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Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.
Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.
Evolving conditions at the terminus of Thwaites Glacier will be important in determining the rate of its future sea-level contribution over the coming decades. Here, we use remote-sensing observations to investigate recent changes (2000–2018) in the structure and velocity of Thwaites Glacier and its floating tongue. We show that the main trunk of Thwaites Glacier has accelerated by 38% over this period, while its previously intact floating tongue has transitioned to a weaker mélange of fractured icebergs bounded by sea ice. However, the rate of structural weakening and acceleration was not uniform across the observational period and we identify two periods of rapid acceleration and structural weakening (2006–2012; 2016–2018), separated by a period of deceleration and re-advance of the structurally-intact shear margin boundary (2012–2015). The timing of these accelerations/decelerations strongly suggests a link to variable ocean forcing. The weakened tongue now has some dependency on landfast sea ice for structural integrity and is vulnerable to changes in landfast ice persistency. Future reductions in landfast sea ice could manifest from changes in climate and/or the imminent removal of the B-22A iceberg from the Thwaites embayment. Such changes could have important implications for the integrity of the ice tongue and future glacier discharge.
Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003–2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.
Places such as Poverty Point, Mound City, and Chaco Canyon remind us that the siting of ritual infrastructure in ancient North America was a matter of cosmological precedent. The cosmic gravity of these places gathered persons periodically in numbers that challenged routine production. Ritual economies intensified, but beyond the material demands of hosting people, the siting of these places and the timing of gatherings were cosmic work that preconfigured these outcomes. A first millennium AD civic-ceremonial center on the northern Gulf Coast of Florida illustrates the rationale for holding feasts on the end of a parabolic dune that it shared with an existing mortuary facility. Archaeofauna from large pits at Shell Mound support the inference that feasts were timed to summer solstices. Gatherings were large, judging from the infrastructure in support of feasts and efforts to intensify production through oyster mariculture and the construction of a large tidal fish trap. The 250-year history of summer solstice feasts at Shell Mound reinforces the premise that ritual economies were not simply the amplification of routine production. It also suggests that the ecological potential for intensification was secondary to the cosmic significance of solstice-oriented dunes and their connection to mortuary and world-renewal ceremonialism.
Limpets and barnacles are important components of intertidal assemblages worldwide. This study examines the effects of barnacles on the foraging behaviour of the limpet Patella vulgata, which is the main algal grazer in the North-west Atlantic. The behaviour of limpets on a vertical seawall on the Isle of Man (UK) was investigated using autonomous radio-telemetry, comparing their activity patterns on plots characterized by dense barnacle cover and plots from which the barnacles had been removed. Limpet behaviour was investigated at mid-shore level, but two different elevations were considered. This experiment revealed a significant effect of barnacle cover on the activity of P. vulgata. Limpets on smooth surfaces spent a greater proportion of total time active than did limpets on barnacles. Movement activity was also greater in areas that were lower down in the tidal range. In general, limpets were either predominantly active during diurnal high or nocturnal low tides and always avoided nocturnal high tides. Individuals on barnacles at the higher elevation concentrated their activity during nocturnal low water. All the other groups of limpets (smooth surfaces on the upper level and all individuals on the lower shore) had more excursions centred around daylight hours with an equal distribution of activity between periods of low and high water. Inter-individual variability was, however, pronounced.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
Growth failure is prevalent among infants with CHD. A Standardized Clinical Assessment and Management Plan was introduced at Boston Children’s Hospital’s cardiac medical ward to identify patients with growth failure, evaluate relevant contributing conditions, and recommend a management plan including collaboration with nutrition physicians.
The objective of this study was to determine whether enrolled patients had improved growth compared with historical controls.
A total of 29 patients were enrolled in the period July, 2013–June, 2014. In all, 42 historical controls who met eligibility criteria for enrolment were selected for comparison from patients admitted to the same ward in the period June, 2010–June, 2011. Patients with CHD aged <1 year , with growth failure defined as weight-for-age z-score <−2, or failure to sustain adequate weight gain were eligible for participation. Primary outcome was change in weight-for-age z-score from enrolment to most recent weight measurement among patients with at least 6 months of follow-up.
Control patients were older at baseline admission weight (118 versus 95 days, p=0.33), and had a higher weight-for-age z-score, −2.9 (−3.1, −2.6) versus −3.7 (−4.3, −3.0) (p=0.02), compared with enrolled patients. Enrolled patients had greater gain in weight-for-age z-score, 2.7 (2.0, 3.4) versus 1.8 (1.5, 2.2) (p=0.03), from baseline to most recent follow-up.
Patients enrolled in a nutrition-focused protocol had greater weight improvement than historical controls. Identification of growth failure and collaboration with a nutrition support team was associated with improved weight gain among CHD patients experiencing growth failure. CHD programmes should consider a structural approach, including nutrition expertise to address growth failure.
A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.
In August 2015, Public Health England detected an outbreak of Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 caused by contaminated salad leaves in a mixed leaf prepacked salad product from a national retailer. The implicated leaves were cultivated at five different farms and the zoonotic source of the outbreak strain was not determined. In March 2016, additional isolates from new cases were identified that shared a recent common ancestor with the outbreak strain. A case–case study involving the cases identified in 2016 revealed that ovine exposures were associated with illness (n = 16; AOR 8·24; 95% CI 1·55–39·74). By mapping the recent movement of sheep and lambs across the United Kingdom, epidemiological links were established between the cases reporting ovine exposures. Given the close phylogenetic relationship between the outbreak strain and the isolates from cases with ovine exposures, it is plausible that ovine faeces may have contaminated the salad leaves via untreated irrigation water or run-off from fields nearby. Timely and targeted veterinary and environmental sampling should be considered during foodborne outbreaks of STEC, particularly where ready to eat vegetables and salads are implicated.
