The academic impact of paediatric research agendas: a descriptive analysis.

BACKGROUND: Increasingly, researchers are involving children and young people in designing paediatric research agendas, but as far as we were able to determine, only one report exists on the academic impact of such an agenda. In our opinion, the importance of insight into the impact of research agendas designed together with children and young people cannot be overstated. The first aim of our study was therefore to develop a method to describe the academic impact of paediatric research agendas. Our second aim was to describe the academic impact of research agendas developed by involving children and young people. METHODS: We based our method on aspects of the Research Impact Framework developed by Kuruvilla and colleagues and the Payback Framework developed by Donovan and Hanney. We named it Descriptive Academic Impact Analysis of Paediatric Research Agendas, consisting of five steps: [1] Identification of paediatric research agendas, [2] Citation analysis, [3] Impact analysis, [4] Author assessment, and [5] Classification of the ease of determining traceability. RESULTS: We included 31 paediatric research agendas that were designed by involving children and young people. These agendas were cited 517 times, ranging from 0 to 71 citations. A total of 131 new studies (25%) were published, ranging from 0 to 23 per paediatric research agenda, based on at least one of the research priorities from the agenda. Sixty studies (46%) were developed by at least one of the first, second, or last authors of the paediatric research agenda on which the studies were based. Based on their accessibility and the ease with which we could identify the studies as being agenda-based, we categorised 44 studies (34%) as easy, 62 studies (47%) as medium, and 25 studies (19%) as difficult to identify. CONCLUSION: This study reports on the development of a method to describe the academic impact of paediatric research agendas and it offers insight into the impact of 31 such agendas. We recommend that our results be used as a guide for designing future paediatric research agendas, especially by including ways of tracing the academic impact of new studies concerning the agendas' research priorities.

Increasingly, researchers are involving children and young people in designing paediatric research agendas. However, few researchers have described the impact of these agendas on the research undertaken. We strongly believe that it is important to know how such agendas affect research, what their impact is. One of the reasons paediatric research agendas are being designed is to create a clear overview of what the research questions are that need to be investigated - if this question is left unanswered, why bother designing the agendas at all? Therefore, we developed a 5-step tool to identify these agendas and to describe their impact. We tested our tool on 31 paediatric research agendas that were designed together with children and young people. These agendas were mentioned 517 times, 131 new studies were based on these agendas, and 60 studies were performed by the same authors who had designed the agendas. Of the new studies, we found 44 that were easy to identify, 62 that were fairly easy, and 25 that were difficult to identify as being based on paediatric research agendas. We hope that our results will serve as a useful guide for future researchers who aim to involve children and young people in designing research agendas. Especially, if ways are included to trace the impact of new studies in relation to the most important questions stated in the original research agendas.

Prognostic value of the electrocardiogram in patients with bicuspid aortic valve disease.

BACKGROUND: Identifying bicuspid aortic valve (BAV) patients at risk for cardiac events remains challenging and the role of the electrocardiogram (ECG) has not yet been described. Therefore, this study aims to describe ECG parameters in BAV patients, and investigate their prognostic value. METHODS: In this single-center prospective study patients with BAV without a prior aortic valve replacement (AVR) were included. Transthoracic echocardiogram and 12­lead resting-ECG were obtained. Associations between ECG parameters and the composite endpoint of all-cause mortality and AVR were assessed using Cox-proportional hazard analysis. RESULTS: 120 patients with BAV were included (median age 30 years, 61% male). Median aortic jet velocity was 2.4 m/s [IQR: 1.7-3.4] and 5 patients (4%) had severe aortic regurgitation. All patients were in sinus rhythm. Any ECG abnormality was present in 57 patients (48%). Median PR-interval was 156 [IQR: 138-170] msec. A deviating QRS axis was found in 17 patients (14%) and Cornell criteria for LVH were fulfilled in 20 patients (17%). Repolarization abnormalities were present in 12 patients (10%). Median follow-up duration was 7.0 [6.3-9.8] years, during which 23 patients underwent AVR and 2 patients died. After adjusting for age, a longer PR-interval was associated with worse intervention-free survival (HR 1.02, 95% CI: 1.01-1.04). CONCLUSION: Almost half of the patients with BAV had abnormalities on their ECG. Moreover, the PR-interval may be an interesting prognostic marker for intervention-free survival in BAV patients.

Blood Biomarkers Predict 10-Year Clinical Outcomes in Adult Patients With Congenital Heart Disease.

