Search

The E0 transition strength in the 22+→21+ transitions of 58,60,62Ni have been determined for the first time following a series of measurements at the Australian National University (ANU) and the University of Kentucky (UK). The CAESAR Compton-suppressed HPGe array and the Super-e solenoid at ANU were used to measure the δ(E2/M1) mixing ratio and internal conversion coefficient of each transition following inelastic proton scattering. Level half-lives, δ(E2/M1) mixing ratios and γ-ray branching ratios were measured at UK following inelastic neutron scattering. The new spectroscopic information was used to determine the E0 strengths. These are the first 2+→2+ E0 transition strengths measured in nuclei with spherical ground states and the E0 component is found to be unexpectedly large; in fact, these are amongst the largest E0 transition strengths in medium and heavy nuclei reported to date. Keywords: Electric monopole (E0) transitions, Internal conversion, Mixing ratios, Nuclear structure

Background: People with a chronic condition such as Parkinson’s disease (PD) struggle with acceptance and finding meaning in life. Consciousness coaching could be a valuable addition in addressing these issues. Objective: We aim to evaluate the user experiences and potential effectiveness of consciousness coaching for people with PD (PwPD). Methods: We performed a pilot randomized controlled trial including PwPD in Hoehn & Yahr stage 1–3. People with cognitive impairments, severe psychiatric disorders, or those who did not have a clear issue to address with consciousness coaching, were excluded. PwPD were randomly allocated to either receiving 6 months of consciousness coaching in addition to usual care or to usual care alone. To explore experiences we performed semi-structured qualitative interviews with all PwPD in the intervention group. Potential effects were explored using questionnaires on quality of life, activities of daily life, self-management and non-motor symptoms at baseline and after 6 months. Results: We included 39 PwPD, 19 participants in the intervention group and 20 in the control group. Based on the interviews, we identified a number of themes and codes. In general PwPD experienced consciousness coaching as confronting but supportive in reaching their goals and in taking more responsibility for their lives. Quantitatively, we did not find a difference between groups for any of the outcomes. Conclusions: Consciousness coaching was considered valuable by most participants in this study and may be an interesting addition to PD treatment. We did not find any effects of the intervention on PD symptoms or quality of life.

Background: Aim of this study was to investigate immune cells and subsets in different stages of human coronary artery disease with a novel multiplex immunohistochemistry (mIHC) technique. Methods: Human left anterior descending coronary artery specimens were analyzed: eccentric intimal thickening (N = 11), pathological intimal thickening (N = 10), fibroatheroma (N = 9), and fibrous plaque (N = 9). Eccentric intimal thickening was considered normal, and pathological intimal thickening, fibroatheroma, and fibrous plaque were considered diseased coronary arteries. Two mIHC panels, consisting of six and five primary antibodies, autofluoresence, and DAPI, were used to detect adaptive and innate immune cells. Via semi-automated analysis, (sub)types of immune cells in whole plaques and specific plaque regions were quantified. Results: Increased numbers of CD3+ T cells (P

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease with a fast increasing prevalence. Several pharmacological and non-pharmacological interventions are available to alleviate symptoms. Technology can be used to improve the efficiency, accessibility and feasibility of these treatments. Although many technologies are available, only few are actually implemented in daily clinical practice. Aim: Here, we study the barriers and facilitators, as experienced by patients, caregivers and/or healthcare providers, to successful implement technology for PD management. Methods: We performed a systematic literature search in the PubMed and Embase databases until June 2022. Two independent raters screened the titles, abstracts and full texts on: 1) people with PD; 2) using technology for disease management; 3) qualitative research methods providing patients’, caregivers and/or healthcare providers’ perspective, and; 4) full text available in English or Dutch. Case studies, reviews and conference abstracts were excluded. Results: We found 5420 unique articles of which 34 were included in this study. Five categories were made: cueing (n = 3), exergaming (n = 3), remote monitoring using wearable sensors (n = 10), telerehabilitation (n = 8) and remote consultation (n = 10). The main barriers reported across categories were unfamiliarity with technology, high costs, technical issues and (motor) symptoms hampering the use of some technologies. Facilitators included good usability, experiencing beneficial effects and feeling safe whilst using the technology. Conclusion: Although only few articles presented a qualitative evaluation of technologies, we found some important barriers and facilitators that may help to bridge the gap between the fast developing technological world and actual implementation in day-to-day living with PD.

Background: Females, people with young-onset PD and older individuals, and non-white populations are historically underrepresented in clinical Parkinson’s disease (PD) research. Furthermore, research traditionally focused predominantly on motor symptoms of PD. Including a representative and diverse group of people with PD and also studying non-motor symptoms is warranted to better understand heterogeneity in PD and to generalize research findings. Objective: This project aimed to determine whether, within a consecutive series of PD studies performed within a single center in the Netherlands: (1) the proportion of included females, mean age and proportion of native Dutch people changed over time; and 2) reports of the ethnicity of participants and the proportion of studies with non-motor outcomes changed over time. Methods: Characteristics of participants and non-motor outcomes were analyzed using a unique dataset of summary statistics of studies with a large number of participants conducted at a single center during a 19-year period (2003–2021). Results: Results indicate no relationship between calendar time and proportion of females (mean 39 %), mean age (66 years), proportion of studies that reported ethnicity, and proportion of native Dutch people in studies (range 97–100 %). The proportion of participants in whom non-motor symptoms were assessed increased, but this difference was consistent with chance. Conclusion: Study participants in this center reflect the PD population in the Netherlands in terms of sex, but older individuals and non-native Dutch individuals are under-represented. We have still a lot to do in ensuring adequate representation and diversity in PD patients within our research.

