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Overview
Mark is a physician scientist training in Clinical Immunology at the Immunodeficiency Centre for Wales, Cardiff, United Kingdom (UK).
His training to date highlights a track record of commitment to excellence in clinical research. Graduating with distinction in Clinical Medicine and degree in Molecular Medicine from Oxford Medical School, he subsequently gained medical registration with the Royal College of Physicians (MRCP UK) with specific placements in respiratory medicine, rheumatology, cardiology, and vascular surgery providing relevant clinical exposure to a career in Clinical Immunology.
Mark recently completed the King’s College Medical Immunology MSc top of the year alongside Part I for the Royal College of Pathology Examinations. These were conducted alongside clinical practice in Cardiff, demonstrating time management, laboratory skills, and capability for cross-site working.
Mark's clinical roles have included coordination of the All-Wales Primary Immunodeficiency Bone Marrow Transplant Multi-disciplinary Team. This setting continues to provide unique insights into extreme and rare manifestations of human illness caused by monogenic disorders, leading to a particular interest in how mutations in the STAT3 gene lead to multi-system effects from immune deficiency, infection, to widespread vascular abnormalities (tortuosity, ectasia, and aneurysms).
To date, Mark has led development and delivery of 5 REC-approved observational clinical studies, which have all resulted in successful international presentation & publications. This included the first description of clozapine-associated hypogammaglobulinaemia, allowing Mark to spearhead a successful multi-disciplinary team funding bid for a national validation study (£229k) and win appointment as a Welsh Clinical Academic Trainee (WCAT) Lecturer. Whilst a specialist immunology trainee he also helped setup and coordinate the Burden of Infection in Primary Antibody Deficiency (BIPAD) study. By performing detailed longitudinal symptom and pathogen profiling in patients and healthy controls, this study charts the difference in symptoms and infections that remains despite current medical therapies.
The COVID-19 pandemic has demanded a pivot in Mark's doctoral study time towards understanding of epidemiological and immunological risk factors for development of severe disease following SARS-CoV-2 infection.
Publication
2023
- Ponsford, M. 2023. Nosocomial transmission and immunocompromise as risk factors for exposure and adverse outcomes associated with novel pandemic coronavirus SARS-CoV-2 disease (COVID-19).. PhD Thesis, Cardiff University.
2022
- Jefferies, R., Ponsford, M. J., Davies, C., Williams, S. J. and Barry, S. 2022. Strategies to promote guideline adoption: lessons learned from the implementation of a national COVID-19 hospital guideline across NHS Wales. Future Healthcare Journal 9(3), pp. 262-267. (10.7861/fhj.2022-0028)
- Morgan, C., Jolles, S., Ponsford, M. J., Evans, K. and Carne, E. 2022. Immunodeficient patient experience of emergency switch from intravenous to rapid push subcutaneous immunoglobulin replacement therapy during coronavirus disease 2019 shielding. Current Opinion in Allergy and Clinical Immunology 22(6), pp. 371-379. (10.1097/ACI.0000000000000864)
- Asderakis, A. et al. 2022. An analysis of serological response and infection outcomes following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 vaccines in kidney and kidney pancreas transplants. Transplantation 106(7), pp. 1421-1429. (10.1097/tp.0000000000004105)
