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  1. Article ; Online: Monitoring antihypertensive drug concentrations to determine nonadherence in hypertensive patients with or without a kidney transplant.

    Peeters, Laura E J / Hesselink, Dennis A / Lafeber, Melvin / Severs, David / van den Hoogen, Martijn W F / Sonneveld, Michelle A H / Ramakers, Christian R B / Bahmany, Soma / van Gelder, Teun / Koch, Birgit C P / Versmissen, Jorie

    Journal of hypertension

    2023  Volume 41, Issue 8, Page(s) 1239–1244

    Abstract: ... adherence rate to AHDs was 78.2% ( n  = 111 patients), with the highest adherence rate for irbesartan (100 ... n  = 9) and lowest adherence rate for bumetanide ( n  = 69%, n  = 13). In further analysis, only ...

    Abstract Background: Nonadherence to antihypertensive drugs (AHDs) is a major contributor to pseudo-resistant hypertension. The primary objective of this study was to determine the prevalence of nonadherence to AHDs among patients visiting the nephrology and vascular outpatient clinics.
    Methods: Patients were eligible to participate in this prospective observational study if they used at least two AHDs that could be measured with a validated UHPLC-MS/MS method and had an office blood pressure at least 140 and/or at least 90 mmHg. For resistant hypertension, included patients had to use at least three AHDs including a diuretic or four AHDs. Adherence was assessed by measuring drug concentrations in blood. The complete absence of drug in blood was defined as nonadherence. A posthoc analysis was performed to determine the influence of a having a kidney transplant on the adherence rates.
    Results: One hundred and forty-two patients were included of whom 66 patients fulfilled the definition of resistant hypertension. The overall adherence rate to AHDs was 78.2% ( n  = 111 patients), with the highest adherence rate for irbesartan (100%, n  = 9) and lowest adherence rate for bumetanide ( n  = 69%, n  = 13). In further analysis, only kidney transplantation could be identified as an important factor for adherence (adjusted odds ratio = 3.35; 95% confidence interval 1.23-9.09). A posthoc analysis showed that patients with a kidney transplant were more likely to be adherent to AHDs (non-KT cohort 64.0% vs. KT-cohort 85.7%, χ 2 (2) = 10.34, P  = 0.006).
    Conclusion: The adherence rate to AHDs in hypertensive patients was high (78.2%) and even higher after a kidney transplant (85.7%). Furthermore, patients after kidney transplant had a lower risk of being nonadherent to AHDs.
    MeSH term(s) Humans ; Antihypertensive Agents/therapeutic use ; Kidney Transplantation ; Tandem Mass Spectrometry ; Medication Adherence ; Hypertension/drug therapy
    Chemical Substances Antihypertensive Agents
    Language English
    Publishing date 2023-05-06
    Publishing country Netherlands
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000003459
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  2. Article: Minder separeren, veiligheid creëren; het concept ‘veiligheidsgevoel’ in beeld gebracht.

    Severs, C J / Hondius, A J K / Schene, A H

    Tijdschrift voor psychiatrie

    2017  Volume 59, Issue 1, Page(s) 20–29

    Abstract: ... hierarchical clusteranalysis) with the knowledge of professionals from psychiatric practice (N=24), first ... on an individual basis and then as a group (N=8).
    RESULTS: The participants generated and prioritised a total ...

    Title translation Does less seclusion create a safer environment? An attempt to map the concept of 'feeling safe'.
    Abstract Background: The degree of restraint imposed by a psychiatrist seems to be influenced by the safety of the team. So far, there have been few attempts to map the concept of 'feeling safe'.<br/> AIM: To analyse, define and quantify the concept of 'feeling safe'.<br/> METHOD: Concept mapping involves combining, in a structured way, qualitative (item collection) and quantitative methods (multi-dimensional scaling and hierarchical clusteranalysis) with the knowledge of professionals from psychiatric practice (N=24), first on an individual basis and then as a group (N=8).<br/> RESULTS: The participants generated and prioritised a total of 97 different items. These were then divided into six clusters: organisational structure, professionalism of team members, increased expertise, marginal conditions, internal and external features of the hospital building, views on mental health care and policy. Group members gave almost equal priority to the clusters, but they assigned different degrees of importance to separate items (ranging from 4.63 to 2.38 on a five-point scale).<br/> CONCLUSION: Concept mapping is an adequate method of defining the concept of 'feeling safe'. Professionalism of the team and qualities such as openness and ability to communicate, expertise and trusting one's colleagues and having an adequate alarm system available are all important factors that help to make employees 'feel safe' in their respective departments.
    Language Dutch
    Publishing date 2017
    Publishing country Netherlands
    Document type Journal Article ; English Abstract
    ZDB-ID 604662-9
    ISSN 0303-7339
    ISSN 0303-7339
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  3. Article ; Online: Calcium channel blockers in pancreatic cancer: increased overall survival in a retrospective cohort study.

    Tingle, Samuel J / Severs, George R / Moir, John A G / White, Steven A

    Anti-cancer drugs

    2020  Volume 31, Issue 7, Page(s) 737–741

    Abstract: ... radiotherapy, age, hypertension and sex. Participants prescribed CCB (n = 30) were more likely to be older (P ...

    Abstract Repurposing commonly prescribed noncancer medications for use in oncology has substantial advantages over de-novo development of anticancer drugs. Calcium signalling has been implicated in many of the hallmarks of cancer. Previous in-vitro and in-vivo studies have shown that calcium channel blockers (CCBs) are able to promote apoptosis, inhibit proliferation and prevent invasion and metastasis in a variety of cancer types. This retrospective cohort study aimed to translate this into the clinic by investigating the effect of CCBs on survival in pancreatic cancer. One hundred sixty-four patients with unresectable pancreatic ductal adenocarcinoma were included. Data were collected on CCB prescription, and for a range of other potentially important prognostic factors: ECOG performance status, AJCC cancer stage, chemotherapy regimen, radiotherapy, age, hypertension and sex. Participants prescribed CCB (n = 30) were more likely to be older (P = 0.004) and have hypertension (P < 0.0005); baseline demographics were otherwise similar between groups. On adjusted cox regression patients prescribed CCBs demonstrated significantly improved overall survival; hazard ratio -0.496 (0.297-0.827; P = 0.007). Performance status (P < 0.0005), tumour stage (P < 0.0005), chemotherapy regimen (P < 0.0005), radiotherapy (0.002) and age (P = 0.012) were also independent predictors of survival. The Kaplan-Meier estimated median survival was 15.3 months for patients prescribed CCBs versus 10.1 months for patients not prescribed CCBs (P = 0.131). This study supports previous work suggesting CCBs may be beneficial in pancreatic cancer. Further work on larger datasets will allow for subgroup analysis delineating the effects of specific CCBs in combination with different forms of chemotherapy, paving the way for future prospective studies.
    MeSH term(s) Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Calcium Channel Blockers/administration & dosage ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/mortality ; Cohort Studies ; Deoxycytidine/administration & dosage ; Deoxycytidine/analogs & derivatives ; Female ; Fluorouracil/administration & dosage ; Humans ; Irinotecan/administration & dosage ; Kaplan-Meier Estimate ; Leucovorin/administration & dosage ; Male ; Middle Aged ; Oxaliplatin/administration & dosage ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/mortality ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; United Kingdom/epidemiology
    Chemical Substances Calcium Channel Blockers ; folfirinox ; Oxaliplatin (04ZR38536J) ; Deoxycytidine (0W860991D6) ; Irinotecan (7673326042) ; gemcitabine (B76N6SBZ8R) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2020-07-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 1065301-6
    ISSN 1473-5741 ; 0959-4973
    ISSN (online) 1473-5741
    ISSN 0959-4973
    DOI 10.1097/CAD.0000000000000947
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  4. Article ; Online: High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice.

    Costello, Hannah M / Krilis, Georgios / Grenier, Celine / Severs, David / Czopek, Alicja / Ivy, Jessica R / Nixon, Mark / Holmes, Megan C / Livingstone, Dawn E W / Hoorn, Ewout J / Dhaun, Neeraj / Bailey, Matthew A

    Cardiovascular research

    2022  Volume 119, Issue 8, Page(s) 1740–1750

    Abstract: Aims: High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the ... ...