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP <76 ng/L showed a 10-year heart failure-free survival of 98.5%. Conclusions: Blood biomarkers have prognostic value in ACHD. NT-proBNP improves risk prediction and is able to identify low-risk patients. Its routine use should be implemented in ACHD.

Inhibition of both NOX and TNF-α exerts substantial renoprotective effects in renal ischemia reperfusion injury rat model.

BACKGROUND AND AIMS: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach. METHODS: Identification of a disease module with potential drug targets was performed utilizing Disease Module Detection algorithm using NADPH oxidases (NOXs) as seeds. We then assessed the protective effect of a multitarget network pharmacology targeting the identified module in a rat model of RIRI. Rats were divided into five groups; sham, RIRI, and RIRI treated with setanaxib (NOX inhibitor, 10 mg/kg), etanercept (TNF-α inhibitor, 10 mg/kg), and setanaxib and etanercept (5 mg/kg each). Kidney functions, histopathological changes and oxidative stress markers (MDA and reduced GSH) were assessed. Immunohistochemistry of inflammatory (TNF-α, NF-κB) apoptotic (cCasp-3, Bax/Bcl 2), fibrotic (α-SMA) and proteolysis (MMP-9) markers was performed. RESULTS: Our in-silico analysis yielded a disease module with TNF receptor 1 (TNFR1A) as the closest target to both NOX1 and NOX2. Targeting this module by a low-dose combination of setanaxib, and etanercept, resulted in a synergistic effect and ameliorated ischemic AKI in rats. This was evidenced by improved kidney function and reduced expression of inflammatory, apoptotic, proteolytic and fibrotic markers. CONCLUSIONS: Our findings show that applying a multitarget network pharmacology approach allows synergistic renoprotective effect in ischemic AKI and might pave the way towards translational success.

Blood and Imaging Biomarkers in the Long-term Follow-up of Bicuspid Aortic Valve Patients.

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods: Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-ß). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results: A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-ß were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e' ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care.

Contexte: La bicuspide valvulaire aortique (BVA) est une anomalie cardiaque congénitale fréquente. Les patients atteints d'une BVA présentent des risques de complications à long terme, comme la sténose valvulaire ou la régurgitation valvulaire. Cette étude visait 1) à évaluer les différences entre les sexes en ce qui concerne les biomarqueurs sanguins et les biomarqueurs à l'imagerie; et 2) à décrire la valeur pronostique à long terme des biomarqueurs sanguins et échocardiographiques. Méthodologie: Des patients de 2 études de cohortes observationnelles prospectives ont été inclus dans l'analyse. Des échantillons de sang veineux ont été prélevés, et des échocardiographies transthoraciques, y compris le suivi des marqueurs acoustiques, ont été effectuées. Les biomarqueurs sanguins analysés étaient les suivants : indice de distribution des globules rouges (IDR), créatinine, protéine C-réactive (CRP), troponine T, propeptide natriurétique de type B N-terminal (NT-proBNP) et facteur de croissance transformant ß (TGF-ß). Les différences entre les sexes ont été analysées au départ. Les liens entre les biomarqueurs et la survie sans arythmie et sans intervention ont été déterminés par la régression de Cox, avec correction en fonction de l'âge et du sexe. Résultats: Cent quatre-vingt-deux patients présentant une BVA étaient inclus (âge médian de 34 [écart interquartile : 23-46] ans, 55,5 % hommes). La CRP, la NT-proBNP et l'IDR étaient plus élevées chez les femmes, alors que la créatinine, la troponine T et le TGF-ß étaient plus élevés chez les hommes. Après une période de suivi médiane de 6,9 (écart interquartile : 6,5-9,9) ans, les taux de survie sans arythmie et sans intervention étaient respectivement de 81,0 % et de 73,1 %. La NT-proBNP a été associée à la survie sans arythmie (rapport des risques instantanés [RRI] : 1,94, p = 0,005) et à la survie sans intervention (RRI : 2,06, p = 0,002). À l'échocardiographie, des valeurs élevées pour la taille de l'oreillette gauche, le diamètre télédiastolique du ventricule gauche (VG), l'indice de masse du VG et le rapport E/e' étaient associées à un faible taux de survie sans arythmie, alors que des valeurs élevées pour la taille de l'oreillette gauche, l'indice de masse du VG, la vitesse maximale aortique et la régurgitation aortique étaient associées à un faible taux de survie sans intervention. Conclusions: Les biomarqueurs sanguins variaient en fonction du sexe des personnes présentant une BVA. Outre les paramètres systoliques du VG, la fonction VG diastolique et la NT-proBNP devraient être davantage utilisées comme marqueurs pronostiques en soins cliniques.

