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Byline: Tim Cant Aled Jones meets rave and Macaulay Culkin goes jungle While some songs have been sampled so many times that you're more accustomed to hearing elements of them [...]

The National Placement Evaluation Centre (NPEC) undertakes nursing and midwifery student placement feedback in order for stakeholders to provide improvements in clinical education. The initiative to report the quality of [...]

Byline: Tim Cant Rejuvenate your mind, body and spirit with these vintage ambient jungle sounds If, today, you were asked to imagine humanity's future, you'd probably describe a bleak, technological [...]

Byline: Tim Cant If you yearn for the days of the Yamaha SY85, can't get enough of old E-MUs or want to get your Kawai kicks for free, read on [...]

Byline: Tim Cant Maybe the secret to musical success isn't to be original, but to try as hard as you can to sound like somebody else... In today's attention economy, [...]

Nurses have an important role in asthma care, whether as prescribers, or as asthma educators in primary care, hospital clinics or with the Asthma and Respiratory Foundation. This article looks [...]

The immensely popular DAW enters its eleventh chapter with an array of new tools and features Ableton has a long-held tradition of incrementally improving its software rather than radically altering [...]

Lymphoproliferation and autoimmune cytopenias characterise autoimmune lymphoproliferative syndrome. Other conditions sharing these manifestations have been termed autoimmune lymphoproliferative syndrome-like diseases, although they are frequently more severe. The aim of this study was to define the genetic, clinical, and immunological features of these disorders to improve their diagnostic classification.

Sudden cardiac arrest (SCA) is the leading cause of sudden death in athletes during high-level, organised sport. Patient-related and event-related factors provide an opportunity for rapid intervention and the potential for high survival rates. The aim of this consensus was to develop a best-practice guideline for dedicated field-of-play medical teams responding to SCA during an organised sporting event. A task-and-finish group from Resuscitation Council UK identified a stakeholder group of relevant experts and cardiac arrest survivors in March and April 2022. Together, they developed a best-practice guideline using the best available evidence. A public consultation period further refined the guideline before it was finalised in December 2023. Any sudden collapse, without rapid recovery during sporting activity, should be considered an SCA until proven otherwise. Field-of-play medical teams should be empowered to access the collapsed athlete as soon as possible and perform initial essential interventions in situ. This includes a suggested minimum of three cycles of cardiopulmonary resuscitation and defibrillation in persistent shockable rhythms while other aspects of advanced life support are initiated. There should be careful organisation and practice of the medical response, including plans to transport athletes to dedicated facilities for definitive medical care. This best-practice guideline complements, rather than supersedes, existing resuscitation guidelines. It provides a clear approach to how to best treat an athlete with SCA and how to organise the medical response so treatments are delivered effectively and optimise outcomes.

The phosphoinositide 3-kinase (PI3K) pathway regulates diverse cellular processes, with finely tuned PI3Kδ activity being crucial for immune cell development and function. Genetic hyperactivation of PI3Kδ causes the inborn error of immunity activated phosphoinositide 3-kinase δ syndrome (APDS). Several PI3Kδ inhibitors have been investigated as treatment options for APDS, but only leniolisib has shown both efficacy and tolerability. In contrast, severe immune-mediated adverse events such as colitis, neutropenia, and hepatotoxicity have been observed with other PI3Kδ inhibitors, particularly those indicated for hematological malignancies. We propose that leniolisib is distinguished from other PI3Kδ inhibitors due to its structure, specific inhibitory properties selectively targeting the δ isoform without overinhibition of the δ or γ isoforms, and the precise match between APDS mechanism of disease and drug mechanism of action.