    Abstract Aims: High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic-pituitary-adrenal axis activation and leads to sustained glucocorticoid excess.
    Methods and results: In male C57BL/6 mice, high salt intake for 2-8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic-pituitary-adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic-pituitary-adrenal axis activation by high salt diet.
    Conclusion: Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells.
    MeSH term(s) Humans ; Mice ; Animals ; Male ; Glucocorticoids/metabolism ; Hypothalamo-Hypophyseal System/metabolism ; Sodium Chloride, Dietary ; Pituitary-Adrenal System/metabolism ; Mice, Inbred C57BL ; Vasopressins/genetics ; Vasopressins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
    Chemical Substances Glucocorticoids ; Sodium Chloride, Dietary ; Vasopressins (11000-17-2) ; RNA, Messenger
    Language English
    Publishing date 2022-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvac160
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  5. Article ; Online: Characterizing the glycosylation state of therapeutic recombinant glycoproteins.

    Samuels, Nicole / Kates, David / Liu, Jun / Severs, Joanne

    Methods in molecular biology (Clifton, N.J.)

    2013  Volume 951, Page(s) 323–334

    Abstract: As an increasing number of recombinant therapeutic glycoproteins are manufactured and investigated, the importance of their attached glycans is becoming more widely reported and understood. Regulatory agencies expect detailed "extended characterization" ... ...

    Abstract As an increasing number of recombinant therapeutic glycoproteins are manufactured and investigated, the importance of their attached glycans is becoming more widely reported and understood. Regulatory agencies expect detailed "extended characterization" of the glycoprotein as well as routine, well-controlled "release assays" with specifications to be employed for quality control of each manufactured lot. In this chapter we will briefly discuss relevant glycan issues in the area of therapeutic recombinant glycoprotein manufacture and describe in detail two assays that are employed in the development of, for example, recombinant Factor VIII for the treatment of hemophilia.
    MeSH term(s) Chromatography, High Pressure Liquid ; Factor VIII/metabolism ; Factor VIII/therapeutic use ; Glycoproteins/chemistry ; Glycoproteins/metabolism ; Glycoproteins/therapeutic use ; Glycosylation ; Hemophilia A/drug therapy ; Humans ; Mass Spectrometry ; Oligosaccharides/metabolism ; Proteolysis ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Recombinant Proteins/therapeutic use ; Thrombin/metabolism
    Chemical Substances Glycoproteins ; Oligosaccharides ; Recombinant Proteins ; Factor VIII (9001-27-8) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-146-2_22
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  6. Article ; Online: Evidence for Missing Positive Results for Human Papilloma Virus 45 (HPV-45) and HPV-59 with the SPF

    van Eer, Kahren / Leussink, Suzan / Severs, Tim T / van Marm-Wattimena, Naomi / Woestenberg, Petra J / Bogaards, Johannes A / King, Audrey J

    Journal of clinical microbiology

    2020  Volume 58, Issue 11

    Abstract: Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum ... ...

    Abstract Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF
    MeSH term(s) DNA, Viral ; Female ; Humans ; Papillomaviridae/genetics ; Papillomavirus Infections/diagnosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Vaccines
    Chemical Substances DNA, Viral ; Vaccines
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.01626-20
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  7. Article: The cardiac muscle cell.

    Severs, N J

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2000  Volume 22, Issue 2, Page(s) 188–199

    Abstract: The cardiac myocyte is the most physically energetic cell in the body, contracting constantly, without tiring, 3 billion times or more in an average human lifespan. By coordinating its beating activity with that of its 3 billion neighbours in the main ... ...

    Abstract The cardiac myocyte is the most physically energetic cell in the body, contracting constantly, without tiring, 3 billion times or more in an average human lifespan. By coordinating its beating activity with that of its 3 billion neighbours in the main pump of the human heart, over 7,000 litres of blood are pumped per day, without conscious effort, along 100,000 miles of blood vessels. A detailed picture of the membrane organisation of the cardiac muscle cell underpins our understanding of how the electrical impulse, generated within the heart, stimulates coordinated contraction of the cardiac chambers. This article highlights, with the aid of modern cellular imaging methods, key components of the membrane machinery responsible for coupling electrical excitation and contraction in the cardiomyocyte, focusing on plasma membrane/sarcoplasmic reticulum and plasma membrane/plasma membrane junctions. BioEssays 22:188-199, 2000.
    MeSH term(s) Arrhythmias, Cardiac/pathology ; Arrhythmias, Cardiac/physiopathology ; Cell Differentiation ; Cell Membrane/physiology ; Cell Membrane/ultrastructure ; Connexins/physiology ; Freeze Fracturing ; Gap Junctions/physiology ; Gap Junctions/ultrastructure ; Heart/physiology ; Heart Diseases/pathology ; Heart Diseases/physiopathology ; Humans ; Microscopy, Electron ; Myocardial Contraction/physiology ; Myocardium/cytology ; Sarcoplasmic Reticulum/physiology ; Sarcoplasmic Reticulum/ultrastructure
    Chemical Substances Connexins
    Language English
    Publishing date 2000-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/(SICI)1521-1878(200002)22:2<188::AID-BIES10>3.0.CO;2-T
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  8. Article: Gap junction remodeling and cardiac arrhythmogenesis: cause or coincidence?

