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About us
Who are we?
Balanced Minds is a UK organisation set up in 2011. We provide compassion-focused psychological services and resources. We have offices in London and Edinburgh, and offer therapy, coaching, supervision, training workshops, consultation and workplace wellbeing.
Our approach is grounded in compassion, and the principles and evidence based effectiveness of Compassionate Mind Training (CMT) and Compassion Focused Therapy (CFT) developed initially by Professor Paul Gilbert.
Our approach
Life can be hard at times – work, relationships, financial concerns, and health worries. Sometimes these struggles ease on their own, or through strategies that we already have access to.
However, when it feels like we're stuck in the mud of our difficulties, when we can't find a path out of our struggles, we can help you to find your balance again. Whether this is through understanding yourself more, or learning new strategies to manage the difficulties you're facing, Balanced Minds has a variety of services that can help you get on track again.
Our services
We are passionate about providing different ways for people to access helpful, evidence based psychological interventions. We have a team of warm, caring and experienced therapists who provide individual, group, couples and family therapy. We also run a variety of innovative wellbeing courses and retreats, and have a variety of audio and self-help materials that may help you learn to manage your difficulties in new ways.
Alongside this, we also provide consultation and courses for workplaces, as well as training courses and supervision for other therapists. Please take a look at these pages to learn more about this.
Meet our therapists
Dr Chris Irons
Clinical Psychologist & Director
Read more about Chris
Chris is a Clinical Psychologist, and completed his training at the University of Sheffield (UK). He has many years of experience working in the NHS, and is now co-director of Balanced Minds. Here, he provides psychological assessment, formulation, therapy and training courses. In his clinical work, he uses Compassion Focused Therapy (CFT; Gilbert & Irons, 2005) in working with people with a wide range of mental and physical health distress.
In his therapeutic work, Chris strives to create a safe, caring and containing space to support people in exploring their distress, and finding ways to alleviate this. He is experienced therapist who is mindful and appreciative of difference (e.g. gender, ethnicity, religion, sexual orientation).
Chris has worked with Paul Gilbert, the developer of CFT, since 1999, and has been interested in the theoretical and clinical developments and adaptations of CFT as a science based psychotherapeutic approach. He is one of the leading trainers and supervisors of Compassion Focused Therapy, and regularly presents in the UK and internationally on CFT and more generally, self-compassion.
Chris gained his research Ph.D from the University of Derby (UK) under the supervision of Professor Paul Gilbert. He has published many research articles, book chapters and books on CFT.
2011 – PGDip Cognitive Behavioural Therapy (CBT), Royal Holloway
2007 – DClinPsy Clinical Psychology, University of Sheffield
2007 – PhD Psychology, University of Derby
2001 – BSc Psychology, Aston University
Registration and accreditation:
HCPC Registered Clinical Psychologist (PYL15842)
Key publications:
See research page (balancedminds.com/research)
Key trainings:
See events page (balancedminds.com/events)
Dr Korina Ioannou
Clinical Psychologist & Director
Read more about Korina
Korina completed her Doctorate in Clinical Psychology in 2008 at Manchester University, UK. She has many years of experience working in the NHS, with individuals with a wide variety of mental health problems, including experience of working in an eating disorder service.
Korina has specialist training in Cognitive Analytic Therapy (CAT) and Compassion Focused Therapy (CFT). In her private practice she implements these approaches in a flexible and cooperative manner, integrating elements from cognitive behavioural therapy, mindfulness and psychodynamic principles. Her specialist interests include relationship difficulties, trauma, anxiety, depression, low self-esteem and eating disorders. Korina offers assessments and therapy to individuals and couples, and works in time-limited and long term contracts. Korina speaks English and Greek.
2011-2014 – Introductory and Advanced training in Compassion Focused Therapy (CFT)
2013 – Practitioner Diploma in Cognitive Analytic Therapy (CAT), Sheffield Halam University/ACAT
2008 – Doctorate in Clinical Psychology (ClinPsyD), Manchester University
2004 – Master of Arts (MA) in Clinical Behavioural Applications in Mental Health Settings, City University New York
2001- Bachelor of Science Psychology (BSc), University College London
Registration and accreditation:
BPS Charted Clinical Psychologist (096816)
HCPC Registered Clinical Psychologist (PYL1583)
ACAT Accredited CAT Practitioner
See literature page (balancedminds.com/literature)
Dr Charlie Heriot-Maitland
Clinical Psychologist & Director
Read more about Charlie
Charlie completed his clinical psychology training at the University of Oxford, and has provided psychological therapies in a variety of NHS settings (2006-2014). He now runs a private therapy practice for Balanced Minds in London and Edinburgh, where he provides psychological assessments, formulations, and interventions that integrate different therapeutic approaches, in particular compassion-focused therapy (CFT) and cognitive-behavioural therapy (CBT), but also drawing on other mindfulness-based and emotion-focused therapies.
The shorter-term interventions he offers (10-20 sessions) are more structured and content-driven, and the longer-term interventions are more exploratory and process-driven.
He works with people with a range of mental health difficulties, usually on a one-to-one basis, but is happy to involve others (e.g. partners and families), and will always attend to the broader social context of mental health difficulties (relationships, culture etc).
Charlie's academic and research interests mainly lie in the application of CFT in psychosis, and he has been awarded a Fellowship by the UK Medical Research Council (2014-2019) to forward the scientific knowledge this area at King's College London and University of Glasgow.
2010 – DClinPsych Clinical Psychology, University of Oxford
2003 – BSc Psychology, University College London
Registration and accreditation:
BPS Charted Clinical Psychologist (171852)
HCPC Registered Clinical Psychologist (PYL25704)
BABCP Accredited CBT Therapist (140566)
Recognised provider for private health insurers:
Aviva (600109605); AXA PPP Healthcare (CH03720); Bupa (30027601); Cigna Healthcare (210211); Exeter Family Friendly (CH03720); SimplyHealth (CH03720); VitalityHealth (SP075760)
Key publications:
See research page (balancedminds.com/research)
Key trainings:
Dr Heriot-Maitland runs compassion training workshops for practitioners and the general public. See events page (balancedminds.com/events)
Link to Charlie's LinkedIn page:
Dr Alison Flynn
Clinical Psychologist & Associate
Read more about Alison
Alison works in the NHS, private practice and as a Clinical Supervisor in a charity working with young offenders. She works with children, adolescents and adults and can offer adapted therapy for people with autism spectrum diagnoses and learning disabilities.
Alison has worked with people who present with depression and anxiety, as well as difficulties including; self-harm, suicidality, psychosis, complex trauma, anger and aggression.
She gained her doctorate in Clinical Psychology at University of East London, where there is an emphasis on thinking about the relationship between distress and the world we live in – from our workplace to the political system.
Her doctoral research thesis explored shame and social rank. Alison is a keen CFT Therapist and has completed further training in Narrative Therapy. She is interested in telling the stories of our lives in ways that make us stronger. Also trained in Motivational Interviewing, Alison has found this approach compliments CFT where we may feel unsure or ambivalent about change.
Alison was drawn to CFT by its practice of 'preparing the body to help the mind'. She has found this approach to be emotive, creative and flexible, particularly because it does not rely solely on talking. Alison continues to develop her own compassionate practice and hopes to offer a safe, confidential space for those seeking support and change.
As a therapist, Alison takes a whole hearted approach to working with people. She appreciates difference and intersectionality in Gender, Geography, Race, Religion, Age, Ability, Appearance, Class, Culture, Ethnicity, Education, Employment, Sexuality, Sexual Orientation, and Spirituality.
Dr Shelley Kerr
Clinical Psychologist & Associate
Read more about Shelley
Dr Shelley Kerr is a Clinical Psychologist with specialist training in Compassion Focused Therapy (CFT), Dialectical Behaviour Therapy (DBT), and Cognitive Behaviour Therapy (CBT). She is passionate about helping people find balance and value in their emotions, so they can live the lives they want for themselves. Within her clinical experience, Shelley has seen the power of compassion in releasing people from the suffering that comes with cycles of shame and self criticism. As a result of this experience together with the growing body of evidence for CFT, Shelley takes a compassion focused approach to therapy.
Within her therapeutic work, she strives to create a safe, warm and non-judgemental space to support people to explore their difficulties and find ways to create positive change. She is grateful to be able to share her compassion and experience with people who wish to take the courageous and sometimes painful steps toward becoming the version of themselves they want to be.
Shelley has extensive experience in working with people struggling with intense emotions, relationship difficulties, trauma, self harm, suicidal behaviours, chronic shame and low self esteem. She is well versed in helping people find a way forward from anxiety and depression.
Shelley worked for a decade in a specialist NHS, DBT service for people suffering with overwhelming emotions and high levels of risk. She established a CFT pathway within this service, including group and individual therapy.
In line with the ethos of CFT and DBT, Shelley believes that personal practice is essential. She therefore maintains a commitment to cultivate mindfulness and compassion in her everyday life.
In addition to therapy, Shelley is passionate about supporting other therapists through clinical supervision and training. Shelley is a trainer with the Compassionate Mind Foundation, delivering the three day introductory workshop alongside Dr Chris Irons.
