Postinfantile Giant Cell Hepatitis Secondary to Rheumatoid Arthritis.

Postinfantile giant cell hepatitis (PIGCH), also known as syncytial giant cell hepatitis, continues to be a poorly defined and rare disease presentation in the adult population. Although a common finding in neonates, there is limited literature on the disease process, causes, and treatment success of PIGCH in adults. A strong association between autoimmune disorders and PIGCH, considerably so in the case of autoimmune hepatitis, has been established. However, there have been limited to no reports of PIGCH secondary to rheumatoid arthritis. Our clinical case aims to bring forth a vignette of PIGCH to spotlight this ill-defined disease in the adult population and highlight some of the proposed causes, treatments, and laboratory markers.

Sex differences in the temporal dynamics of autistic children's natural conversations.

BACKGROUND: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification. METHODS: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min "get-to-know-you" conversation with a young adult confederate that was unaware of children's diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age. RESULTS: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates' speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group. LIMITATIONS: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample. CONCLUSION: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children.

Use of qualitative behavioural assessment to investigate affective states of housed dairy cows under different environmental conditions.

In addition to the reduction of suboptimal welfare, there is now a need to provide farmed animals with positive opportunities to provide confidence that they have experienced a life worth living. Diversification of the environment through environmental enrichment strategies is one suggested avenue for providing animals with opportunities for positive experiences. The provision of more stimulating environmental conditions has been widely implemented in other animal production industries, based on evidenced welfare benefits. However, the implementation of enrichment on dairy farms is limited. In addition to this, the relationship between enrichment and dairy cows' affective states is an under-researched area. One specific welfare benefit of enrichment strategies which has been observed in a number of species, is increased affective wellbeing. This study investigated whether the provision of different forms of environmental enrichment resources would impact the affective states of housed dairy cows. This was measured by Qualitative Behavioural Assessment, currently a promising positive welfare indicator. Two groups of cows experienced three treatment periods; (i) access to an indoor novel object, (ii) access to an outdoor concrete yard and (iii) simultaneous access to both resources. Principal component analysis was used to analyse qualitative behavioural assessment scores, which yielded two principal components. The first principal component was most positively associated with the terms "content/relaxed/positively occupied" and had the most negative associations with the terms 'fearful/bored'. A second principal component was most positively associated with the terms "lively/inquisitive/playful" and was most negatively associated with the terms "apathetic/bored". Treatment period had a significant effect on both principal components, with cows being assessed as more content, relaxed and positively occupied and less fearful and bored, during periods of access to additional environmental resources. Similarly, cows were scored as livelier, more inquisitive and less bored and apathetic, during treatment periods compared to standard housing conditions. Concurrent with research in other species, these results suggest that the provision of additional environmental resources facilitates positive experiences and therefore enhanced affective states for housed dairy cows.

Sex differences in social and emotional insight in youth with and without autism.

Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions.

Conversational adaptation in children and teens with autism: Differences in talkativeness across contexts.

Successful social communication is complex; it relies on effectively deploying and continuously revising one's behavior to fit the needs of a given conversation, partner, and context. For example, a skilled conversationalist may instinctively become less talkative with a quiet partner and more talkative with a chattier one. Prior research suggests that behavioral flexibility across social contexts can be a particular challenge for individuals with autism spectrum condition (ASC), and that difficulty adapting to the changing needs of a conversation contributes to communicative breakdowns and poor social outcomes. In this study, we examine whether reduced conversational adaptation, as measured by talkativeness, differentiates 48 verbally fluent children and teens with ASC from 50 neurotypical (NT) peers matched on age, intelligence quotient, and sex ratio. Participants completed the Contextual Assessment of Social Skills with two novel conversation partners. The first acted interested in the conversation and talked more (Interested condition), while the second acted bored and talked less (Bored condition). Results revealed that NT participants emulated their conversation partner's behavior by being more talkative in the Interested condition as compared to the Bored condition (z = 9.92, p < 0.001). In contrast, the ASC group did not differentially adapt their behavior to the Bored versus Interested context, instead remaining consistently talkative in both (p = 0.88). The results of this study have implications for understanding social communication and behavioral adaptation in ASC, and may be valuable for clinicians interested in improving conversational competence in verbally fluent individuals with autism. LAY SUMMARY: Social communication-including everyday conversations-can be challenging for individuals on the autism spectrum. In successful conversations, people tend to adjust aspects of their language to be more similar to their partners'. In this study, we found that children and teens with autism did not change their own talkativeness in response to a social partner who was more or less talkative, whereas neurotypical peers did. These findings have clinical implications for improving conversational competence in verbally fluent individuals with autism.

