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Background and Purpose: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers. Methods: We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis. Results: We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0–3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 [95% CI, 0.5–1.2]). Conclusions: Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS.

BACKGROUND: With increasing knowledge of beta-lactam pharmacodynamics and interpatient and intrapatient variability in pharmacokinetics, the usefulness of therapeutic drug monitoring (TDM) is becoming increasingly clear. However, little research has been conducted to identify potential barriers and facilitators in the clinical implementation of beta-lactam TDM. This study provides an overview of the current practices of beta-lactam TDM and barriers and facilitators in its implementation. METHODS: A systematic search was conducted using the Ovid MEDLINE database in April 2021, without restrictions on the publication date. All studies reporting the implementation of beta-lactam antibiotic TDM in critically ill patients through questionnaires or surveys were included in this review. RESULTS: Six eligible studies were identified from 215 records, all of which were cross-sectional. All studies identified barriers and facilitators in the implementation of beta-lactam TDM in critically ill patients. The main barriers were insufficient knowledge about various aspects regarding the implementation of beta-lactam TDM and the unavailability of assays. Furthermore, a delay in the acquisition of TDM results reduces the probability of physicians altering drug dosages. Finally, doubts about the cost-effectiveness and clinical effectiveness of beta-lactam TDM in critically ill patients hinder broad implementation. Moreover, to improve the willingness of physicians to use beta-lactam TDM, collaboration between physicians and clinical pharmacists and clinical microbiologists should be strengthened. CONCLUSIONS: Although the evidence for application of beta-lactam TDM continues to grow, its clinical implementation remains limited. To enable optimal implementation of these antibiotics in critically ill patients, several barriers need to be overcome regarding logistics, equipment availability, clinical evidence, and proof of cost-effectiveness.

Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Context: A research agenda for oral health care was established in the Netherlands using the Dialogue Model. This project served as a case study in which we applied boundary-work theory as a framework to understand boundaries (ie demarcations) between and within groups, and how these boundaries can be overcome. Objective: To gain insights into the boundaries encountered when setting a research agenda, we analysed how this agenda served as a boundary object (ie circumstances, situations or material that connect actor groups and allow boundary crossing) that facilitated crossing boundaries and uniting the perspectives of patients and practitioners. Methods: We used a thematic approach to analyse researchers' observations, meeting materials, emails, interviews with patients (n = 11) and a survey among patients and practitioners (n = 18). Results: Setting the research agenda helped to cross boundaries in oral health care, which demonstrates its role as a boundary object. First, this made it possible to integrate research topics representing the perspectives and priorities of all patients and also to unite those perspectives. It was essential to involve practitioners at an early stage of the project so that they could better accept the patients' perspectives. This resulted in support for an integrated research agenda, which facilitated the crossing of boundaries. Conclusions: The research agenda-setting project was found to serve as a boundary object in uniting the perspectives and priorities of patients and practitioners. Patient contribution: Patient involvement in this case study was structured in the process of research agenda setting using the Dialogue Model.

Supplemental Digital Content is available in the text., Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (

The research questions for this study were as follows: (1) is the Parker Mobility Score (PMS) associated with discharge disposition and hospital length of stay (HLOS) of geriatric traumatic hip fracture patients? (2) Can the PMS be incorporated in a decision tree for the prediction of discharge disposition of geriatric traumatic hip fracture patients upon admittance. A dual-center retrospective cohort study was conducted at two level II trauma centers. All patients aged 70 years and older with traumatic hip fractures undergoing surgery in 2018 and 2019 were included consecutively (n = 649). A χ2 automatic interaction detection analysis was performed to determine the association of the PMS (and other variables) with discharge disposition and HLOS and predict discharge destination. The decision tree for discharge disposition classified patients with an overall accuracy of 82.1% and a positive predictive value of 91% for discharge to a rehabilitation facility. The PMS had the second most significant effect on discharge disposition (χ2 = 22.409, p

Purpose Hip fractures are a common health problem among the elderly with an increasing incidence. They are associated with high mortality and morbidity. Optimal pain management remains challenging and inadequate pain control is known for negatively affecting outcomes. Loco-regional anaesthetics (LRA) have been proven to benefit pain management and to lower the risks of opioid use and -related side effects. We aimed to evaluate the use and efficacy of different LRA in elderly hip fracture patients. Methods Single-center cohort study of elderly hip fracture patients, who were treated in central Switzerland. We compared patients who received LRA in the form of a femoral nerve block (FNB) or a continuous femoral nerve catheter (CFNC) with patients who did not receive LRA. Primary outcomes were pain—as measured in perioperative morphine use—hospital length of stay (HLOS), postoperative complications, postoperative falls and mortality. Results 407 patients were included for analysis. Mean age was 85.2 (SD6.3). There was a significant difference in intraoperative morphine use between the groups (p = 0.007). Postoperative morphine use differed significantly and was lowest in patients with FNB and highest in patients without LRA (p Conclusions This article shows that LRA in the form of FNB and CFNC causes a significant decrease in postoperative opioid consumption. Differences between single-shot FNB or CFNC were minimal. There were no significant differences in clinical outcomes such as HLOS, delirium, 30-day and 90-day mortality and postoperative falls. We suggest that use of LRA should be incorporated in the perioperative treatment of elderly patients with a hip fracture. For future research, we recommend evaluating the number of postoperative complications and mortality.

Background: Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited.Objective: To determine the potential value of the standing test to aid LQTS diagnostics in children.Methods: In a prospective cohort including children (≤18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes.Results: We included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc ≥ 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%-98%) and slightly decreased specificity (58%, 95% CI: 47%-70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%-99%; specificity 53%, 95% CI: 42%-65%). When a baseline QTc ≥ 440 ms was accompanied by a QTc ≥ 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%-99%) at the expense of a further specificity decrease (41%, 95% CI: 30%-52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children.Conclusion: In children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children.

Many studies have focussed on the implementation and outcomes of geriatric care pathways (GCPs); however, little is known about the possible impact of clinical practices on these pathways. A comparison was made between two traumageriatric care models, one Swiss (CH) and one Dutch (NL), to assess whether these models would perform similarly despite the possible differences in local clinical practices. This cohort study included all patients aged 70 years or older with a unilateral hip fracture who underwent surgery in 2014 and 2015. The primary outcomes were mortality and complications. Secondary outcomes were time to surgical intervention, hospital length of stay (HLOS), differences in surgical treatment and the number of patients who needed secondary surgical intervention. A total of 752 patients were included. No differences were seen in mortality at 30 days, 90 days and 1 year post-operatively. In CH, fewer patients had a complicated course (43.5% vs. 51.3%; p = 0.048) and fewer patients were diagnosed with delirium (7.9% vs. 18.3%; p

Objectives: The aim of this study was to develop a research agenda based on the most important information needs concerning the effects and outcomes of oral healthcare provided by oral healthcare professionals (OHPs). Methods: A two-stage survey study was used to identify and prioritise topics for future research. The first survey generated topics based on information needs by OHPs. Topics were clustered thematically and overlapping topics were merged in 84 research themes. In the second survey, respondents selected their top 5 from the 84 research themes. Themes were sorted by the rank number based on rank sum. Results: In the first survey, 937 topics were suggested. Almost half (n = 430, 46%) were identified as topics related to endodontology, cariology, oral medicine/surgery or tooth restoration. Topics were grouped in 84 research themes, covering 10 research domains. These were prioritised by 235 OHPs. Behaviour change for oral health and oral healthcare for geriatric patients ranked as most important. Conclusions: Consultation of OHPs has resulted in a research agenda, which can be used to inform programming future oral health research. The highest prioritised research themes have an interdisciplinary nature, mainly concern oral disease prevention and are under-represented in the current oral healthcare research portfolio.

Newborn screening efforts focusing on the quantification of T cell receptor excision circles (TRECs), as a biomarker for abnormal thymic production of T cells, have allowed for the identification and definitive treatment of severe combined immunodeficiency (SCID) in asymptomatic neonates. With the adoption of TREC quantification in Guthrie cards across the USA and abroad, typical, and atypical SCID constitutes only ~ 10% of cases identified with abnormal TRECs associated with T cell lymphopenia. Several other non-SCID-related conditions may be identified by newborn screening in a term infant. Thus, it is important for physicians to recognize that other factors, such as prematurity, are often associated with low TRECs initially, but often improve with age. This paper focuses on a challenge that immunologists face: the diagnostic evaluation and management of cases in which abnormal TRECs are associated with variants of T cell lymphopenia in the absence of a genetically defined form of typical or atypical SCID. Various syndromes associated with T cell impairment, secondary forms of T cell lymphopenia, and idiopathic T cell lymphopenia are identified using this screening approach. Yet there is no consensus or guidelines to assist in the evaluation and management of these newborns, despite representing 90% of the patients identified, resulting in significant work for the clinical teams until a diagnosis is made. Using a case-based approach, we review pearls relevant to the evaluation of these newborns, as well as the management dilemmas for the families and team related to the resolution of genetic ambiguities.

