Helping community-based students on a final consolidation placement make the transition to registered practice.

The pressure of role transition on new nurse registrants has affected recruitment and retention, which, along with an ageing workforce, has resulted in a global shortage of nurses that is now reaching crisis point. This article examines and discusses what can be done to attract and prepare the future workforce in the community, focusing on helping students to make the transition to registered practice that begins during their final consolidation of practice placement. There is currently limited evidence on the effectiveness of how community placement teams prepare finalist students for registered practice and this could be seen as an opportunity lost given the urgent need to recruit more registered nurses to work in primary care. Recommendations for enhancing this crucial stage of the student journey are made, and a case for the need to know more from students about how they experience their final practice placement when allocated to a community setting is presented

Emergent order in the kagome Ising magnet Dy3_3Mg2_2Sb3_3O14_{14}

The Ising model-in which degrees of freedom (spins) are binary valued (up/down)-is a cornerstone of statistical physics that shows rich behaviour when spins occupy a highly frustrated lattice such as kagome. Here we show that the layered Ising magnet Dy$_3$Mg$_2$Sb$_3$O$_{14}$ hosts an emergent order predicted theoretically for individual kagome layers of in-plane Ising spins. Neutron-scattering and bulk thermomagnetic measurements reveal a phase transition at ~0.3 K from a disordered spin-ice-like regime to an emergent charge ordered state, in which emergent magnetic charge degrees of freedom exhibit three-dimensional order while spins remain partially disordered. Monte Carlo simulations show that an interplay of inter-layer interactions, spin canting and chemical disorder stabilizes this state. Our results establish Dy$_3$Mg$_2$Sb$_3$O$_{14}$ as a tuneable system to study interacting emergent charges arising from kagome Ising frustration.Work at Cambridge was supported through the Winton Programme for the Physics of Sustainability. The work of J.A.M.P., X.B. and M.M. and facilities at Georgia Tech were supported by the College of Sciences through M.M. start-up funds. J.A.M.P. gratefully acknowledges Churchill College, Cambridge for the provision of a Junior Research Fellowship. H.S.O. acknowledges a Teaching Scholarship (Overseas) from the Ministry of Education, Singapore. J.O.H. is grateful to the Engineering and Physical Sciences Research Council (EPSRC) for funding. C.C. was supported by EPSRC Grant No. EP/G049394/1, and the EPSRC NetworkPlus on ‘Emergence and Physics far from Equilibrium’. Experiments at the ISIS Pulsed Neutron and Muon Source were supported by a beamtime allocation from the Science and Technology Facilities Council. This work utilized facilities at the NIST Center for Neutron Research. Monte Carlo simulations were performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/) and the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk/, for which access was provided by an ARCHER Instant Access scheme)

Issues potentially affecting quality of life arising from long-term medicines use: a qualitative study

Background Polypharmacy is increasing and managing large number of medicines may create a burden for patients. Many patients have negative views of medicines and their use can adversely affect quality of life. No studies have specifically explored the impact of general long-term medicines use on quality of life. Objective To determine the issues which patients taking long-term medicines consider affect their day-to-day lives, including quality of life. Setting Four primary care general practices in North West England Methods Face-to-face interviews with adults living at home, prescribed four or more regular medicines for at least 1 year. Interviewees were identified from primary care medical records and purposively selected to ensure different types of medicines use. Interviews were recorded, transcribed and analysed thematically. Results Twenty-one interviews were conducted and analysed. Patients used an average of 7.8 medicines, 51 % were preventive, 40 % for symptom relief and 9 % treatment. Eight themes emerged: relationships with health professionals, practicalities, information, efficacy, side effects, attitudes, impact and control. Ability to discuss medicines with health professionals varied and many views were coloured by negative experiences, mainly with doctors. All interviewees had developed routines for using multiple medicines, some requiring considerable effort. Few felt able to exert control over medicines routines specified by health professionals. Over half sought additional information about medicines whereas others avoided this, trusting in doctors to guide their medicines use. Patients recognised their inability to assess efficacy for many medicines, notably those used for prophylaxis. All were concerned about possible side effects and some had poor experiences of discussing concerns with doctors. Medicines led to restrictions on social activities and personal life to the extent that, for some, life can revolve around medicines. Conclusion There is a multiplicity and complexity of issues surrounding medicines use, which impact on day-to-day lives for patients with long-term conditions. While most patients adapt to long-term medicines use, others did so at some cost to their quality of life

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Clinical characteristics and role of early cardiac magnetic resonance imaging in patients with suspected ST-elevation myocardial infarction and normal coronary arteries