Shelley's doctorate research focused on the healing potential of gratitude and kindness. Other research interests have included suicidal behaviour, personality disorder, and compassion.
Qualifications and Training:
2018 – Post Graduate Certificate in Compassion Focused Therapy
2015 – Advanced Supervisor Training, University College London
2013 – Introductory and Advanced training in Compassion Focused Therapy
2010 – Supervisor Training, University College London
2009 – DBT Intensive Core Training with Dr Janet Feigenbaum, NELFT
2008 – Doctorate in Clinical Psychology (DClinPsy), Griffith University, Brisbane, Australia
2001 – Bachelor of Psychology with Honours (BPsych Hons, First Class), University of New England, Armidale, Australia
Registration and accreditation:
HCPC Registered Clinical Psychologist (PYL26447)
SfDBT Accredited DBT Therapist
Recognised provider for private health insurers:
Shelley is a registered practitioner with Bupa, Aviva, AXA PPP Healthcare, and Vitality Health.
See literature page (balancedminds.com/literature)
Shima Bhunjun
Counselling Psychologist & Associate
Read more about Shima
Shima is a Chartered Counselling Psychologist trained in CBT and experienced in working with a wide range of mental health problems such as depression, social anxiety, PTSD, generalised anxiety, alcohol abuse and adjustment to long term health conditions amongst others.
Shima has been accredited with the British Association for Cognitive & Behavioural Psychotherapies (BABCP) since 2013 and have 9 years post qualification experience, with much of my clinical work taking place within an NHS setting. I also work with a student population at a London based university providing both CFT and CBT therapy to support students with mental health difficulties through their academic careers. I have a keen interest in Compassion Focused Therapy and have been integrating the approach into my clinical work over the last 4 years and find it to be a very rewarding experience.
Shima aims to provide a safe and confidential space for individuals to explore and reflect upon thoughts and feelings, and to facilitate the change process in a way that feels collaborative, respectful and in line with the goals of the individuals that I work with.
• Advanced Training in Compassion Focused Therapy for groups 2016
• Advanced Training in Compassion Focused Therapy 2014
• Behavioural Couples Therapy Training 2014
• Compassion Focused Therapy Training 2013
• CBT for Insomnia 2013
• Post Graduate Diploma in Cognitive Behavioural Therapy 2008
• Advanced Practitioner Diploma in Counselling Psychology 2008
• Practitioner Diploma in Counselling Psychology 2006
• MSc Counselling Psychology 2004
• Post Graduate Diploma Certificate Psychology 2002
• Psychology & Sociology BA Hons 1999
Dr Rita Intili
Clinical Psychologist & Associate
Read more about Rita
Rita works as a Consultant Clinical Psychologist in the NHS. She has worked in the NHS for over 23 years across a variety of settings, including hospital, community and GP surgeries. Rita has extensive experience in assessing and treating adults with wide-ranging psychological difficulties of varying complexity, such as generalised anxiety disorder, panic disorder, social anxiety, phobias, OCD, depression, bipolar affective disorder, schizophrenia and trauma. She specialises in working with individuals who experience interpersonal difficulties and enduring and intense emotional dysregulation.
Rita has supervised Clinical Psychologists, Counselling Psychologists and Trainee Clinical Psychologists in the NHS for over 20 years. She has been a Liaison Tutor and has been involved in the selection of Clinical Psychology Trainees for the University College London Doctorate course for over 10 years. She has also been an external examiner for the Professional Clinical Psychology Doctorate course at University East London.
Rita draws upon evidence-based interventions using a combination of Cognitive Behavioural Therapy, Mindfulness Based Therapy, Dialectical Behavioural Therapy, and Compassion Focused Therapy (CFT). Over the years, Rita has become increasingly more interested in developing and applying CFT in her practise in response to the growing evidence indicating the benefits of cultivating compassion for psychological health and well being.
Rita feels it a privilege to assist others in their journey of personal development and growth. She offers a warm, understanding, non-judgemental approach, aimed at helping individuals make sense of their emotional difficulties, move toward their aspirations and improve their quality of life.
Rita is bilingual. She speaks English and Italian.
Dr Michelle Wilson
Clinical Psychologist & Associate
Read more about Michelle
Michelle is a clinical psychologist that has worked in the NHS for over 10 years. She gained her clinical psychology doctorate from University College London (UCL). Since then she has worked in a range of clinical settings, working in both mental and physical health services, with children and adults. Part of her clinical experience has been focused on working with individuals struggling with eating disorders and co-morbid difficulties such as depression. Alongside this, Michelle has focused on working within physical health settings. She has worked in Plastic and Reconstructive Surgery, Dermatology and Chronic Wound Care and Lymphoedema services, supporting individual with challenges such as adjustment to diagnosis, appearance concerns, trauma and difficulties engaging with physical health care treatments.
More recently, Michelle has worked extensively in weight management services supporting adults with obesity. Specifically she has worked with individuals who have difficulties with emotional / binge eating, body image concerns, depression and anxiety. Michelle has specific interests in shame and stigma associated with weight related difficulties and has used compassion-focused approaches in relation to this with clients she has worked with. She continually works on developing her compassion-focused therapy skills and knowledge, including development of her own compassionate practice. Michelle also has an interest in Acceptance and Commitment therapy approaches and uses this flexibly within her work depending on the needs of the individual.
As a therapist, Michelle takes an open, non-judgemental and warm approach. She is deeply committed to developing a clear understanding of the issues most pertinent to the individual she is working with, and supporting them to make changes such that they can live their lives in a way that is meaningful and most consistent with their values and hopes.
In addition to this above, Michelle currently also works on a doctorate in clinical psychology training course, teaching and training individuals to practice as clinical psychologists. As part of this, Michelle is passionate about engaging in research, with her research interests laying in obesity, stigma and incorporating compassion focused self-practice into clinical training.
BPS Charted Clinical Psychologist (225307)
HCPC Registered Clinical Psychologist (PYL29910)
2007 BSc (Hons) Psychology (First Class with BPS Undergraduate Award for highest achieved
Psychology degree at Essex University 2007)
Essex University
2010 Postgraduate Certificate Clinical Applications of Psychology (Merit)
Newman University College Birmingham
2013 Doctorate in Clinical Psychology (DClinPsy)
University College London
Additional relevant training:
2009 CBT Boot Camp: Cognitive Therapy Training
Cognitive workshops
2013 Introduction to Cognitive Analytic Therapy
East London NHS Foundation Trust
2014 Foundation Skills in Working with Trauma
Charlie Waller Institute, University of Reading
2015 Enhanced CBT for eating disorders (CBT-E)
The Centre for Research on Eating Disorders (CREDO) Oxford
2015 ACT as a brief intervention: Focused Acceptance and Commitment Therapy (FACT)
Contextual Consulting
2016 Essential obesity: Psychological approaches
National Centre for Eating Disorders (NCFED)
2016 Acceptance and Commitment Therapy Clinical Skills Building Intensive – Intermediate Level
Contextual Consulting
2016 Acceptance and Commitment Therapy for Physical Health Problems
Contextual Consulting
2017 Introduction to the theory and practice of Compassion Focused Therapy
The Compassionate Mind Foundation
Dr Rowan Reiss
Clinical Psychologist & Associate
Read more about Rowan
Rowan is a clinical psychologist and has worked in the NHS for 17 years. She has She has extensive experience of working with adults, young adults and adolescents who are affected by depression and anxiety, as well as difficulties including OCD, self-harm, suicidality, psychosis, PTSD and complex trauma resulting in intense and overwhelming emotions.
She gained her doctorate in clinical psychology from the University of East London, where there is an emphasis on understanding the contextual factors in the development of a person's distress – from family, to work, to political and societal influences. She is passionate about supporting people to process their experiences within an understanding of how their context has shaped their worldview, their sense of self and their difficulties.
Rowan is trained in Compassion Focussed Therapy, Dialectical Behavioural Therapy, Cognitive Behavioural Therapy, in narrative and systemic approaches and in trauma-informed approaches. In her NHS role she has worked to develop and integrate CFT approaches, including group-based work, within the services provided. As advocated within both CFT and DBT approaches, Rowan maintains her own daily mindfulness practice.
As a qualified music therapist Rowan is also interested in the non-verbal elements of communication and is committed to enabling people to access therapy in an attuned way, at a pace they are comfortable with. She is interested in the notion of 'readiness' for therapy and focused her doctoral research in this area.
Rowan integrates CFT into her professional practice, supporting her patients to understand their difficulties from a non-judgemental perspective, externalising and processing issues that have come into their lives. Rowan offers a safe, non-judgemental space to support people to make sense of their experiences and their difficulties.
Qualifications and Training
– 2020 Supervisor Training, UCL
– 2019 ADOS2, UCL Great Ormond Street Hospital Institute of Child Health
– 2018 DBT Skills Training with British Isles DBT Training
– 2013 Doctorate in Clinical Psychology, University of East London
– 2011 MSc Psychology, UEL
– 2003 PGDip Music Therapy, Guildhall
Registration and Accreditation
HCPC Registered Clinical Psychologist PYL36029
Dr Zara Christie
Clinical Psychologist & Associate
Read more about Zara
Zara is a Clinical Psychologist working in both the NHS and private practice. She gained her Doctorate in Clinical Psychology from the University of Glasgow. At Balanced Minds, Zara offers assessment and Compassion Focused Therapy to help individuals to work through and overcome difficulties including depression, anxiety, low self-esteem, relationship difficulties, post-traumatic stress disorder and complex trauma.