    Severs, N J

    Journal of cellular and molecular medicine

    2000  Volume 5, Issue 4, Page(s) 355–366

    Abstract: Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte-to-myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins and, in in vitro expression systems, gap- ... ...

    Abstract Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte-to-myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins and, in in vitro expression systems, gap-junctional channels composed of different connexin types exhibit different biophysical properties. In common with other tissues, the heart expresses multiple connexin isoforms. Spatially defined patterns of expression of three connexin isoforms - connexin43, connexin40 and connexin45 - form the cell-to-cell conduction pathways responsible for the orderly spread of current flow that governs the normal cardiac rhythm. Remodeling of gap junction organization and connexin expression is a common feature of human heart disease conditions in which there is an arrhythmic tendency. This remodeling may take the form of disturbances in the distribution of gap junctions and/or quantitative alterations in connexin expression, notably reduced ventricular connexin43 levels. The idea that such changes may contribute to the development of a pro-arrhythmic substrate in the diseased heart has gained ground over the last decade. Recent studies using transgenic mice models have raised new opportunities to explore the significance of gap junction remodeling in the diseased heart.
    MeSH term(s) Animals ; Arrhythmias, Cardiac/etiology ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/pathology ; Connexins/metabolism ; Gap Junctions/metabolism ; Gap Junctions/ultrastructure ; Humans ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/ultrastructure
    Chemical Substances Connexins
    Language English
    Publishing date 2000-04-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-1838 ; 1582-4934
    ISSN (online) 1582-4934
    ISSN 1582-1838 ; 1582-4934
    DOI 10.1111/j.1582-4934.2001.tb00170.x
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  9. Article ; Online: Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease

    Visser, Wesley / van de Braak, Elma / de Mik‐van Egmond, Anneke / van der Burgh, Anna / de Roos, Nicole / Jans, Inez / van der Hoef, Iris / Olieman, Joanne / Hoorn, Ewout / Severs, David

    Journal of cachexia, sarcopenia and muscle

    a systematic review and meta‐analysis

    2023  Volume 14, Issue 6

    Abstract: Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the ... ...

    Abstract Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m2, and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P < 0.001) and functionality assessed with the sit-to-stand test (SMD −0.31 [95% CI −0.52 to 0.11], P = 0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.
    Keywords Life Science
    Subject code 610
    Language English
    Publishing country nl
    Document type Article ; Online
    ZDB-ID 2586864-0
    ISSN 2190-6009 ; 2190-5991
    ISSN (online) 2190-6009
    ISSN 2190-5991
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  10. Article ; Online: Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease.

    Blijdorp, Charles J / Severs, David / Musterd-Bhaggoe, Usha M / Gansevoort, Ronald T / Zietse, Robert / Hoorn, Ewout J

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2020  Volume 36, Issue 12, Page(s) 2248–2255

    Abstract: ... included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m2, 2.5 years follow-up ...

    Abstract Background: Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown.
    Methods: Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m2, 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid-base parameters (urinary ammonium excretion).
    Results: Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21-7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06-1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (-0.12 mL/min/1.73 m2/year, 95% CI -0.20 to -0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth.
    Conclusions: In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD.
    MeSH term(s) Bicarbonates ; Disease Progression ; Glomerular Filtration Rate ; Humans ; Kidney ; Polycystic Kidney, Autosomal Dominant/complications
    Chemical Substances Bicarbonates
    Language English
    Publishing date 2020-12-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfaa283
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