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Papillon treatment is a form of contact X-ray brachytherapy (CXB) which is used as an alternative to surgery for rectal cancer. This study aimed to audit patients who were referred for and treated with CXB over a 6-year period against guidelines derived from a critical review of the evidence base.
Materials and methods:
Patient demographics, tumour characteristics and outcome data were gathered for 31 patients referred for CXB. A critical review of the evidence identified consensus referral criteria and outcome data against which to audit patients.
Referral criteria were derived from six published studies. These applied to patients unfit for surgery or stoma-averse. All referred patients had a visible tumour or scar with a tumour size under 3 cm and sited less than 12 cm from the anal verge. Nodal status varied from N0 to N2, but there was no metastatic disease present. The audited cohort demonstrated demographic equivalence, while the initial clinical complete response and recurrence rates were also comparable.
This audit confirmed the validity of referral and treatment protocols and should guide future referrals until evidence from ongoing studies becomes available. These findings should contribute to the development of robust national guidelines.
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
Computational acceleration of performance metric-based materials discovery via high-throughput screening and machine learning methods is becoming widespread. Nevertheless, development and optimization of the opto-electronic properties that depend on dilute concentrations of point defects in new materials have not significantly benefited from these advances. Here, the authors present an informatics and simulation suite to computationally accelerate these processes. This will enable faster and more fundamental materials research, and reduce the cost and time associated with the materials development cycle. Analogous to the new avenues enabled by current first-principles-based property databases, this type of framework will open entire new research frontiers as it proliferates.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Through autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N = 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.
Most current models of nonnative speech perception (e.g., extended perceptual assimilation model, PAM-L2, Best & Tyler, 2007; speech learning model, Flege, 1995; native language magnet model, Kuhl, 1993) base their predictions on the native/nonnative status of individual phonetic/phonological segments. This paper demonstrates that the phonotactic properties of Japanese influence the perception of natively contrasting consonants and suggests that phonotactic influence must be formally incorporated in these models. We first propose that by extending the perceptual categories outlined in PAM-L2 to incorporate sequences of sounds, we can account for the effects of differences in native and nonnative phonotactics on nonnative and cross-language segmental perception. In addition, we test predictions based on such an extension in two perceptual experiments. In Experiment 1, Japanese listeners categorized and rated vowel–consonant–vowel strings in combinations that either obeyed or violated Japanese phonotactics. The participants categorized phonotactically illegal strings to the perceptually nearest (legal) categories. In Experiment 2, participants discriminated the same strings in AXB discrimination tests. Our results show that Japanese listeners are more accurate and have faster response times when discriminating between legal strings than between legal and illegal strings. These findings expose serious shortcomings in currently accepted nonnative perception models, which offer no framework for the influence of native language phonotactics.
The American College of Cardiology Quality Network enables national benchmarking and collaborative quality improvement through vetted metrics. We describe here our initial experience with the Quality Network.
Quarterly data for metrics pertaining to chest pain, Kawasaki disease, tetralogy of Fallot, elevated body mass index, and others were shared with the collaboratives for benchmarking. National improvement efforts focussed on counselling for elevated body mass index and 22q11.2 testing in tetralogy of Fallot. Improvement strategies included developing multi-disciplinary workgroups, educational materials, and electronic health record advances.
Chest pain metric performance was high compared with national means: obtaining family history (90–100% versus 51–77%), electrocardiogram (100% versus 89–99%), and echocardiogram for exertional complaints (95–100% versus 74–96%). Kawasaki metric performance was high, including obtaining coronary measurements (100% versus 85–97%), prescribing aspirin (100% versus 86–99%), follow-up with imaging (100% versus 85–98%), and documenting no activity restriction without coronary aneurysms (83–100% versus 64–93%). Counselling for elevated body mass index was variable (25–75% versus 31–50%) throughout quality improvement efforts. Testing for 22q11.2 deletion in tetralogy of Fallot patients was consistently above the national mean (60–85% versus 54–68%) with improved genetics data capture.
