Relative expression of hormone receptors by endothelial and smooth muscle cells in proliferative and non-proliferative areas of congenital arteriovenous malformations.

BACKGROUND: Episodic growth due to microvascular proliferations (MVP) has been reported in congenital arteriovenous malformations (AVM), which are normally quiescent lesions composed of mature malformed vessels. Since AVM also may worsen under conditions of hormonal dysregulation, we hypothesized that hormonal influences may stimulate this process of vasoproliferative growth through potential interactions with hormone receptors (HR). METHODS: 13 Cases of AVM tissue with histologically documented vasoproliferative growth were analyzed quantitatively for the presence and tissue localization of estrogen receptor (ER), progesterone receptor (PGR), growth hormone receptor (GHR) and follicle-stimulating hormone receptor (FSHR) in relation to resident cells of interest (endothelial cells (EC), smooth muscle cells (SMC) and mast cells (MC)) by applying multiplex immunohistochemistry (IHC) staining. Expression patterns in lesions with MVP and mature vessels were quantified and compared. Available fresh frozen tissues of 3 AVM samples were used to confirm the presence of HR using Reverse-Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR). RESULTS: All four HR studied were expressed in all cases within EC and SMC in areas of MVP and mature vessels, but not in normal skin tissue. ER, GHR, and FSHR showed more expression in EC of MVP and in SMC of mature vessels. RT-qPCR confirmed presence of all 4 HR in both areas. CONCLUSION: Expression of ER, PGR, GHR, and FSHR in vasoproliferative areas of congenital AVM could explain onset of sudden symptomatic growth, as has observed in a subpopulation of patients. These findings may have implications for eventual anti-hormonal targeted therapy in the lesions involved.

The Observable Movement Quality scale for patients with low back pain (OMQ-LBP): validity and reliability in a primary care setting of physical therapy.

BACKGROUND: The Observable Movement Quality scale for patients with low back pain (OMQ-LBP) is a newly developed measurement instrument for use in primary care settings of physical and exercise therapists to assess movement quality (MQ) of patients with low back pain (LBP). OBJECTIVE: This study aims to determine validity, reliability and feasibility of the OMQ-LBP. The OMQ-LBP consists of a standardized movement circuit (performed twice) consisting of five daily activities problematic for LBP patients, which are scored with an 11-item observation list. METHODS: Construct validity was determined by testing seven hypotheses on associations between constructs (n = 85 patients with LBP) and four hypotheses on known group differences (n = 85 patients with LBP and n = 63 healthy controls; n = 35 matched participant-patients having VAS-pain ≥ 20 mm during and/or after both circuits and healthy controls). Internal consistency was analyzed with Cronbach's alpha (n = 85 patients with LBP). For inter- and intra-rater reliability Intraclass Correlation Coefficient (ICC) values were examined (n = 14 therapists: seven primary care physical therapists and seven exercise therapists). Additionally, content validity and feasibility were determined using thematic analysis of a brief interview with participants, patients (n = 38) and therapists (n = 14). RESULTS: After Bonferroni correction 2/7 associations between constructs and 2/4 significant group differences were confirmed. Cronbach's alpha was 0,79. The ICC-values of interrater reliability of the OMQ-LBP total score and the duration score were 0.56 and 0.99 and intra-rater reliability 0.82 and 0,93, respectively. Thematic analysis revealed five themes. Three themes elucidate that both patients and therapists perceived the content of the OMQ-LBP as valid. The fourth theme exhibits that OMQ-LBP provides a clear and unambiguous language for MQ in patients with LBP. Theme 5 depicts that the OMQ-LBP seems feasible, but video recording is time-consuming. CONCLUSIONS: The OMQ-LBP is a promising standardized observational assessment of MQ during the five most problematic daily activities in patients with LBP. It is expected that uniform and objective description and evaluation of MQ add value to clinical reasoning and facilitate uniform communication with patients and colleagues.