Objective: A lack of demonstrated clinical benefit precludes radiotherapy (RT) from being recommended for pN1/pN2 penile cancer (PeCa) lesions; but it may be recommended in case of extranodal (pN3) disease or for positive resection margins. Perineal urethrostomy (PU) is a technique of urinary diversion in patients with PeCa requiring total or subtotal penectomy as primary therapy. Prior studies suggest PU failure rates of up to 30%, without specific mention of the potential role of RT. When RT is delivered for PeCa it is usually to the pre-pubic fat, groin and lateral pelvis, and not to the region of the PU. Here we describe the role of perioperative RT in a large, multi-institutional registry of PU for PeCa. Methods: In our cohort, 299 patients from seven international, high-volume centers in Belgium, Brazil, China, Netherlands, United Kingdom and the United States underwent PU as urinary diversion for PeCa between 2000 and 2020. Demographic and clinicopathologic characteristics were reviewed. Results: Median patient age was 67 years and median follow-up was 19 months. Seven patients (2.3%) received pre-operative RT; six of them with chemotherapy. 37 received RT post-operatively, 21 (57%) with chemotherapy. Stenosis of the PU occurred in 35 (12%) of the total population. The majority of these patients (74%) required surgical revision at a median of 6.1 months post-operatively. RT delivery was neither significantly related to PU stenosis (p = 0.16) or to subsequent revision (p = 0.75). Conclusion: Receipt of RT was not significantly associated with increased stenosis risk in PeCa patients who underwent PU.

Background: Mothers of children with fetal alcohol spectrum disorders tend to have lower weight compared to other mothers. Yet how alcohol and maternal weight may predispose infants to poorer physical growth and neurodevelopmental trajectories is relatively unexplained. Methods: South African mothers (n = 406) were recruited prenatally and their offspring were provided standardized dysmorphology and neurodevelopment examinations at 6 weeks and 9 months of age. Maternal weight was obtained postpartum, and linear mixed modeling determined whether postpartum maternal weight and prenatal alcohol exposure significantly influenced infant growth, dysmorphology, and neurodevelopment within the first year of life. Results: Postpartum maternal weight was positively associated with birth length, weight, and head circumference centile, but the rate of growth from birth to nine months was similar among all infants. Maternal weight was inversely associated with dysmorphology. Many infants in this population were performing within the borderline or extremely low range. Higher maternal weight was associated with significantly better cognitive and motor performance at 6 weeks; however, the rate of developmental growth was similar among all infants, regardless of postpartum maternal weight. Conclusion: Higher postpartum maternal weight may be a protective factor but does not eliminate the adverse effects of alcohol on infant growth and dysmorphology. Regardless of maternal weight, alcohol remains a powerful teratogen and moderate to high use prenatally can result in adverse infant physical and neurocognitive development.

Carriers of a pathogenic germline mutations in the PTEN gene, a well-known tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, e.g. breast, thyroid, endometrial and colon cancer. This is called PTEN Hamartomous Tumor Syndrome (PHTS). PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. The effects of PTEN on the immune system have been studied in murine knockout models demonstrating that loss of PTEN function leads to dysregulation of the immune response. This results in susceptibility to autoimmunity, impaired B cell class switching with subsequent hypogammaglobulinemia. Additionally, a decreased ability of dendritic cells to prime CD8+ T cells was observed, leading to impaired tumor eradication. Immune dysfunction in PHTS patients has not yet been extensively studied but might be a manageable contributing factor to the increased cancer risk in PHTS.

Stress urinary incontinence is not a deadly disease, but for the large population of women suffering from it, it is a very important issue. Especially in the continuously aging population all over the world, there is more and more need for treatment of this serious medical condition. Treatment of female stress urinary incontinence exists already for ages. In the 20th century invasive treatments like Burch colposuspension and pubovaginal slings were the mainstay of surgical treatments. The introduction of the midurethral sling made the procedure less invasive and accessible for more caregivers. Luckily there are many options available and the field is developing quickly. In recent years many new medical devices have been developed, that increase the number of treatment options available and make it possible to find a suitable solution for the individual patient based on subjective and objective results and the chances of complications. This manuscript provides an introduction to the therapeutical options that are available nowadays for female stress urinary incontinence. Keywords: Female, Stress urinary incontinence, Treatment, Urinary incontinence, Pelvic floor muscle training, Suburethral slings

Summary: Plasmacytoid dendritic cells (pDCs) and type 2 conventional dendritic cells (cDC2s) are currently under evaluation for use in cancer vaccines. Although both DC subsets can activate adaptive and innate lymphocytes, their capacity to recruit such cells is rarely considered. Here, we show that pDCs and cDC2s display a striking difference in chemokine secretion, which correlates with the recruitment of distinct types of immune effector cells. Activated pDCs express high levels of CXCR3 ligands and attract more CD8+ T cells, CD56+ T cells, and γδ T cells in vitro, compared to cDC2s. Skin from melanoma patients shows an influx of immune effector cells following intradermal vaccination with pDCs or cDC2s, with pDCs inducing the strongest influx of lymphocytes known to possess cytolytic activity. These findings suggest that combining both DC subsets could unite the preferred chemoattractive properties of pDCs with the superior T cell priming properties of cDC2s to ultimately enhance vaccine efficacy. : Human plasmacytoid dendritic cells and type 2 conventional dendritic cells are currently used in cancer vaccines to induce antitumor immune responses. van Beek et al. compared their chemoattractive properties and identified a striking difference in chemokine secretion, resulting in the attraction of distinct immune effector cells. Keywords: pDC, cDC2, chemokines, migration, DC vaccines

Dendritic cells (DCs) play a key role in orchestrating adaptive immune responses. In human blood, three distinct subsets exist: plasmacytoid DCs (pDCs) and BDCA3+ and CD1c+ myeloid DCs. In addition, a DC-like CD16+ monocyte has been reported. Although RNA-expression profiles have been previously compared, protein expression data may provide a different picture. Here, we exploited label-free quantitative mass spectrometry to compare and identify differences in primary human DC subset proteins. Moreover, we integrated these proteomic data with existing mRNA data to derive robust cell-specific expression signatures with more than 400 differentially expressed proteins between subsets, forming a solid basis for investigation of subset-specific functions. We illustrated this by extracting subset identification markers and by demonstrating that pDCs lack caspase-1 and only express low levels of other inflammasome-related proteins. In accordance, pDCs were incapable of interleukin (IL)-1β secretion in response to ATP.