Zara strives to create a safe space and works collaboratively to help individuals overcome their difficulties in a non-judgmental and compassionate way. She offers tailored interventions focused on alleviating distress and achieving an individual's therapeutic goals. She is able to involve significant others in therapy, if appropriate. Zara is motivated to help people balance complex emotions and live a life consistent with their values.
Zara has worked in the NHS for the last nine years, and specialises in working with adults with complex difficulties from varied socio-economic backgrounds. She integrates a range of therapeutic models including Compassion Focused Therapy, Cognitive Behavioural Therapy and Interpersonal Psychotherapy. Drawing on her broad experience, she provides holistic and person-centred therapeutic approaches to help individuals achieve and maintain meaningful changes in their life. Zara has worked with children and adults, both in community and inpatient settings, and where required, provided therapy through interpreters. She also has experience providing supervision to other therapists.
2014 – Doctorate in Clinical Psychology, University of Glasgow
2009 – BSc Psychology, 1st Class Honours, University of Leeds
Relevant post-doctoral training:
2018 – Interpersonal Psychotherapy Training (University of Edinburgh)
2016 – NES (NHS Education Scotland) Specialist CBT Supervision Training
2016 – NES Specialist Supervision Module for New Supervisors
2016 – NES Prolonged Exposure Training for Post-Traumatic Stress Disorder
2015 – Using Compassion Focused Therapy to work with emotional memories in shame-based trauma with Dr Deborah Lee
2015 – Introduction to the theory and practice of Compassion Focused Therapy with Dr Chris Irons
2015 – NES Generic Supervision Competencies Training
2015 – Behavioural Family Therapy Training
Registration and accreditation:
HCPC Registered Clinical Psychologist: PYL31485
Jen Wood
Psychotherapist & Associate
Read more about Jen
Jen is a psychotherapist, coach and mindfulness teacher with specialist training in Cognitive Behavioural Therapy (CBT), Compassion Focussed Therapy (CFT) and Schema Therapy. She believes that everyone has the inner resources to find relief from anxiety, stress and fear which can be caused by work or life pressures or health challenges. Sometimes, though, life feels overwhelming; one in four people in the UK live with stress, anxiety or depression. As our desire to have, be and do more increases, so our pace of life can become more frantic. It's at times like this that we need help to get back in balance and rediscover our zest for life. Jen empowers people to reconnect with their inner resources, to overcome life's challenges and live life to the full.
Jen uses compassion in her personal practice, as well as in her therapeutic work, coaching and mindfulness teaching. She now chooses to work in a compassion focused way, because she has found it so helpful both personally and professionally. Her CBT and mindfulness teaching training also had a strong compassion focused component.
She has experience of 12 years of leading a therapy service within a palliative care setting, and 11 years leading a service in a centre for children with special needs, and their families. She has worked in a perinatal mental health service, and now works in private practice.
She is skilled in helping people with low self-esteem, anxiety, depression and pain, as well as burnout, work and relationship difficulties, trauma, self-harm and shame.
Jen aims to create a safe, warm and non-judgemental space to support people to explore their difficulties and find ways to create positive change and reconnect with their inner resources.
Aside from her therapeutic work, she has a wide experience of life, having taught English in schools, run international festivals and conferences and worked as a clinical hypnotherapist.
Jen enjoys the outdoors, yoga, meditation and spending time with her fox red Labradors.
Qualifications and Training:
2019 – Introductory training in Compassion Focused Therapy
2019 – Mindfulness Teacher
2018 – Self Compassion in Psychotherapy
2018 – Supervisor Training
2018 – Schema Therapy Training
2017 – Advanced Clinical Skills
2016 – Diploma in Counselling and Groupwork – A Cognitive Behavioural Therapy Approach
2016 – Nonviolent/Compassionate Communication Training
2016 – Diploma Life Coaching
2013 – Diploma in Clinical Hypnotherapy and Neurolinguistic Programming (NLP)
2012 – Master Practitioner NLP Coaching
1995 – PGCE English
1991 – MA Hons (English)
Registration and accreditation:
Mindfulness Association Mindfulness Teacher
Working towards accreditation with BABCP
Dr Lexy Rose
Clinical Psychologist & Associate
Read more about Lexy
Lexy has worked with a diverse range of client difficulties across a variety of contexts. Her therapeutic approach focuses on using warmth and curiosity, recognising that the way people understand themselves and others is through their social upbringing and personal experiences and that they develop coping strategies based on these.
Lexy first develops a shared understanding of the presenting problems, including a client's personal strengths and values. Her therapeutic approach is informed by Compassion Focused Therapy, as well as, where appropriate, the principles of Cognitive Behavioural Therapy (both 'traditional' and '3rd wave' approaches, such as mindfulness). Lexy will always adapt techniques based on a client's needs.
Lexy's areas of interest include working with adults with problems with anxiety, feeling low, self-criticism, and longer-standing difficulties. Alongside private practice, Lexy works in the NHS, working with adults with learning disabilities and neurodevelopmental disorders including Autism Spectrum Disorder.
2016 – Doctorate in Clinical Psychology (DClinPsy), Institute of Psychiatry, Psychology & Neuroscience (IOPPN) (King's College London, KCL)
2013 – PGCert, Evidence-Based Psychological Treatments (IAPT Pathway), Reading University
2012 – MSc (Distinction) Mental Health Studies, IOPPN (KCL)
2010 – BA (1st Class) Experimental Psychology, Oxford University
Registration and accreditation:
HCPC Registered Clinical Psychologist (PYL33644)
BPS Chartered Member (406744)
Key Publications:
– Rose, A. V., McIntyre, R., & Rimes, K. A. (2018) Compassion focused intervention for highly self-critical individuals: Pilot study. Behavioural & Cognitive Psychotherapy, 46, 583 – 600.
– Rose, A. V., & Rimes, K. A. (2018). Self‐criticism self‐report measures: Systematic review. Psychology and Psychotherapy: Theory, Research and Practice, 91, 450 – 489.
Key training:
2019 – Compassion Focused Therapy Introductory & Advanced Clinical Skills Workshop (Compassionate Mind Foundation)
Jim Clark
Psychotherapist & Associate
Read more about Jim
Jim is an experienced BABCP accredited psychotherapist, and mindfulness and meditation teacher. His journey began in the arts and music industry in London and Glasgow in the 1990s. In 2000 he started a regular meditation practice, and shortly afterwards he decided to retrain as a mental health nurse. He went on to complete cognitive behavioural therapy (CBT) training and has worked for many years in different settings in the NHS as a nurse, a specialist CBT therapist, and a mindfulness teacher, trainer and supervisor.
Since 2015 Jim has been working in private practice in London offering individual therapy and teaching more than 30 8-week mindfulness courses. He now offers individual therapy online. He loves working with people and helping them learn how to be their own therapists by managing difficulties more effectively, connecting with what matters, and choosing paths that lead to greater nourishment, fulfilment, healing and ease.
Jim can offer individualised assessment, formulation and therapy for clients seeking help with a wide range of issues. He works in a client centred way, creating a warm and safe space to explore whatever issues his clients wish to bring. These can include relationship difficulties, stress at work and/or home, creative blocks and challenging life decisions, low mood and depression, anxiety and worry, problems around eating, sleep difficulties, obsessive thoughts and behaviours, traumatic memories or events, and addictions.
His therapy approach is based in the cognitive behavioural tradition. Jim has a particular interest and appreciation for compassion focused therapy (CFT) and acceptance and commitment therapy (ACT), and depending on the client's needs, he will draw upon and integrate other therapeutic approaches including functional analytic psychotherapy (FAP), motivational interviewing, and mindfulness based cognitive therapy (MBCT).
Jim is committed to a non-discriminatory practice. His approach is kink friendly and sex positive. He is appreciative of differences however they are experienced and perceived by the client, be that by gender, sex, age, sexual orientation, ethnicity, religion or belief. He doesn't assume he will always get it right, and welcomes feedback from clients to know if there are ways they can feel more comfortable opening up around these or other issues.