BackgroundIn the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel.Laboratory structure and resourceThe DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists.Laboratory resultsOver 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started.ConclusionsThrough a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

IntroductionThe acquisition and retention of militarily relevant surgical knowledge and skills are vital to enable expert management of combat casualties on operations. Opportunities for skill sustainment have reduced due to the cessation of combat operations in Iraq and Afghanistan and lack of military-relevant trauma in UK civilian practice.MethodsA voluntary, anonymous online survey study was sent to all UK Defence Medical Services (DMS) surgical consultants and higher surgical trainees in Trauma and Orthopaedics, Plastic and Reconstructive, and General and Vascular surgical specialties (three largest surgical specialties in the DMS in terms of numbers). The online questionnaire tool included 20 questions using multiple choice and free text to assess respondents’ subjective feelings of preparedness for deployment as surgeons for trauma patients.ResultsThere were 71 of 108 (66%) responses. Sixty-four (90%) respondents were regular armed forces, and 46 (65%) worked in a Major Trauma Centre (MTC). Thirty-three (47%) had never deployed on operations in a surgical role. Nineteen (27%) felt they had sufficient exposure to penetrating trauma. When asked ‘How well do you feel your training and clinical practice prepares you for a surgical deployment?’ on a scale of 1–10, trainees scored significantly lower than consultants (6 (IQR 4–7) vs 8 (IQR 7–9), respectively; p<0.001). There was no significant difference in scores between regular and reservists, or between those working at an MTC versus non-MTC. Respondents suggested high-volume trauma training and overseas trauma centre fellowships, simulation, cadaveric and live-tissue training would help their preparedness.ConclusionsThere was a feeling among a sample of UK DMS consultants and trainees that better preparedness is required for them to deploy confidently as a surgeon for combat casualties. The responses suggest that UK DMS surgical training requires urgent attention if current surgeons are to be ready for their role on deployed operations.

Quantitative analysis of binary mixtures of tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) and tris(8-hydroxyquinolinato)aluminum (Alq3) by using an artificial neural network (ANN) system to mass spectra was attempted based on the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study (TW2 A31) to evaluate matrix-effect correction and to investigate interface determination. Monolayers of binary mixtures having different Ir(ppy)3ratios (0, 0.25, 0.50, 0.75, and 1.00), and the multilayers containing these mixtures and pure samples were measured using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with different primary ion beams, OrbiSIMS (SIMS with both Orbitrap and ToF mass spectrometers), laser desorption ionization (LDI), desorption/ionization induced by neutral clusters (DINeC), and X-ray photoelectron spectroscopy (XPS). The mass spectra were analyzed using a simple ANN with one hidden layer. The Ir(ppy)3ratios of the unknown samples and the interfaces of the multilayers were predicted using the simple ANN system, even though the mass spectra of binary mixtures exhibited matrix effects. The Ir(ppy)3ratios at the interfaces indicated by the simple ANN were consistent with the XPS results and the ToF-SIMS depth profiles. The simple ANN system not only provided quantitative information on unknown samples, but also indicated important mass peaks related to each molecule in the samples without a prioriinformation. The important mass peaks indicated by the simple ANN depended on the ionization process. The simple ANN results of the spectra sets obtained by a softer ionization method, such as LDI and DINeC, suggested large ions such as trimers. From the first step of the investigation to build an ANN model for evaluating mixture samples influenced by matrix effects, it was indicated that the simple ANN method is useful for obtaining candidate mass peaks for identification and for assuming mixture conditions that are helpful for further analysis.

Nanoparticles used for medical applications commonly possess coatings or surface functionalities intended to provide specific behavior in vivo, for example, the use of PEG to provide stealth properties. Direct, quantitative measurement of the surface chemistry and composition of such systems in a hydrated environment has thus far not been demonstrated, yet such measurements are of great importance for the development of nanomedicine systems. Here we demonstrate the first use of cryo-XPS for the measurement of two PEG-functionalized nanomedicines: a polymeric drug delivery system and a lipid nanoparticle mRNA carrier. The observed differences between cryo-XPS and standard XPS measurements indicate the potential of cryo-XPS for providing quantitative measurements of such nanoparticle systems in hydrated conditions.