Friend matters: sex differences in social language during autism diagnostic interviews.

BACKGROUND: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys' and girls' socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. METHODS: School-aged girls and boys with autism (N = 101, 25 females; aged 6-15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. RESULTS: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. LIMITATIONS: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS: Autistic girls used significantly more social words than boys during a diagnostic assessment-despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit.

Mass food challenges in a vacant COVID-19 stepdown facility: Exceptional opportunity provides a model for the future.

BACKGROUND: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi-elective procedures. For allergic children in Ireland, already waiting up to 4 years for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative, there were approx 900 children on the Children's Health Ireland (CHI) waiting list. In July 2020, a project was facilitated by short-term (6 weeks) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive (HSE), Ireland. The aim of this study was to achieve the rapid roll-out of an offsite OFC service, delivering high throughput of long waiting patients, while aligning with existing hospital policies and quality standards, international allergy guidelines and national social distancing standards. METHODS: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant paediatric allergists, consultant paediatricians, trainees and allergy clinical nurse specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors (BP, pulse and oxygen saturation) and bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardized food challenge protocols were created. Access to the onsite hotel chef facilitated food preparation. A risk register was established. RESULTS: After 6 weeks of planning, the remote centre became operational on 7/9/2020, with the capacity of 27 OFC/day. 474 challenges were commenced: 465 (98%) were completed and 9 (2%) were inconclusive. 135 (29%) OFCs were positive, with 25 (5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days. CONCLUSIONS: Oral food challenges remain a vital tool in the care of allergic children, with their cost saving and quality-of-life benefits negatively affected by a delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy-in-even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era.

Peroxisomes and pancreatic beta-cell lipo-dysfunction.

AIMS: Pancreatic beta-cell lipo-dysfunction decreases insulin secretion and predisposes to the development of type 2 diabetes. Through targeted Pex11ß knockdown and peroxisome depletion, our aim was to investigate the specific contribution of peroxisomes to palmitate mediated pancreatic beta-cell dysfunction. METHODS: MIN6 cells were transfected with probes targeted against Pex11ß, a regulator of peroxisome abundance, or with scrambled control probes. Peroxisome abundance was measured by PMP-70 protein expression. 48 h post transfection, cells were incubated with 250 µM palmitate or BSA control for a further 48 h before measurement of glucose stimulated insulin secretion and of reactive oxygen species. RESULTS: Pex11ß knockdown decreased target gene expression by >80% compared with the scrambled control (P<0.001). This led to decreased PMP-70 expression (p<0.01) and a 22% decrease in peroxisome number (p<0.05). At 25 mM glucose, palmitate treatment decreased insulin secretion by 64% in the scrambled control cells (2.54±0.25 vs 7.07±0.83 [mean±SEM] ng/h/µg protein; Palmitate vs BSA P<0.001), but by just 37% in the Pex11ß knockdown cells. Comparing responses in the presence of palmitate, insulin secretion at 25 mM glucose was significantly greater in the Pex11ß knockdown cells compared with the scrambled controls (4.04±0.46 vs 2.54±0.25 ng/h/µg protein; p<0.05). Reactive oxygen species generation with palmitate was lower in the Pex11ß knockdown cells compared with the scrambled controls (P<0.001). CONCLUSION: Pex11ß knockdown decreased peroxisome abundance, decreased palmitate mediated reactive oxygen species generation, and reversed the inhibitory effect of palmitate on insulin secretion. These findings reveal a distinct role of peroxisomes in palmitate mediated beta-cell dysfunction.

Group B streptococcal disease in the mother and newborn-A review.

Group B Streptococcus, a common commensal in the gut of humans and in the lower genital tract in women, remains an important cause of neonatal mortality and morbidity. The incidence of early onset disease has fallen markedly in countries that test women for carriage at 35-37 weeks of pregnancy and then offer intrapartum prophylaxis with penicillin during labour. Countries that do not test, but instead employ a risk factor approach, have not seen a similar fall. There are concerns about the effect on the neonatal microbiome of widespread use of antibiotic prophylaxis during labour, but so far the effects seem minor and temporary. Vaccination against GBS would be acceptable to most women and GBS vaccines are in the early stages of development. Tweetable abstract: Group B Strep is a key cause of infection, death and disability in young babies. Antibiotics given in labour remain the mainstay of prevention, until a vaccine is available.

PCR for the detection of pathogens in neonatal early onset sepsis.

BACKGROUND: A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS: Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS: Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION: Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.

Pathophysiological Mechanism of Extravasation via Umbilical Venous Catheters.

A rare complication of umbilical venous catheter (UVC) insertion is the extravasation of the infusate into the peritoneal cavity. We report 3 cases of abdominal extravasation of parenteral nutrition (PN) fluid via UVCs. Two of these cases presented as "acute abdomen" which were assumed to be necrotizing enterocolitis clinically; however, during postmortem, PN ascites and liver necrosis were found. A further case is described in an infant with congenital diaphragmatic hernia. While we were unable to ascertain direct vessel perforation by the catheter in any of these cases, based on pathological and histological examination, the proposed mechanism of PN fluid extravasation is leakage through microinjuries of liver vessel walls and necrotic parenchyma. PN extravasation should be considered as a differential diagnosis of acute abdomen when PN is infused via an UVC presumably as PN may have a direct irritant effect on the peritoneum.

Epidemiology of UK neonatal infections: the neonIN infection surveillance network.

OBJECTIVE: To describe the epidemiology of neonatal infection over the past decade in UK neonatal units. DESIGN: Retrospective analysis of prospectively collected infection surveillance network data from 2005 to 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns on participating neonatal units who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of appropriate antibiotics. RESULTS: 2171 episodes of neonatal infection in 1922 infants were recorded. The incidence of infection was 6.1/1000 live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of infection showed a statistically significant reduction over time with reductions in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth), and infection was more common in premature (<37 weeks gestation) and low birth weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS, while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes of LOS. CONCLUSIONS: This paper describes the epidemiology of neonatal infection in the UK over the past decade. These data enable benchmarking of practice and inform areas of future research and guideline development. The results support the hypothesis that the introduction of infection prevention care bundles and antibiotic stewardship programmes in the UK has reduced the burden of LOS.

Antimicrobial resistance in UK neonatal units: neonIN infection surveillance network.

OBJECTIVE: To define the susceptibilities of the common causative pathogens of neonatal sepsis in the UK. DESIGN: Retrospective analysis of the prospectively collected neonIN infection surveillance network data between 2005 and 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns admitted to participating neonatal units who return a positive blood, cerebrospinal fluid or urine culture and are treated with at least 5 days of appropriate antibiotics. RESULTS: 1568 isolates with recorded antimicrobial data were collected including 328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates. The majority of EOS pathogens (>92%) were susceptible to the four empirical commonly used antimicrobial combinations (eg, 93% for benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32 weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93% vs 86%, p=0.211). CONCLUSIONS: This analysis provides insights into the patterns of antimicrobial resistance among UK neonatal pathogens. These data will inform areas of future research and can be used to update national evidence-based guidelines on antimicrobial usage.