- Ponsford, M. J. et al. 2022. COVID-19 vaccine uptake and efficacy in a national immunodeficiency cohort. Journal of Clinical Immunology 42, pp. 728-731. (10.1007/s10875-022-01223-7)
- Ponsford, M. J. et al. 2022. Examining the utility of extended laboratory panel testing in the emergency department for risk stratification of patients with COVID-19: a single-centre retrospective service evaluation. Journal of Clinical Pathology 75(4), pp. 255-262. (10.1136/jclinpath-2020-207157)
- Bradley, R. E. et al. 2022. Persistent COVID-19 infection in Wiskott-Aldrich syndrome cleared following therapeutic vaccination: a case report. Journal of Clinical Immunology 42, pp. 32-35. (10.1007/s10875-021-01158-5)
2021
- Ponsford, M. J. et al. 2021. Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults. Thorax 76(12), pp. 1246-1249. (10.1136/thoraxjnl-2021-216964)
- Shillitoe, B. M. J. et al. 2021. Haematopoietic stem cell transplant for norovirus-induced intestinal failure in X-linked agammaglobulinemia. Journal of Clinical Immunology 41, pp. 1574 -1581. (10.1007/s10875-021-01088-2)
- Faustini, S. E. et al. 2021. Development of a high sensitivity ELISA detecting IgG, A & M antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva. Immunology 164(1), pp. 135-147. (10.1111/imm.13349)
- Ponsford, M. J., Shillitoe, B. M., Humphreys, I. R., Gennery, A. R. and Jolles, S. 2021. COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency. Current Opinion in Allergy and Clinical Immunology (10.1097/ACI.0000000000000792)
- Harrison, S. C. et al. 2021. Hematopoietic stem cell transplantation resolves the immune deficit associated with STAT3-Dominant-Negative Hyper-IgE Syndrome. Journal of Clinical Immunology 41, pp. 934-943. (10.1007/s10875-021-00971-2)
- Norris, K. et al. 2021. High-throughput STELA provides a rapid test for the diagnosis of telomere biology disorders. Human Genetics 140, pp. 945-955. (10.1007/s00439-021-02257-4)
- Moat, S. J. et al. 2021. Development of a high throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens. Annals of Clinical Biochemistry 58(2) (10.1177/0004563220981106)
- Ponsford, M. J. et al. 2021. Increased respiratory viral detection and symptom burden among patients with primary antibody deficiency: results from the BIPAD study. The Journal of Allergy and Clinical Immunology: In Practice 9(2), pp. 735-744.e6. (10.1016/j.jaip.2020.08.016)
2020
- Ponsford, M. J. et al. 2020. Cardiometabolic traits, sepsis, and severe COVID-19. Circulation 142(18), pp. 1791–1793. (10.1161/CIRCULATIONAHA.120.050753)
- Zelek, W. M. et al. 2020. Complement inhibition with the C5 blocker LFG316 in severe COVID-19. American Journal of Respiratory and Critical Care Medicine 202(9), pp. 1304-1308. (10.1164/rccm.202007-2778LE)
- Gill, D. and Ponsford, M. J. 2020. Testing for antibodies to SARS-CoV-2. The BMJ 371, article number: m4288. (10.1136/bmj.m4288)
- Ponsford, M. J. et al. 2020. Hematopoietic stem cell transplantation and vasculopathy associated with STAT3-dominant-negative hyper-IgE syndrome. Frontiers in Pediatrics 8, article number: 575. (10.3389/fped.2020.00575)
- Williams, F., Ponsford, M., El-Shanawany, T., Macdonald, L., Jolles, S. and Williams, P. 2020. Improved anaphylaxis referral rates to specialized services from an emergency department. Clinical and Experimental Allergy 50(8), pp. 973-976. (10.1111/cea.13673)
- Ponsford, M. J. et al. 2020. Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID). Journal of Clinical Pathology 73, pp. 587-592. (10.1136/jclinpath-2019-206235)
- Thaventhiran, J. E. D. et al. 2020. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature 583, pp. 90-95. (10.1038/s41586-020-2265-1)