[Manifestations of Turner syndrome: don't miss the diagnosis]. / Uitingsvormen van Turner-syndroom.

Turner syndrome (TS) is one of the most common sex chromosomal abnormalities affecting girls and women. Diagnosis of this condition can be delayed due to a variation in clinical presentation, although an early age at diagnosis is important for several reasons. It enables psychosocial support for girls and their parents; early initiation of growth hormone therapy; puberty induction at an appropriate age; early recognition of comorbidities, such as cardiac or renal abnormalities; and timely removal of the gonads in girls with Y-chromosomal material, who are at risk for gonadoblastoma. By increasing the knowledge of health care professionals and implementing screening programs for girls with short stature, delayed puberty and/or congenital heart disease such as coarctation of the aorta, more girls might be diagnosed at an early age. This allows for lifelong follow up, which is indicated to prevent morbidity and mortality in the long term.

[Active life termination in children aged 1-12 years]. / Actieve levensbeëindiging bij kinderen van 1-12 jaar.

In this article we discuss active termination of life in children aged 1-12 years. It is expected that in 2024 active termination of life will be regulated for children between the ages of 1 and 12 who suffer unbearably, when other options to relieve their suffering are not enough. Using a case, we describe how a request for active termination of life in a child can arise and how physicians can respond to it.

Shared decision-making in pediatric palliative care in the Netherlands.

Shared decision-making (SDM) is a process in which health care professionals (HCPs) involve parents and children - when appropriate- to decide together on future treatment. These decisions are based on values that are important for the family, goals of care and preferences for future care and treatment. Elucidation of these values and preferences is preferably done early in the disease trajectory via so-called Advance Care Planning (ACP) conversations. In the Netherlands, ACP and SDM are being adopted by most health care professionals. This has happened only recently. Ten years ago, ACP and SDM were unknown concepts for the vast majority of Dutch HCPs. Today, interest in these conversational approaches is booming in both daily practice and in research. This rise has been reinforced by two recent major advancements in Dutch pediatric palliative care: the Individual Care Plan (ICP) and the Dutch Evidence-Based Guideline on Pediatric Palliative Care (DGPPC). Despite this positive evolution, a lot of work is still ahead. ACP and SDM demand a change in mindset from the traditional paternalistic approach by which the HCP 'knows what is best for this child' to a more humble and open approach in which (non-medical) factors that are important to the child and family and may influence the final treatment decision. Such changes in mindset don't happen overnight. In this article we describe the situation of pediatric palliative care in the Netherlands, with focus on the recent evolution of ACP and SDM.

Heart rate: an accessible risk indicator in adult congenital heart disease.

BACKGROUND: Higher resting heart rate has been described as a risk factor for adverse outcome in healthy individuals and cardiovascular patients. The aim of this study was to evaluate resting heart rate as risk factor in adult congenital heart disease (ACHD). METHODS: In this prospective observational cohort study, patients with moderate or complex ACHD were included at routine outpatient visit. Standard 12-lead ECGs were obtained in rest. Heart rate was obtained from the ECG automatically by the Modular ECG Analysis System (MEANS). The primary endpoint was all-cause mortality and the secondary endpoint was a composite of all-cause mortality and heart failure. Survival was derived using the Kaplan-Meier estimator. Subgroups based on heart rate tertiles were compared by the log-rank test. Cox proportional hazards models were adjusted for clinical factors including age, sex and diagnosis (moderate vs complex ACHD). RESULTS: A total of 556 patients were included (median age 32 years (IQR 24-41), 57.6% male). Mean heart rate was 69±13 bpm. Negative chronotropic medication was used by 74 (13.3%) patients. During a median follow-up of 10.1 (IQR 9.6-10.5) years, 36 patients (6.5%) died and 83 (14.9%) reached the secondary endpoint. Patients with higher heart rates had significantly lower survival and heart failure-free survival. After adjusting for clinical factors, heart rate remained associated with mortality (HR 1.57 per 10 bpm, 95% CI 1.26 to 1.96) and mortality or heart failure (HR 1.33 per 10 bpm, 95% CI 1.13 to 1.57). CONCLUSION: Higher heart rate is associated with lower survival and heart failure-free survival in ACHD.

