Successes, challenges and needs regarding rural health medical education in continental central America: A literature review and narrative synthesis

Introduction: Central American countries, like many others, face a shortage of rural health physicians. Most medical schools in this region are located in urban areas and focus on tertiary care training rather than on community health or primary care, which are better suited for rural practice. However, many countries require young physicians to do community service in rural communities to address healthcare provider shortages. This study aimed to: (a) synthesize what is known about the current state of medical education preparing physicians for rural practice in this region, and (b) identify common needs, challenges and opportunities for improving medical education in this area. Methods: A comprehensive literature review was conducted between December 2013 and May 2014. The stepwise, reproducible search process included English and Spanish language resources from both data-based web search engines (PubMed, Web of Science/Web of Knowledge, ERIC and Google Scholar) and the grey literature. Search criteria included MeSH terms: ‘medical education’, ‘rural health’, ‘primary care’, ‘community medicine’, ‘social service’, in conjunction with ‘Central America’, ‘Latin America’, ‘Mexico’, ‘Guatemala’, ‘Belize’, ‘El Salvador’, ‘Nicaragua’, ‘Honduras’, ‘Costa Rica’ and ‘Panama’. Articles were included in the review if they (1) were published after 1984; (2) focused on medical education for rural health, primary care, community health; and (3) involved the countries of interest. A narrative synthesis of the content of resources meeting inclusion criteria was done using qualitative research methods to identify common themes pertaining to the study goals. Results: The search revealed 20 resources that met inclusion criteria. Only four of the 20 were research articles; therefore, information about this subject was primarily derived from expert opinion. Thematic analysis revealed the historical existence of several innovative programs that directly address rural medicine training needs, suggesting that expertise is present in this region. However, numerous challenges limit sustainability or expansion of successful programs. Common challenges include: (a) physicians’ exposure to rural medicine primarily takes place during social service commitment time, rather than during formal medical training; (b) innovative educational programs are often not sustainable due to financial and leadership challenges; (c) the majority of physician manpower is in urban areas, resulting in few rural physician role models and teachers; and (d) there is insufficient collaboration to establish clinical and educational systems to meet rural health needs. Recurring suggestions for curricular changes include: (a) making primary care training a core component of medical school education; and (b) expanding medical school curricula in crosscultural communication and social determinants of disease. Suggestions for health system changes include: (a) improving living and working conditions for rural physicians; and (b) establishing partnerships between educational, governmental and non-governmental organizations and rural community leadership, to promote rural health training and systems. Conclusions: Expertise in rural medicine and training exists in continental Central America. However, there are numerous challenges to improving medical education to meet the needs of rural communities. Overcoming these challenges will require creative solutions, new partnerships, and evaluation and dissemination of successful educational programs. There is a great need for further research on this topic

No Evidence of a Drug-Drug Interaction Between Letermovir (MK-8228) and Mycophenolate Mofetil

Introduction: Letermovir (MK-8228) is a potent, oncedaily inhibitor of the cytomegalovirus (CMV) terminase complex that is being developed for the prophylaxis of CMV infection in transplant patients. This study evaluated the pharmacokinetic interactions, safety, and tolerability of letermovir when coadministered in healthy subjects with mycophenolate mofetil (MMF), which is the morpholinoethyl ester prodrug of mycophenolic acid (MPA). Methods: This was an open-label trial in 14 healthy female subjects that explored the pharmacokinetic parameters of a single 1 g oral dose of MMF administered alone on Day 1 and coadministered on Day 12 with 480 mg oral once-daily letermovir given on Day 5 and from Day 8 continued through Day 16. Letermovir PK was assessed at single dose (Day 5) and at steady state on Day 12 (with MMF) and Day 16 (alone following MMF washout). Results: Coadministration of 480 mg qd letermovir at steady state with a single dose of 1 g of MMF had no effect on the pharmacokinetics of MPA. The MPA AUC0-inf and Cmax geometric mean ratios (GMRs) [90% confidence interval] for the comparison (MMF with letermovir/ MMF alone) were 1.08 [0.96, 1.21] and 0.96 [0.81, 1.13], respectively. Coadministration of a single dose of 1 g MMF with 480 mg qd letermovir at steady state had no clinically meaningful effect on the pharmacokinetics of letermovir, with AUC0-24 and Cmax GMR of 1.18 [1.04, 1.32] and 1.11 [0.93, 1.34], respectively. The letermovir geometric mean accumulation ratio (Day 16/Day 5) and 95% CI were 1.13 [0.90, 1.42] for AUC0-24 and 1.01 [ 0.79, 1.28] f or Cmax, indicating that accumulation of letermovir when administered as daily doses is minimal. All related AEs were reported as mild in severity and resolved. Conclusions: Multiple-dose administration of 480 mg letermovir daily with a single dose of 1 g MMF was generally well tolerated by the healthy subjects in this study. Coadministration of letermovir and MMF had no clinically meaningful effect on the PK of letermovir or MPA. Letermovir and MMF may be coadministered without dose adjustment

Protein kinase Cepsilon is important for migration of neuroblastoma cells

<p>Abstract</p> <p>Background</p> <p>Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility.</p> <p>Methods</p> <p>PKC isoforms were downregulated with siRNA or modulated with activators and inhibitors. Migration was analyzed with scratch and transwell assays. Protein phosphorylation and expression levels were measured with Western blot.</p> <p>Results</p> <p>Stimulation with 12-<it>O</it>-tetradecanoylphorbol-13-acetate (TPA) induced migration of SK-N-BE(2)C neuroblastoma cells. Treatment with the general protein kinase C (PKC) inhibitor GF109203X and the inhibitor of classical isoforms Gö6976 inhibited migration while an inhibitor of PKCβ isoforms did not have an effect. Downregulation of PKCε, but not of PKCα or PKCδ, with siRNA led to a suppression of both basal and TPA-stimulated migration. Experiments using PD98059 and LY294002, inhibitors of the Erk and phosphatidylinositol 3-kinase (PI3K) pathways, respectively, showed that PI3K is not necessary for TPA-induced migration. The Erk pathway might be involved in TPA-induced migration but not in migration driven by PKCε. TPA induced phosphorylation of the PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS) which was suppressed by the PKC inhibitors. Treatment with siRNA oligonucleotides against different PKC isoforms before stimulation with TPA did not influence the phosphorylation of MARCKS.</p> <p>Conclusion</p> <p>PKCε is important for migration of SK-N-BE(2)C neuroblastoma cells. Neither the Erk pathway nor MARCKS are critical downstream targets of PKCε but they may be involved in TPA-mediated migration.</p

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations