Diffusion Paths for Micro Cogeneration Using Hydrogen in the Netherlands

We estimate the diffusion of micro cogeneration systems (MiCoGen) using hydrogen produced from natural gas in the Netherlands for the 2000-2050 period on the basis of economical factors. The diffusion is important for the transition to a hydrogen economy based on renewables, with natural gas paving the way for hydrogen from renewables which. For three scenarios full diffusion takes place in the period 2020-2050. The most important factors behind the diffusion are: growing energy demand, resulting in lower hydrogen costs and higher energy costs in the reference case and lower costs of MiCoGen stemming from learning economies. The model is very ad-vanced by considering all costs components for heterogeneous users which have been calculated for the entire diffusion period. It is the first threshold diffusion model that is being applied to the diffusion of technological clusters involving new or adapted infrastructures.diffusion model, hydrogen, hydrogen economy, micro cogeneration

Parental intimate partner homicide and its consequences for children: protocol for a population-based study

BACKGROUND: The loss of a parent due to intimate partner homicide has a major impact on children. Professionals involved have to make far-reaching decisions regarding placement, guardianship, mental health care and contact with the perpetrating parent, without an evidence base to guide these decisions. We introduce a study protocol to a) systematically describe the demographics, circumstances, mental health and wellbeing of children bereaved by intimate partner homicide and b) build a predictive model of factors associated with children's mental health and wellbeing after intimate partner homicide. METHODS/DESIGN: This study focuses on children bereaved by parental intimate partner homicide in the Netherlands over a period of 20 years (1993 - 2012). It involves an incidence study to identify all Dutch intimate partner homicide cases between 1993 and 2012 by which children have been bereaved; systematic case reviews to describe the demographics, circumstances and care trajectories of these children; and a mixed-methods study to assess mental health, wellbeing, and experiences regarding decisions made and care provided. DISCUSSION: Clinical experience and initial research suggest that the children involved often need long-term intensive mental health and case management. The costs of these services are extensive and the stakes are high. This study lays the foundation for an international dataset and evidence-informed decision making

Present and future cost of alkaline and PEM electrolyser stacks

We use complementary bottom-up and top-down approaches to assess the current cost of AE and PEM stacks and how the costs are expected to come down by 2030. The total AE and PEM stack cost reduce from a range of 242–388 €/kW and 384–1071 €/kW in 2020 to 52–79 €/kW and 63–234 €/kW in 2030 respectively. The main drivers of these cost reductions are an increased current density and a reduction and/or replacement of expensive materials with cheaper alternatives. To a lesser extent, manufacturing and labor costs reduction is expected due to mass manufacturing at a GW scale. The total cost decrease is less prominent for AE than PEM due to AE's maturity. The uncertainty range for PEM stacks is due to the low TRL associated with the advanced design PEM stack.</p

Present and future cost of alkaline and PEM electrolyser stacks

We use complementary bottom-up and top-down approaches to assess the current cost of AE and PEM stacks and how the costs are expected to come down by 2030. The total AE and PEM stack cost reduce from a range of 242–388 €/kW and 384–1071 €/kW in 2020 to 52–79 €/kW and 63–234 €/kW in 2030 respectively. The main drivers of these cost reductions are an increased current density and a reduction and/or replacement of expensive materials with cheaper alternatives. To a lesser extent, manufacturing and labor costs reduction is expected due to mass manufacturing at a GW scale. The total cost decrease is less prominent for AE than PEM due to AE's maturity. The uncertainty range for PEM stacks is due to the low TRL associated with the advanced design PEM stack.</p

Biomechanical response of ultrathin slices of hypertrophic cardiomyopathy tissue to myosin modulator mavacamten

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder of the heart, but effective treatment options remain limited. Mavacamten, a direct myosin modulator, has been presented as novel pharmacological therapy for HCM. The aim of this study was to analyze the biomechanical response of HCM tissue to Mavacamten using living myocardial slices (LMS). LMS (n = 58) from patients with HCM (n = 10) were cultured under electromechanical stimulation, and Verapamil and Mavacamten were administered on consecutive days to evaluate their effects on cardiac biomechanics. Mavacamten and Verapamil reduced contractile force and dF/dt and increased time-to-relaxation in a similar manner. Yet, the time-to-peak of the cardiac contraction was prolonged after administration of Mavacamten (221.0 ms (208.8 – 236.3) vs. 237.7 (221.0 – 254.7), p = 0.004). In addition, Mavacamten prolonged the functional refractory period (FRP) (330 ms (304 − 351) vs. 355 ms (313 − 370), p = 0.023) and better preserved twitch force with increasing stimulation frequencies, compared to Verapamil. As such, Mavacamten reduced (hyper-)contractility and prolonged contraction duration of HCM LMS, suggesting a reduction in cardiac wall stress. Also, Mavacamten might protect against the development of ventricular tachyarrhythmias due to prolongation of the FRP, and improve toleration of tachycardia due to better preservation of twitch force at tachycardiac stimulation frequencies.</p