Older adults are often affected by a decline of mental and physical abilities, which results in frailty, anxiety and reclusiveness. They often live alone; family and friends cannot visit them on a regular basis and thus they suffer from social exclusion and loneliness. TACTILE tackles this problem by fostering an active lifestyle and the wellbeing of the elderlies. TACTILE’s novelty is the use of Mixed Reality that makes the remote partner virtually present. Continuous user feedback collected in three workshops guarantees that the user interaction and experience will meet the end users’ needs. In this paper we describe the TACTILE system and its components, the strong end-user involvement, and the results from the second user workshop, where the second prototype was tested. The system will be validated in final field trials in two test countries – Austria and the Netherlands – with the elderly people and secondary end-users (family members and caregivers).

Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID) known as severe combined immune deficiency caused by adenosine deaminase defects (ADA-SCID). Most affected infants can receive a diagnosis while still asymptomatic by using an SCID newborn screening test, allowing early initiation of therapy. We review the evidence currently available and propose a consensus management strategy. In addition to treatment of the immune deficiency seen in patients with ADA-SCID, patients should be followed for specific noninfectious respiratory, neurological, and biochemical complications associated with ADA deficiency. All patients should initially receive enzyme replacement therapy (ERT), followed by definitive treatment with either of 2 equal first-line options. If an HLA-matched sibling donor or HLA-matched family donor is available, allogeneic hematopoietic stem cell transplantation (HSCT) should be pursued. The excellent safety and efficacy observed in more than 100 patients with ADA-SCID who received gammaretrovirus- or lentivirus-mediated autologous hematopoietic stem cell gene therapy (HSC-GT) since 2000 now positions HSC-GT as an equal alternative. If HLA-matched sibling donor/HLA-matched family donor HSCT or HSC-GT are not available or have failed, ERT can be continued or reinstituted, and HSCT with alternative donors should be considered. The outcomes of novel HSCT, ERT, and HSC-GT strategies should be evaluated prospectively in "real-life" conditions to further inform these management guidelines.

Background The aim of this study is to investigate the impact of the coronavirus disease 2019 (COVID-19) lockdown period on the number and type of vascular procedures performed in the operating theater. Methods A total of 38 patients who underwent 46 vascular procedures during the lockdown period of March 16th until April 30th, 2020, were included. The control groups consisted of 29 patients in 2019 and 54 patients in 2018 who underwent 36 and 66 vascular procedures, respectively, in the same time period. Data were analyzed using SPSS Statistics. Results Our study shows that the lockdown during the COVID-19 pandemic resulted in a significant increase in the number of major amputations (42% in 2020 vs. 18% and 15% in 2019 and 2020, respectively; P-value 0.019). Furthermore, we observed a statistically significant difference in the degree of tissue loss as categorized by the Rutherford classification (P-value 0.007). During the lockdown period, patients presented with more extensive ischemic damage when than previous years. We observed no difference in vascular surgical care for patients with an aortic aneurysm. Conclusions Measurements taken during the lockdown period have a significant effect on non–COVID-19 vascular patient care, which leads to an increased severe morbidity. In the future, policy makers should be aware of the impact of their measurements on vulnerable patient groups such as those with peripheral arterial occlusive disease. For these patients, medical care should be easily accessible and adequate.

Key Points 3D organoid T-cell differentiation from a few hundred peripheral blood CD34+ cells was successfully achieved. 3D organoid T-cell differentiation could help physicians distinguish intrinsic from extrinsic defects underlying a clinical SCID phenotype.

Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. We herein report the 2019 phenotypic classification, including the 65 new conditions. The diagnostic algorithms are based on clinical and laboratory phenotypes for each of the ten broad categories of IEI.

Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have a profound effect on clinical management decisions. Therefore clinical providers must demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established a work group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.

Background and Purpose: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. Methods: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0–2) and the extra cost per quality-adjusted life year gained. Results: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, −$16 839 [95% CI, −$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%–22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04–0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. Conclusions: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695 ; Unique identifier: NL695. URL: https://www.isrctn.com ; Unique identifier: ISRCTN10888758.