Introduction: The effect of neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer, at increased risk of failing current treatment regimens, is unknown. This study compared the complete response rate and long-term survival of these patients treated with or without neoadjuvant chemotherapy prior to chemoradiotherapy., Materials and Methods: Patients with high-risk locally advanced rectal cancer, who were surgically treated or entered a watch and wait approach after neoadjuvant chemoradiotherapy with or without neoadjuvant chemotherapy in Erasmus Medical Centre or Catharina Hospital between 2016 and 2020, were retrospectively identified. High-risk was defined as the presence of tumour invasion into the mesorectal fascia, grade 4 extramural venous invasion, enlarged lateral lymph nodes, or tumour deposits. The primary endpoint was complete response rate, which was defined as a histopathological complete response or a sustained (during 12 months) clinical complete response. Long-term oncological outcomes were evaluated based on Kaplan-Meier and Cox regression survival analyses., Results: The neoadjuvant chemotherapy group consisted of 64 patients, of whom 61 (95.3 %) were treated with chemotherapy prior to chemoradiotherapy, the chemoradiotherapy group of 194 patients. The complete response rates were 25.0 % and 9.8 %, respectively (P = 0.002). The estimated 3-year overall survival was 92.2 % in the neoadjuvant chemotherapy group versus 66.9 % in the chemoradiotherapy group., Conclusion: Excellent oncological outcomes were observed in patients with high-risk locally advanced rectal cancer selected during a multidisciplinary team (MDT) meeting for neoadjuvant chemotherapy and chemoradiotherapy. The actual difference with patients treated with chemoradiotherapy alone should be investigated in prospective trials. Pretreatment referral to expert MDTs is encouraged., Competing Interests: Declarations of interest The authors have no disclosures of interest., (Copyright © 2025 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning. The objective of this study was to determine the effectiveness of MTB treatment recommendations for patients with rare and complex mutational profiles as implemented in the MTB of the University Medical Center Groningen (UMCG-MTB) in 2019-2020., Patients and Methods: A retrospective follow-up study was carried out to determine the clinical outcome of patients with uncommon or rare (combinations of) molecular aberrations for whom targeted therapy was recommended as the next line of treatment by the UMCG-MTB in 2019 and 2020., Results: The UMCG-MTB recommended targeted therapy as the next line of treatment in 132 of 327 patients: 37 in clinical trials, 67 in the on-label setting, and 28 in the off-label setting. For on- and off-label treatment recommendations, congruence of recommended and received treatment was 85% in patients with available follow-up (67/79). Treatment with on-label therapy resulted in a response rate of 50% (21/42), a median progression-free survival (PFS) of 6.3 months [interquartile range (IQR) 2.9-14.9 months], and median overall survival (OS) of 15.8 months (IQR 6.4-34.2 months). Treatment with off-label therapy resulted in a response rate of 53% (8/15), a median PFS of 5.1 months (IQR 1.9-7.3 months), and a median OS of 17.7 months (IQR 5.1-23.7 months)., Conclusion: Treatment with MTB-recommended next-line targeted therapy for patients with often heavily pretreated cancer with rare and complex mutational profiles resulted in positive overall responses in over half of patients. Off-label use of targeted therapies, for which there is sufficient rationale as determined by an MTB, is an effective treatment strategy. This study underlines the relevance of discussing patients with rare and complex mutational profiles in an MTB., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Chronic hypercapnia, defined by elevated blood CO 2 levels, is a serious complication most prevalent in severe COPD. It negatively impacts quality of life, increases hospitalization rates, and elevates mortality risks. However, not all severe COPD patients develop chronic hypercapnia, and its underlying mechanisms remain unclear. Identifying clinical and pathophysiological predictors of hypercapnia is essential for tailored treatment strategies. This study investigates the relationship between hypercapnia and patient characteristics, lung function, and CT scan features to identify potential therapeutic targets., Methods: This cross-sectional study included 1526 COPD patients from three cohorts: a standard care cohort and two research cohorts (NCT04023409; NCT03053973). Data collected included demographic and clinical information, blood gases, lung function (FEV 1 , FVC, TLC, RV, DLCOc), and high-resolution CT scans (lung volumes, air trapping, emphysema scores, airway wall thickness (Pi10), and diaphragm indices)., Results: Hypercapnia prevalence increased with COPD severity. Hypercapnic patients were older, more likely to smoke, and had more comorbidities. They exhibited lower FEV 1 and FVC, and higher RV/TLC ratios, with CT scans showing lower emphysema scores and greater Pi10. Multivariate analysis identified lower PaO 2 , FEV 1 % predicted, and emphysema scores, along with higher RV/TLC ratios and NT-proBNP levels, as independent predictors of PaCO 2 , collectively explaining 46.3 % of the variance., Conclusion: COPD patients with chronic hypercapnia are characterized by higher smoking rates, lower PaO 2 levels, poorer lung function, less emphysema, and increased airway pathology. These findings underscore the multifactorial nature of hypercapnia in COPD, highlighting the need for personalized therapeutic strategies targeting these factors to improve outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dirk-Jan Slebos reports relationships with PulmonX Corp, USA (consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement), Nuvaira, USA (consulting or advisory, funding grants, and speaking and lecture fees), PulmAir, USA (funding grants), Apreo, USA (consulting or advisory and funding grants), MoreAir, USA (consulting or advisory), and FreeFlowMedical, USA (funding grants). Peter J. Wijkstra reports a relationship with the European Respiratory Society (board membership), ResMed (funding grants), and Philips (consulting or advisory and funding grants). Marieke L. Duiverman reports relationships with Vivisol (funding grants and speaking and lecture fees), ResMed (funding grants), Fisher & Paykel (funding grants), Löwenstein B.V. (funding grants), Sencure B.V. (funding grants), Chiesi (speaking and lecture fees), Breas (speaking and lecture fees), and AstraZeneca (speaking and lecture fees). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

