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The contribution of hippocampal circuits to high-capacity episodic memory is often attributed to the large number of orthogonal activity patterns that may be stored in these networks. Evidence for high-capacity storage in the hippocampus is missing, however. When animals are tested in pairs of environments, different combinations of place cells are recruited, consistent with the notion of independent representations. However, the extent to which representations remain independent across larger numbers of environments has not been determined. To investigate whether spatial firing patterns recur when animals are exposed to multiple environments, we tested rats in 11 recording boxes, each in a different room, allowing for 55 comparisons of place maps in each animal. In each environment, activity was recorded from neuronal ensembles in hippocampal area CA3, with an average of 30 active cells per animal. Representations were highly correlated between repeated tests in the same room but remained orthogonal across all combinations of different rooms, with minimal overlap in the active cell samples from each environment. A low proportion of cells had activity in many rooms but the firing locations of these cells were completely uncorrelated. Taken together, the results suggest that the number of independent spatial representations stored in hippocampal area CA3 is large, with minimal recurrence of spatial firing patterns across environments. Significance The hippocampus is thought to store a large number of experiences that, despite their similarity, can be individually retrieved with minimal interference. Studies have shown that place cells in hippocampal area CA3 form statistically independent representations of pairs of environments. It has remained unclear, however, whether CA3 place cells maintain this independence when the number of environments is increased. We recorded activity from CA3 in 11 environments with nearly identical geometric features. Spatial firing patterns remained uncorrelated across all 55 pairs of environments, with minimal overlap in the populations of active cells. The data suggest that the capacity of the CA3 network is large and speak against extensive recurrence of spatial motifs across experiences.

Severe combined immunodeficiency (SCID) and other T cell lymphopenias can be detected during newborn screening (NBS) by measuring T cell receptor excision circles (TRECs) in dried blood spot (DBS) DNA. Second tier next generation sequencing (NGS) with an amplicon based targeted gene panel using the same DBS DNA was introduced as part of our prospective pilot research project in 2015. With parental consent, 21 000 newborns were TREC-tested in the pilot. Three newborns were identified with SCID, and disease-causing variants in , and were confirmed by NGS on the initial DBS DNA. The molecular findings directed follow-up and therapy: the -SCID underwent early hematopoietic stem cell transplantation (HSCT) without any complications; the leaky SCID received prophylactic antibiotics, antifungals, and immunoglobulin infusions, and underwent HSCT at 1 year of age. The child with -SCID had complete Hirschsprung disease and died at 1 month of age. Since January 2018, all newborns in Norway have been offered NBS for SCID using 1st tier TRECs and 2nd tier gene panel NGS on DBS DNA. During the first 20 months of nationwide SCID screening an additional 88 000 newborns were TREC tested, and four new SCID cases were identified. Disease-causing variants in , and were molecularly confirmed on day 8, 15, 8 and 6, respectively after birth, using the initial NBS blood spot. Targeted gene panel NGS integrated into the NBS algorithm rapidly delineated the specific molecular diagnoses and provided information useful for management, targeted therapy and follow-up i.e., X rays and CT scans were avoided in the radiosensitive SCID. Second tier targeted NGS on the same DBS DNA as the TREC test provided instant confirmation or exclusion of SCID, and made it possible to use a less stringent TREC cut-off value. This allowed for the detection of leaky SCIDs, and simultaneously reduced the number of control samples, recalls and false positives. Mothers were instructed to stop breastfeeding until maternal (CMV) status was determined. Our limited data suggest that shorter time-interval from birth to intervention, may prevent breast milk transmitted CMV infection in classical SCID.

Purpose GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype–phenotype correlations makes the decision regarding “who and when” to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT. Methods All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients’ medical records. Results Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype–phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively. Conclusion Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the “optimal window” for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.