Analyzing social networks is challenging. Key features of relational data require the use of non-standard statistical methods such as developing system-specific null, or reference, models that randomize one or more components of the observed data. Here we review a variety of randomization procedures that generate reference models for social network analysis. Reference models provide an expectation for hypothesis-testing when analyzing network data. We outline the key stages in producing an effective reference model and detail four approaches for generating reference distributions: permutation, resampling, sampling from a distribution, and generative models. We highlight when each type of approach would be appropriate and note potential pitfalls for researchers to avoid. Throughout, we illustrate our points with examples from a simulated social system. Our aim is to provide social network researchers with a deeper understanding of analytical approaches to enhance their confidence when tailoring reference models to specific research questions.

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nose was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios—varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

Introduction Due to the aging population the incidence of Low Energy Fractures (LEF) increases. LEF have high mortality and morbidity rates and often cause elderly to lose independence. Patient-reported outcomes, such as Quality of Life (QoL) and patient satisfaction (PS) are needed to evaluate treatment, estimate cost-benefit analyses, and to improve clinical decision-making and patient-centered care. Objective The primary goal was to evaluate QoL and PS in patients with LEF, and to compare QoL scores to the community dwelling population. Second, we observed the amount and type of physiotherapy (PT) sessions the patients conducted. Methods A single-center cohort study was conducted in Switzerland. Patients between 50 and 85 years, who were treated in the hospital for LEF, were followed 1 year after initial fracture. Data on QoL were obtained through the Euroqol-5-Dimension questionnaire-3-Level (EQ-5D-3L) and the EQ VAS (visual analog scale). PS was measured by a VAS on satisfaction with treatment outcome. Data on PT sessions, mobility and use of analgesics were collected by telephone interviews and written surveys. Results were compared between the different fracture locations and subgroup analyses were performed for age categories. Results 411 patients were included for analysis. The median scores of the EQ-5D-3L index—VAS and PS were 0.90 (0.75–1.0), 90 (71.3–95) and 100 (90–100). Significant differences in all scores were found between fracture location ( P < .05), with hip fracture patients and patients with a malleolar fracture scoring lowest in all measures. QoL index in hip fracture patients was 0.76 (0.70–1.00), QoL VAS 80 (70–90), and PS 95 (80–100). Median amount of PT sessions in all patients was 18 (9–27) and a significant difference was found between fracture locations. Patients with a fracture of the humerus received the highest amount of PT sessions 27 (18–36), hip fracture patients had a median of 18 (9–27) sessions. Conclusion At follow-up, QoL throughout all patients with a LEF was comparable to a normal population. Remarkably, though hip fracture patients seem to suffer from a clinically relevant loss of QoL, they received fewer PT sessions and performed fewer long-lasting home training than patients with a humerus fracture. Intensive, progressive rehabilitation with a high frequency of supervised training is recommended after hip fracture. The low frequency of PT sessions found in this study is unsatisfying. In hip fracture patients and in patients with a malleolar fracture, especially when aged over 75 years, more efforts are required to improve rehabilitation and subsequently QoL.

Elderly people are frequently affected by a decline of mental and physical abilities, which results in anxiety, frailty and reclusiveness. Often, they live alone, spatially separated from their families or friends, unable to meet them on a regular basis. The TACTILE project addresses these challenges and fosters an active lifestyle and well-being of older adults via an enjoyable, innovative, and user-friendly Mixed Reality (MR) solution. The system enables training both the cognitive and physical state using MR technology and maintaining social contacts by connecting seniors with family and friends. Cognitive trainings are provided by conventional and physically available board games - such as Ludo - that are completed with virtual game pieces of a remote partner. Since the system uses real physical game pieces, the user experiences a tactile feedback that enables a more familiar feeling and thus novel way of digital interaction. Physical trainings are provided by a virtual avatar that explains and shows dedicated exercises, adaptable to the individual needs and physical restrictions of the user. Thus, the avatar accompanies the user during the physical training in a more natural way.

Supplemental Digital Content is available in the text., Background: Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice. Methods: We analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)—a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category. Results: Of 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0–2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13–1.60] for mild WML and 1.67 [95% CI, 1.39–2.01] for moderate-to-severe WML; Ptrend