The Quality Network promotes meaningful benchmarking and collaborative quality improvement. Our high performance for chest pain and Kawasaki metrics is likely related to previous improvement efforts in chest pain management and a dedicated Kawasaki team. Uptake of counselling for elevated body mass index is variable; stronger engagement among numerous providers is needed. Recommendations for 22q11.2 testing in tetralogy of Fallot were widely recognised and implemented.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.
The mental and physical health of individuals with a psychotic illness are typically poor. Access to psychosocial interventions is important but currently limited. Telephone-delivered interventions may assist. In the current systematic review, we aim to summarise and critically analyse evidence for telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (i) relapse, (ii) adherence to psychiatric medication and/or (iii) modifiable cardiovascular disease risk behaviours.
Ten peer-reviewed and four grey literature databases were searched for English-language studies examining psychosocial telephone-delivered interventions targeting relapse, medication adherence and/or health behaviours in adults with a psychotic disorder. Study heterogeneity precluded meta-analyses.
Twenty trials [13 randomised controlled trials (RCTs)] were included, involving 2473 participants (relapse prevention = 867; medication adherence = 1273; and health behaviour = 333). Five of eight RCTs targeting relapse prevention and one of three targeting medication adherence reported at least 50% of outcomes in favour of the telephone-delivered intervention. The two health-behaviour RCTs found comparable levels of improvement across treatment conditions.
Although most interventions combined telephone and face-to-face delivery, there was evidence to support the benefit of entirely telephone-delivered interventions. Telephone interventions represent a potentially feasible and effective option for improving key health priorities among people with psychotic disorders. Further methodologically rigorous evaluations are warranted.
Gary P. Baker, Research Associate at the University of East Anglia, and a Researcher at the University of Groningen in the Netherlands.,
Craig L. Lambert, Lecturer in Maritime History at the University of Southampton.,
David Simpkin, Teacher of History at Birkenhead Sixth-Form College.,
J. J. N. Palmer
Given the contribution Andrew Ayton has made to the study of late medieval military history we hope he is not surprised by the production of a Festschrift in his honour. All the editors of this volume were supervised by Andrew for their doctoral studies, and all no doubt thrashed out the general outlines to their theses in one of the infamous ‘Ayton’ meetings that regularly ran into the late evening. Andrew's enthusiasm for his subject was infectious and it is to his credit that many of his former students have gone on to publish contributions on late medieval military and naval history. The papers featured in the present volume highlight the important international impact Andrew's work has had on his students and academic colleagues.
Andrew, a native of Dorset, is in his own words ‘a country dweller at heart’ but has spent much of his working life in the big city. He studied as an undergraduate at the University of Hull in the early 1980s, during which time he undertook several modules taught by Professor John Palmer. John's module on the Hundred Years’ War in particular seems to have kindled Andrew's interest in medieval military history and military communities; it certainly began a fruitful association between two like-minded scholars which was to span some three decades until John's retirement in 2002. Andrew often visited John's home to discuss their latest research and he will be pleased to know he is remembered with some affection by John's children.
After graduating, Andrew spent a brief spell in a ‘real’ job, before returning to Hull to study for his Ph.D. under John Palmer – ‘The Warhorse and Military Service under Edward III’ – and from 1985 to 1987 Andrew was employed, alongside Virginia Davis, on John's Domesday Project. This was a role for which Andrew was particularly well equipped. He had taken John Palmer's special subject on the Domesday Book as an undergraduate, which had provided him with the essential background plus the basic computing skills – in particular related to databases – needed for the research: rare qualifications in the mid-1980s. This period, of course, included the 900th anniversary of Domesday Book, which for Andrew and Virginia entailed a frenetic year, giving lectures and demonstrations around the UK while trying to keep to a research schedule and do some work on their own account.