[A PhD completed. Positive effects for multidisciplinary orofacial treatment on tinnitus complaints]. / Serie: Hora est. Positieve effecten van multidisciplinaire orofaciale therapie op tinnitusklachten.

Tinnitus can be influenced by somatosensory input from the temporomandibular area and is then called somatic tinnitus. However, not much research has been conducted on whether orofacial treatment can decrease tinnitus severity in patients with somatic tinnitus. Therefore, the purpose of this thesis was 1) to evaluate the effect of orofacial treatment on tinnitus complaints, 2) to investigate potential prognostic indicators for a positive treatment outcome after orofacial therapy, and 3) to explore to what extent a decrease in temporomandibular disorder contributes to a reduction in tinnitus severity. In this thesis, it was found that orofacial therapy can reduce tinnitus severity in 61% of the patients with temporomandibular-related somatic tinnitus. Specifically, young female patients with a shorter duration of their tinnitus have the best prognosis. The analysis showed that 35% of the decrease of the tinnitus severity can be explained by the reduction in temporomandibular disorder.

Advanced drinking water production by 1 kDa hollow fiber nanofiltration - Biological activated carbon filtration (HFNF - BACF) enhances biological stability and reduces micropollutant levels compared with conventional surface water treatment.

This study comprehensively investigates the quality of drinking water produced by novel advanced treatment encompassing 1 kDa hollow fiber nanofiltration (HFNF) - Biological Activated Carbon Filtration (BACF) from (reservoir) surface water, and compares this with drinking water after conventional 'CSF' pretreatment (coagulation - flocculation - sedimentation - media filtration - UV-disinfection) - BACF. The objective of HFNF - BACF treatment is to enhance the drinking water's quality in increased biological stability, reduced concentrations of organic micropollutants (OMP), and improvement in other chemical-physical parameters, whilst maintaining sufficient hardness to avoid subsequent remineralization. For this study a large suite of quality parameters was extensively monitored in pilot plants during nearly two years, enabling the incorporation of seasonal effects. HFNF - BACF treatment accomplished a similarly high level of biological stability as regrowth-free drinking waters (total organic carbon (DOC) 0.6 mg/L, assimilable organic carbon (AOC) 4 µg/L Ac-C and <1 µg/L biopolymer-C, total microbial growth potential (MGP) as BPC14 50 ng d/L and as BGP 170 × 103 cells/mL), unlike the conventional treatment (1.9 mg/L, 10 µg/L, 9 µg/L, 130 ng d/L and 170 × 103 cells/mL, respectively) where regrowth occurred in its distribution network. Average OMP removal, including perfluoro-alkyl substances (PFAS), by HFNF - BACF (54%) was higher than conventional treatment (37%). This improvement was mainly attributable to rejection in the HFNF membrane step, indicating that the DOC concentration after HFNF pretreatment was not yet sufficiently low to eliminate competitive adsorption and/or preloading in the BACF (confirmed by laboratory experiments). The advanced treatment also performed better in turbidity, particulates and most trace metals. Importantly, hardness retention by HFNF was only moderate, rendering remineralization unnecessary. Overall, this study demonstrates the superior performance in water quality of advanced HFNF - BACF treatment compared to conventional treatment.

Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials.