Education and qualifications
2019-20 – Diploma in Online Counselling and Psychotherapy, OCST
2012-14 – Mindfulness Based Cognitive Therapy, Master of Studies (Distinction), Oxford University
2010-12 – Cognitive Behavioural Therapy, Post Grad Diploma (Merit), London South Bank University
2006 – DipHE (Distinction), Mental Health Nursing, King's College London
1994 – BA (with honours), Fine Art, Glasgow School of Art
Selected clinical training
2020 – Functional Analytic Psychotherapy, Matthew Skinta
2019 – CBT+ Supercharging your CBT with CFT, ACT and DBT, Fiona Kennerly
2019 – ACT Assisted Psychedelic Retreat, Mindfulness Training Ltd
2018 – Mindfulness Based Compassionate Living Teacher Training, Erik van den Brink
2018 – Relational Frame Theory, Louise McHugh
2017 – Functional Analytic Psychotherapy, Jonathan Kanter
2017 – Acceptance and Commitment Therapy year-long pathway, Mindfulness Training Ltd
2016 – Mindfulness Supervisor Training, Mindfulness Network
2016 – Compassionate Mind Training 8-week course, Balanced Minds
2015-16 – Introductory and Advanced training in Compassion Focused Therapy, Paul Gilbert
2015-16 – Introductory and Advanced training in Acceptance and Commitment Therapy (ACT for depression and anxiety, ACT for teens, ACT and mindfulness for trauma) with Russ Harris
2009 – Mindfulness Teacher Training retreat, Bangor University
2008 – Dual Diagnosis and Motivational Interviewing training, South London & Maudlsey NHS Trust
Professional registration, accreditation and professional memberships
Registered with the Nursing and Midwifery Council (NMC) as a mental health nurse
Full Accreditation with the British Association of Behavioural and Cognitive Psychotherapies (BABCP)
Listed Mindfulness Teacher with the British Association of Mindfulness Based Approaches (BAMBA)
Professional Member of the Association of Counselling and Psychotherapy Online (ACT
Dr Melissa Albany
Clinical Psychologist & Associate
Read more about Melissa
Melissa is a Clinical Psychologist and completed her training at the University of Plymouth as a mature age student. She has worked for six years in the NHS in Adult mental health services specialising in working with people who have experienced complex trauma and interpersonal difficulties. She has a developing interest in dissociation. She is now branching out into private practice. Melissa utilises an integrative approach with an emphasis on a compassion-focussed therapeutic approach to a broad range of difficulties. She is trained in EMDR which is used in trauma processing and has an interest in relational therapies drawing on cognitive, systemic and attachment models of understanding. She also has an interest in feminist and ecological theory and how this can influence psychological health focussing on our connection to our environment and others.
Previously she has worked in the criminal justice system in addictions and has worked with groups addressing domestic violence. Melissa was supervised by a leading researcher and practitioner in attachment approaches. Melissa has also worked in the media industry in a variety of roles.
Melissa employs a therapeutic approach which is aimed at fostering a warm and empathic relationship with clients.
Dr Becca Lewis
Clinical Psychologist & Associate
Read more about Becca
Rebecca is a Clinical Psychologist who gained her Doctorate from Royal Holloway, University of London. She has worked in the NHS for the last 8 years and currently holds a senior NHS post working with people who have been affected by cancer. Rebecca has experience of working with individuals facing a range of difficulties in life, including depression and anxiety, stress, low self-esteem, trauma, psychosis, difficulties with sex and people living with long-term health conditions, including cancer and HIV.
Within her practice, Rebecca aims to provide an empathic, non-judgemental space in which people feel safe to explore their difficulties and make changes in life. Rebecca works collaboratively with clients and is always guided by the clients hopes and wishes for therapy. She is able to offer therapy which is structured and focussed or more exploratory.
Rebecca was drawn to Compassion Focussed Therapy because she believes that it provides a comprehensive understanding of why humans experience emotional distress, whilst also offering practical strategies to promote wellbeing and reduce distress. As well as CFT, Rebecca's practice also incorporates ideas and techniques from other evidence-based therapies, including Acceptance and Commitment Therapy, Cognitive Behavioural Therapy and Mindfulness.
Dr Bec Harvey
Clinical Psychologist & Associate
Read more about Bec
Rebecca qualified as a Clinical Psychologist after attending the University of Surrey's doctorate programme. She has 8 years of experience working in the NHS within various settings including a community based crisis service as well as, learning disability, older adults and children services. Rebecca currently works in a specialist paediatric role within the Neurology department at Great Ormond Street Hospital.
Rebecca applies a compassionate and collaborative approach to therapeutic work, often creating bespoke intervention packages which are client-led. She enjoys working with a number of therapeutic models such as Cognitive Behavioural Therapy, systemically informed therapy, Acceptance and Commitment Therapy and narrative approaches. She also regularly engages her clients in mindfulness and imagery based exercises.
Rebecca's research interests are focused on creating effective interventions that reduce mental contamination. She is also curious about how compassion focused therapy can be applied to obsessive compulsive presentations. More recently she is providing industry consultation to the creators of a novel mental health app in relation to clinical safety and user accessibility.


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Implication for health policy/practice/research/medical education:
Vitamin D is known as a distinctive hormone made in the skin from exposure to sunshine. 1,25-dihydroxyvitamin D3 can stimulate the absorption of intestinal calcium by 30%–40% and phosphorus by 80%. Moreover, it increases the absorption of minerals from the skeletal system. Vitamin D deficiency decreases the absorption of dietary calcium and phosphorus from the intestine and subsequently, leads to an increase in the levels of PTH. Here are some studies on the prevalence of vitamin D deficiency in women.
Please cite this paper as: Tamadon MR. On the occasion of world kidney day 2018 with the theme of kidney disease in women; vitamin D deficiency and kidney diseases in women. J Renal Inj Prev. 2018;7(1):33-34. DOI: 10.15171/jrip.2018.07.
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Citrobacter rodentium causes an attaching and effacing infection of the mouse colon. Surprisingly, protective adaptive immunity against this mucosal pathogen requires a systemic T-cell-dependent antibody response. To define CD4+ T-cell effector functions promoting this systemic defense of infected epithelial surfaces, studies were undertaken in weaning-age mice lacking costimulatory molecules CD28 or CD40L or cytokines gamma interferon (IFN-γ) or interleukin-4 (IL-4). Adoptive transfer of CD4+ T cells from wild-type, CD28−/−, CD40L−/−, or IFN-γ−/− donors to CD4−/− recipients delineated functions of these CD4+ T-cell-expressed molecules on the outcome of infection. Wild-type and IL-4−/− mice successfully resolved infection, while 70% of IFN-γ−/− mice survived. In contrast, all CD28−/− mice succumbed during acute infection. While fewer than half of CD40L−/− mice succumbed acutely, surviving mice failed to clear infection, resulting in progressive mucosal destruction, polymicrobial sepsis, and death 1 to 2 weeks later than in CD28−/− mice. Downstream of CD28-mediated effects, CD4+ T-cell-expressed CD40L proved essential for generating acute pathogen-specific immunoglobulin M (IgM) and early IgG, which reduced pathogen burdens. However, deficiency of CD4+ T-cell-expressed IFN-γ did not adversely impact survival or development of protective antibody in adoptively transferred CD4−/− recipients, though it impacted Th1 antibody responses. These findings demonstrate that CD4+ T-cell-expressed CD40L promotes the rapid production of protective systemic antibody during acute infection, while deficiencies of IL-4 or of CD4+ T-cell-expressed IFN-γ can be overcome. These findings have important implications for understanding the role of T-helper-cell responses during infections involving mucosal surfaces.
Citrobacter rodentium serves as the mouse model for studying the pathogenesis and host responses to attaching and effacing pathogens. These pathogens cause significant morbidity and mortality among infants and children in the developing world and among animals of agricultural significance. As with related pathogens, including the enteropathogenic Escherichia coli, C. rodentium causes a self-limited infection of the apical surface of the gut epithelium (2, 14, 16). The noninvasive nature of this infection provides a model for dissecting events associated with infections of mucosal surfaces, including the host responses needed to resolve them. This infection also serves as the primary mouse model of infectious colitis, providing a rigorous system for understanding microbial contributions to gut inflammation and pathways involved in its successful resolution.
Primary infection with C. rodentium progresses through three distinct phases, a useful schema for defining points at which elements of innate and adaptive immunity impact host defense. First, colonization and proliferation of the pathogen start with successful introduction of C. rodentium into the colon. After initial adhesion (4), attaching and effacing lesions form, mediated by the bacterial adhesin intimin and type III secreted bacterial proteins, including the translocated intimin receptor, Tir (7, 8, 18). Innate defenses, including epithelial-produced β-defensins, affect early colonization and proliferation of C. rodentium in the colon (13, 24). The presence of mucosal antibody also appears to impact the initial kinetics of bacterial growth (2, 15, 28). Second, by the onset of symptomatic infection 7 to 10 days after inoculation, the developing pathogen burden has triggered a number of epithelial responses, including the hallmark hyperplastic response and production of antimicrobial factors (14, 24). Previous studies have also demonstrated protective roles for proinflammatory cascades resulting in secretion of gamma interferon (IFN-γ) and tumor necrosis factor alpha member cytokines in the colon (9, 10, 24, 26). Interestingly, acute infection primarily recruits CD4+ T cells into the colon, though abscess formation in proximity to densely colonized areas intermittently disrupts epithelial integrity, creating the potential for polymicrobial sepsis as C. rodentium and lesser numbers of commensals gain entrance to host tissues (2). While adult immunocompetent hosts control this aspect of the infection, it contributes to the lethality and morbidity seen in immature animals and populations with defects in B cells and CD4+ T cells (2, 25). Third, most mice resolve infection within 4 weeks after initial inoculation. Immunocompetent hosts clear the pathogen, with resolution of inflammation and return of epithelial proliferation to a baseline state.