ASSESSMENT OF VANCOMYCIN CONCENTRATIONS IN SYRINGES PREPARED WITHIN A WARD SETTING.

AIM: Vancomycin is used as a second line antibiotic in the treatment of late onset neonatal infection for its activity against coagulase negative staphylococci. Vancomycin infusions are prepared within a ward setting for administration to neonates. Differences in preparation techniques on the ward have previously been recognised as a potential source of variation in vancomycin concentrations, as compared to concentrations in pre-made preparations. This study analyses a consecutive series of vancomycin syringes prepared in a ward for administration to neonates, to determine how accurate the concentration of each preparation was compared to the expected concentration. METHOD: Vancomycin concentrations were determined by UV analysis (λ=280 nm) with a UV spectrophotometer (Jenway Genova Plus). A calibration curve for vancomycin was created (R2=0.9996) by manufacturing a series of solutions of vancomycin hydrochloride in glucose 5% w/v.Samples of vancomycin from syringes from which doses were administered to neonates were then analysed to assess their concentration. For each syringe, mean vancomycin concentration±standard deviation was calculated (n=3).Reasonable errors in preparations were calculated based on errors in each step of the preparation process. Theoretical error was calculated based on apparatus used, and experimental error was recorded based on a simulated process. Two preparation methods were compared; the method complying with that described in the local formulary, 1 and an alternative method reported by the nurses preparing the dose. RESULTS: Analysis of results showed that concentration of the vancomycin syringes prepared ranged from 0.85 to 8.24 mg/mL. The expected concentration was 4.17 mg/ml.Theoretical error in preparation of vancomycin doses was lower with the formulary-compliant method1 versus an alternative method, as were variations in in vancomycin concentration.Depending on the type of error (theoretical or experimental) and method by which vancomycin syringes were prepared (formulary1 or alternative method), the percentage of syringes with vancomycin concentration outside of the specified ranges varied from 20%-43%. This is higher compared to the findings of the Department of Health2, where it was found that 19.2% of morphine infusions prepared by nurses in the neonatal intensive care unit were outside British Pharmacopoeia concentration limits. CONCLUSION: Preparation of vancomycin doses should follow the formulary method1 to minimise variation in concentration of the final product. Alternatively, pre-made syringes may be preferred as an alternative to ward-made syringes as this removes individualised preparation as a source of error.

AN AUDIT OF VANCOMYCIN PLASMA CONCENTRATIONS WHEN VANCOMYCIN IS ADMINISTERED BY CONTINUOUS INTRAVENOUS INFUSION IN NEONATES.