BACKGROUND: Neoadjuvant ipilimumab plus nivolumab has yielded high response rates in patients with macroscopic stage III melanoma. These response rates translated to high short-term survival rates. However, data on long-term survival and disease recurrence are lacking. PATIENTS AND METHODS: In OpACIN, 20 patients with macroscopic stage III melanoma were randomized to ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w four cycles of adjuvant or split two cycles of neoadjuvant and two adjuvant. In OpACIN-neo, 86 patients with macroscopic stage III melanoma were randomized to arm A (2× ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w; n = 30), arm B (2× ipilimumab 1 mg/kg plus nivolumab 3 mg/kg q3w; n = 30), or arm C (2× ipilimumab 3 mg/kg q3w plus 2× nivolumab 3 mg/kg q2w; n = 26) followed by surgery. RESULTS: The median recurrence-free survival (RFS) and overall survival (OS) were not reached in either trial. After a median follow-up of 69 months for OpACIN, 1/7 patients with a pathologic response to neoadjuvant therapy had disease recurrence. The estimated 5-year RFS and OS rates for the neoadjuvant arm were 70% and 90% versus 60% and 70% for the adjuvant arm. After a median follow-up of 47 months for OpACIN-neo, the estimated 3-year RFS and OS rates were 82% and 92%, respectively. The estimated 3-year RFS rate for OpACIN-neo was 95% for patients with a pathologic response versus 37% for patients without a pathologic response (P < 0.001). In multiple regression analyses, pathologic response was the strongest predictor of disease recurrence. Of the 12 patients with distant disease recurrence after neoadjuvant therapy, 5 responded to subsequent anti-PD-1 and 8 to targeted therapy, although 7 patients showed progression after the initial response. CONCLUSIONS: Updated data confirm the high survival rates after neoadjuvant combination checkpoint inhibition in macroscopic stage III melanoma, especially for patients with a pathologic response. Pathologic response is the strongest surrogate marker for long-term outcome.

Modeling micropollutant removal by nanofiltration and reverse osmosis membranes: considerations and challenges.

Organic micropollutants (OMPs) in drinking water constitute a potential risk to human health; therefore, effective removal of these pollutants is required. Nanofiltration (NF) and reverse osmosis (RO) are promising membrane-based technologies to remove OMPs. In NF and RO, the rejection of OMPs depends on the properties and characteristics of the membrane, the solute, and the solution. In this review, we discuss how these properties can be included in models to study and predict the rejection of OMPs. Initially, an OMP classification is proposed to capture the relevant properties of 58 OMPs. Following the methodology described in this study, more and new OMPs can be easily included in this classification. The classification aims to increase the comprehension and mechanistic understanding of OMP removal. Based on the physicochemical principles used to classify the 58 OMPs, it is expected that other OMPs in the same groups will be similarly rejected. From this classification, we present an overview of the rejection mechanisms involved in the removal of specific OMP groups. For instance, we discuss the removal of OMPs classified as perfluoroalkyl substances (e.g., perfluorooctanoic acid, PFOA). These substances are highly relevant due to their human toxicity at extremely low concentration as well as their persistence and omnipresence in the environment. Finally, we discuss how the rejection of OMPs can be predicted by describing both the membrane-solution interface and calculating the transport of solutes inside the membrane. We illustrate the importance and impact of different rejection mechanisms and interfacial phenomena on OMP removal and propose an extended Nernst-Plank equation to calculate the transport of solutes across the membrane due to convection, diffusion, and electromigration. Finally, we show how the theory discussed in this review leads to improved predictions of OMP rejection by the membranes.

The significance of the biomass subfraction of high-MW organic carbon for the microbial growth and maintenance potential of disinfectant-free drinking water produced from surface water.