- Burgess, S., Ponsford, M. J. and Gill, D. 2020. Are we underestimating seroprevalence of SARS-CoV-2?. The BMJ 370, article number: m3364. (10.1136/bmj.m3364)
2019
- Ponsford, M. J., Pecoraro, A. and Jolles, S. 2019. Clozapine-associated secondary antibody deficiency. Current Opinion in Allergy and Clinical Immunology 19(6), pp. 553-562. (10.1097/ACI.0000000000000592)
- Gorman, K. M. et al. 2019. Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia. American Journal of Human Genetics 104(5), pp. 948-956. (10.1016/j.ajhg.2019.03.005)
- Ponsford, M. et al. 2019. Clozapine is associated with secondary antibody deficiency. British Journal of Psychiatry 214(2), pp. 83-89. (10.1192/bjp.2018.152)
- Ponsford, M. J. and Jolles, S. 2019. Antibody deficiency in patients taking clozapine. British Medical Journal 364, article number: 1483. (10.1136/bmj.l483)
- Tange, C. E. et al. 2019. Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay. Journal of Clinical Laboratory Analysis 33(1), article number: e22627. (10.1002/jcla.22627)
2018
- Ponsford, M. J., Rae, W. and Klocperk, A. 2018. What is new in HIES? Recent insights from the interface of primary immune deficiency and atopy.. Current Opinion in Allergy and Clinical Immunology 18(6), pp. 445-452. (10.1097/aci.0000000000000481)
- Ponsford, M. J. et al. 2018. Hyper IgE in the allergy clinic-- when is it primary immunodeficiency?. Allergy 73(11), pp. 2122-2136. (10.1111/all.13578)
- Hartono, S. P., Vargas-Hernández, A., Ponsford, M. J., Chinn, I. K., Jolles, S., Wilson, K. and Forbes, L. R. 2018. Novel STAT1 gain-of-function mutation presenting as combined immunodeficiency. Journal of Clinical Immunology 38(7), pp. 753-756. (10.1007/s10875-018-0554-3)
- Whitworth, J. et al. 2018. Comprehensive cancer-predisposition gene testing in an adult multiple primary tumor series shows a broad range of deleterious variants and atypical tumor phenotypes. American Journal of Human Genetics 103(1), pp. 3-18. (10.1016/j.ajhg.2018.04.013)
- Evans, C. et al. 2018. Measurement of Typhim Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency. Clinical and Experimental Immunology 192(3), pp. 292-301. (10.1111/cei.13105)
- Tange, C. E. et al. 2018. Quantification of human complement C2 protein using an automated turbidimetric immunoassay. Clinical Chemistry and Laboratory Medicine 56(9), pp. 1498-1506. (10.1515/cclm-2017-1068)
2017
- Carne, E., Ponsford, M., El-Shanawany, T. and Jolles, S. 2017. Skin necrosis following subcutaneous immunoglobulin (SCIg). Journal of Clinical Immunology 37(1), pp. 27-28. (10.1007/s10875-016-0346-6)
2015
- Carne, E., Ponsford, M., El-Shanawany, T., Williams, P., Pickersgill, T. and Jolles, S. 2015. Five years of self-administered hyaluronidase facilitated subcutaneous immunoglobulin (fSCIg) home therapy in a patient with primary immunodeficiency. Journal of Clinical Pathology 69(1), pp. 87-88. (10.1136/jclinpath-2015-202901)
- Ponsford, M. et al. 2015. Facilitated subcutaneous immunoglobulin (fSCIg) therapy - practical considerations. Clinical and Experimental Immunology 182(3), pp. 302-313. (10.1111/cei.12694)
2013
- Gill, D., Bruce, D. J., Ponsford, M. J., Cranley, J. and Goodacre, T. E. 2013. Long-term follow-up of patients undergoing free tissue transfer to the lower limb following trauma. European Journal of Plastic Surgery 36(7), pp. 431-442. (10.1007/s00238-013-0826-3)
2012
- Gill, D. et al. 2012. Laboratory sample turnaround times: do they cause delays in the ED?. Journal of Evaluation in Clinical Practice 18(1), pp. 121-127. (10.1111/j.1365-2753.2010.01545.x)
- Ponsford, M. J. et al. 2012. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. Journal of Infectious Diseases 205(4), pp. 663-671. (10.1093/infdis/jir812)