AIM: To compare continuous intravenous infusions of vancomycin in achieving desired therapeutic plasma concentrations against an intermittent bolus regimen. METHOD: Data were collected for all babies who received a continuous infusion of vancomycin on our Neonatal Intensive Care Unit (NICU) between October 2014 and March 2015. The regimen is based on that of another hospital (Hospital A) and comprised of a loading dose of 15 mg/kg over 1 hour followed by a continuous infusion of 20-50 mg/kg/day according to creatinine and corrected gestational age (CGA). The desired therapeutic range is 15-25 mg/L. The data recorded were date and time vancomycin was commenced, corrected gestational age (CGA), day of life and creatinine level at commencement, and the dose administered in mg/kg/day. Plasma concentrations were recorded as first, second or subsequent. Babies who switched from intermittent regimen were excluded. Results were analysed according to plasma concentration i.e. first, second or subsequent and stratified by CGA, day of life and creatinine level.All concentrations were obtained retrospectively for the period January to July 2014 when vancomycin was administered by intermittent bolus regimen to allow comparison of effectiveness.The doses of vancomycin were prepared at ward level by trained neonatal nurses as there is no aseptic facility onsite.We also compared our findings with those of another hospital from 2012. RESULTS: 49 babies received continuous vancomycin infusions and 115 plasma concentrations were analysed.Overall 62% of concentrations were within desired therapeutic range. This comprised 60.8% of first concentration, 60% of second concentration and 65.6% of subsequent concentrations. In relation to gestational age, 55.9% of concentrations for those 23-28+6 weeks CGA, 59.4% of concentrations for those 29-34+6 weeks CGA and 70.2% of concentrations for those >35 weeks CGA were in the therapeutic range.84.6% of concentrations for those 0-6 days old, 58% of concentrations for those 7-28 days old and 60% of concentrations for those >29 days old were in therapeutic range. 62% of concentrations for those with a Cr<50 micromol/L, 69% of concentrations for those with a Cr50-70 micromol/L and 50% of concentrations for those with a Cr>70 micromol/L were in the desired therapeutic range.Adjusting the data to allow for 10% variability in the target range achieved 71.3% of all concentrations in desired therapeutic range (13.5-27.5 mg/L).Compared to the plasma concentrations obtained on intermittent bolus regimen the percentage of concentrations in the desired therapeutic range has increased from 28% to 62%.Compared to the other hospital's data, the percentage of concentrations in the desired therapeutic range is lower at 62% compared to their 77%. CONCLUSION: Continuous infusions of vancomycin are more effective than intermittent bolus dosing in achieving desired therapeutic concentrations. Stratification of results has not shown any appreciable difference between the groups receiving vancomycin. However, extrapolation of our findings to those from other work, where prefilled syringes prepared in pharmacy are used is limited. It is known that there is significant variability from the desired target concentration of syringes prepared at ward level. There is a need to look at procuring prefilled vancomycin syringes and undertaking a re-audit.

Interprofessional learning, impression management, and spontaneity in the acute healthcare setting.

Spontaneous learning is integral to definitions of interprofessional learning (IPL) because it has been suggested that spontaneous learning can be deeply connected with the work that people do in collaboration with colleagues via their professional networks. However, its nature and the processes involved are not well understood. Goffman's theory of impression management offers a useful theoretical framework to consider the way in which interaction in the workplace connects to spontaneous learning. This article explores the current literature to investigate the usefulness of this framework to better understand and identify spontaneous learning in the workplace. Aspects such as the connections between spontaneous learning occurring in formal and informal work activities, the spaces in which it occurs, and the influence of professional networking are considered. It is proposed that research directed to developing a better understanding of the nature of spontaneous learning in IPL will assist in connecting this learning to formal IPL curricula, enhancing IPL and patient outcomes.

The influence student placement experience can have on the employment choices of graduates: A paediatric nursing context.

This paper explores how the student placement experience may influence employment choices in the context of paediatric nursing. A qualitative research methodology was used. Data was collected using semi structured interviews at a tertiary teaching hospital. The sample group comprised of six newly qualified nurses who had completed their Bachelor of Nursing less than 12 months before the interview. They had completed at least one clinical placement at the site of data collection in their 2nd or 3rd year of undergraduate nursing studies. The main themes contributing to the student nurse experience within the context of paediatric nursing included the wish to work with children, a job being available, support during clinical placements and assistance with future career planning while on placement. The support experienced by student nurses during their clinical placement was seen to have a very positive influence on their future employment choices. Group de-briefing to support mutual understanding and sharing was seen to be a highly positive aspect of a clinical placement. Also how students were treated by clinical staff was a key factor that influenced future employment choices.

GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia.

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis. To define TAM, we prospectively analyzed clinical findings, blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of 200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of 200 (8.5%), all with blasts >10%. Furthermore low-abundance GATA1 mutant clones were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%; sensitivity ∼0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No clinical or hematologic features distinguished these 18 neonates. We suggest the term "silent TAM" for neonates with DS with GATA1 mutations detectable only by NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC, NGS-based methods can identify neonates with small GATA1 mutant clones.