Drinking water must be sufficiently biostable to avoid excessive microbial and invertebrate growth in disinfectant-free distribution systems. The production of biologically stable drinking water is challenging for conventional surface water treatment plants using reservoirs as feed water due to the presence of slowly biodegradable particulate and high-molecular weight biopolymeric organic carbon (high-MW OC) which increases the Microbial Growth Potential (MGP) in the feed water and produced drinking water. The study presented here provides new insights in the relationship between high-MW OC and MGP for a full-scale surface water treatment plant. Controlled-conditions addition series experiments showed that MGP increases linearly with the high-MW OC concentration with a seasonally variable ratio. Laboratory filtration indicated that MGP is mainly attributable to the high-MW OC subfraction of >  0.12 µm particle size coinciding with microbial biomass. Intensive field monitoring revealed clear seasonal patterns in the plant's feed water and treated water levels of high-MW OC, biomass and MGP. These parameters reach maximum levels in the periods of high water temperature with the notable exception of the treated water's high-MW OC concentration which exhibits an opposite seasonal pattern (reflecting seasonally variable removal in the treatment). Moreover, the field monitoring showed that MGP correlates well with the concentrations of biodegradable biopolymeric OC and with microbial biomass measured as ATP (adenosine triphosphate) and cell counts, but not with the total high-MW OC concentration in the treated water. Theoretical estimations showed that the OC quantities present in and consumed by the microbial biomass are in the same order of magnitude as slowly biodegradable biopolymers. From these results it is concluded that specifically the microbial biomass-associated and biodegradable biopolymeric OC subfraction of the totally present high-MW OC is important for MGP. Finally, the MGP-assay results and theoretical calculations showed for the high-MW OC matrix that the microbial biomass' OC consumption for maintenance is significant vis-á-vis that for growth, and that stable and high levels of biomass are sustained in the treated water which may adversely affect biological stability in the distribution network.

Selective adsorption of nitrate over chloride in microporous carbons.

Activated carbon is the most common electrode material used in electrosorption processes such as water desalination with capacitive deionization (CDI). CDI is a cyclic process to remove ions from aqueous solutions by transferring charge from one electrode to another. When multiple salts are present in a solution, the removal of each ionic species can be different, resulting in selective ion separations. This ion selectivity is the result of combined effects, such as differences in the hydrated size and valence of the ions. In the present work, we study ion selectivity from salt mixtures with two different monovalent ions, chloride and nitrate. We run adsorption experiment in microporous carbons (i.e., without applying a voltage), as well as electrosorption experiments (i.e., based on applying a voltage between two carbon electrodes). Our results show that i) during adsorption and electrosorption, activated carbon removes much more nitrate than chloride; ii) at equilibrium, ion selectivity does not depend strongly on the composition of the water, but does depend on charging voltage in CDI; and iii) during electrosorption, ion selectivity is time-dependent. We modify the amphoteric Donnan model by including an additional affinity of nitrate to carbon. We find good agreement between our experimental results and the theory. Both show very high selectivity towards nitrate over chloride, [Formula: see text] ∼10, when no voltage is applied, or when the voltage is low. The selectivity gradually decreases with increasing charging voltage to [Formula: see text] ∼6 at Vch = 1.2 V. Despite this decrease, the affinity-effect for nitrate continues to play an important role also at a high voltage. In general, we can conclude that our work provides new insights in the importance of carbon-ion interactions for electrochemical water desalination.

Enhancing biological stability of disinfectant-free drinking water by reducing high molecular weight organic compounds with ultrafiltration posttreatment.