Objective:To analyze the incidence of submucous cleft palate (SMCP) in a large national database and raise awareness among referring providers: pediatricians, speech pathologists, and dentists to minimize delay in diagnosis.Design:Retrospective cohort study.Setting:Tertiary setting.Patients:Patients were extracted from the “Dutch Association for Cleft and Craniofacial Anomalies” database. A total of 6916 patients were included from 1997 until 2018 and divided into 2 groups (ie, SMCP versus cleft palate [CP]). Patients born before 1997 and adopted patients were excluded.Interventions:Clefts were classified as either hard of soft palatal involvement based on anatomical landmarks at first consultation.Main Outcome Measures:Primary outcomes were the patient characteristics in both groups (ie, gender, birth weight, gestational age, and additional anomalies). Secondary outcome was the time of diagnosis among subgroups.Results:In total, 532 patients were diagnosed with SMCP (7.7%). Birth weight, gestational age, and additional anomalies did not differ between subgroups, but there were more males in the SMCP group ( P < .001). The median age of diagnosis of the SMCP group was significantly higher than of the CP group (987 vs 27 days; P < .001). Over the course of 22 years, the time of diagnosis for SMCP did not decrease.Conclusion:Submucous cleft palate represents

Modern robots are mainly controlled by monolithic black-box controllers provided by the individual manufacturers. In research institutions the first version of the Robot Operating System (ROS1) is widely used for different applications. However, ROS1 lacks real-time capable communication. The ongoing development of ROS2 promises to break this paradigm. By employing Data Distribution Service (DDS) as a middleware the modular architecture aims at providing realtime capabilities. This study assesses the current prospects and limitations of ROS2. It gains novel insights towards improved and, in particular, reliable results regarding latencies and jitter. To this end, the allocation and transmission of ROS2 messages is evaluated in an example application for robotic control. An oscilloscope is applied for external validation of the measurements in such a time-synchronized distributed network. The complete application is set up from non-real-time object detection towards real-time control via ROS2 and EtherCAT. An in-depth evaluation of the ROS2 communication stack on a single host and in distributed setups is included. With real-time safe memory allocation and highly privileged ROS2 processes real-time capabilities are ensured.

Introduction Infants with SCID are treated with hematopoietic cell transplantation (HCT) or gene therapy (GT). Caregiver perceptions of pre-treatment counseling and understanding of durability of HCT/GT are poorly understood. Methods A survey was designed and distributed to families of patients with SCID. Topics in the questionnaire included SCID genotype and treatment, family recollections of pre-treatment counseling and present clinical status. Results 151 surveys were analyzed. 132 were treated with HCT, 19 with GT. From counseling received, 37% expected HCT/GT would lead to “cure”; 43% expected HCT/GT would last a lifetime. Of 136 living patients, 59% reported overall good health but 65% reported some persistent health challenges. Conclusions For some, interpretation of the word “cure” varied, leading to misunderstanding regarding need for continued medical evaluations and additional therapies. Clear communication regarding the importance of lifelong follow-up, no matter the treatment outcome, will help to optimize good health and quality of life.

The Global Forum on Tuberculosis (TB) Vaccines was held virtually from 20 to 22 April 2021, marking its 20th anniversary. The Global Forum on TB Vaccines is the world's largest gathering of stakeholders striving to develop new vaccines to prevent TB. The program included more than 60 speakers in 11 scientific sessions, panel discussions, and workshops. It provided an overview of the state of the field, and an opportunity to share the latest research findings, as well as new and innovative approaches to TB vaccine research and development (R&D). This year, it was held against the backdrop of the COVID-19 pandemic and convened researchers, developers, funders, and other stakeholders remotely to discuss opportunities and challenges for TB vaccine R&D in these unprecedented times.

Background Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia. Objectives This study sought to determine whether standardized screening terminology could overcome a Babylonian confusion and whether improved case definitions would promote international exchange of knowledge. Methods A systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs. Results The study's recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and nonactionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance. Conclusions By bringing together the previously unconnected public health screening community and clinical immunology community, these SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. This study proposes that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide.

Introduction The aim of this study was to compare the effectiveness of exercise versus hot water immersion heat reacclimation (HRA) protocols. Methods Twenty-four participants completed a heat stress test (HST; 33°C, 65% RH), which involved cycling at a power output equivalent to 1.5 W·kg-1 for 35 min whereby thermophysiological variables were measured. This was followed by a graded exercise test until exhaustion. HST1 was before a 10-d controlled hyperthermia (CH) heat acclimation (HA) protocol and HST2 immediately after. Participants completed HST3 after a 28-d decay period without heat exposure and were then separated into three groups to complete a 5-d HRA protocol: A control group (CH-CON, n = 8); a hot water immersion group (CH-HWI, n = 8), and a controlled hyperthermia group (CH-CH, n = 8). This was followed by HST4. Results Compared with HST1, time to exhaustion and thermal comfort improved; resting rectal temperature (Tre), end of exercise Tre, and mean skin temperature (Tsk) were lower; and whole body sweat rate (WBSR) was greater in HST2 for all groups (P < 0.05). After a 28-d decay, only WBSR, time to exhaustion, and mean Tsk returned to pre-HA values. Of these decayed variables, only WBSR was reinstated after HRA; the improvement was observed in both the CH-CH and the CH-HWI groups (P < 0.05). Conclusion The data suggest that HRA protocol may not be necessary for cardiovascular and thermal adaptations within a 28-d decay period, as long as a 10-d CH-HA protocol has successfully induced these physiological adaptations. For sweat adaptations, a 5-d CH or HWI-HRA protocol can reinstate the lost adaptations.