According to the arousal-mood hypothesis, changes in arousal and mood when exposed to auditory stimulation underlie the detrimental effects or improvements in cognitive performance. Findings supporting or against this hypothesis are, however, often based on subjective ratings of arousal rather than autonomic/physiological indices of arousal. To assess the arousal-mood hypothesis, we carried out a systematic review of the literature on 31 studies investigating cardiac, electrodermal, and pupillometry measures when exposed to different types of auditory stimulation (music, ambient noise, white noise, and binaural beats) in relation to cognitive performance. Our review suggests that the effects of music, noise, or binaural beats on cardiac, electrodermal, and pupillometry measures in relation to cognitive performance are either mixed or insufficient to draw conclusions. Importantly, the evidence for or against the arousal-mood hypothesis is at best indirect because autonomic arousal and cognitive performance are often considered separately. Future research is needed to directly evaluate the effects of auditory stimulation on autonomic arousal and cognitive performance holistically., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Birth plans can be used to facilitate shared decision-making in childbirth. A birth plan is a document reflecting women's preferences for birth, which they discuss with their maternity care provider., Aim: This scoping review aims to synthesize current findings on the role of birth plans for shared decision-making around birth choices of pregnant women in maternity care., Methods: We conducted a scoping review using the Joanna Briggs Institute three-step search strategy in multiple databases PubMed, EMBASE, CINAHL, Web of Science, PsycINFO. We synthesized the results using a metasynthesis approach to identify themes and subthemes., Results: From the 21 articles included, five themes were identified: birth plan as a tool for shared decision-making, autonomy, sense of control, professionalism of the care provider, and trust. Primarily, midwives seemed to use birth plans to explore and facilitate women's choices around birth. Other healthcare providers involved in studies were obstetricians and nurses. The interrelationship between care providers and women, the attitude of care providers and women towards each other and the birth plan, and how providers and women use the birth plan influence shared decision-making., Discussion and Conclusion: Birth plans can facilitate shared decision-making, and women's sense of autonomy and control before, during, and after giving birth. When discussing the birth plan, exploring different scenarios may help women prepare for unforeseen circumstances. This will likely facilitate shared decision-making even if the birth process is not unfolding as hoped for., Competing Interests: Declaration of Competing Interest Not declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to ambient noise and air pollution may affect the manifestation and severity of Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). However, evidence is limited, and most studies solely assessed environmental exposures during pregnancy and early childhood., Objective: To examine the longitudinal effects of ambient noise and air pollutants on ASD and ADHD symptom severity during adolescence and early adulthood., Methods: Using a longitudinal design, we included 2750 children between 10 and 12 years old from the TRacking Adolescents' Individual Lives Survey (TRAILS) in the Netherlands, who were assessed in 6 waves from 2001 to 2017. ASD was measured by the Children's Social Behavior Questionnaire and the Adult Social Behavior Questionnaire. ADHD was measured by Child Behavior Checklist and the Adult Behavior Checklist. Ambient noise and air pollution exposures, including Ozone (O 3 ), soot, sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), particulate matter 2.5 (PM 2.5 ), and PM 10 were modeled at the residential level according to standardized protocols. The longitudinal associations between exposures and symptom outcomes were examined using linear mixed models., Results: We found evidence that higher levels of exposure to PM were associated with more severe ASD and ADHD symptoms. This association decreased over time. We did not observe any other consistent associations of noise or other air pollutants with ASD and ADHD severity., Conclusion: The current study provides evidence for the negative impact of PM on ASD and ADHD symptoms. We did not find evidence of the negative health impact of other air pollutants and noise exposures on ASD or ADHD symptoms. Our study adds more evidence on the presence of associations between PM air pollution and neurodevelopmental diseases among adolescents and young adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Indonesia is one of the world's economies contributing the most to greenhouse gas (GHG) emissions from the global food system. This study aimed to quantify the environmental impacts of Indonesian vegetable production and the relative contribution of different farm inputs. Data were collected from 322 vegetable farms in the Lembang sub-district in West Java. A Life Cycle Assessment (LCA) was carried out to estimate global warming potential (GWP), acidification potential (AP), freshwater eutrophication potential (EP), and abiotic resource depletion. Results of the LCA showed that GHG emissions were 14.1 t CO 2 eq ha -1 yr -1 (0.5 t CO 2 eq t -1 ), AP was 39.3 kg SO 2 eq ha -1 yr -1 (1.4 kg SO 2 eq t -1 ), EP was 45.3 kg PO 4 eq ha -1 yr -1 (1.7 kg PO 4 eq,), and depletion of phosphate, potash, and fossil fuel resources were 60.0 kg P 2 O 5, 101 kg K 2 O, and 6299 MJ ha -1 yr -1 , respectively (1.9 kg P 2 O 5 , 3.7 kg K 2 O, and 281 MJ t -1 ). Organic fertilizer use contributed the most to impact categories of global warming, freshwater eutrophication, and acidification, followed by synthetic fertilizer. The sensitivity analysis showed that yield and organic fertilizer use explained most of the variation in GHG emission per ton product. Therefore, it is recommended to include organic fertilizer use in the fertilizer advisory system for vegetable production in Indonesia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Enteric fermentation and manure methane emissions from livestock are major anthropogenic greenhouse gas emissions. In general, direct measurements of farm-scale methane emissions are scarce due to the source complexity and the limitations of existing atmospheric sampling methods. Using an innovative UAV-based active AirCore system, we have performed accurate atmospheric measurements of CH 4 mole fractions downwind of a dairy cow farm in the Netherlands on four individual days during the period from March 2017 to March 2019. The total CH 4 emission rates from the farm were determined using the UAV-based mass balance approach to be 1.1-2.4 g/s. After subtracting estimated emission factors of manure onsite, we derived the enteric emission factors to be 0.20-0.51 kgCH 4 /AU/d (1 AU = 500 kg animal weight) of dairy cows. We show that the uncertainties of the estimates were dominated by the variabilities in the wind speed and the angle between the wind and the flight transect. Furthermore, nonsimultaneous sampling in the vertical direction of the plume is one of the main limiting factors to achieving accurate estimate of the CH 4 emissions from the farm. In addition, a N 2 O tracer release experiment at the farm was performed when both a UAV and a mobile van were present to simultaneously sample the N 2 O tracer and the CH 4 plumes from the farm, improving the source quantification with a correction factor of 1.04 and 1.22 for the inverse Gaussian approach and for the mass balance approach, respectively. The UAV-based active AirCore system is capable of providing useful estimates of CH 4 emissions from dairy cow farms. The uncertainties of the estimates can be improved when combined with accurate measurements of local wind speed and direction or when combined with a tracer approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The invaluable health, economic and social impacts of vaccination are hard to exaggerate. The ability to stabilize vaccines is urgently required for their equitable distribution without the dependence on the 'cold-chain' logistics. Herein, for the first time we report biomimetic-mineralization of live-viral vaccines using metal-organic frameworks (MOFs) to enhance their storage stability from days to months. Applying ZIF-8 and aluminium fumarate (Alfum), the Newcastle Disease Virus (NDV) V4 strain and Influenza A WSN strain were encapsulated with remarkable retention of their viral titre. The ZIF-8@NDV, ZIF-8@WSN and Alfum@WSN composites were validated for live-virus recovery using a tissue culture infectious dose (TCID 50 ) assay. With the objective of long-term stabilization, we developed a novel, trehalose (T) and skim milk (SM) stabilized, freeze-dried MOF@Vaccine composite, ZIF-8@NDV+T/SM. The thermal stability of this composite was investigated and compared with the control NDV and non-encapsulated, freeze-dried NDV+T/SM composite at 4 °C, RT, and 37 °C over a period of 12 weeks. We demonstrate the fragility of the control NDV vaccine which lost all viability at RT and 37°C by 12 and 4 weeks, respectively. Comparing the freeze-dried counterparts, the MOF encapsulated ZIF-8@NDV+T/SM demonstrated significant enhancement in stability of the NDV+T/SM composite especially at RT and 37 °C upto 12 weeks. STATEMENT OF SIGNIFICANCE: Vaccination is undoubtedly one of the most effective medical interventions, saving millions of lives each year. However, the requirement of 'cold-chain' logistics is a major impediment to widespread immunization. Live viral vaccines (LVVs) are widely used vaccine types with proven efficacy and low cost. Nonetheless, their complex composition increases their susceptability to thermal stress. Several LVV thermostabilization approaches have been investigated, including their complex engineering and the facile addition of stabilizers. Still, the lack of a universal approach urgently requires finding a stabilization technique especially when additives alone may not be sufficient. Herein, we demonstrate MOF biomimetic-mineralization technology to encapsulate LVVs developing an optimised composite which significantly preserves vaccines without refrigeration for extended periods of time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Papillary Renal Cell Carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC) and a distinct entity, although heterogenous, associated with poor outcomes. The treatment landscape of metastatic pRCC (mpRCC) relied so far on targeted therapies, mimicking previous developments in metastatic clear-cell renal cell carcinoma. However, antiangiogenics as well as mTOR inhibitors retain only limited activity in mpRCC. As development of immune checkpoint inhibitors (ICI) is now underway in patients with mpRCC, we aimed at discussing early activity data and potential for future therapeutic strategies in monotherapy or combination. Expression of immune checkpoints such as PD-L1 and infiltrative immune cells in pRCC could provide insights into their potential immunogenicity, although this is currently poorly described. Based on retrospective and prospective data, efficacy of ICI as single agent remains limited. Combinations with tyrosine-kinase inhibitors, notably with anti-MET inhibitors, harbor promising response rates and may enter the standard of care in untreated patients. Collaborative work is needed to refine the molecular and immune landscape of pRCC, and pursue efforts to set up predictive biomarker-driven clinical trials in these rare tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the clinical relevance of indeterminate lung nodules (ILN) in patients with locally recurrent rectal cancer (LRRC) treated in a tertiary referral centre., Methods: All patients with LRRC diagnosed between 2000 and 2017 were retrospectively reviewed. Reports of staging chest CT-scans were evaluated for ILN. Patients with distant metastases including lung metastases at time of LRRC diagnosis were excluded. Overall (OS), progression-free survival (PFS) and the cumulative incidence of lung metastases were compared between patients with and without ILN., Results: In total 556 patients with LRRC were treated during the study period. In the 243 patients eligible for analysis, 68 (28%) had ILN at LRRC diagnosis. Median OS was 37 months for both the patients with and without ILN (p = 0.37). Median PFS was 14 months for the patients with ILN and 16 months for patients without ILN (p = 0.80). After correction for potential confounding, ILN present at LRRC diagnosis was not associated with impaired OS or PFS (adjusted hazards ratio [95% confidence interval]: 0.81 [0.54-1.22] and 1.09 [0.75-1.59]). The 5-year cumulative incidence of lung metastases was 31% in patients with ILN and 28% in patients without ILN (p = 0.19)., Conclusion: Our study shows that ILN are present in roughly a quarter of patients with LRRC. No differences in OS, PFS, or the cumulative incidence of lung metastases were found between patients with and without ILN at LRRC diagnosis. These results suggest that ILN are of little to no clinical relevance in patients with LRRC., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