Articles
- Jefferies, R., Ponsford, M. J., Davies, C., Williams, S. J. and Barry, S. 2022. Strategies to promote guideline adoption: lessons learned from the implementation of a national COVID-19 hospital guideline across NHS Wales. Future Healthcare Journal 9(3), pp. 262-267. (10.7861/fhj.2022-0028)
- Morgan, C., Jolles, S., Ponsford, M. J., Evans, K. and Carne, E. 2022. Immunodeficient patient experience of emergency switch from intravenous to rapid push subcutaneous immunoglobulin replacement therapy during coronavirus disease 2019 shielding. Current Opinion in Allergy and Clinical Immunology 22(6), pp. 371-379. (10.1097/ACI.0000000000000864)
- Asderakis, A. et al. 2022. An analysis of serological response and infection outcomes following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 vaccines in kidney and kidney pancreas transplants. Transplantation 106(7), pp. 1421-1429. (10.1097/tp.0000000000004105)
- Ponsford, M. J. et al. 2022. COVID-19 vaccine uptake and efficacy in a national immunodeficiency cohort. Journal of Clinical Immunology 42, pp. 728-731. (10.1007/s10875-022-01223-7)
- Ponsford, M. J. et al. 2022. Examining the utility of extended laboratory panel testing in the emergency department for risk stratification of patients with COVID-19: a single-centre retrospective service evaluation. Journal of Clinical Pathology 75(4), pp. 255-262. (10.1136/jclinpath-2020-207157)
- Bradley, R. E. et al. 2022. Persistent COVID-19 infection in Wiskott-Aldrich syndrome cleared following therapeutic vaccination: a case report. Journal of Clinical Immunology 42, pp. 32-35. (10.1007/s10875-021-01158-5)
- Ponsford, M. J. et al. 2021. Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults. Thorax 76(12), pp. 1246-1249. (10.1136/thoraxjnl-2021-216964)
- Shillitoe, B. M. J. et al. 2021. Haematopoietic stem cell transplant for norovirus-induced intestinal failure in X-linked agammaglobulinemia. Journal of Clinical Immunology 41, pp. 1574 -1581. (10.1007/s10875-021-01088-2)
- Faustini, S. E. et al. 2021. Development of a high sensitivity ELISA detecting IgG, A & M antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva. Immunology 164(1), pp. 135-147. (10.1111/imm.13349)
- Ponsford, M. J., Shillitoe, B. M., Humphreys, I. R., Gennery, A. R. and Jolles, S. 2021. COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency. Current Opinion in Allergy and Clinical Immunology (10.1097/ACI.0000000000000792)
- Harrison, S. C. et al. 2021. Hematopoietic stem cell transplantation resolves the immune deficit associated with STAT3-Dominant-Negative Hyper-IgE Syndrome. Journal of Clinical Immunology 41, pp. 934-943. (10.1007/s10875-021-00971-2)
- Norris, K. et al. 2021. High-throughput STELA provides a rapid test for the diagnosis of telomere biology disorders. Human Genetics 140, pp. 945-955. (10.1007/s00439-021-02257-4)
- Moat, S. J. et al. 2021. Development of a high throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens. Annals of Clinical Biochemistry 58(2) (10.1177/0004563220981106)
- Ponsford, M. J. et al. 2021. Increased respiratory viral detection and symptom burden among patients with primary antibody deficiency: results from the BIPAD study. The Journal of Allergy and Clinical Immunology: In Practice 9(2), pp. 735-744.e6. (10.1016/j.jaip.2020.08.016)
- Ponsford, M. J. et al. 2020. Cardiometabolic traits, sepsis, and severe COVID-19. Circulation 142(18), pp. 1791–1793. (10.1161/CIRCULATIONAHA.120.050753)
- Zelek, W. M. et al. 2020. Complement inhibition with the C5 blocker LFG316 in severe COVID-19. American Journal of Respiratory and Critical Care Medicine 202(9), pp. 1304-1308. (10.1164/rccm.202007-2778LE)