A variety of conditions other than acute myocardial infarction may cause ST-elevation. Our objective was to evaluate the impact of cardiac magnetic resonance (CMR) on differential diagnosis from a prospective series of patients with suspected ST-elevation myocardial infarction (STEMI) and completely normal coronary arteries. Among 1,145 patients with suspected STEMI, 49 patients had completely normal coronary arteries and entered a prospective registry. CMR was done within 24 h, if possible, and included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after gadolineum administration (global relative enhancement; gRE), and late gadolineum enhancement (LGE). All patients were asked for a follow-up CMR after approximately 3 months. The incidence of patients with suspected STEMI and normal coronary arteries was 4.3% and mean age was 45 ± 14 years (STEMI group 64 ± 13 years; P < 0.001). 55% had a recent history of infection. Cardiac biomarkers showed a moderate elevation on admission. There was a significant change from baseline to follow-up for LV end-diastolic volumes (EDV) (P < 0.001), LV mass (P < 0.05), mean T2 ratio (P < 0.05), and LGE volume (P < 0.05). Major diagnostic groups were myocarditis (29%), pericarditis (27%), and takotsubo cardiomyopathy (10%). 18% were regarded as non-diagnostic. The study showed an incidence of 4.3% of patients with suspected STEMI and completely normal coronary arteries. Early CMR was valuable in the evaluation of the differential diagnoses and to exclude myocardial abnormalities in patients with uncertain aetiology. Further studies are needed for the assessment of long-term outcome

Grb2 monomer-dimer equilibrium determines normal versus oncogenic function

The adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions. Grb2 plays a pivotal role in tyrosine kinase-mediated signal transduction including linking receptor tyrosine kinases to the Ras/mitogen-activated protein (MAP) kinase pathway, which is implicated in oncogenic outcome. Grb2 exists in a constitutive equilibrium between monomeric and dimeric states. Here we show that only monomeric Grb2 is capable of binding to SOS and upregulating MAP kinase signalling and that the dimeric state is inhibitory to this process. Phosphorylation of tyrosine 160 (Y160) on Grb2, or binding of a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation. Phosphorylation of Y160 on Grb2 is readily detectable in the malignant forms of human prostate, colon and breast cancers. The self-association/dissociation of Grb2 represents a switch that regulates MAP kinase activity and hence controls cancer progression

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

$\textbf{Aim}$ We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. $\textbf{Methods}$ In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). $\textbf{Results}$ Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10$^{-4}$) and INS rs2585 (P-value = 7 × 10$^{-4}$), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10$^{-3}$) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10$^{-3}$), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10$^{-6}$, n = 981, r$^{2}$ = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10$^{-3}$, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10$^{-8}$, rs2585, P-value = 3.6 × 10$^{-5}$) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10$^{-8}$), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). $\textbf{Conclusion}$ This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.This work was supported by the Evelyn Trust (grant number EW9035322); Diabetes UK (grant number 11/0004241); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (grant number RG1644); the Medical Research Council (grant number 7500001180); European Union Framework 5 (grant number QLK4-1999-01422); the Mothercare Charitable Foundation (grant number RG54608); Newlife Foundation for Disabled Children (grant number 07/20); the World Cancer Research Fund International (grant number 2004/03); and the National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study work was supported by the National Institutes of Health (grant numbers HD-34242, HD-34243, HG-004415, and CA-141688); the Institutes of Health Research–INMD (grant number 110791); and by the American Diabetes Association

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Bond between microwave cured repair and concrete substrate

The bond strength between a concrete substrate and repair patch is critical to its durability. This paper investigates the effect of microwave curing the freshly applied repair, for 45 min at 132 Watts, on the 28 day bond strength between substrate concrete and different commercial repair materials. The repairs were applied at different ambient temperatures of 20, 10, 2 and −5 °C. Tensile split tests on repaired cube specimens were performed to determine the interfacial bond strength. The ability of microwave curing to prevent the detrimental effects of freezing at early age on the bond and compressive strength of repair patches is investigated. Experimental results show that microwave curing prevents loss of long term (28 day) repair/substrate bond strength of repair materials applied at freezing temperatures (−5 °C), relative to the repairs applied at higher temperatures (2–20 °C), except one lightweight repair formulation. In comparison, the control samples (non-microwave cured) of repairs applied at −5 °C suffered severe loss of bond strength and compressive strength due to early age freezing. In addition, no adverse effects on the bond strength and a small reduction of 6.75% in the 28 day compressive strength are observed in the early age microwave cured repairs applied at ambient temperatures of 2–20 °C. The repair/substrate bond strength is independent of the compressive strength of the repair material at all temperatures of repair application. Microwave curing can accelerate the concrete repair process and facilitate construction activity in cold weather