The development of T-cell-dependent serum antibody proved the critical adaptive response needed to survive and resolve this primary infection of a mucosal surface (2). This response consists of CD4+ T-cell-dependent serum immunoglobulin M (IgM) and evolving IgG predominated by the Th1-biased isotype IgG2c, the IgG2a allotype produced in C57BL/6 mice. Surprisingly, this response did not require CD4+ T-cell or B-cell responses in mucosal tissues, as evidenced by survival and resolution of infection in mice lacking β7-integrins, adhesion molecules facilitating binding of lymphocytes to the mucosal addressing cell adhesion molecule (MAdCAM) that permits entry into mucosal sites, including the GALT (2). These findings indicate that protective adaptive responses against attaching and effacing pathogens do not need to occur in the same tissue compartment as the primary site of infection.
Activation of naïve T cells through costimulatory molecules such as CD28 or ICOS leads to the expression of downstream effector costimulatory molecules, including CD40L, OX40, and CD27, each of which impacts Th1/Th2 differentiation, cytokine production, and end effects on B-cell stimulation, germinal center formation, and antibody production (1, 11, 12, 21, 29, 30).
However, when framed in the context of infection with a noninvasive mucosal pathogen, we know remarkably little regarding how these CD4+ T-cell effector functions facilitate host survival and resolution of infection. We thus undertook infection studies with mice lacking CD28, CD40L, IFN-γ, or interleukin-4 (IL-4), molecules with potential impact on host defense against C. rodentium. Adoptive transfer of wild-type CD28−, CD40L−, or IFN-γ− CD4+ T cells into CD4−/− recipients subsequently elucidated the functional roles of these CD4+ T-cell-expressed molecules on the generation of protective antibody, control of pathogen burdens, and resolution of infection. We found that CD28 and CD40L were dominant in providing T-cell help for protective antibody responses, while single deficiency of IL-4 or of CD4+ T-cell-expressed IFN-γ did not produce an appreciable impact upon successful resolution of infection.
Bacterial strains. Citrobacter rodentium strain DBS 100 and mouse commensal E. coli cells were cultured on MacConkey agar (Remel Inc.) or in Luria-Bertani (LB) broth (2).
Mouse strains.CD45.1+ and CD45.2+ wild-type and CD45.2+ CD28−/−, CD40L−/−, IFN-γ−/− IL-4−/−, and CD4−/− C57BL/6 mice were obtained from Jackson Laboratories (Bar Harbor, ME), housed as previously described (2). All methods and procedures were carried out in accordance with Animal Care and Use Committee-approved protocols.
Infection of mice.Weaning-age mice were fasted 8 h prior to oral inoculation with 5 × 108 CFU of C. rodentium. Animals were allowed access to food after inoculation. All manipulations were performed in BL-2 biosafety cabinets. During infection, moribund animals or those showing unalleviated distress were euthanized.
Survival studies.A least six mice of each C57BL/6 strain were analyzed in a minimum of two independent experiments. Log rank and chi-square analyses were carried out in Prism 4.0 to determine median survival time and statistical significance. A P value of <0.05 was considered significant.
Tissue collection, histology, and immunofluorescence.Samples of spleen, liver, mesenteric lymph node (MLN), small intestine, and colon were placed in 10% Formalin in phosphate-buffered saline (PBS), or in tissue blocks containing OCT (Tissue-Tek) and snap-frozen. The colon was dissected to the anal canal and removed en bloc. Five-micrometer sections were stained with hematoxylin and eosin. Immunofluorescent staining was performed on frozen sections fixed in cold methanol for 5 min, washed in PBS, and blocked for 10 min in PBS plus 5% mouse serum prior to staining with rat anti-mouse E-cadherin (Zymed) and recognized with rabbit anti-rat Ig conjugated to AMCA (Jackson Immunochemical), hamster anti-mouse CD3ε conjugated to fluorescein isothiocyanate (FITC) (Caltag), rat anti-mouse CD4 conjugated to phycoerythrin (PE; Caltag), rat anti-mouse CD45.1-FITC (eBiosciences), and Hoechst nuclear dye (bis-benzimide; Sigma Chemical; 1 mg/ml stock solution diluted 1:10,000).
Colony counts.Distal colon, spleen, and liver were weighed, homogenized, serially diluted, and plated in triplicate to MacConkey agar. C. rodentium and E. coli colonies were counted after 24 h of incubation at 37°C to determine log10 CFU per gram of tissue. Lower detection limits were 20 CFU/gram spleen (log10 = 1.3), 8 CFU/gram liver (log10 = 0.9), and 12 CFU/gram colon or fecal pellets (log10 = 1.1).
Preparation of serum and fecal lysates.Serum prepared from whole blood was collected by periorbital eye bleed from sevoflurane-anesthetized mice. For preparation of fecal lysates, fecal pellets were collected from mice, weighed, and subjected to two sequential extractions in fecal lysate extraction buffer (0.1% Tween 20 plus 10 μl Sigma protease inhibitors/ml); 0.5 ml of buffer was added per 0.1 g of material for each extraction. Material was vortexed for 20 min and spun for 10 min at 12,000 rpm, and supernatant was passed over a 0.22-μm-filter spin tube (Corning). Sequentially collected supernatants from the same sample were pooled to result in 1 ml of lysate per 0.1 g of fecal material.
Immunoglobulin enzyme-linked immunosorbent assays.Antibody enzyme-linked immunosorbent assays were performed by coating 96-well plates with heat killed C. rodentium. Plates were incubated overnight washed with PBS plus 0.05% Tween 20, blocked in 10% soy milk (8th Continent) plus PBS plus 0.05% Tween 20 and washed prior to addition of serially diluted serum or fecal lysates. Samples were incubated for 2 h at room temperature and washed, and bound antibody was detected with goat anti-mouse IgA, IgM, IgG1, IgG2b, IgG2c, or IgG3 (Southern Biotechnology Associates) conjugated to alkaline phosphatase. After 1 h of incubation at room temperature, washed plates were developed with p-nitrophenyl phosphate (PNPP; Sigma), read in a Molecular Devices reader, and analyzed in SoftMAX 4.0 with a four-parameter fit of mean absorbance at an optical density of 405 nm of each sample versus the reciprocal of the dilution. Interpolation with the resulting equation was used to define the relative endpoint titer yielding an optical density of 405 nm of 0.15. The minimum detectable titer was 50.
Serum transfers.Adoptive transfer of serum from mice was performed as previously described (2). Briefly, wild-type, CD40L−/−, or IFN-γ−/− donors were infected 2 weeks prior to CD4−/− recipients. On days 3, 4, and 5 after inoculation of CD4−/− recipients with C. rodentium, whole blood was collected from acutely infected donors, allowed to clot, and filter sterilized prior to immediate administration of 0.25 ml serum to each recipient. Each CD4−/− recipient received serum only from wild-type, CD40L−/−, or IFN-γ−/− donors to assess the protective capacity of the acute antibody responses in donor mice. Survival of CD4−/− recipients was monitored for 6 weeks after infection with C. rodentium.
T-cell purification.Spleen and mesenteric lymph node were harvested from naïve 5-week-old CD45.1+ or CD45.2+ wild-type mice or CD45.2+ CD28−/−, CD40L−/−, or IFN-γ−/− C57BL/6 mice. Tissues were macerated through a 70-μm mesh filter (Becton Dickinson) into 10 ml of RPMI plus 10% calf serum (R10; Gibco). Cells were spun for 5 min at 1,500 rpm at 4°C, and red cells were lysed. Preparations were spun and washed with R10, and the cell concentration was determined. Control preparations were suspended to deliver 20 million unfractionated cells to recipient mice. Remaining cells were suspended to 2.5 × 108 cells/ml for purification with CD4+ or CD8+ T-cell magnetic bead purification kits, performed per the manufacturer's specifications (Miltenyi). Purified cells were stained with rat anti-mouse CD4, CD8α, CD19, GR1, F4/80, or rat isotype control conjugated to phycoerythrin (Caltag) and analyzed on a Becton-Dickinson fluorescence-activated cell sorter (FACS) Scan device. CD4+ T-cell preparations gave ≥96% CD4+ T cells, ≤1% CD19+ B cells, <1% CD8+ T cells, <1% F4/80+ macrophages, or GR1+ neutrophils and ≤1% dead cells. The resulting suspensions were passed over a 40-μm mesh filter and suspended in RPMI to deliver ∼5 million cells per recipient mouse at 23 days of age. Recipients were orally inoculated with C. rodentium as described 2 days after adoptive transfer. Administration of 5 million purified CD4+ T cells conferred a significant survival phenotype in CD4−/− recipients infected with C. rodentium, but administration of 20 million unfractionated cells, 5 million CD8+ T cells, or 500,000 CD4+ T cells did not.
