To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. This study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillusrhamnosus and Bifidobacteriumlactis), or both (MIPB) for five weeks. They were then provided with high fat diet (HFD) for one week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16.5 and tissue collection at GD18.5. Neither MI or PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2, and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.
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.
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.
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.
The effect of small noise in a smooth dynamical system is negligible on any finite time interval; in this paper we study situations where the effect persists on intervals increasing to ∞. Such an asymptotic regime occurs when the system starts from an initial condition that is sufficiently close to an unstable fixed point. In this case, under appropriate scaling, the trajectory converges to a solution of the unperturbed system started from a certain random initial condition. In this paper we consider the case of one-dimensional diffusions on the positive half-line; this case often arises as a scaling limit in population dynamics.
Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.
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.
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.
Sir Robert Knolles’ chevauchée through northern France between August and December 1370 is arguably the most fascinating English expedition of the fourteenth century. Outwardly it displayed all the hallmarks of a structurally uniform English army typical of the period: fully-mounted mixed retinues of roughly equal numbers of men-at-arms and archers, with their pay and other terms of service likely to have been stipulated by contracts of indenture. Yet in other respects the army was entirely unconventional. The pay, terms of service under which the men were to serve, and the senior command structure were novel. It was also the last campaign in the fourteenth century for which charters of pardon for military service were issued in significant numbers and, unconventionally, they were issued prior to the campaign – for service to be rendered – rather than after it. It was also the only English force of the entire period which came apart at the seams in the field, fragmenting into four divisions due to bickering between its commanders and their subordinates, with disastrous consequences. The newly appointed French Constable, Bertrand du Guesclin, confronted and defeated two of the four divisions in pitched battle, temporarily reversing the French King Charles V's Fabian strategy and dealing a huge military, and perhaps psychological, blow to the English.
To fully comprehend why the failure of this army was so important for future English martial organisation, and contributed to an overhaul of English war strategy, it is necessary to examine the army's organisational and structural framework, its command hierarchy, and the bonds between its personnel, to see how these differed, if at all, from other armies of the period, and what bearing, if any, these factors had on why it imploded so spectacularly.
Preparations for War
Since the renewal of Anglo-French hostilities in 1369, the English had largely been on the back foot. Charles V's forces had begun recapturing lands in south-western France that had been ceded to Edward III by the Treaty of Brétigny in 1360. Two English armies sent to France in 1369 had alleviated some of the pressure but achieved little else. At a Great Council in London in February 1370, it was decided to launch another expedition to France in the summer of four thousand men, part of a joint enterprise with Charles II of Évreux, king of Navarre.