Migrants are able to provide firms with knowledge about their country of origin. This can become a valuable source of knowledge for firms in the process of internationalization. Relating to a Knowledge-Based-View perspective, this paper explains how the resource commitment of firms to foreign countries is contingent on immigration from those countries: Immigrants’ country knowledge reduces uncertainty and makes the governance of foreign operations more efficient. Moreover, this paper connects the relevance of knowledge for firm internationalization to institutional characteristics in immigrants’ home and host countries, both of which policymakers can shape. We test predictions on more than 13,000 observations over a 14-year period (2003–2016). The paper identifies economically significant contingencies of a positive effect of immigration, which are robust to changes in model specification, measurement, and sampling. The results indicate how immigration can shape firms’ investments abroad and have implications for developing policy as well as international business theory.

Purpose: Hip fractures in geriatric patients have high morbidity and mortality rates. The implementation of a multidisciplinary geriatric care pathway (GCP) may improve treatment for this patient population. This study focusses on two level II hospitals with a different treatment protocols. A comparison was made between a multidisciplinary GCP and extensive standard care with a focus on geriatric hip fracture patients to assess if a multidisciplinary GCP leads to lower mortality and morbidity. Methods: This retrospective cohort study included patients aged 70 years or older with a unilateral proximal hip fracture who underwent surgery between January 2014 and December 2015. The primary outcome measures complications and 30-day mortality. Secondary outcome measures were time to surgery, hospital length of stay (HLOS) and secondary surgical interventions. Results: This study included a total of 898 patients. No differences were found between major postoperative complications, 30-day mortality, HLOS or the amount of secondary surgical interventions. Conclusions: Mortality, major complications, HLOS and the amount of secondary surgical interventions showed no differences between both hospitals. This inter-hospital comparison of two types of geriatric care models showed no outcome that favours one specific geriatric care model over another. This provides opportunities for future studies to get a better understanding of what specific factors of geriatric care models contribute most to an improvement in the treatment of this patient population and decide which approach is most cost effective.

In the United States, significant improvement in diagnosis and outcomes for children affected with severe combined immunodeficiency has followed institution of newborn screening using an assay to measure T-cell receptor excision circles in newborn dried blood spot specimens. Key to this outcome is the avoidance of infectious complications in infants with severe combined immunodeficiency.

Improvement in the optoelectronic performance of halide perovskite semiconductors requires the identification and suppression of nonradiative carrier trapping processes. The iodine interstitial has been established as a deep level defect and implicated as an active recombination center. We analyze the quantum mechanics of carrier trapping. Fast and irreversible electron capture by the neutral iodine interstitial is found. The effective Huang-Rhys factor exceeds 300, indicative of the strong electron-phonon coupling that is possible in soft semiconductors. The accepting phonon mode has a frequency of 53 cm-1 and has an associated electron capture coefficient of 1 × 10-10 cm3 s-1. The inverse participation ratio is used to quantify the localization of phonon modes associated with the transition. We infer that suppression of octahedral rotations is an important factor to enhance defect tolerance.

This paper explores how the rational theory of memory summarized in Anderson (1991) can inform the computational psycholinguistic models of human parsing. It is shown that transition-based parsing is particularly suitable to be combined with Anderson's theory of memory systems. The combination of the rational theory of memory with the transition-based parsers results in a model of sentence processing that is data-driven and can be embedded in the cognitive architecture Adaptive Control of Thought-Rational (ACT-R). The predictions of the parser are tested against qualitative data (garden-path sentences) and a self-paced reading corpus (the Natural Stories corpus).