FACS analysis of tissues from adoptively transferred mice.Tissues from wild-type, control, and adoptively transferred CD4−/− recipients were obtained at day 15 postinoculation (day 17 posttransfer). Spleen and MLN were macerated through 70-μm filters. Distal colon was opened and flushed with cold Hanks buffered saline solution (Gibco) and placed on parafilm, and the mucosa was gently scraped with a sterile razor blade. Scraped material was placed in cold HBSS, pelleted at 1,500 rpm prior to two 15-min incubations at 37°C in HBSS plus 10% fetal calf serum (FCS) plus antibiotics plus 2 mM EDTA to release epithelial cells from stromal cells. Material was resuspended in R10 plus type IV collagenase (dispase) plus 10 U/ml of DNase (Pierce) and underwent two 20-min incubations at 37°C. Collected fractions were passed over 40-μm Nytex mesh filters, spun, washed twice in R10, and resuspended for staining with species and isotype-specific controls (Caltag), hamster anti-mouse CD3e-cychrome (Pharmingen), CD4-PE or -FITC, CD8α-PE or -FITC, CD19-PE, F4/80-PE, and FITC-conjugated anti-mouse CD45.1 or CD45.2 (eBiosciences). In mice receiving purified CD45.1+ CD4+ T cells, CD8+, CD19+, or other CD45.1+ cells remained at <0.5% at 15 days after transfer. By FACS analysis, cells within the lymphocyte gate were gated by CD3 positivity in FL-3 and analyzed for CD4 or CD8α expression in FL-1 to determine the percentages of CD4+ and CD8+ T cells from these locations. Mice adoptively transferred with CD45.1+ cells were gated on CD45.1+ in the FL-1 channel and analyzed in FL-2 for CD4 expression and FL-3 for CD3 expression to determine the phenotype of the transferred cell populations.
IFN-γ, CD28, and CD40L impact survival of infection with C. rodentium.Survival studies with wild-type, CD28−/−, CD40L−/−, IFN-γ−/−, and IL-4−/− mice defined critical junctures during infection requiring expression of these molecules. Animals were infected at 21 days of age, a time during which mice are more susceptible to infection with C. rodentium and one modeling the development of symptomatic infections caused by attaching-and-effacing pathogens in susceptible populations, including human children and young animals. Whereas all wild-type (Fig. 1A) and IL-4-deficient (Fig. 1B) mice survived infection, 100% of CD28−/− mice succumbed during acute infection (Fig. 1C). While 40% of CD40L−/− animals succumbed during acute infection (Fig. 1D), the remaining 60% succumbed over the next 2 weeks, during the time that wild-type mice cleared C. rodentium from the colon. IFN-γ−/− mice demonstrated 30% lethality during acute infection with survival of remaining animals (Fig. 1E). These findings indicated that costimulatory events mediated by CD28 impacted necessary host responses during acute infection. Surprisingly, costimulation mediated by CD40L impacted events associated with both acute and resolution stages of infection, while deficiency of IFN-γ demonstrated a milder but still important contribution toward survival of acute infection.
Deficiency of CD28 or CD40L leads to development of polymicrobial sepsis, damage to colon and internal organs, and defects in bacterial clearance.Wild-type mice characteristically develop peak pathogen burdens 2 weeks into infection, with numbers exceeding 1 × 108 CFU of C. rodentium per gram of colon (Fig. 2A). In spite of this pathogen burden, the colonic epithelium remains grossly intact with rare breaks associated with abscess formation and efflux of neutrophils into the lumen (Fig. 3A) (2). The pathogen burden declines 3 to 4 logs over the next week, with the majority of animals clearing C. rodentium within 4 weeks (Fig. 2A and 3E). The same pattern was found in mice lacking IL-4 (data not shown).
All knockout strains demonstrated colonic burdens of C. rodentium similar to those of wild-type mice during initial colonization and proliferation (Fig. 2A to D). By 15 days of infection, CD28−/− mice demonstrated a half-log-higher colonic burden of C. rodentium than wild-type or other knockout strains of mice (Fig. 2B). Histologically, the distal colon of CD28−/− mice also demonstrated more frequent focal abscesses and breaks in epithelial integrity than those found in wild-type or IFN-γ- or CD40L-deficient mice (Fig. 3A to D) (data not shown). However, while pathogen burdens in wild-type mice dropped >3 logs between 15 and 21 days of infection (Fig. 2A), the pathogen burden remained constant or rose in surviving CD40L−/− mice (Fig. 2C). This failure to clear the colonic infection was associated with increasing destruction of the gut mucosa (Fig. 3F). The pathogen burden in IFN-γ−/− mice remained comparable to that in wild-type mice, except for a mean 10-day lag in clearance of colonic C. rodentium and delayed resolution of mucosal inflammation (Fig. 2D and 3G and H).
Investigation of CFU in liver and spleen revealed key defects. Prior studies in mice lacking CD4+ T cells demonstrated worsening polymicrobial sepsis by day 15 of infection, characterized by systemic spread of C. rodentium and lesser numbers of commensal species (2), events that were infrequent in wild-type mice (Fig. 2E and I). CD28−/− mice demonstrated a similar septic picture characterized by the presence of C. rodentium and commensal E. coli in spleen and liver (Fig. 2F and J). The liver in particular demonstrated frequent focal abscesses and hepatocyte damage (Fig. 3J). CD40L−/− mice developed a milder septic picture (Fig. 2G and K) with less damage to internal organs by day 15 of infection (Fig. 3K). However, at later time points, numbers of C. rodentium and E. coli increased in CD40L−/− mice (Fig. 2G and K) as did damage to internal organs, liver in particular (Fig. 3L). In contrast, IFN-γ−/− mice displayed milder sepsis acutely that resolved in surviving animals (Fig. 2H and L).
T-cell costimulation mediated by CD28 and CD40L is required for development of protective antibody responses against C. rodentium.We next determined the effect of CD28, CD40L, or IFN-γ deficiency on acute antibody responses against C. rodentium. Wild-type mice infected with C. rodentium characteristically develop strong pathogen-specific serum IgM responses that peak approximately 2 weeks after oral inoculation (Fig. 4A, squares). IgG responses rise above baseline and peak over subsequent weeks (2). The IgG responses at day 15 of infection in wild-type mice demonstrate rising production of IgG2b (Fig. 4C) and Th1-dependent IgG2c (Fig. 4D).
In contrast to the early antibody profile seen in wild-type mice, CD28-deficient mice failed to mount significant pathogen-specific antibody at 15 days of infection (Fig. 4A to E, triangles). Lack of CD40L impaired the production of acute-pathogen-specific IgM (Fig. 4A, triangles) and IgG, with the exception of minimal titers of IgG2b at day 15 (Fig. 4D). This lack of significant IgG reactivity persisted in CD40L−/− mice surviving beyond day 15 of infection (data not shown). IFN-γ−/− mice developed total pathogen-specific Ig responses comparable to those of wild-type mice, with IgG2b (Fig. 4D, diamonds) and/or IgG3 (Fig. 4E) developing in the absence of IgG2c (Fig. 4C).
Analyses of immunoglobulin titers in feces demonstrated a similar striking impact on the development of C. rodentium-specific antibody that reached the bowel lumen. At day 15 of infection, wild-type and IFN-γ−/− mice demonstrated comparable titers of reactive fecal IgM, IgA, and IgG2b, the primary IgG isotype detected. In contrast, CD28−/− mice demonstrated limited fecal IgA responses, in the absence of detectable anti-Citrobacter IgG (Fig. 4F to J). Likewise, titers of reactive fecal IgM, IgA, and IgG were significantly reduced in CD40L−/− mice. Though CD40L−/− mice produced detectable IgG2b against C. rodentium (Fig. 4H), these titers were 10-fold lower than those found in wild-type or IFN-γ−/− mice.
We next assessed the protective capacity of the acute-phase serum Ig responses produced in CD40L- and IFN-γ-deficient mice. Previous studies demonstrated that administration of serum or purified serum Ig from infected wild-type donors to highly susceptible CD4−/− mice protected recipients from infection with C. rodentium (2). As shown in Fig. 5A, transfer of wild-type acute-phase serum protected 100% of CD4−/− recipients, as did transfer of serum from IFN-γ−/− donors. While serum transfer from CD40L−/− mice provided a survival advantage of 7.45 days, it failed to protect CD4−/− recipients. These data indicate that the limited pathogen-specific Ig response produced in CD40L−/− mice extends survival of CD4−/− recipients but fails to provide complete protection. Though IFN-γ impacts the profile of reactive IgG, its production was not required to generate protective antibody.
Adoptive transfer of CD4+ T cells protects CD4−/− recipients against infection with C. rodentium.To determine the specific contributions of CD4+ T-cell-expressed CD28, CD40L, and IFN-γ, we adoptively transferred 5 million wild-type or specifically deficient CD4+ T cells into CD4−/− recipients subsequently infected with C. rodentium. Transfer of CD45.1+ CD4+ T cells to CD45.2+ CD4−/− donors assessed the degree of reconstitution in uninfected and infected recipient mice 2 weeks after transfer (Table 1). Subsequent transfers used CD45.2+ CD4+ T cells from wild-type, CD28−/−, CD40L−/−, or IFN-γ−/− donors. Recipients receiving CD4+ CD28− T cells demonstrated poor reconstitution of the CD4+ T-cell compartment in spleen, MLN, and colon 2 weeks after transfer (Table 1), while recipients of CD4+ CD40L− T cells demonstrated slightly improved reconstitution of the spleen and MLN but limited reconstitution of the colon (Table 1).