The highly-conserved Grainyhead-like (Grhl) transcription factors are critical regulators of embryogenesis that regulate cellular survival, proliferation, migration and epithelial integrity, especially during the formation of the craniofacial skeleton. Family member Grhl2 is expressed throughout epithelial tissues during development, and loss of Grhl2 function leads to significant defects in neurulation, abdominal wall closure, formation of the face and fusion of the maxilla/palate. Whereas numerous downstream target genes of Grhl2 have been identified, very little is known about how this crucial developmental transcription factor itself is regulated. Here, using in silico and in utero expression analyses and functional deletion in mice, we have identified a novel 2.4 ​kb enhancer element (mm1286) that drives reporter gene expression in a pattern that strongly recapitulates endogenous Grhl2 in the craniofacial primordia, modulates Grhl2 expression in these tissues, and augments Grhl2-mediated closure of the secondary palate. Deletion of this genomic element, in the context of inactivation of one allele of Grhl2 (through generation of double heterozygous Grhl2 +/ - ;mm1286 +/ - mice), results in a significant predisposition to palatal clefting at birth. Moreover, we found that a highly conserved 325 bp region of mm1286 is both necessary and sufficient for mediating the craniofacial-specific enhancer activity of this region, and that an extremely well-conserved 12-bp sequence within this element (CTGTCAAACAGGT) substantially determines full enhancer function. Together, these data provide valuable new insights into the upstream genomic regulatory landscape responsible for transcriptional control of Grhl2 during palatal closure., (Copyright © 2019. Published by Elsevier Inc.)