Background and objective: Falls in elderly cause injury, mortality, and loss of independence, making Fear of Falling (FoF) a common health problem. FoF relates to activity restriction and increased fall risk. A voluntary intervention including fall risk assessment and prevention strategies was implemented to reduce falls in elderly patients with low energy fractures (LEF). The primary purpose of this study was to evaluate FoF and the number of subsequent falls in trauma patients one year after a LEF. The secondary aim was to examine how FoF affects patients’ lives in terms of Quality of Life (QoL), mobility, and activity levels. Finally, participation in the voluntary fall prevention program (FPP) was evaluated. Materials and Methods: Observational cohort study in one Swiss trauma center. LEF patients, treated between 2012 and 2015, were analyzed one year after injury. Primary outcomes were Falls-Efficacy Score-International (FES-I) and number of subsequent falls. Secondary outcomes were EuroQoL-5-Dimensions-3-Levels (EQ5D-3L), mobility, activity levels, and participation in the FPP. Subgroup analysis was performed for different age categories. Results: 411 patients were included for analysis. Mean age was 72 ± 9.3, mean FES-I was 21.1 ± 7.7. Forty percent experienced FoF. A significant negative correlation between FoF and QoL (R = 0.64, p &lt, 0.001) was found. High FoF correlated with lower activity levels (R= −0.288, 0.001). Six percent visited the FPP. Conclusions: At follow-up, 40% suffered from FoF which seems to negatively affect patients’ QoL. Nevertheless, participation in the FPP was low. Simply informing patients about their susceptibility to falls and recommending participation in FPPs seems insufficient to motivate and recruit patients into FPPs. We suggest implementing repeated fall risk- and FoF screenings as standard procedures in the follow-up of LEF, especially in patients aged over 75 years.

BackgroundRandomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice.MethodsThe Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death.ResultsOf 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, pConclusionsWithout the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window.

BackgroundCytomegalovirus (CMV) serostatus of recipient (R) and donor (D) influences hematopoietic stem cell transplant (HSCT) outcome. However, it is not a reliable indicator of CMV infection in primary immunodeficiency disorder (PIDD) recipients who are unable to make adequate antigen-specific immunoglobulin (Ig) or who receive intravenous Ig (IVIg) prior to testing.ObjectiveSince no data exist on PIDD with unknown CMV serostatus, we aimed to evaluate the relationship between pre-HSCT recipient and donor serostatus and incidence of CMV infection in recipients with unknown serostatus.MethodsA retrospective analysis of all pediatric PIDD HSCTs (2007-2018) was performed at University of California San Francisco. Recipients were separated into categories based on pre-transplant serostatus: 1) seropositive (R(+)), 2) seronegative (R(-)), and 3) unknown serostatus (R(x)). Patients with pre-HSCT active CMV viremia were excluded.ResultsA total of 90 patients were included, 69% male. The overall incidence of CMV infection was 20%, but varied in R(+), R(-), and R(x) at 80%, 0%, and 14%, (P-value=.0001). Similarly, 5-year survival differed among groups, 60% R(+), 100% R(-), and 90% of R(x) (P-value=.0045). There was no difference in CMV reactivation by donor serostatus (P-value=.29), however, faster time to clearance of CMV was observed for R(x)/D(+) group (median 9.5days (IQR 2.5-18), P-value=.024).ConclusionWe identify a novel group of recipients, R(x), with an intermediate level of survival and CMV incidence post-HSCT, when compared to seropositive and seronegative recipients. No evidence of CMV transmission from D(+) in R(-) and R(x) was observed. We believe R(x) should be considered as a separate category in future studies to better delineate recipient risk status.

The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects. ispartof: JOURNAL OF CLINICAL IMMUNOLOGY vol:41 issue:3 pages:666-679 ispartof: location:Netherlands status: published

Background: Although depression and personality disorders (PDs) often co-occur, less is known about the impact of PDs on health-related quality of life (HRQOL) in patients with depression. This study explores the differences in HRQOL of depressed patients with and without PD.Methods: Baseline data of 397 patients with depression from two randomised controlled trials were used for this analysis. HRQOL was measured with the EuroQol-5D (EQ-5D). Differences were examined between three groups: patients with 1) depression-only, 2) depression and comorbid PD and 3) PD and comorbid depression. The EQ-5D scores of the groups were compared with linear regression.Results: HRQOL scores were lower in the depression-only group than the depression + PD group, even though depression severity was higher in patients with PD. HRQOL in the PD +/- depression group did not differ from the other groups. In addition, no associations were found between the type or severity of PD and HRQOL. Discussion: These findings could indicate that patients with PD are less affected by the impact of depression on HRQOL. In addition, the EQ-5D might not adequately capture the impact of PD on quality of life. Further research is needed to compare the EQ-5D with quality of life instruments that include more life domains.Limitations: Two study samples are combined, and therefore not designed to compare the three groups directly. Generalisation of the results should be done with caution.Conclusion: Depressed patients with PD report higher HRQOL than depression-only patients. Although higher HRQOL, patients with PD report more severe depressions than depressed-only patients.