Adoptive transfer produced profound phenotypic effects upon survival of C. rodentium infection. Eighty percent of CD4−/− recipients receiving wild-type CD4+ T cells successfully resolved infection (Fig. 6A). Transfer of CD4+ CD28− T cells produced survival comparable to that with control CD4−/− mice receiving media (14.8 days; Fig. 6B and E), while transfer of CD4+ CD40L− T cells extended the mean survival to 20.7 days (Fig. 6C). Surprisingly, transfer of CD4+ IFN-γ− T cells (Fig. 6D) produced survival comparable to that of mice receiving wild-type CD4+ T cells.
The differences in survival were associated with development of a protective profile of acute-phase serum antibody. Recipients transferred with wild-type CD4+ T cells demonstrated acute pathogen-specific serum IgM comparable to that with wild-type mice and near-normal levels of IgG2b and IgG2c (Fig. 7, inverted triangles). Mice receiving CD4+ CD28− T cells demonstrated poor pathogen-specific responses (Fig. 7, diamonds). Though transfer of CD4+ CD40L− T cells produced a mild elevation in pathogen-specific IgM (Fig. 7, circles) and IgG2b (Fig. 7, circles), pathogen-specific IgM remained >5-fold lower and pathogen-specific IgG 10-fold lower than the titers found in mice receiving wild-type CD4+ T cells (Fig. 7). Transfer of CD4+ IFN-γ− T cells resulted in comparable titers of total pathogen-specific serum IgM and IgG with compensatory titers of IgG2b (Fig. 7B, asterisks) and IgG3 (Fig. 7D, asterisks) in the absence of detectable IgG2c (Fig. 7C).
These titers correlated with lower pathogen burdens at day 15 of infection in internal organs. Transfer of wild-type CD4+ T cells or CD4+ IFN-γ− T cells produced a ≥2-log decrease in the number of pathogenic bacteria found in the spleen when compared with CD4−/− mice receiving CD4+ CD28− T cells or media (Fig. 8A; P < 0.01). Though recipients receiving CD4+ CD40L− T cells developed lower mean burdens in spleen than CD4−/− mice, this difference was not significant (log10 CFU of C. rodentium/gram of tissue of 3.6 versus 4.3; P = 0.06).
Our findings have further elucidated the complicated interplay between mucosal and systemic adaptive immunity in controlling a primary infection of a mucosal surface. Unlike phylogenetically related members of the Enterobacteriaceae including Salmonella enterica serovar Typhimurium, Shigella, and enteric Yersinia species, C. rodentium does not establish a primarily invasive or intracellular infection. However, the infections caused by each of these pathogens involve contact with epithelial surfaces and the potential for direct microbial or host-mediated damage to the mucosa (3, 23). The adherence of high bacterial burdens of enteropathogenic E. coli or of C. rodentium to mucosal surfaces makes this process all the more important in the pathogenesis of infections caused by attaching and effacing pathogens. Epithelial disruptions provide passive portals through which pathogenic and commensal species may enter, creating the potential for polymicrobial sepsis. This microbiologial "bystander effect" remains an underappreciated pathological mechanism that can occur with any process damaging the gut epithelial barrier and can contribute to the morbidity and mortality of mucosal infections in immature and immunocompromised populations (2, 6).
Adaptive immunity to C. rodentium requires development of a systemic and CD4+ T-cell-dependent antibody response. This response is necessary in mice infected at the weaning transition or at older ages (2, 25). As demonstrated in mice lacking β7-integrins, these responses need not occur in proximity to the primary mucosal site of infection
During primary infection with C. rodentium, CD28 clearly affects the in vivo survival and proliferation of CD4+ T-helper cells, impacting downstream effector functions and development of protective antibody. More significantly, CD4+ T-cell-expressed CD40L provides a key costimulatory effector function needed to develop protective antibody responses. While more than half of CD40L−/− mice, or CD4−/− mice receiving serum from CD40L−/− donors, survived the normal period of acute infection, animals failed to resolve colonic infection and ultimately succumbed to profound polymicrobial sepsis. As systemic IgG responses have been implicated in the clearance of colonic C. rodentium (15), the lack of reactive IgG in CD40L−/− mice could explain this protracted course of infection among CD40L−/− mice and CD4−/− mice receiving serum or CD4+ CD40L− T cells from CD40L−/− donors.
Surprisingly, deficiency of IL-4 or of CD4+ T-cell-produced IFN-γ did not adversely impact the host's ability to develop protective antibody and survive infection. The roles played by IL-4 or CD4+ T-cell-expressed IFN-γ in the resolution of this infection may thus be small, or alternatively they may be overcome through other mechanisms in the deficient host. Furthermore, IFN-γ produced by populations other than CD4+ T cells, including NK cells, neutrophils, macrophages, or dendritic cells, may promote key effector functions needed for host defense, including macrophage activation, neutrophil recruitment, and aspects of epithelial defense, including the induction of antimicrobial defensins (19, 24).
However, the profile of protective antibody generated in wild-type mice indicates the development of IFN-γ and other cytokine responses in a normal host. The dependence of the IgG2c response on CD4+ T-cell-expressed IFN-γ demonstrates that immunocompetent mice generate Th1 responses during mucosal infection with C. rodentium. The codevelopment of Citrobacter-specific IgG2b, an IgG isotype promoted by transforming growth factor β1 (5, 17), further suggests contributions of regulatory cytokine responses. Dissecting the manner and locations in which these responses develop may be key to discerning how the normal host evolves and controls proinflammatory responses generated during mucosal infections.
Protective serum antibody responses in acute infection consisted of pathogen-specific IgM with evolving IgG2b/IgG2c or IgG2b/IgG3 responses. These profiles are consistent with complement-fixing antibodies and convalescent IgG responses that bind with high affinity to myeloid FcγR1 receptors and FcγRII/III receptors (20). Whereas pathogen-specific IgM develops during the point in infection when a naïve host is most susceptible to the development of sepsis, pathogen-specific IgG, and not mucosal IgA, has been demonstrated to help clear the colonic infection (15). Our data demonstrate that reactive IgG, IgG2b in particular, enters the lumen through an ill-defined mechanism, whether through damaged or leaky epithelium, FcRn-mediated epithelial transport, or uptake and release via the hepatobiliary system (22, 27). Effector functions of reactive antibody could thus include a combination of complement-mediated, phagocytic and direct antimicrobial functions, acting in systemic and mucosal locations.
We have defined key effector functions of CD4+ T cells during infection with the attaching and effacing pathogen C. rodentium. CD4+ T-cell-expressed CD28 and CD40L promote the development of protective humoral immunity during this primary infection of a mucosal surface, while deficiency of IL-4 or CD4+ T-cell-expressed IFN-γ have limited functional effects. These systemic adaptive immunological responses are essential for control of infections previously thought to be localized to the gastrointestinal tract. The development of a CD4+ T-cell adoptive transfer model with a robust survival phenotype provides a powerful tool to further dissect the evolution of differential Th responses in mucosal and systemic locations and to study CD4+ T-cell and antibody-mediated processes leading to successful resolution of mucosal infections and associated inflammation.
We thank Shannon Bowes and Monica Wang for technical assistance and Terry and David Bowman for histological processing.
This work was supported by funding from NIH grants R01 AI38578, K08 AI051734, and R21 AI059628. L.B. is a recipient of a K08 Career Development Award from the National Institutes of Health.
- Received 14 June 2005.
- Returned for modification 21 September 2005.
- Accepted 24 October 2005.
- Copyright © 2006 American Society for Microbiology


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Master's Perspective #04: Biblical Prophecy
11 Chapters
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11 Chapters
(Foreword by John F. MacArthur Jr.)A series designed for pastors and Bible students features the writings of notable Bible scholars and teachers on topical issues. Chapters in this series previously appeared in The Master's Seminary Journal.
Christ's return will fulfill the believer's expectation of being conformed to His likeness, a future reality that helps transform the present life of the Christian. Learning what the Bible teaches about the future matures us in Christ, keeping our focus on that great day when we will be caught up to meet Him in the clouds. The contributions to this work examine critical themes associated with the end times and Christ's return. Chapters by notable scholars such as Stephen J. Nichols, Kenneth L. Barker, Larry D. Pettegrew, and Robert L. Thomas include: "The Mission of Israel and of the Messiah in the Plan of God" "Literary Genre and the Hermeneutics of the Apocalypse" "The Kingdoms of Christ in the Apocalypse" "Premillennialism in the Book of Daniel" "Dispensationalists and Spirit Baptism"
- Catalogue Code 178421
- Product Code 0825431824
- Pages 288
- Department Academic
- Category Theology
- Sub-Category Eschatology
- Publisher Kregel Publications
- Publication Date Mar 2002
- Dimensions 111 x 111 x 16mm
- Weight 0.503kg
Richard L Mayhue (Ed)
Dr. Richard Mayhue(Th.D., Grace Theological Seminary) is Senior Vice President and Dean of The Master's Seminary, Sun Valley, California, where has also teaches theology and pastoral ministry. In more than twenty-five years of ministry Dr. Mayhue has served as a pastor, trained pastors, and written, edited or contibuted to more than fifteen books.