Chronic postsurgical pain (CPSP) following laparoscopic donor nephrectomy (LDN) is a disregarded topic. In this cross-sectional study, all consecutive patients who underwent an LDN at the Radboud University Medical Center (Radboudumc; 2003-2016) were approached for participation. Five hundred twelve living kidney donors were included and asked to complete two questionnaires, including the McGill Pain Questionnaire and the RAND Short Form-36 Health Status Inventory (RAND SF-36) regarding their health-related quality of life (HRQoL). The mean prevalence of CPSP following LDN was 5.7%, with a mean follow-up time of 6 years. Possible predictors of CPSP following LDN are severe early postoperative pain, previous abdominal surgery, and preexisting backache. The RAND SF-36 revealed an impaired HRQoL in patients with CPSP when compared to patients without CPSP. In conclusion, this study revealed that the prevalence of CPSP following LDN is substantial. Given the possible association between the presence of CPSP and impaired HRQoL scores, living kidney donors should be well informed in the preoperative phase about the risk of CPSP., (© 2019 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: ABCA4-associated disease, a recessive retinal dystrophy, is hallmarked by a large proportion of patients with only one pathogenic ABCA4 variant, suggestive for missing heritability., Methods: By locus-specific analysis of ABCA4, combined with extensive functional studies, we aimed to unravel the missing alleles in a cohort of 67 patients (p), with one (p = 64) or no (p = 3) identified coding pathogenic variants of ABCA4., Results: We identified eight pathogenic (deep-)intronic ABCA4 splice variants, of which five are novel and six structural variants, four of which are novel, including two duplications. Together, these variants account for the missing alleles in 40.3% of patients. Furthermore, two novel variants with a putative cis-regulatory effect were identified. The common hypomorphic variant c.5603A>T p.(Asn1868Ile) was found as a candidate second allele in 43.3% of patients. Overall, we have elucidated the missing heritability in 83.6% of our cohort. In addition, we successfully rescued three deep-intronic variants using antisense oligonucleotide (AON)-mediated treatment in HEK 293-T cells and in patient-derived fibroblast cells., Conclusion: Noncoding pathogenic variants, novel structural variants, and a common hypomorphic allele of the ABCA4 gene explain the majority of unsolved cases with ABCA4-associated disease, rendering this retinopathy a model for missing heritability in autosomal recessive disorders.

Objective: To investigate the effect of including an online decision aid (DA) during prostate cancer treatment counseling on decisional regret and information satisfaction in a one-year follow-up., Methods: Within a cluster RCT, 18 Dutch hospitals were randomized to DA counseling or care-as-usual, patients (n = 382) initially completed questionnaires directly after treatment decision making. Six and twelve months later regret (Decisional Regret Scale) and information satisfaction (SCIP-B) were assessed. Anxious and depressive symptoms (HADS) was included as possible covariate., Results: After 12 months, 43 participants (15%) regretted their treatment choice and 105 participants (36%) were dissatisfied with the information that was received at the time of decision-making, regardless of being exposed to the DA. Anxious and depressive symptoms at follow-up were associated with regret and information dissatisfaction., Conclusion: No long-term benefical effects emerged from DA usage compared to patients who underwent standard counseling., Practice Implications: During PCa treatment counseling, healthcare providers should be aware of anxious and depressive symptoms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