This paper considers the changing face of clinical education and the emergence of screen-based virtual simulation (VS). Virtual forms of education have emerged with advancing technology, advantages of blended and [...]

This paper raises issues about the quality of nursing and midwifery students' clinical placements in Australia. Clinical training hours have dropped noticeably across theyears, with Australian nursingstudents undertaking a bachelor's [...]

Computer-based virtual simulation in nursing is a rapidly developing field. A summary of current research could benefit nursing faculty who are incorporating this pedagogy into online teaching due to social distancing requirements. This umbrella review aimed to explore the use and effectiveness of virtual simulations in prelicensure nursing education. Our umbrella review approach was informed by The Johanna Briggs Institute guidelines. The 18 included reviews captured the experiences of over 7600 nursing students who engaged with five different virtual (screen-based) simulation modalities. Results indicated that virtual simulations can be effective in developing nursing students' knowledge and psychomotor and psychosocial skills, for example, in medication administration and communication. There was no study that showed a conclusive benefit of virtual simulations for developing clinical reasoning. Students enjoyed virtual simulations, claiming they were accessible, fun, and engaging ways to learn. Many benefits of virtual simulations and some technological challenges were identified in a mapped model. In the future, more rigorous and experimental studies are needed to confirm effects on learning outcomes. Nursing curriculum designers need to define the place and purposes of the pedagogy to ensure that knowledge and skills learned during virtual simulations can be applied to real-world, patient-centered care.

The evidence is clear that child sexual abuse is a public health concern internationally. Prevention of child sexual abuse requires a variety of interventions including those that stop individuals from either sexually assaulting a child or viewing sexually abusive online images. In contrast, most current approaches internationally focus on criminal justice strategies aimed at preventing reoffending rather than stopping the first offence. Additionally, and albeit there is a general paucity of relevant scholarship, there are few signs of countries adopting coherent, unified and evidence-based strategies to prevent individuals at risk of harming a child becoming actual or repeat offenders. The focus of interventions to date is largely on prevention at the tertiary end. Understanding and adopting an integrated public health approach represents an opportunity to incorporate a range of primary, secondary and tertiary prevention interventions and develop comprehensive prevention strategies at local, national, or international levels. A comprehensive approach to prevention targeted at stopping offending in the first place is required, and it needs to be able to recognise the complex nature of offending and the diversity therein. Research shows that those who harm children are diverse in their age and gender, the children they sexually abuse—intra-familial/extra-familial, prepubescent/pubescent, peer/younger children, male or female—and the type of abuse—contact, non-contact, or online. Preventing child sexual abuse is complex and requires more than an ad hoc collection of unrelated programs, if it is to succeed. This paper synthesises and integrates the disparate scholarly literature on the potential and actual perpetrators of child sexual abuse and responses to and prevention of such abuse. It recommends an increased focus on primary prevention within a comprehensive public health approach as a conceptual framework to prevent the occurrence of child sexual abuse. A systems approach is taken to develop the proposed conceptual framework.

For our 50th issue, we wanted to celebrate what BP has been about over the last 15 years. We also wanted to inspire those who might be picking up a [...]

In my first year at Park View School I was repeatedly asked where I was from, and ' England' was never a credible answer. 'No, I mean, like, where are [...]