Robert L Thomas (Ed)
Robert L. Thomas (Ph.D., Dallas Theological Seminary) is professor of New Testament at The Master's Seminary. He is the author or coauthor of numerous books and other works, including the commentaries on 1 and 2 Thessalonians in the Holt series.


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Aspiring entrepreneurs frequently approach me personally being an angel investor, touting their revolutionary idea for yet another online site that is https://datingmentor.org/ourtime-review/ dating. We agree the requirement is offered, with over 91 million interested singles between the chronilogical age of 19 and 45 around the globe. Yet very little one in e-commerce makes hardly any money, I see since it comes with a larger list of challenges than most other opportunities.
Hence, we encourage one to evaluate these challenges as truth checks for your own personel company concept — dating or perhaps — before spending your entire some time some body else's cash in vain.
1. The marketplace has already been oversaturated with rivals.
Based on data, there are many than 5,000 sites that are dating with 1,000 brand brand brand new people showing up on a yearly basis. I suggest you look for another opportunity where the number of competitors you can find is less than 10 if you check your market on Google and find numbers like these.
2. This company is affected with the 'Facebook model' startup issue.
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For a fresh startup, the easiest way to make sure success would be to register patents or other intellectual home to help keep future rivals from copying your success. Dating just isn't a very clinical procedure, together with first-mover benefit was already taken. Consider this challenge for the most useful concept.
4. Separation from current businesses that are major little.
In fact, dating is a type of social network, so Facebook could effortlessly boost their solutions in this way, in the event that market traction of other people was obvious. Bing or other the search engines could include image-matching or any other focus to recapture the forex market. The greatest startups have actually genuine differentiation.
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Internet dating frauds to have cash or attention are a really typical and problem that is growing relating to a few articles in the Huffington Post. First of all, 40 % of regular web site users already are married. If the brand brand new concept has that exact same prospect of misuse, can it be well worth the chance to your reputation?
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Investors and clients alike would you like to see return that may be calculated contrary to the expenses. Value propositions such as "easier to use" or "find better partners" seldom contend with terms like "half the price" or "50-percent quicker." Make fully sure your brand new innovation features a quantifiable value idea.
7. Watch out for high return and minimal commitment circumstances.
Loyal repeat customers who become locked in by a top price of switching will be the fantasy of each and every investor and business that is smart. Online dating services lose clients quickly whenever a match is found by them– or once they don't locate a match. Try to find a continuing income opportunity with low consumer churn potential.
8. Stay away from company areas that aren't squeaky clean.
Internet dating sites are tagged as having failure that is historically high and a hint of company hustle, so they really are precluded by expert investors. Other people in this category would include on the web gambling, financial obligation work-at-home and collection offerings. Your brand new possibility should avoid these qualms.
Yet the web dating market, like almost every other one, has its own brand new possibilities for those of you entrepreneurs ready to think further away from field. Current people that we have noticed entail DoggiesMatch for pet dating, OurTime for singles over 50 and SupernaturalDating for paranormal enthusiasts. Despite the fact that these all interesting that is sound please don't ask me personally to take a position.
I usually tell business owners that even if you should be bootstrapping and not trying to find investors, it is nevertheless crucial to put on outside investor thinking to the new endeavor. As creator, you're constantly the largest investors and may apply the reality that is same.
Just how well does your latest startup idea prevent the challenges outlined right right here? Your livelihood and success may well be determined by it.


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Count Gensokyo
Hands of Fate
Gerome said:"Is there anything else? We should get a move on. This monster could be getting up to who knows what!"Hekapoo used her dimensional scissors to open a portal to the infamous asylum and walked out of the way for the rest of the group, "Spiders first."2099 gazed toward the portal for a moment, and upon collecting himself, glanced at Hekapoo briefly. "See you on the other side then," he only said, giving a two-fingered wave before hopping right into the portal.
Cynthia rested a hand on her hip as she watched the gang of spider-people hop through the tear in space, one-by-one.
On the other side lay a kind of place she'd never seen before...
...Someplace where she was bound to be a fish out of water.
But wherever evil existed, the soon-to-be-legendary hero, Cynthia, would follow!
Think of something cool to shout before the action...come on, Cynthia!
The knight straddled her pegasus, taking the opportunity to use the dagger at her hip to sharpen the edge of her battle-worn lance before it was her turn to enter.
"For those who shed innocent blood here today..."
As "Spider-Ham" hobbled through the portal with those stubby little legs of his, Cynthia quickly blurted something out and kicked her horse into action.
"I'll show no mercy! Here I come! HIYAAH!"
Cynthia shot her head in Gerome's direction, giving him an encouraging smile and a nod of her head before teleporting from one side of the planet to the other.
Phantom Thief of Hearts Bixir Verite Thepotatogod
Mitsuru Kirijo, esteemed head of the Kirijo Group, sat cross-legged across from her client at the other end of the long table. The white light of the mid-day sun bounced off the glassy surface of the table.
The two were alone in the room. Each move of their eyes―each shift of their postures―seemed perfectly calculated.
"So...you won't accept our buying your stock, even with the terms that have been laid out?"
"Correct. The Kirijo Group doesn't have any immediate plans to open to public capital."
"I see."
The man brushed at his spotless suit as if to wipe non-existent dust off it.
"...Would you mind if I stepped out and took a call? I promise it won't take long."
Mitsuru smiled.
"Go ahead."
"Excuse me."
The man rose from his chair and made a leisurely exit from the meeting room, probably for a much-needed coffee break and yet another word with his boss.
Mitsuru glanced at her watch. It had already been two hours.
If this kept up for much longer, she'd be missing a meeting with an old friend at the airport.
It's almost as if he can't deviate from his superior's script...
Mitsuru couldn't blame him for taking so many cautious steps in this negotiation, though. At this stage, the Togami Corporation was in dire straits. Who at that company could have anticipated a systematic assassination of its leadership at the hands of a terrorist group? That had happened months ago, and the company was still reeling from the aftermath.
Mitsuru looked out the window, her features reflecting the tension in her thoughts.
'Ultimate Despair'...what's your aim? Can 'Despair' itself be a goal worth seeking?
Ever since the Togami assassinations went public, Mitsuru had immediately taken the initiative to ramp up security for herself and the other major executives. Despite the tremendous costs it had taken to implement, she could rest easy knowing that they could sleep soundly at night following that string of terrible incidents.
. . .
"Safety" hadn't been a concern for her forefathers. Even in this day and age, Mitsuru had to work around-the-clock to right every one of their wrongs. Such was her duty—as a leader, and as the last of her family's bloodline.
Minutes passed, and the man representing the Togami Corporation re-entered.
Mitsuru felt her watch and phone vibrate rapidly.
"I'm terribly sorry for this taking so long, Kirijo-sama," he said before taking a seat.
Mitsuru checked her watch once again. This time, she held an entirely different expression—one of grave seriousness.
"Is something wrong, Kirijo-sama...? Can we continue?"
A shrill beeping noise began ringing from the device. Mitsuru hastily shoved herself away from the table.
The worst was coming to pass.
"This is an emergency. We'll have to schedule some other time."
And before the man could offer anything in retort, Mitsuru had already rushed out into the hallway.
She immediately relayed the signal to all nearby available operatives amid the hurried clacks of her heels.
"Akihiko? Akihiko, do you read?!"
The rough voice of a young man who had clearly been fumbling for his phone came from the other end of the call.
"I'm here. What's the situation?"
"That was Jameson at Ravencroft. The only time he would send a distress signal like that—"
Mitsuru pushed through the front doors of the building, heading right for the limousine that was waiting for her at the curb ahead.
Akihiko's voice faltered as he realised the gravity of the situation. "Is if...something dangerous was breaking out...and heading right for us."
Mitsuru sprang into the passenger's seat as her chauffeur roared the vehicle off the pavement.
"I'm afraid we'll need to be braced for the worst possible scenario. Cletus Kasady has breached containment."
Mitsuru heard the clap of Akihiko's loud footsteps on the speakers.
"Guess I'll just have to be ready for him before he reaches the island, huh?!"
"Go to Clair Avenue. I'll be sending a chopper your way."
"Alright. Anyone else coming?"
"One of our Anti-Shadow Weapons is already en route."
"Great. We're gonna need all the firepower we can get."
"I'll be meeting you at Port Island Station. He landed there once, and he's going to do it again."
"He just wants to get his hands bloody as soon as possible...tch."
"That's exactly why we can't let it happen again."
Mitsuru thumbed for another name high in her list of contacts.
"I need someone else on the line. Call me if something comes up."
. . .
"History tends to repeats itself."
That is a saying often attributed to large-scale societal cycles looping over the passing of centuries and decades.
But in the span of a few short years, the people of Tatsumi Patch had witnessed firsthand the heartbreaking effects of unspeakable violence. Few had fully healed the scars from when their loved ones were torn apart by a blood-red psycopath, and when no one's son or daughter returned from the halls of Hope's Peak Academy a few months later, those wounds were re-opened.
A few years ago, Cletus Kasady had unknowingly fed the engine of Despair with an inspirational act of massacre.
And now, Despair had brought the same man back to for an encore of that act he held so dearly in his cold, dead heart—indiscriminate slaughter of the innocent.
Phantom Thief of Hearts Bixir Verite Thepotatogod
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