Michael Fitzpatrick

In November of 2022, Sebastian Mallaby sat down with Demis Hassabis, co-founder of DeepMind, to discuss the broad approach to the book Mallaby intended to write, a profile of both Hassabis and the current state of AI technology, with all its seemingly limitless potential and its risks. Hassabis, whose startup had been acquired by Google, was the leading voice on AI research and application and the meeting was the first of dozens that would ultimately inform the book.

Andy Burnham has voiced his support for rent caps — they’re not all they’re made out to be, says one Brit who challenged the Austrian capital’s system

Introduction Characterising interactions between intestinal adaptive immune cells and their microenvironment is essential to understand drivers of intestinal remodelling in coeliac disease (CeD). We previously used spatial transcriptomics (ST) to identify putative lymphoid structures in CeD (FitzPatrick et al., Nature Immunology 2025), representing sites of putative gluten-specific T-B cell interactions. However, these structures have not been described at single cell resolution, limiting our understanding of their role in CeD. We sought to profile the spatial landscape of the coeliac duodenum, focusing on adaptive immune responses and epithelial barrier function.Methods We performed sub-cellular resolution imaging-based ST (Xenium, 10x Genomics) on 18 duodenal biopsy sections (active CeD (ACD), n=7; treated CeD (TCD), n=5; non-coeliac controls (NCC), n=6) with a targeted panel of 322 genes. We validated and extended this dataset with a further ST experiment featuring 20 sections (ACD, n=7; TCD, n=7; NCC, n=6) profiled with a panel of 5101 genes.Results Our first ST experiment yielded a dataset of over 30 million transcripts detected across 385,384 cells, representing epithelial, stromal, immune, endothelial, and secretory compartments. We identified lymphoid aggregates in both ACD and TCD, in some cases exhibiting organised structure with separate T- and B-cell areas and evidence of germinal centre activity.Our second experiment with a larger gene panel expands our data with an additional 150 million transcripts detected across 462,030 cells representing all major small intestinal cell types. Epithelial gene expression demonstrated spatial zonation of absorptive and metabolic function along the crypt-villus axis which was altered in ACD. The epithelium was supported by sub-epithelial stromal telocytes, which were reduced in ACD.Lymphoid aggregates (LA) containing B cells and CD4+ T cells were present in several CeD samples in both datasets, but less common in controls. Aggregates displayed various levels of organisation, with larger aggregates often extending into the submucosa. CeD samples contained distinct macrophage populations that localised to epithelial lesions and LA. LA also featured stromal cells resembling fibroblastic reticular cells, previously implicated in inflammatory bowel disease (Kinchen et al., Cell 2018), as well as follicular-associated epithelium (M cells), which may be involved in luminal antigen presentation.Conclusions We used spatial transcriptomics to localise cellular interactions and disease processes in the duodenum in CeD, specifically lymphoid aggregates as the site of T-B cell interactions. We link this with changes in tissue structure and function.

Introduction Intestinal transplant (ITx) is a treatment option for patients with irreversible intestinal failure (IF) and complications of long-term parenteral nutrition (PN). ITx includes a range of procedures, including both liver and non-liver containing grafts, which differ greatly in indications, clinical outcomes and complication rates. Despite this, ITx outcomes are commonly reported collectively. We aimed to quantify clinical outcomes from patients who had undergone isolated small bowel transplantation (ISBTx).Methods A retrospective review of patient charts who underwent ISBTx at a single UK transplant centre over a 16-year period (01/01/09-31/12/25) was conducted, including demographics, patient and graft survival, incidence of rejection, Graft vs Host Disease (GvHD) and Post-Transplant Lymphoproliferative Disorders (PTLD). Patients who received ISBTx for malignant disease were excluded. Statistical analysis was performed using Kaplan-Meier survival curves (R studio).Results Forty-five patients underwent ISBTx during the study period, with an average age at time of transplantation of 45.5 years (24-63 years). Patient survival at 1 year was 93.3%, at 5 years was 72.3% and at 10 years was 49.7% ([figure 1][1]).Explant of the transplant graft occurred in 11 cases (24%), average time to graft explant 2.7 years. Causes of graft explant were graft ischaemia (4), acute rejection (4), chronic rejection (2) and one for patient choice. Three patients were re-transplanted, while other patients were restarted on PN. There was four cases of PTLD and no cases of GVHD.Acute rejection occurred in 49% of patients. Of these, 23% had grade 1 histological rejection, 27% grade 2 and 50% grade 3. 11% developed chronic rejection. 59% of acute rejection episodes occurred in the first year, and 59% of cases were successfully treated with first-line pulsed methylprednisolone monotherapy. The median hospital stay post-transplant was 51 days (20-197 days), with a median ITU stay of 8.4 days (1-69 days).Conclusions ISBTx for benign IF indications delivers excellent outcomes in a cohort of patients that are at high risk of death if they remain on PN. Rejection remains a significant challenge, although this is treatable if detected early. Most patients achieve nutritional autonomy with excellent quality of life.![Abstract O39 Figure 1][2]Abstract O39 Figure 1 Kaplan-Meir survival analysis post isolated small bowel transplant[1]: #F1 [2]: pending:yes

A commemoration event has been held at Belfast City Hall to mark the 110th anniversary of the Battle of the Somme.

A commemoration event has been held at Belfast City Hall to mark the 110th anniversary of the Battle of the Somme. The ceremony was held in the Garden of Remembrance.

Climate change is affecting the yields and flavour of the traditional Japanese tea matcha, but studying its seedlings' genetic tolerance for heat could future-proof the crop

Torki Alomare says two of his children were injured in an attack on his home on Sunday, shortly before his parents' house was also attacked.

Torki Alomare says two of his children were injured in an attack on his home on Sunday, shortly before his parents' house was also attacked.

The defendant, who cannot be named for legal reasons, is accused of 14 counts of indecently assaulting a female and three counts of committing an act of gross indecency with a child.