A Longitudinal Study of Pediatricians Early in their Careers: PLACES

The American Academy of Pediatrics (AAP) launched the Pediatrician Life and Career Experience Study (PLACES), a longitudinal study that tracks the personal and professional experiences of early career pediatricians, in 2012. We used a multipronged approach to develop the study methodology and survey domains and items, including review of existing literature and qualitative research with the target population. We chose to include 2 cohorts of US pediatricians on the basis of residency graduation dates, including 1 group who were several years out of residency (2002–2004 Residency Graduates Cohort) and a second group who recently graduated from residency at study launch (2009–2011 Residency Graduates Cohort). Recruitment into PLACES was a 2-stage process: (1) random sample recruitment from the target population and completion of an initial intake survey and (2) completion of the first Annual Survey by pediatricians who responded positively to stage 1. Overall, 41.2% of pediatricians randomly selected to participate in PLACES indicated positive interest in the study by completing intake surveys; of this group, 1804 (93.7%) completed the first Annual Survey and were considered enrolled in PLACES. Participants were more likely to be female, AAP members, and graduates of US medical schools compared with the target sample; weights were calculated to adjust for these differences. We will survey PLACES pediatricians 2 times per year. PLACES data will allow the AAP to examine career and life choices and transitions experienced by early-career pediatricians

Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in Melanoma skin cancer cell lines

Plasma Chemistry and Plasma Processing, 27(2): pp. 163-176.Initiation of apoptosis, or programmed cell death, is an important issue in cancer treatment as cancer cells frequently have acquired the ability to block apoptosis and thus are more resistant to chemotherapeutic drugs. Targeted and perhaps selective destruction of cancerous tissue is desirable for many reasons, ranging from the enhancement of or aid to current medical methods to problems currently lacking a solution, i.e. lung cancer. Demonstrated in this publication is the inactivation (killing) of human Melanoma skin cancer cell lines, in vitro, by Floating Electrode Dielectric Barrier Discharge plasma. Not only are these cells shown to be killed immediately by high doses of plasma treatment,but low doses are shown to promote apoptotic behavior as detected by TUNEL staining and subsequent flow cytometry. It is shown that plasma acts on the cells directly and not by “poisoning” the solution surrounding the cells, even through a layer of such solution. Potential mechanisms of interaction of plasma with cells are discussed and further steps are proposed to develop an understanding of such systems

An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes

Two collections of oligonucleotides have been designed for preparing pangenomic human and mouse microarrays. A total of 148 993 and 121 703 oligonucleotides were designed against human and mouse transcripts. Quality scores were created in order to select 25 342 human and 24 109 mouse oligonucleotides. They correspond to: (i) a BLAST-specificity score; (ii) the number of expressed sequence tags matching each probe; (iii) the distance to the 3′ end of the target mRNA. Scores were also used to compare in silico the two microarrays with commercial microarrays. The sets described here, called RNG/MRC collections, appear at least as specific and sensitive as those from the commercial platforms. The RNG/MRC collections have now been used by an Anglo-French consortium to distribute more than 3500 microarrays to the academic community. Ad hoc identification of tissue-specific transcripts and a ∼80% correlation with hybridizations performed on Affymetrix GeneChip™ suggest that the RNG/MRC microarrays perform well. This work provides a comprehensive open resource for investigators working on human and mouse transcriptomes, as well as a generic method to generate new microarray collections in other organisms. All information related to these probes, as well as additional information about commercial microarrays have been stored in a freely-accessible database called MEDIANTE

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation

Does directly observed therapy (DOT) reduce drug resistant tuberculosis?

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices.</p> <p>Methods</p> <p>Genotype clusters were defined as 2 or more patient members with matching IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses.</p> <p>Results</p> <p>Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6).</p> <p>Conclusions</p> <p>Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.</p

A search for neutral Higgs bosons in the MSSM and models with two scalar field doublets

A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan.A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172 GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan

Spin alignment of leading K∗(892)0K^{*}(892)^{0} mesons in hadronic Z0Z^0 decays

Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K ∗ (892) 0 mesons from hadronic Z 0 decays have been measured over the full range of K ∗ 0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x p values above 0.3, with the matrix element ϱ 00 rising to 0.66 ± 0.11 for x p > 0.7. The values of the real part of the off-diagonal element ϱ 1 - 1 are negative at large x p , with a weighted average value of −0.09 ± 0.03 for x p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the q q system from the Z 0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x p range. The K ∗ 0 fragmentation function has also been measured and the total rate determined to be 0.74 ± 0.02 ± 0.02 K ∗ (892) 0 mesons per hadronic Z 0 decay