Las lesiones del complejo tobillo-pie son los trastornos musculoesqueléticos más frecuentes en los servicios de urgencias, pero también en el ámbito deportivo y en la práctica clínica. Alrededor del 25% de las mujeres y los varones padecen estos trastornos musculoesqueléticos, con una amplia variedad de afecciones que incluyen, por ejemplo, esguinces, fracturas, osteoartritis y tendinopatías. Pueden afectar a las actividades de la vida diaria, causando diversos grados de discapacidad, que suele ser temporal pero que puede tener una repercusión socioeconómica significativa. Por lo tanto, una evaluación clínica completa es esencial para evaluar la situación con precisión y luego orientar las mejores decisiones terapéuticas. Sin embargo, esto se basa en un enfoque complejo conocido como «razonamiento clínico». Por ello, el presente artículo ha sido redactado por un grupo de expertos en este campo de la kinesiterapia musculoesquelética, con el fin de identificar los diversos componentes que se tienen en cuenta durante la evaluación de este complejo articular. Por consiguiente, sobre la base del modelo de la Clasificación Internacional del Funcionamiento y la Discapacidad, se han incluido los elementos clínicos y científicos más relevantes. Se trata de proporcionar una evaluación completa y didáctica de cada componente de este modelo para la exploración física de los trastornos musculoesqueléticos más comunes del tobillo y el retropié. En conclusión, la evaluación musculoesquelética de esta región es multifactorial y compleja, y también está relacionada con la situación del mediopié y del antepié, que no se tratará aquí. No obstante, el uso de pruebas o la agrupación de pruebas con los mejores valores clinimétricos mejora la precisión del diagnóstico. Sin embargo, todavía se necesitan más estudios para establecer clústeres de pruebas para los numerosos trastornos musculoesqueléticos del tobillo y el pie. Además, es evidente que debe fomentarse la cooperación multidisciplinar entre médicos, kinesiterapeutas y podólogos para esta región del cuerpo.

Le lesioni della regione caviglia-piede sono i disturbi muscoloscheletrici più frequenti in Pronto Soccorso, ma anche sui campi sportivi o nella pratica clinica. Circa il 25% delle donne e degli uomini soffre di questi disturbi muscoloscheletrici, con un’ampia varietà di patologie, tra cui, per esempio, distorsioni, fratture, artrosi e tendinopatie. Queste possono avere ripercussioni sulle attività della vita quotidiana, determinando una disabilità più o meno significativa, che è certo generalmente temporanea ma che può avere un impatto socioeconomico significativo. Pertanto, è indispensabile un bilancio clinico completo che consenta innanzitutto di valutare con precisione la situazione per poi orientare al meglio le decisioni terapeutiche. Tuttavia, esso si basa su un approccio complesso denominato “ragionamento clinico”. Ecco perché questo articolo è stato scritto da un gruppo di esperti in questo campo della fisioterapia muscoloscheletrica, al fine di identificare le diverse componenti che entrano in gioco nella valutazione di questa regione. Di conseguenza, sulla base del modello della Classificazione Internazionale del Funzionamento e della Disabilità, sono stati inseriti i vari elementi clinici e scientifici più pertinenti. Questo al fine di offrire una valutazione completa e didattica di ogni componente di questo modello per l’esame clinico specifico per i più comuni disturbi muscoloscheletrici della caviglia e del retropiede. In conclusione, la valutazione muscoloscheletrica di questa regione è multifattoriale e complessa ed è anche correlata alla situazione del meso- e dell’avampiede, che non è stata affrontata. Tuttavia, l’uso di test o il raggruppamento di test con i migliori valori clinimetrici migliorano l’accuratezza della diagnosi. Comunque, devono ancora essere condotti ulteriori studi al fine di stabilire gruppi di test per tutti i numerosi disturbi muscoloscheletrici della caviglia e del piede. Inoltre, per questa regione corporea deve chiaramente essere incoraggiata una collaborazione multidisciplinare tra medici, fisioterapisti e podologi.