The production of biologically stable drinking water is challenging in conventional surface water treatment plants. However, attainment of biological stability is essential to avoid regrowth in disinfectant-free distribution systems. A novel application of ultrafiltration as a posttreatment step to enhance biological stability of drinking water produced in an existing conventional surface water treatment plant was investigated. The conventional full-scale plant comprised coagulation/sedimentation/filtration, UV-disinfection, biological activated carbon filtration and chlorine dioxide post-disinfection. The produced water exhibited substantial regrowth of Aeromonads, invertebrates and colony counts in the distribution network. Recent literature attributes this phenomenon to the specific presence of slowly biodegradable, high molecular weight (MW) biopolymeric organic compounds. Hence, the aim of this study is to enhance the biological stability of conventionally treated surface water by reducing the concentration of high-MW organic compounds. For this purpose, biological active carbon filtrate was subjected to ultrafiltration with membrane pore sizes of 10 kDa, 150 kDa and 0.12 µm respectively, operating in parallel. The UF performance was evaluated in terms of the achieved reduction in particulate and high-MW organic carbon (PHMOC); the biopolymer fraction in Liquid Chromatography-Organic Carbon Detection; biomass (cells, ATP); Assimilable Organic Carbon (AOC) by the AOC-P17/NOX method for easily biodegradable, low-MW compounds and by the AOC-A3 method for slowly biodegradable, high-MW compounds; and overall microbial growth potential (MGP) as assessed by Biomass Production Potential (BPP) and Bacterial Growth Potential (BGP) bio-assays. Results showed increasing removal of high-MW organic carbon with decreasing UF pore size, i.e., 30%, 60% and 70% removal was observed for the 0.12 µm, 150 kDa and 10 kDa membranes, respectively. Biomass and particulates retention was more than 95% for all UF membranes. AOC-A3, BPP and BGP were substantially reduced by 90%, 70% and 50%, respectively. These respective reductions were similar for all three UF membranes despite their difference in pore size. Easily biodegradable organic compounds (as AOC-P17/NOX) were not reduced by any of the membranes, which was in accordance with expectations considering the low MW of the compounds involved. Based on the obtained results, growth potential appears to be largely attributable to high-MW organic compounds which are retained by a 0.12 µm UF membrane. Furthermore, the quality of all three UF permeates was equal to or better than in reference cases (literature data) which exhibit little regrowth in their disinfectant-free distribution networks. The results demonstrate that ultrafiltration posttreatment in conventional surface water treatment plants is a potentially promising approach to enhance the biological stability of drinking water.

Correction to: Cardiovascular causes of sudden unexpected death in children and adolescents (0-17 years) : A nationwide autopsy study in the Netherlands.

Correction to:Neth Heart J 2018 https://doi.org/10.1007/s12471-018-1152-y In the version of the article originally published online, there was an error in the 'Methods and results' section of the Abstract. It is stated that 'In the 10-14 year group, hypertrophic cardiomyopathy (n = 1) and ruptured ….

Cardiovascular causes of sudden unexpected death in children and adolescents (0-17 years) : A nationwide autopsy study in the Netherlands.

BACKGROUND: Little is known about the causes of unexpected death in minors (0-17 years). In young adults an important cause is cardiovascular disease, with primary arrhythmogenic disorders, atherosclerotic events, cardiomyopathies and myocarditis as main contributors. The aim of this autopsy study was to determine the contribution of cardiovascular disease to unexpected death in minors. METHODS AND RESULTS: In the Netherlands, systematic investigation of all cases of unexplained death in minors was compulsory in a nationwide governmental project during a 15-month period. Autopsies were performed according to a standardised protocol (autopsy rate 85%). A cardiovascular cause of death was found in 13/56 cases (23%). In the group <1 year, the main cardiovascular causes were various congenital defects (n = 3) and myocarditis (n = 2). In the 1-9 year group, no cardiovascular causes were found. In the 10-14 year group, coronary anomalies (n = 2) and arrhythmogenic cardiomyopathy (n = 1) were observed. In the 15­17 year group, hypertrophic cardiomyopathy (n = 1) and ruptured ascending aortic aneurysm (n = 1) were among the observed cardiovascular causes [corrected]. In 14/56 (25%) cases autopsy revealed no structural abnormalities that could explain the sudden death, mostly in the group <1 year. CONCLUSION: This national cohort with a high autopsy rate reveals a high incidence (23%) of cardiovascular diseases as the pathological substrate of sudden unexpected death in children. Another high percentage of minors (25%) showed no structural abnormalities, with the possibility of a genetic arrhythmia. These findings underline the importance of systematic autopsy in sudden death in minors, with implications for cardiogenetic screening of relatives.

Energy consumption in capacitive deionization - Constant current versus constant voltage operation.