- Gill, D. and Ponsford, M. J. 2020. Testing for antibodies to SARS-CoV-2. The BMJ 371, article number: m4288. (10.1136/bmj.m4288)
- Ponsford, M. J. et al. 2020. Hematopoietic stem cell transplantation and vasculopathy associated with STAT3-dominant-negative hyper-IgE syndrome. Frontiers in Pediatrics 8, article number: 575. (10.3389/fped.2020.00575)
- Williams, F., Ponsford, M., El-Shanawany, T., Macdonald, L., Jolles, S. and Williams, P. 2020. Improved anaphylaxis referral rates to specialized services from an emergency department. Clinical and Experimental Allergy 50(8), pp. 973-976. (10.1111/cea.13673)
- Ponsford, M. J. et al. 2020. Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID). Journal of Clinical Pathology 73, pp. 587-592. (10.1136/jclinpath-2019-206235)
- Thaventhiran, J. E. D. et al. 2020. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature 583, pp. 90-95. (10.1038/s41586-020-2265-1)
- Burgess, S., Ponsford, M. J. and Gill, D. 2020. Are we underestimating seroprevalence of SARS-CoV-2?. The BMJ 370, article number: m3364. (10.1136/bmj.m3364)
- Ponsford, M. J., Pecoraro, A. and Jolles, S. 2019. Clozapine-associated secondary antibody deficiency. Current Opinion in Allergy and Clinical Immunology 19(6), pp. 553-562. (10.1097/ACI.0000000000000592)
- Gorman, K. M. et al. 2019. Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia. American Journal of Human Genetics 104(5), pp. 948-956. (10.1016/j.ajhg.2019.03.005)
- Ponsford, M. et al. 2019. Clozapine is associated with secondary antibody deficiency. British Journal of Psychiatry 214(2), pp. 83-89. (10.1192/bjp.2018.152)
- Ponsford, M. J. and Jolles, S. 2019. Antibody deficiency in patients taking clozapine. British Medical Journal 364, article number: 1483. (10.1136/bmj.l483)
- Tange, C. E. et al. 2019. Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay. Journal of Clinical Laboratory Analysis 33(1), article number: e22627. (10.1002/jcla.22627)
- Ponsford, M. J., Rae, W. and Klocperk, A. 2018. What is new in HIES? Recent insights from the interface of primary immune deficiency and atopy.. Current Opinion in Allergy and Clinical Immunology 18(6), pp. 445-452. (10.1097/aci.0000000000000481)
- Ponsford, M. J. et al. 2018. Hyper IgE in the allergy clinic-- when is it primary immunodeficiency?. Allergy 73(11), pp. 2122-2136. (10.1111/all.13578)
- Hartono, S. P., Vargas-Hernández, A., Ponsford, M. J., Chinn, I. K., Jolles, S., Wilson, K. and Forbes, L. R. 2018. Novel STAT1 gain-of-function mutation presenting as combined immunodeficiency. Journal of Clinical Immunology 38(7), pp. 753-756. (10.1007/s10875-018-0554-3)
- Whitworth, J. et al. 2018. Comprehensive cancer-predisposition gene testing in an adult multiple primary tumor series shows a broad range of deleterious variants and atypical tumor phenotypes. American Journal of Human Genetics 103(1), pp. 3-18. (10.1016/j.ajhg.2018.04.013)
- Evans, C. et al. 2018. Measurement of Typhim Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency. Clinical and Experimental Immunology 192(3), pp. 292-301. (10.1111/cei.13105)
- Tange, C. E. et al. 2018. Quantification of human complement C2 protein using an automated turbidimetric immunoassay. Clinical Chemistry and Laboratory Medicine 56(9), pp. 1498-1506. (10.1515/cclm-2017-1068)
- Carne, E., Ponsford, M., El-Shanawany, T. and Jolles, S. 2017. Skin necrosis following subcutaneous immunoglobulin (SCIg). Journal of Clinical Immunology 37(1), pp. 27-28. (10.1007/s10875-016-0346-6)