Hematopoietic cell transplantation (HCT) has become standard-of-care for an increasing number of inborn errors of immunity (IEI). This report is the first to compare transplant outcomes according to T-cell–replete (ie, T-replete) HLA-matched grafts using alemtuzumab (n = 117) and T-cell–depleted (ie, T-depleted) HLA-mismatched grafts using T-cell receptor-αβ (TCRαβ)/CD19 depletion (n = 47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, peripheral blood stem cell (PBSC) in 85 (73%), and cord blood in 7 (6%). TCRαβ/CD19 depletion was performed on PBSCs from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year overall survival (OS) and event-free survival for the entire cohort were 85% (77%-90%) and 79% (69%-86%), respectively. Analysis according to age at transplant revealed a comparable 3-year OS between T-replete grafts (88%; 76%-94%) and T-depleted grafts (87%; 64%-96%) in younger patients (aged <5 years at HCT). For older patients (aged >5 years), the OS was significantly lower in T-depleted grafts (55%; 23%-78%) compared with T-replete grafts (87%; 68%-95%) (P = .03). Grade III to IV acute graft-versus-host disease was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete cord blood, and 2% of T-depleted PBSC (P = .73). Higher incidence of viremia (P < .001) and delayed CD3 reconstitution (P = .003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCRαβ/CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft.

We present a case of a dentigerous cyst associated with an unerupted premolar tooth, and its surgical management in a 4-year-old child. Of note, 8 months prior to presentation, the patient was seen for extraction of multiple primary teeth under general anaesthesia. At the time of extraction, there were no signs of extra- or intra-oral mandibular swellings. Dentigerous cysts are one of the most common paediatric intra-osseous lesions. This case highlights the importance of taking a thorough dental history and the benefit of a multidisciplinary approach. This report also demonstrates the surgical management of this lesion, which included surgical excisional biopsy under general anaesthesia.CPD/Clinical Relevance:The reader should consider dentigerous cysts as a differential diagnosis in paediatric patients who present with dental swellings.

Outsourcing may not be an efficient and effective process for all organizations. Although significant cost savings can be achieved, these may result not from improved operations and management practices but from innovation and staff reductions. Organizations should target and evaluate potential internal improvements before deciding to outsource., What has been happening over recent years The changes that have taken place since the mid-1980s have altered the shape of public sector organizations, perhaps forever. It seems unlikely that [...]

Information obtained from a quantitative and qualitative investigation undertaken in autumn 1991-spring 1992 gives a useful insight into the range and type of collaboration between general practice-based community and practice nurses. There seems to be good support and communications between practice nurses, district nurses and health visitors, but the full potential of the nurses' skills can be restricted by the clear division of labour within general practice. Working patterns will have to be changed before all the skills of the primary health care team can be fully used.

The days of having the Cinque Terre to yourself are long gone. The string of villages along the Ligurian coast in Italy is far too exposed. Rick Steves wanders the [...]

Bronchiectasis is predominantly a neutrophilic inflammatory disease. There are no established therapies that directly target neutrophilic inflammation because little is understood of the underlying mechanisms leading to severe disease. Neutrophil extracellular trap (NET) formation is a method of host defence that has been implicated in multiple inflammatory diseases. We aimed to investigate the role of NETs in disease severity and treatment response in bronchiectasis.

Purpose: The UK government introduced a nationwide lockdown on the 23rd March 2020 to prevent the spread of COVID-19. All elective hospital and dental practice assessments and procedures were mandated to stop. Key hospital dental workers were required to work, and Guy’s and St Thomas’ NHS Foundation Trust became a designated Urgent Dental Care Centre (UDC) for the greater London area. The paediatric dental emergency walk-in service was suspended and replaced with a telephone triage system and evaluation of digital images sent by parents/carers when needed. The aim of this paper is to describe the emergency service provided by staff in the department of Paediatric Dentistry at St Thomas’ Hospital during the first lockdown. Methods: A prospective service evaluation of the modified paediatric dental emergency service was carried out between 25th March and 29th May 2020. Results: Four-hundred and sixty-four patients accessed the paediatric dental emergency service via telephone during the service evaluation period. Of these, 192 (41%) had dental pain, 121 (26%) had pain and swelling of dental origin, and 89 (19%) had trauma. Conclusions: Remote telephone consultations and digital photographs were useful to screen emergency paediatric dental patients, but lack of face-to-face consultations with radiographic assessment and access to general anaesthetic services were major limiting factors.

As one of the leading Latin American economies (along with Brazil), and the country with the highest number of international free trade agreements, Mexico has experienced big changes regarding training [...]

There are recognised difficulties internationally with acquisition and retention of skills among deployed military general surgeons. These are compounded by reduced trauma workload in non-deployed roles or during low tempo or limited activity deployments, and the winding-down of combat operations in Iraq and Afghanistan. We summarise the relevant military-run courses, military-civilian collaborations and potential future strategies that have been used to address skill sets and competencies of deployed surgeons. We use examples from the American, British, Danish, French, German and Swedish Armed Forces. There is variation between nations in training, with a combination of didactic lectures, simulation training and trauma placements in civilian settings at home and overseas. Data regarding effectiveness of these techniques are sparse. It is likely that combat surgical skill-set acquisition and maintenance requires a combination of employment at a high-volume trauma centre during a surgeon’s non-deployed role, together with military-specific courses and high-fidelity simulation to fill skill gaps. There are multiple newer modalities of training that require further evaluation if they are to prove effective in the future. We aimed to summarise the current methods used internationally to ensure acquisition and retention of vital skill sets for these surgeons.

Workers at the Orion recycling plant in East London spend their days sorting construction waste. It is dirty and difficult work, made worse by a lack of adequate safety equipment. [...]

British architect Piers Gough, long regarded as an eccentric, is finally being recognized by the British cultural establishment. Gough, a founding partner of London-based CZWG, has designed only two public buildings, one of them being a small public toilet in west London. Among other projects in which he has been involved are up-market loft conversions, apartment blocks and private housing developments. Gough believes that architecture should be enjoyable and says that his main ambition is to design an important cultural building, such as a modern art gallery.

The ability to measure the internal chemical distribution of particles is of significant benefit to the development and testing of products relevant to the pharmaceutical, agrichemical, and food industries. These include nanomedicine particle carriers, such as those used in anticancer drugs, vaccines, and viral carriers for gene therapies. In this work, we carefully investigated the sputtering behavior of spherical organic particles using an argon cluster beam and scanning electron microscopy (SEM). Based on these observations, we then developed a geometrical model to interpret useful chemical depth profiles of polymeric particles by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) in conjunction with argon cluster sputtering. We found that change in the shape of isolated particles may be modeled in a simple manner by assuming a constant sputtering yield across the particle surface. Furthermore, packed particles undergo an interesting geometry transition during the sputtering process, which can primarily be explained and modeled by a shadowing effect from other particles in the vicinity. We successfully applied this model to analyze the structure and chemistry of nonideal polymeric core–shell particles. We show that with some knowledge of the materials’ sputtering yields, the particle diameter can approximately be determined by using XPS or calibrated SIMS and that the fractional volume of the core in the particle can be measured. Furthermore, the analysis provides a radial distribution of the core material within the particle. This distribution is in accord with transmission electron microscopy data available on the same materials. The radial distribution demonstrates that the cores are randomly positioned within the particles but avoid a region close to the surface. This work demonstrates that it is possible to use a simple model to describe the shape change of organic spherical particles during argon cluster sputtering and interpret chemical measurements by XPS and SIMS methods.

Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation. By whole-exome sequencing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regulator of gene expression: ten-eleven translocation methylcytosine dioxygenase 2 (TET2). Mutated TET2 protein was absent or enzymatically defective for 5-hydroxymethylating activity, resulting in whole-blood DNA hypermethylation. Circulating T cells showed an abnormal immunophenotype including expanded double-negative, but depleted follicular helper, T-cell compartments and impaired Fas-dependent apoptosis in 2 of 3 patients. Moreover, TET2-deficient B cells showed defective class-switch recombination. The hematopoietic potential of patient-derived induced pluripotent stem cells was skewed toward the myeloid lineage. These are the first reported cases of autosomal-recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma. This disease phenotype demonstrates the broad role of TET2 within the human immune system.