A time-course study was conducted to resolve discrepancies in the literature and better define aspects of the Eimeria maxima life cycle such, as sites of development and both morphology and number of asexual stages. Broiler chickens were inoculated orally with five million E. maxima oocysts (APU1), and were necropsied at regular intervals from 12 to 120 h p.i. Small intestine tissue sections and smears were examined for developmental stages. The jejunum contained the highest numbers of developmental stages. At 12 h p.i., sporozoites were observed inside a parasitophorous vacuole (PV) in the epithelial villi and the lamina propria. By 24 h, sporozoites enclosed by a PV were observed in enterocytes of the glands of Lieberkühn. At 48 h p.i., sporozoites, elongated immature and mature schizonts, were all seen in the glands with merozoites budding off from a residual body. By 60 h, second-generation, sausage-shaped schizonts containing up to 12 merozoites were observed around a residual body in the villar tip of invaded enterocytes. At 72 and 96 h, profuse schizogony associated with third- and fourth-generation schizonts was observed throughout the villus. At 120 h, another generation (fifth) of schizonts were seen in villar tips as well as in subepithelium where gamonts and oocysts were also present; a few gamonts were in epithelium. Our finding of maximum parasitization of E. maxima in jejunum is important because this region is critical for nutrient absorption and weight gain.
For most common infections requiring hospitalization, antibiotic treatment is completed after hospital discharge. Postdischarge therapy is often unnecessarily broad spectrum and prolonged. We developed an intervention to improve antibiotic selection and shorten treatment durations.
Single center, quasi-experimental retrospective cohort study
Patients prescribed oral antibiotics at hospital discharge before (July 2012–June 2013) and after (October 2014–February 2015) an intervention consisting of (1) institutional guidance for oral step-down antibiotic selection and duration of therapy and (2) pharmacy audit of discharge prescriptions with real-time prescribing recommendations to providers. The primary outcomes measured were total prescribed duration of therapy and use of antibiotics with broad gram-negative activity (ie, fluoroquinolones or amoxicillin-clavulanate).
Overall, 300 cases from the preintervention period and 200 cases from the intervention period were included. Compared with the preintervention period, the use of antibiotics with broad gram-negative activity decreased during the intervention (51% vs 40%; P=.02), particularly fluoroquinolones (38% vs 25%; P=.002). The total duration of therapy decreased from a median of 10 days (interquartile range [IQR], 7–13 days) to 9 days (IQR, 6–13 days) but did not reach statistical significance (P=.13). However, the duration prescribed at discharge declined from 6 days (IQR, 4–10 days) to 5 days (IQR, 3–7 days) (P=.003). During the intervention, there was a nonsignificant increase in the overall appropriateness of discharge prescriptions from 52% to 66% (P=.15).
A multifaceted intervention to optimize antibiotic prescribing at hospital discharge was associated with less frequent use of antibiotics with broad gram-negative activity and shorter postdischarge treatment durations.
To evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis.
We compared 2 time periods: January 2003–June 2007 when FQs were recommended as first-line therapy, and July 2007–December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis.
Overall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%–32%) decrease in FQ use (P<.001), and a nonsignificant 6% (95% CI, −2% to 15%) increase in NFT use (P=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of −0.4% per quarter (95% CI, −0.6% to −0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed.
In an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance.
In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2–92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0–157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.
Fifteen confirmed cases and 15 possible cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 21/28 were linked to direct contact with lambs at a ‘Lambing Live’ event in the North West of England between 29 March and 21 April 2014. Twenty-one (70%) of the cases were female, 23 (77%) were children aged <16 years, of whom 14 (46%) were in the 0–5 years age group. Five children developed haemolytic uraemic syndrome. Multilocus variable number tandem repeat analysis (MLVA) profiles on 14 human cases were indistinguishable, and 6/10 animal isolates had a MLVA profile identical to the outbreak profile. Whole-genome sequencing analysis revealed that all isolates, both human and animal, fell within a 5-single nucleotide polymorphism cluster indicating the isolates belonged to the same point source. On inspection of the premises, extensive and uncontrolled physical contact between visitors and animals was occuring within the animal pens and during bottle-feeding. Public areas were visibly contaminated with animal faeces. Information to visitors, and the infection control awareness demonstrated by staff, was inadequate. Managing the risk to visitors of STEC O157 infection at animal petting events and open farms requires implementation of stringent control measures by the operator, as outlined in the industry code of practice. Enforcement action is sometimes required to prevent high-risk activities taking place at both permanent and temporary attractions.
Echinococcus granulosus (sensu lato) is now recognized as an assemblage of cryptic species, which differ considerably in morphology, development, host specificity (including infectivity/pathogenicity for humans) and other aspects. One of these species, E. granulosus sensu stricto (s.s.), is now clearly identified as the principal agent causing cystic echinococcosis in humans. Previous studies of a small section of the cox1 and nadh1 genes identified two variants of E. granulosus s.s. to be present in Australia; however, no further work has been carried out to characterize the microdiversity of the parasite in its territory. We have analysed the sequence of the full length of the cox1 gene (1609 bp) from 37 isolates of E. granulosus from different hosts and geographic regions of Australia. The analysis shows that seven haplotypes of E. granulosus s.s. not previously described were found, together with five haplotypes known to be present in other parts of the world, including the haplotype EG01 which is widespread and present in all endemic regions. These data extend knowledge related to the geographical spread and host range of E. granulosus s.s. in a country such as Australia in which the parasite established around 200 years ago.
Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.
Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.
Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.
Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.
This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.