In the field of Capacitive Deionization (CDI), it has become a common notion that constant current (CC) operation consumes significantly less energy than constant voltage operation (CV). Arguments in support of this claim are that in CC operation the endpoint voltage is reached only at the end of the charging step, and thus the average cell voltage during charging is lower than the endpoint voltage, and that in CC operation we can recover part of the invested energy during discharge. Though these arguments are correct, in the present work based on experiments and theory, we conclude that in operation of a well-defined CDI cycle, this does not lead, for the case we analyze, to the general conclusion that CC operation is more energy efficient. Instead, we find that without energy recovery there is no difference in energy consumption between CC and CV operation. Including 50% energy recovery, we find that indeed CC is more energy efficient, but also in CV much energy can be recovered. Important in the analysis is to precisely define the desalination objective function, such as that per unit total operational time -including both the charge and discharge steps- a certain desalination quantity and water recovery must be achieved. Another point is that also in CV operation energy recovery is possible by discharge at a non-zero cell voltage. To aid the analysis we present a new method of data representation where energy consumption is plotted against desalination. In addition, we propose that one must analyze the full range of combinations of cycle times, voltages and currents, and only compare the best cycles, to be able to conclude which operational mode is optimal for a given desalination objective. We discuss three methods to make this analysis in a rigorous way, two experimental and one combining experiments and theory. We use the last method and present results of this analysis.

Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

Slowly biodegradable organic compounds impact the biostability of non-chlorinated drinking water produced from surface water.

It is possible to distribute drinking water without a disinfectant residual when the treated water is biologically stable. The objective of this study was to determine the impact of easily and slowly biodegradable compounds on the biostability of the drinking water at three full-scale production plants which use the same surface water, and on the regrowth conditions in the related distribution systems. Easily biodegradable compounds in the drinking water were determined with AOC-P17/Nox during 2012-2015. Slowly biodegradable organic compounds measured as particulate and/or high-molecular organic carbon (PHMOC), were monitored at the inlet and after the different treatment stages of the three treatments during the same period. The results show that PHMOC (300-470 µg C L-1) was approximately 10% of the TOC in the surface water and was removed to 50-100 µg C L-1. The PHMOC in the water consisted of 40-60% of carbohydrates and 10% of proteins. A significant and strong positive correlation was observed for PHMOC concentrations and two recently introduced bioassay methods for slowly biodegradable compounds (AOC-A3 and biomass production potential, BPC14). Moreover, these three parameters in the biological active carbon effluent (BACF) of the three plants showed a positive correlation with regrowth in the drinking water distribution system, which was assessed with Aeromonas, heterotrophic plate counts, coliforms and large invertebrates. In contrast, the AOC-P17/Nox concentrations did not correlate with these regrowth parameters. We therefore conclude that slowly biodegradable compounds in the treated water from these treatment plants seem to have a greater impact on regrowth in the distribution system than easily biodegradable compounds.

Theory of pH changes in water desalination by capacitive deionization.

In electrochemical water desalination, a large difference in pH can develop between feed and effluent water. These pH changes can affect the long-term stability of membranes and electrodes. Often Faradaic reactions are implicated to explain these pH changes. However, quantitative theory has not been developed yet to underpin these considerations. We develop a theory for electrochemical water desalination which includes not only Faradaic reactions but also the fact that all ions in the water have different mobilities (diffusion coefficients). We quantify the latter effect by microscopic physics-based modeling of pH changes in Membrane Capacitive Deionization (MCDI), a water desalination technology employing porous carbon electrodes and ion-exchange membranes. We derive a dynamic model and include the following phenomena: I) different mobilities of various ions, combined with acid-base equilibrium reactions; II) chemical surface charge groups in the micropores of the porous carbon electrodes, where electrical double layers are formed; and III) Faradaic reactions in the micropores. The theory predicts small pH changes during desalination cycles in MCDI if we only consider phenomena I) and II), but predicts that these pH changes can be much stronger if we consider phenomenon III) as well, which is in line with earlier statements in the literature on the relevance of Faradaic reactions to explain pH fluctuations.

Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown. OBJECTIVE: To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC. METHODS: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes. RESULTS: Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy. CONCLUSION: Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.