According to the European Water Framework Directive (WFD), chemical water quality is assessed by monitoring 45 priority substances. However, observed toxic effects can often not be attributed to these priority substances, and therefore there is an urgent need for an effect-based monitoring strategy that employs bioassays to identify environmental risk. Algal photosynthesis is a sensitive process that can be applied to identify the presence of hazardous herbicides in surface water. Therefore, the aim of this study was to employ an algal photosynthesis bioassay to assess surface water toxicity to algae and to identify the compounds causing the observed effects. To this purpose, Raphidocelis subcapitata was exposed to surface water samples and after 4.5 h photosynthetic efficiency was determined using PAM fluorometry. In this rapid high throughput bioassay, algal photosynthesis was affected by surface water from only one of 39 locations. Single compounds toxicity confirmation elucidated that the observed effect could be solely attributed to the herbicide linuron, which occurred at 110 times the EQS concentration and which is not included in the WFD priority substances list. In conclusion, applying the algal photosynthesis bioassay enables more efficient and effective assessment of toxicity to primary producers because it: (i) identifies the presence of herbicides that would be overlooked by routine chemical WFD monitoring, and (ii) avoids redundant chemical analyses by focusing only on (non-)target screening in samples with demonstrated effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objective: Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults., Methods: Design: A systematic review and meta-analysis., Data Sources: Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately., Results: In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed., Conclusion: Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related falls., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Falls are a major public health problem in older adults. Earlier studies showed that psychotropic medication use increases the risk of falls. The aim of this study is to update the current knowledge by providing a comprehensive systematic review and meta-analysis on psychotropic medication use and falls in older adults., Methods and Design: This study is a systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated psychotropics (antipsychotics, antidepressants, anxiolytics, sedatives, and hypnotics) as risk factors for falls in participants ≥60 years of age or participants with a mean age of ≥70 years. Meta-analyses were performed using generic inverse variance method pooling unadjusted and adjusted odds ratio (OR) estimates separately., Results: In total, 248 studies met the inclusion criteria for qualitative synthesis. Meta-analyses using adjusted data showed the following pooled ORs: antipsychotics 1.54 [95% confidence interval (CI) 1.28-1.85], antidepressants 1.57 (95% Cl 1.43-1.74), tricyclic antidepressants 1.41 (95% CI 1.07-1.86), selective serotonin reuptake inhibitors 2.02 (95% CI 1.85-2.20), benzodiazepines 1.42 (95%, CI 1.22-1.65), long-acting benzodiazepines 1.81 (95%, CI 1.05-3.16), and short-acting benzodiazepines 1.27 (95%, CI 1.04-1.56) Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and healthcare setting., Conclusions: Antipsychotics, antidepressants, and benzodiazepines are consistently associated with a higher risk of falls. It is unclear whether specific subgroups such as short-acting benzodiazepines and selective serotonin reuptake inhibitors are safer in terms of fall risk. Prescription bias could not be accounted for. Future studies need to address pharmacologic subgroups as fall risk may differ depending on specific medication properties. Precise and uniform classification of target medication (Anatomical Therapeutic Chemical Classification) is essential for valid comparisons between studies., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications., Methods and Design: A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately., Results: In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association)., Conclusion: Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Implicit associations influence behaviour, but their impact on cancer screening intentions is unknown., Methods: We assessed implicit associations with cervical cancer screening using an evaluative priming task. Participants were shown primes ('Pap test', neutral or non-word) followed by positive or negative target words. The test is based on the assumption that response times are shorter if primes and targets are strongly associated in the participant's mind. The Dutch screening program targets women aged 30-60, 226 of them completed online assessments twice. Prior to the second assessment participants were randomized to reading versus not reading the leaflet about the cervical screening program., Results: After controlling for knowledge and screen history, response times for 'Pap test' no longer differed between positive and negative targets. Implicit associations were not correlated with explicit attitudes or screening intentions. Reading the screening leaflet resulted in improved knowledge levels (p<0.001), but implicit associations, explicit attitudes, and screening intentions remained similar., Conclusion: Cervical cancer screening intentions were related to explicit attitudes, but not to implicit associations. The screening leaflet did not affect screening intentions., Practice Implications: We recommend achieving a deepened interest in the screening program among risk groups, e.g. by adapting the information leaflet., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To determine the effect of a decision aid (DA) on treatment preferences and to investigate which patient preferences are important for final treatment preferences. We also determined if the patient׳s treatment decision was influenced by the urologist׳s treatment preference., Patients and Methods: Between August 2014 and July 2015, newly diagnosed patients with low-/intermediate-risk prostate cancer were offered to use a web-based DA after diagnosis. Treatment preferences and patient׳s values were extracted from the DA. Urologists׳ treatment preferences were indicated at the time of inclusion., Results: We included 181 patients, of whom 21% preferred active surveillance, 33% radical prostatectomy, 10% brachytherapy, 3% external beam radiotherapy, and 34% did not indicate a specific preferred treatment option after DA use (missing N = 6). Among 67%, treatment preference before DA use did not change after DA use. In men who chose active surveillance after DA use, 97% (37/38) preferred to postpone unnecessary treatment. For radical prostatectomy, 91% (52/57) of the patients valued tumor removal, and for brachytherapy, 88% (15/17) valued incontinence worse than bowel complaints. For 64% (missing N = 21) of the patients, urologists indicated one specific preferred treatment option as most suitable for the patient concerned. Agreement between final treatment decision and urologist׳s preference was lower (κ = 0.68) than between final treatment decision and preferred treatment after DA use (κ = 0.82)., Conclusion: Most patients with prostate cancer chose the treatment in accordance with the post-DA preference and to a lesser extent the urologists preference; implications of this are prospectively investigated in an ongoing study., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate decision-making role preferences and their association with the evaluation of information received in a sample of low-risk and intermediate-risk prostate cancer (Pca) survivors., Methods: Cross-sectional study involved 562 men diagnosed with low-risk or intermediate-risk Pca (median time since diagnosis, 48mo), measuring preferred decision-making role (Control Preference Scale) and the evaluation of information received (EORTC QLQ-INFO25). Analyses were performed using analysis of variance, chi-square tests, and multivariable linear regression models., Results: Men who preferred a passive role were older and less educated than other preference groups and more often selected a noninvasive treatment option (all with P<0.001). The passive role preference group reported having received less information, judged the received information as less helpful, and indicated lower overall satisfaction with information received (all with P<0.05). Role preference groups did not differ in their desire to receive more information., Conclusion: Compared with nonpassive preference groups, the preference for a passive role in Pca treatment decision-making is associated with less satisfaction with the information received., Practice Implications: Assessment of role preferences and tailored information provision could improve satisfaction with information received and perhaps may ultimately lead to improved patient participation in treatment decision-making., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To develop a web-based decision aid (DA) for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH)., Methods: From February-September 2014 we performed a four-stage development method: 1: Two-round Delphi consensus method among urologists, 2: Identifying patients' needs and expectations, 3: Development of DA content and structure, 4: Usability testing with LUTS/BPH patients., Results: 1 (N=15): Dutch urologists reached consensus on 61% of the statements concerning users' criteria, decision options, structure, and medical content. 2 (N=24): Consensus was reached in 69% on statements concerning the need for improvement of information provision, the need for DA development and that the DA should clarify patients' preferences. 3: DA development based on results from stage 1 and stage 2. 4 (N=10): Pros of the DA were clear information provision, systematic design and easy to read and re-read., Conclusion: A LUTS/BPH DA containing VCEs(**) was developed in cooperation with urologists and patients following a structured 4 stage method and was stated to be well accepted., Practice Implications: This method can be adopted for the development of DAs to support other medical decision issues., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Allocation of inevitably limited financial resources for health care requires assessment of an intervention's effectiveness. Interventions likely affect quality of life (QOL) more broadly than is measurable with commonly used health-related QOL utility scales. In line with the World Health Organization's definition of health, a recent Delphi procedure showed that assessment needs to put more emphasis on mental and social dimensions., Objective: To identify the core dimensions of health-related subjective well-being (HR-SWB) for a new, more comprehensive outcome measure., Methods: We formulated items for each domain of an initial Delphi-based set of 21 domains of HR-SWB. We tested these items in a large sample (N = 1143) and used dimensionality analyses to find a smaller number of latent factors., Results: Exploratory factor analysis suggested a five-factor model, which explained 65% of the total variance. Factors related to physical independence, positive affect, negative affect, autonomy, and personal growth. Correlations between the factors ranged from 0.19 to 0.59. A closer inspection of the factors revealed an overlap between the newly identified core dimensions of HR-SWB and the validation scales, but the dimensions of HR-SWB also seemed to reflect additional aspects. This shows that the dimensions of HR-SWB we identified go beyond the existing health-related QOL instruments., Conclusions: We identified a set of five key dimensions to be included in a new, comprehensive measure of HR-SWB that reliably captures these dimensions and fills in the gaps of the existent measures used in economic evaluations., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Introduction: Although limitation of pronation/supination following both-bone forearm fractures in children is often attributed to an angular malunion, no clinical study has compared pronation/supination and angular malalignment of the same child by analysis of prospectively collected clinical data., Aim: The purpose of this trial is to explore whether limitation of pronation/supination can be predicted by the degree of angular malalignment in children who sustained a both-bone forearm fracture., Methods: In four Dutch hospitals, children aged ≤16 years with a both-bone forearm fracture were prospectively followed up consecutive children for 6-9 months. At the final follow-up, pronation/supination and angular malunion on radiographs were determined., Results: Between January 2006 and August 2010, a total of 410 children were prospectively followed up, of which 393 children were included for analysis in this study. The mean age of the children was 8.0 (±3.5) years, of which 63% were male and 40% fractured their dominant arm. The mean time to final examination was 219 (±51) days. Children with a metaphyseal both-bone fracture of the distal forearm with an angular malalignment of ≤15° had a 9-13% chance of developing a clinically relevant limitation (i.e., <50° of pronation and/or supination), while children with an angular malalignment of ≥16° had a 60% chance. Children with diaphyseal both-bone forearm fractures with ≤5° of angular malalignment had a 13% chance of developing a clinically relevant limitation, which showed no significant increase with a further increase of angular malalignment., Conclusions: Children who sustained a both-bone forearm fracture localised in the distal metaphysis have a higher chance of developing a clinically relevant limitation of forearm rotation in case of a more severe angular malalignment, while children with a diaphyseal both-bone forearm fracture had a moderate chance of limitation, irrespective of the severity of the angular malalignment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Current guidelines for the management of dyslipidaemias recommend measuring lipid profiles in the fasting state. The primary lipid targets are traditionally plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. However, triglycerides, apolipoprotein (apo) B and non-high-density lipoprotein-cholesterol (non-HDL-C) are also suitable parameters to assess cardiovascular risk and to guide lipid-lowering therapy. The advantage of the use of these variables is that they can be used in both the fasting and non-fasting state. In most cases, postprandial lipid profiles in combination with apo B are as useful as fasting lipid profiles for the differentiation between familial lipid disorders, such as heterozygous familial hypercholesterolemia, familial combined hyperlipidemia and familial hypertriglyceridemia. This article will address the interpretation, applications and limitations of a non-fasting lipid profile for daily clinical practice., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)