- Carne, E., Ponsford, M., El-Shanawany, T., Williams, P., Pickersgill, T. and Jolles, S. 2015. Five years of self-administered hyaluronidase facilitated subcutaneous immunoglobulin (fSCIg) home therapy in a patient with primary immunodeficiency. Journal of Clinical Pathology 69(1), pp. 87-88. (10.1136/jclinpath-2015-202901)
- Ponsford, M. et al. 2015. Facilitated subcutaneous immunoglobulin (fSCIg) therapy - practical considerations. Clinical and Experimental Immunology 182(3), pp. 302-313. (10.1111/cei.12694)
- Gill, D., Bruce, D. J., Ponsford, M. J., Cranley, J. and Goodacre, T. E. 2013. Long-term follow-up of patients undergoing free tissue transfer to the lower limb following trauma. European Journal of Plastic Surgery 36(7), pp. 431-442. (10.1007/s00238-013-0826-3)
- Gill, D. et al. 2012. Laboratory sample turnaround times: do they cause delays in the ED?. Journal of Evaluation in Clinical Practice 18(1), pp. 121-127. (10.1111/j.1365-2753.2010.01545.x)
- Ponsford, M. J. et al. 2012. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. Journal of Infectious Diseases 205(4), pp. 663-671. (10.1093/infdis/jir812)
Thesis
- Ponsford, M. 2023. Nosocomial transmission and immunocompromise as risk factors for exposure and adverse outcomes associated with novel pandemic coronavirus SARS-CoV-2 disease (COVID-19).. PhD Thesis, Cardiff University.
Teaching
- Introduction for Research and Rare Diseases for Medical Students (Cardiff University, 2016- present)
- Immunology and Allergy for Dental Students (Cardiff University, 2016- present)
- Undergraduate Medical Teaching Programme - using the innovative "Tutemate" platform, Project Coordinator (2013-16)
- Member of the Question Writing Group, Cardiff University (2014-15)
- Embryology tutor (Hertford and Exeter Colleges, 2006-7)
Biography
Honours and awards
- Presenter Prize Royal College of Physicians Wales Annual Poster Competition (2021)
- Presenter Prize 35th Annual School of Medicine & Dentistry Postgraduate Research Day (2020)
- Association of Clinical Pathologists (UK) Career Development Award (2020)
- Travel Award, European Society for Immunodeficiencies (2020)
- Wellcome Trust ISSF3 Clinical Primer Award (2019)
- ESID Summer School in Clinical Immunology (2017)
- Masters in Medical Immunology, King's College London (Distinction; Outstanding Project Prize- 2018)
- EAACI Junior Taskforce Lead (2016/17)
- Bachelor of Medicine & Surgery, Oxford University (Distinction; Prize Viva- 2011)
- Bachelor of Arts, Molecular Medicine, Oxford University (2i - 2008)
Professional memberships
- Association of Clinical Pathologists
- British Medical Association
- British Society for Immunology
- Diplomate of the Royal College of Pathologists
- European Society for Immunodeficiencies (ESID)
- European Academy of Allergy and Clinical Immunology (EAACI)
- Member of the Royal College of Physicians, UK
- Pathological Society of Great Britain and Ireland
- Registered with the General Medical Council
Academic positions
- 2012-13: Academic Foundation Trainee, Betsi Cadwaladr University Health Board
- 2013-16: Academic Core Medical Trainee (Honorary Research Associate), Cardiff University/NHS Wales
- 2016-18: Specialist Trainee Clinical Immunology, Cardiff & Vale University Healthy Board
- 2018- present: Welsh Clinical Academic Trainee (WCAT) Clinical Lecturer
Committees and reviewing
- Peer reviewer for multiple international journals and the Medical Research Council (MRC).
Contact Details
PonsfordM@cardiff.ac.uk
Henry Wellcome Building for Biomedical Research, Room 3F08, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Henry Wellcome Building for Biomedical Research, Room 3F08, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
