 1–2) genetic variant per patient. The ten most often altered genes were (in descending order): TP53, BRCA1, PIK3CA, BRCA2, KRAS, ERBB2 (HER2), TERT promotor, RB1, PIK3R1 and PTEN. Of note, the genetic landscape vastly differed between the studied histotypes. Finally, using ESCAT the clinical evidence of utility for every genetic variant was scored. Only BRCA1/2 pathogenic variants were classified as tier-I. Nearly all patients (151/168; 90%) had an ESCAT tier-II variant, most frequently in TP53 (74%), PIK3CA (9%) and KRAS (7%). In conclusion, our findings imply that although only a small proportion of genetic variants currently have direct impact on ovarian cancer treatment decisions, other variants could help to identify novel (personalized) treatment options to address the poor prognosis of ovarian cancer, particularly in rare histotypes.

Abstract Terbium-149 (T1/2 = 4.1 h, Eα = 3.98 MeV (16.7%), 28 µm range in tissue) is a radionuclide with potential for targeted alpha therapy. Due to the negligible emission of α-emitting daughter nuclides, toxicity to healthy tissue may be reduced in comparison with other α-particle emitters. In this study, terbium-149 was produced via 1.4 GeV proton irradiation of a tantalum target at the CERN-ISOLDE facility. The spallation products were mass separated and implanted on zinc-coated foils and, later, radiochemically processed. Terbium-149 was separated from the co-produced isobaric radioisotopes and the zinc coating from the implantation foil, using cation-exchange and extraction chromatographic techniques, respectively. At the end of separation, up to 260 MBq terbium-149 were obtained with > 99% radionuclidic purity. Radiolabeling experiments were performed with DOTATATE, achieving 50 MBq/nmol apparent molar activity with radiochemical purity > 99%. The chemical purity was determined by inductively coupled plasma–mass spectrometry measurements, which showed lead, copper, iron and zinc only at ppb level. The radiolabeling of the somatostatin analogue DOTATATE with [149Tb]TbCl3 and the subsequent in vivo PET/CT scans conducted in xenografted mice, showing good tumor uptake, further demonstrated product quality and its ability to be used in a preclinical setting.

3D-printed microporous titanium scaffolds enjoy good biointegration with the residuum’s soft and bone tissues, and they promote excellent biomechanical properties in attached prostheses. Implant-associated infection, however, remains a major clinical challenge. Silver-based implant coatings can potentially reduce bacterial growth and inhibit biofilm formation, thereby reducing the risk of periprosthetic infections. In the current study, a 1-µm thick silver coating was prepared on the surface of a 3D-printed microporous titanium alloy with physical vapor deposition (PVD), with a final silver content of 1.00 ± 02 mg/cm2. Cell viability was evaluated with an MTT assay of MC3T3-E1 osteoblasts and human dermal fibroblasts cultured on the surface of the implants, and showed low cytotoxicity for cells during the 14-day follow-up period. Quantitative real-time polymerase chain reaction (RT-PCR) analysis of the relative gene expression of the extracellular matrix components (fibronectin, vitronectin, type I collagen) and cell adhesion markers (α2, α5, αV, β1 integrins) in dermal fibroblasts showed that cell adhesion was not reduced by the silver coating of the microporous implants. An RT-PCR analysis of gene expression related to osteogenic differentiation, including TGF-β1, SMAD4, osteocalcin, osteopontin, and osteonectin in MC3T3-E1 osteoblasts, demonstrated that silver coating did not reduce the osteogenic activity of cells and, to the contrary, enhanced the activity of the TGF-β signaling pathway. For representative sample S5 on day 14, the gene expression levels were 7.15 ± 0.29 (osteonectin), 6.08 ± 0.12 (osteocalcin), and 11.19 ± 0.77 (osteopontin). In conclusion, the data indicate that the silver coating of the microporous titanium implants did not reduce the biointegrative or osteoinductive properties of the titanium scaffold, a finding that argues in favor of applying this coating in designing personalized osseointegrated implants.