One-stop-shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open-label, noninferiority, randomized controlled multicentre trial.

BACKGROUND: Routine punch biopsies are considered to be standard care for diagnosing and subtyping basal cell carcinoma (BCC) when clinically suspected. OBJECTIVES: We assessed the efficacy of a one-stop-shop concept using in vivo reflectance confocal microscopy (RCM) imaging as a diagnostic tool vs. standard care for surgical treatment in patients with clinically suspected BCC. METHODS: In this open-label, parallel-group, noninferiority, randomized controlled multicentre trial we enrolled patients with clinically suspected BCC at two tertiary referral centres in Amsterdam, the Netherlands. Patients were randomly assigned to the RCM one-stop-shop (diagnosing and subtyping using RCM followed by direct surgical excision) or standard care (planned excision based on the histological diagnosis and subtype of a punch biopsy). The primary outcome was the proportion of patients with tumour-free margins after surgical excision of BCC. RESULTS: Of the 95 patients included, 73 (77%) had a BCC histologically confirmed using a surgical excision specimen. All patients (40 of 40, 100%) in the one-stop-shop group had tumour-free margins. In the standard-care group tumour-free margins were found in all but two patients (31 of 33, 94%). The difference in the proportion of patients with tumour-free margins after BCC excision between the one-stop-shop group and the standard-care group was -0·06 (90% confidence interval -0·17-0·01), establishing noninferiority. CONCLUSIONS: The proposed new treatment strategy seems suitable in facilitating early diagnosis and direct treatment for patients with BCC, depending on factors such as availability of RCM, size and site of the lesion, patient preference and whether direct surgical excision is feasible.

Autopsy after transcatheter aortic valve implantation.

Autopsy after transcatheter aortic valve implantation (TAVI) is a new field of interest in cardiovascular pathology. To identify the cause of death, it is important to be familiar with specific findings related to the time interval between the procedure and death. We aimed to provide an overview of the autopsy findings in patients with TAVI in their medical history divided by the timing of death with specific interest in the added value of autopsy over a solely clinically determined cause of death. In 8 European centres, 72 cases with autopsy reports were available. Autopsies were divided according to the time interval of death and reports were analysed. In 32 patients who died ≤72 h postprocedure, mortality resulted from cardiogenic or haemorrhagic shock in 62.5 and 34.4%, respectively. In 31 patients with mortality >72 h to ≤30 days, cardiogenic shock was the cause of death in 51.6% followed by sepsis (22.6%) and respiratory failure (9.7%). Of the nine patients with death >30 days, 88.9% died of sepsis, caused by infective endocarditis in half of them. At total of 12 patients revealed cerebrovascular complications. Autopsy revealed unexpected findings in 61.1% and resulted in a partly or completely different cause of death as was clinically determined. Autopsy on patients who underwent TAVI reveals specific patterns of cardiovascular pathology that clearly relate to the time interval between TAVI and death and significantly adds to the clinical diagnosis. Our data support the role of autopsy including investigation of the cerebrum in the quickly evolving era of cardiac device technology.

Hyperbaric oxygen therapy for sudden sensorineural hearing loss in divers.

OBJECTIVE: Sudden sensorineural hearing loss in divers may be caused by either inner-ear barotrauma or inner-ear decompression sickness. There is no consensus on the best treatment option. This study aimed to evaluate the therapeutic value of hyperbaric oxygen therapy for sudden sensorineural hearing loss in divers. METHOD: A literature review and three cases of divers with sudden sensorineural hearing loss treated with hyperbaric oxygen therapy are presented. RESULTS: Hyperbaric oxygen therapy resulted in hearing improvement in 80 per cent of patients: 39 per cent had hearing improvement and 41 per cent had full recovery. CONCLUSION: Hyperbaric oxygen therapy improved hearing in divers with sudden sensorineural hearing loss.

A lethal case of the dapsone hypersensitivity syndrome involving the myocardium.

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.