Long term outcome after surgical ASD-closure at young age: Longitudinal follow-up up to 50 years after surgery.

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.

Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on ß-arrestin2 expression and molecular markers of neural injury.

BACKGROUND: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood. OBJECTIVES: The current work aimed to investigate the modulatory effects of α- and ß-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in ß-arrestin2 and molecular markers of neural injury in cerebral cortex. METHODS: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, ß-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, ß-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination. RESULTS: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and ß-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, ß-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and ß-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups. CONCLUSION: blocking α- and/or ß-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on ß-arrestin2 levels in the cerebral cortex.

Hepatic ß-arrestins: potential roles in liver health and disease.

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

Warmer temperature during asexual reproduction induce methylome, transcriptomic, and lasting phenotypic changes in Fragaria vesca ecotypes.

Plants must adapt with increasing speed to global warming to maintain their fitness. One rapid adaptation mechanism is epigenetic memory, which may provide organisms sufficient time to adapt to climate change. We studied how the perennial Fragaria vesca adapted to warmer temperatures (28°C vs. 18°C) over three asexual generations. Differences in flowering time, stolon number, and petiole length were induced by warmer temperature in one or more ecotypes after three asexual generations and persisted in a common garden environment. Induced methylome changes differed between the four ecotypes from Norway, Iceland, Italy, and Spain, but shared methylome responses were also identified. Most differentially methylated regions (DMRs) occurred in the CHG context, and most CHG and CHH DMRs were hypermethylated at the warmer temperature. In eight CHG DMR peaks, a highly similar methylation pattern could be observed between ecotypes. On average, 13% of the differentially methylated genes between ecotypes also showed a temperature-induced change in gene expression. We observed ecotype-specific methylation and expression patterns for genes related to gibberellin metabolism, flowering time, and epigenetic mechanisms. Furthermore, we observed a negative correlation with gene expression when repetitive elements were found near (±2 kb) or inside genes. In conclusion, lasting phenotypic changes indicative of an epigenetic memory were induced by warmer temperature and were accompanied by changes in DNA methylation patterns. Both shared methylation patterns and transcriptome differences between F. vesca accessions were observed, indicating that DNA methylation may be involved in both general and ecotype-specific phenotypic variation.

Single-Molecule Reaction-Diffusion.

We propose to capture reaction-diffusion on a molecule-by-molecule basis from the fastest acquirable timescale, namely individual photon arrivals. We illustrate our method on intrinsically disordered human proteins, the linker histone H1.0 as well as its chaperone prothymosin α, as these diffuse through an illuminated confocal spot and interact forming larger ternary complexes on millisecond timescales. Most importantly, single-molecule reaction-diffusion, smRD, reveals single molecule properties without trapping or otherwise confining molecules to surfaces. We achieve smRD within a Bayesian paradigm and term our method Bayes-smRD. Bayes-smRD is further free of the average, bulk, results inherent to the analysis of long photon arrival traces by fluorescence correlation spectroscopy. In learning from thousands of photon arrivals continuous spatial positions and discrete conformational and photophysical state changes, Bayes-smRD estimates kinetic parameters on a molecule-by-molecule basis with two to three orders of magnitude less data than tools such as fluorescence correlation spectroscopy thereby also dramatically reducing sample photodamage.

Life expectancy and end-of-life communication in adult patients with congenital heart disease, 40-53 years after surgery.

Aims: Although survival of patients with congenital heart disease (CHD) improved significantly over time, life expectancy is still not normal. We aimed to investigate how adult patients, their partners, and treating cardiologists estimated the individual life expectancy of CHD patients. Furthermore, preferences regarding end-of-life (EOL) communication were investigated. Methods and results: In this study, we included 202 patients (age: 50 ± 5) who were operated in childhood (<15 years old) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, or transposition of the great arteries. A specific questionnaire was administered to both the patients and their partners, exploring their perceived life expectancy and EOL wishes. Two cardiologists independently assessed the life expectancy of each patient. Most adults with CHD believed their life expectancy to be normal. However, significant differences were found between estimated life expectancy by the cardiologist and patients (female: P = 0.001, male: P = 0.002) with moderate/severe defects, as well as for males with mild defects (P = 0.011). Regarding EOL communication, 85.1% of the patients reported that they never discussed EOL with a healthcare professional. Compared with patients with mild CHD, significantly more patients with moderate/severe defect discussed EOL with a physician (P = 0.011). The wish to discuss EOL with the cardiologist was reported by 49.3% of the patients and 41.7% of their partners. Conclusion: Adult patients, especially with moderate/severe CHD, perceived their life expectancy as normal, whereas cardiologists had a more pessimistic view than their patients. Increased attention is warranted for discussions on life expectancy and EOL to improve patient-tailored care.