For decades, terrorism has been a reality in many European countries and a continuous threat to a great number of European cities. It seriously threatens the safety, the values of democratic states and the rights and liberties of citizens. Over the years, strategies to protect public space against terrorism have strengthened and evolved, mainly focussing on protecting critical infrastructures. However, terrorist attacks are evolving as well. By adapting to new contexts and opportunities, lately public space has turned into an attractive target for terrorist attacks. These areas are considered as “soft targets”. This means that crowded public places including the metro, shopping centres, sports stadiums, bars, restaurants, clubs and commercial sidewalks, being easily accessible to the public constitute easy targets for terrorists to do great harm. In this context, the PRoTECT project aims to strengthen local authorities’ capabilities in public spaces protection by putting in place an overarching concept where tools, technology, training and field demonstrations will improve the awareness of local stakeholders towards improving direct responses to secure public places before, during and after a terrorist threat. In this chapter the results of vulnerability assessments that were conducted in five European countries using a prototype tool developed by the European Commission, as part of the EC funded project PRoTECT, are presented.

Background and Purpose: Thrombectomy with stent retriever and direct aspiration are equally effective in the endovascular treatment of anterior circulation acute ischemic stroke. We report efficacy and safety of initial treatment technique per occlusion segment. Methods: For this study, we analyzed data from the MR CLEAN Registry, a prospective, observational study in all centers that perform endovascular therapy in the Netherlands. We used ordinal logistic regression analysis to compare clinical and technical results of first line direct aspiration treatment with that of stent retriever thrombectomy stratified for occlusion segment. Primary outcome measure was functional outcome at 3 months. Secondary outcome measures included reperfusion grade expressed as the extended Thrombolysis in Cerebral Infarction score, periprocedural complication risk, time to reperfusion, and mortality. Results: Of the 2282 included patients, 1658 (73%) were initially treated with stent retriever and 624 (27%) with aspiration. Four hundred sixty-two patients had an occlusion of the intracranial part of the carotid artery, 1349 of the proximal middle cerebral artery, and 471 of the distal parts of the middle cerebral artery. There was no difference in functional outcome between aspiration and stent retriever thrombectomy (odds ratio, 1.0 [95% CI, 0.9–1.2]) in any of the occlusion segments ( P value for interaction=0.2). Reperfusion rate was higher in the aspiration group (odds ratio, 1.4 [95% CI, 1.1–1.6]) and did not differ between occlusion segments ( P value for interaction=0.6). Procedure times were shorter in the aspiration group (minutes 50 versus 65 minutes; P Conclusions: In unselected patients with anterior circulation infarcts, we observed equal functional outcome of aspiration and stent retriever thrombectomy in all occlusion segments. When aspiration was the first line treatment modality, reperfusion rates were higher and procedure times shorter in all occlusion segments.

Sustainable startups commercializing a clean technology provide an opportunity for a greener future. Despite their high investment risks, cleantech startups increasingly attract corporate venture capital. This paper explores which companies invest venture capital in cleantech startups and why they do it. It includes 26 cases of established companies that invested in cleantech startups founded in Norway between 1999 and 2012. This study broadens the scope of corporate venture capital research. The findings show that corporate venture capital investors are more heterogeneous than assumed in the literature thus far. Firstly, it finds that small and medium enterprises are active corporate venture capital investors. Secondly, it reveals that the motivations to invest are more diverse than hitherto assumed. The study adds to the sustainability literature by empirically revealing that large companies invest corporate venture capital to promote corporate greening to maintain competitiveness.Sustainable startups commercializing a clean technology provide an opportunity for a greener future. Despite their high investment risks, cleantech startups increasingly attract corporate venture capital. This paper explores which companies invest venture capital in cleantech startups and why they do it. It includes 26 cases of established companies that invested in cleantech startups founded in Norway between 1999 and 2012. This study broadens the scope of corporate venture capital research. The findings show that corporate venture capital investors are more heterogeneous than assumed in the literature thus far. Firstly, it finds that small and medium enterprises are active corporate venture capital investors. Secondly, it reveals that the motivations to invest are more diverse than hitherto assumed. The study adds to the sustainability literature by empirically revealing that large companies invest corporate venture capital to promote corporate greening to maintain competitiveness.