Spontaneous excretion of a pseudomembranous intestinal cast in an infant with an acute diarrhoeal illness – a case report and literature review

We present a case of an 8-week-old infant with acute bloody diarrhoea andsubsequent passage of an intestinal cast. An extensive immune and infection work-updid not reveal a causative aetiology. Histopathology indicated the cast represented anintestinal pseudomembrane. 16S bacterial PCR of the pathology specimen wasnegative. The infant required a period of parenteral nutrition due to diarrhoeal lossesbut made a full recovery and had no sequelae from this illness. Intestinal casts are arare occurrence, particularly in paediatrics. It prompts a wide differential which includesacute infection, immunodeficiency and ischaemia. Accurate quantification of stoollosses, appropriate nutrition support and liaison with microbiology colleagues wereessential in this case

Development and external validation of a clinical prediction model to aid coeliac disease diagnosis in primary care:an observational study

BACKGROUND: Coeliac disease (CD) affects approximately 1% of the population, although only a fraction of patients are diagnosed. Our objective was to develop diagnostic prediction models to help decide who should be offered testing for CD in primary care. METHODS: Logistic regression models were developed in Clinical Practice Research Datalink (CPRD) GOLD (between Sep 9, 1987 and Apr 4, 2021, n=107,075) and externally validated in CPRD Aurum (between Jan 1, 1995 and Jan 15, 2021, n=227,915), two UK primary care databases, using (and controlling for) 1:4 nested case-control designs. Candidate predictors included symptoms and chronic conditions identified in current guidelines and using a systematic review of the literature. We used elastic-net regression to further refine the models. FINDINGS: The prediction model included 24, 24, and 21 predictors for children, women, and men, respectively. For children, the strongest predictors were type 1 diabetes, Turner syndrome, IgA deficiency, or first-degree relatives with CD. For women and men, these were anaemia and first-degree relatives. In the development dataset, the models showed good discrimination with a c-statistic of 0·84 (95% CI 0·83–0·84) in children, 0·77 (0·77–0·78) in women, and 0·81 (0·81–0·82) in men. External validation discrimination was lower, potentially because ‘first-degree relative’ was not recorded in the dataset used for validation. Model calibration was poor, tending to overestimate CD risk in all three groups in both datasets. INTERPRETATION: These prediction models could help identify individuals with an increased risk of CD in relatively low prevalence populations such as primary care. Offering a serological test to these patients could increase case finding for CD. However, this involves offering tests to more people than is currently done. Further work is needed in prospective cohorts to refine and confirm the models and assess clinical and cost effectiveness. FUNDING: National Institute for Health Research Health Technology Assessment Programme (grant number NIHR129020

Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis.

Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond to environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), which are also found in human breast cancer, represent a macrophage phenotype similar to that observed during the wound healing response. Importantly, the expression of a wound-like cytokine response within the tumour is clinically associated with poor prognosis in a variety of cancers. We show that co-expression of FAP and HO-1 in macrophages results from an innate early regenerative response driven by IL-6, which both directly regulates HO-1 expression and licenses FAP expression in a skin-like collagen-rich environment. We show that tumours can exploit this response to facilitate transendothelial migration and metastatic spread of the disease, which can be pharmacologically targeted using a clinically relevant HO-1 inhibitor

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Recommended temperature metrics for carbon budget estimates, model evaluation and climate policy

Recent estimates of the amount of carbon dioxide that can still be emitted while achieving the Paris Agreement temperature goals are larger than previously thought. One potential reason for these larger estimates may be the different temperature metrics used to estimate the observed global mean warming for the historical period, as they affect the size of the remaining carbon budget. Here we explain the reasons behind these remaining carbon budget increases, and discuss how methodological choices of the global mean temperature metric and the reference period influence estimates of the remaining carbon budget. We argue that the choice of the temperature metric should depend on the domain of application. For scientific estimates of total or remaining carbon budgets, globally averaged surface air temperature estimates should be used consistently for the past and the future. However, when used to inform the achievement of the Paris Agreement goal, a temperature metric consistent with the science that was underlying and directly informed the Paris Agreement should be applied. The resulting remaining carbon budgets should be calculated using the appropriate metric or adjusted to reflect these differences among temperature metrics. Transparency and understanding of the implications of such choices are crucial to providing useful information that can bridge the science–policy gap

Family physician views about primary care reform in Ontario: a postal questionnaire

BACKGROUND: Primary care reform initiatives in Ontario are proceeding with little information about the views of practicing family physicians. METHODS: A postal questionnaire was sent to 1200 randomly selected family physicians in Ontario five months after the initial invitation to join the Ontario Family Health Network. It sought information about their practice characteristics, their intention to participate in the Network and their views about the organization and financing of primary care. RESULTS: The response rate was 50.3%. While many family physicians recognize the need for change in the delivery of primary care, the majority (72%) did not expect to join the Ontario Family Health Network by 2004, or by some later date (60%). Nor did they favour capitation or rostering, 2 key elements of the proposed reforms. Physicians who favour capitation were 5.5 times more likely to report that they expected to join the Network by 2004, although these practices comprise 5% of the sample. CONCLUSIONS: The results of this survey, conducted five months after the initial offering of primary care reform agreements to all Ontario physicians, suggest that an 80% enrollment target is unrealistic

Effective risk relievers for dimensional perceived risks on mail-order purchase: a case study on speciality foods in the UK

This article examines the effective risk relievers for different dimensions of perceived risk on mail-order purchase of food products. The sample comprised 1,600 active and inactive mail-order specialty food shoppers in the UK. The analysis focused on the correlation coefficients between consumers' levels of perceived risk and their weight on the importance of the risk relievers. Amongst 15 risk relievers, the results implied that there are certain risk relievers attached to higher levels of importance by consumers, who perceive higher levels of risks in certain aspects of mail-order purchase. Therefore, mail-order companies should promote the effective risk relievers to reduce specific dimensions of perceived risks

Next-generation mitogenomics: A comparison of approaches applied to caecilian amphibian phylogeny

Mitochondrial genome (mitogenome) sequences are being generated with increasing speed due to the advances of next-generation sequencing (NGS) technology and associated analytical tools. However, detailed comparisons to explore the utility of alternative NGS approaches applied to the same taxa have not been undertaken. We compared a 'traditional' Sanger sequencing method with two NGS approaches (shotgun sequencing and non-indexed, multiplex amplicon sequencing) on four different sequencing platforms (Illumina's HiSeq and MiSeq, Roche's 454 GS FLX, and Life Technologies' Ion Torrent) to produce seven (near-) complete mitogenomes from six species that form a small radiation of caecilian amphibians from the Seychelles. The fastest, most accurate method of obtaining mitogenome sequences that we tested was direct sequencing of genomic DNA (shotgun sequencing) using the MiSeq platform. Bayesian inference and maximum likelihood analyses using seven different partitioning strategies were unable to resolve compellingly all phylogenetic relationships among the Seychelles caecilian species, indicating the need for additional data in this case