Two-state swimming: Strategy and survival of a model bacterial predator in response to environmental cues.

Bdellovibrio bacteriovorus is a predatory bacterium preying upon Gram-negative bacteria. As such, B. bacteriovorus has the potential to control antibiotic-resistant pathogens and biofilm populations. To survive and reproduce, B. bacteriovorus must locate and infect a host cell. However, in the temporary absence of prey, it is largely unknown how B. bacteriovorus modulate their motility patterns in response to physical or chemical environmental cues to optimize their energy expenditure. To investigate B. bacteriovorus' predation strategy, we track and quantify their motion by measuring speed distributions as a function of starvation time. While an initial unimodal speed distribution relaxing to one for pure diffusion at long times may be expected, instead we observe a bimodal speed distribution with one mode centered around that expected from diffusion and the other centered at higher speeds. What is more, for an increasing amount of time over which B. bacteriovorus is starved, we observe a progressive reweighting from the active swimming state to an apparent diffusive state in the speed distribution. Distributions of trajectory-averaged speeds for B. bacteriovorus are largely unimodal, indicating switching between a faster swim speed and an apparent diffusive state within individual observed trajectories rather than there being distinct active swimming and apparent diffusive populations. We also find that B. bacteriovorus' apparent diffusive state is not merely caused by the diffusion of inviable bacteria as subsequent spiking experiments show that bacteria can be resuscitated and bimodality restored. Indeed, starved B. bacteriovorus may modulate the frequency and duration of active swimming as a means of balancing energy consumption and procurement. Our results thus point to a reweighting of the swimming frequency on a trajectory basis rather than a population level basis.

Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors beyond gestational age.

AIM: The aim of the study was to explore the perspectives of adults born prematurely on guidelines for management at extreme premature birth and personalisation at the limit of viability. METHODS: We conducted four 2-h online focus group interviews in the Netherlands. RESULTS: Twenty-three participants born prematurely were included in this study, ranging in age from 19 to 56 years and representing a variety of health outcomes. Participants shared their perspectives on different types of guidelines for managing extremely premature birth. They agreed that a guideline was necessary to prevent arbitrary treatment decisions and to avoid physician bias. All participants favoured a guideline that is based upon multiple prognostic factors beyond gestational age. They emphasised the importance of discretion, regardless of the type of guideline used. Discussions centred mainly on the heterogeneity of value judgements about outcomes after extreme premature birth. Participants defined personalisation as 'not just looking at numbers and statistics'. They associated personalisation mainly with information provision and decision-making. Participants stressed the importance of involving families in decision-making and taking their care needs seriously. CONCLUSION: Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors and allows for discretion.

Executive functioning of patients with congenital heart disease: 45 years after surgery.

BACKGROUND: Nowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, long-term impact on neurodevelopment and executive functioning in adults with CHD are not completely understood. PURPOSE: To investigate the self- and informant-reported executive functioning in adults with CHD operated in childhood. MATERIAL AND METHODS: Longitudinal study of a cohort of patients (n = 194, median age: 49.9 [46.1-53.8]) who were operated in childhood (< 15 years old) between 1968 and 1980 (median follow-up time: 45 [40-53] years) for one of the following diagnoses: atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis (PS), tetralogy of Fallot (ToF) or transposition of the great arteries (TGA). Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) questionnaire was used to assess self- and informant-reported executive functioning. RESULTS: 40-53 years after surgery, the CHD group did show significantly better executive functioning compared to the norm data. No significant difference was found between mild CHD (ASD, VSD and PS) and moderate/severe CHD (ToF and TGA). Higher education, NYHA class 1 and better exercise capacity were associated with better self-reported executive functioning, whereas females or patients taking psychiatric or cardiac medications reported worse executive functioning. CONCLUSIONS: Our findings suggest favorable outcomes (comparable to normative data) regarding executive functioning in adults with CHD, both self- and informant-reported. However, further study is warranted to explore more in detail the different cognitive domains of executive functioning in these patients.