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy

Background: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. Objective: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. Methods: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. Results: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%–3.6%] vs 2.6% [2.1%–6.4%], P = .541; CB: 1.7% [0.9%–3.1%] vs 1.5% [0.5%–2.8%], P = .600; LVA: 4.7% [1.6%–7.7%] vs 2.9% [2.1%–7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. Conclusion: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy

Background: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. Objective: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. Methods: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. Results: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%–3.6%] vs 2.6% [2.1%–6.4%], P = .541; CB: 1.7% [0.9%–3.1%] vs 1.5% [0.5%–2.8%], P = .600; LVA: 4.7% [1.6%–7.7%] vs 2.9% [2.1%–7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. Conclusion: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population

Functional Genomic mRNA Profiling of Colorectal Adenomas : Identification and Validation of CD44 and Splice Variant CD44v6 as Molecular Imaging Targets

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. High adenoma miss rates, especially seen in high-risk patients, demand for better endoscopic detection. By fluorescently \u27highlighting\u27 specific molecular characteristics, endoscopic molecular imaging has great potential to fulfill this need. To implement this technique effectively, target proteins that distinguish adenomas from normal tissue must be identified. In this study we applied in silico Functional Genomic mRNA (FGmRNA) profiling, which is a recently developed method that results in an enhanced view on the downstream effects of genomic alterations occurring in adenomas on gene expression levels. FGmRNA profiles of sporadic adenomas were compared to normal colon tissue to identify overexpressed genes. We validated the protein expression of the top identified genes, AXIN2, CEMIP, CD44 and JUN, in sporadic adenoma patient samples via immunohistochemistry (IHC). CD44 was identified as the most attractive target protein for imaging purposes and we proved its relevance in high-risk patients by demonstrating CD44 protein overexpression in Lynch lesions. Subsequently, we show that the epithelial splice variant CD44V6 is highly overexpressed in our patient samples and we demonstrated the feasibility of visualizing adenomas in ApcMin/+ mice in vivo by using a fluorescently labeled CD44v6 targeting peptide. In conclusion, via in silico functional genomics and ex vivo protein validation, this study identified CD44 as an attractive molecular target for both sporadic and high-risk Lynch adenomas, and demonstrates the in vivo applicability of a small peptide drug directed against splice variant CD44v6 for adenoma imaging

Functional Genomic mRNA Profiling of Colorectal Adenomas:Identification and in vivo Validation of CD44 and Splice Variant CD44v6 as Molecular Imaging Targets

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. High adenoma miss rates, especially seen in high-risk patients, demand for better endoscopic detection. By fluorescently \u27highlighting\u27 specific molecular characteristics, endoscopic molecular imaging has great potential to fulfill this need. To implement this technique effectively, target proteins that distinguish adenomas from normal tissue must be identified. In this study we applied in silico Functional Genomic mRNA (FGmRNA) profiling, which is a recently developed method that results in an enhanced view on the downstream effects of genomic alterations occurring in adenomas on gene expression levels. FGmRNA profiles of sporadic adenomas were compared to normal colon tissue to identify overexpressed genes. We validated the protein expression of the top identified genes, AXIN2, CEMIP, CD44 and JUN, in sporadic adenoma patient samples via immunohistochemistry (IHC). CD44 was identified as the most attractive target protein for imaging purposes and we proved its relevance in high-risk patients by demonstrating CD44 protein overexpression in Lynch lesions. Subsequently, we show that the epithelial splice variant CD44V6 is highly overexpressed in our patient samples and we demonstrated the feasibility of visualizing adenomas in ApcMin/+ mice in vivo by using a fluorescently labeled CD44v6 targeting peptide. In conclusion, via in silico functional genomics and ex vivo protein validation, this study identified CD44 as an attractive molecular target for both sporadic and high-risk Lynch adenomas, and demonstrates the in vivo applicability of a small peptide drug directed against splice variant CD44v6 for adenoma imaging

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: A randomized controlled trial - BARTrial

Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. Methods: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. Results: Composite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for th