Specialty training for the retention of Malawian doctors: A cost-effectiveness analysis

Few medical schools and sustained emigration have led to low numbers of doctors in many sub-Saharan African countries. The opportunity to undertake specialty training has been shown to be particularly important in retaining doctors. Yet limited training capacity means that doctors are often sent to other countries to specialise, increasing the risk that they may not return. Expanding domestic training, however, may be constrained by the reluctance of doctors to accept training in their home country. We modelled different policy options in an example country, Malawi, to examine the cost-effectiveness of expanding specialty training to retain doctors in sub-Saharan Africa. We designed a Markov model of the physician labour market in Malawi, incorporating data from graduate tracing studies in 2006 and 2012, a 2013 discrete choice experiment on 148 Malawian doctors and 2015 cost data. A government perspective was taken with a time horizon of 40 years. Expanded specialty training in Malawi or South Africa with increasing mandatory service before training was compared against baseline conditions. The outcome measures were cost per doctor-year and cost per specialist-year spent working in the Malawian public sector. Expanding specialty training in Malawi is more cost-effective than training outside Malawi. At least two years of mandatory service would be more cost-effective, with five years adding the most value in terms of doctor-years. After 40 years of expanded specialty training in Malawi, the medical workforce would be over fifty percent larger with over six times the number of specialists compared to current trends. However, the government would need to be willing to pay at least 3.5 times more per doctor-year for a 5% increase and a third more per specialist-year for a four-fold increase. Greater returns are possible from doctors with more flexible training preferences. Sustained funding of specialty training may improve retention in sub-Saharan Africa

COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE

Objective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification

Cell organization in soft media due to active mechanosensing

Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain, they orient parallel and normal to free and clamped surfaces, respectively, and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are upregulated by large effective stiffness in the environment because in this way, build-up of force is more efficient.Comment: Revtex, 7 pages, 4 Postscript files include

The ultimate arc: Differential displacement, oroclinal bending, and vertical axis rotation in the External Betic-Rif arc

The External Betic-Rif arc, which lies between the converging African and Iberian plates, is one of the tightest orogenic arcs on Earth. It is a thin-skinned fold and thrust belt formed in Miocene time around the periphery of the Alborán Domain, an older contractional orogen that underwent extensional collapse coevally with the formation of the thrust belt. Restoration of four sections across the thrust belt, together with kinematic and paleomagnetic analysis, allows a reconstruction of the prethrusting geometry of the Alborán Domain, and the identification of the following processes that contributed to the formation of the arc: (1) The Alborán Domain moved some 250 km westward relative to Iberia and Africa during the Miocene. This initiated the two limbs of the arc on its NW and SW margins, closing to the WSW in the region of Cherafat in northern Morocco. The overall convergence direction on the Iberian side of the arc was between 310° and 295°, and on the African side it was between 235° and 215°. The difference in convergence direction between the two sectors was primarily a result of the relative motion between Africa and Iberia. (2) Extensional collapse of the Alborán Domain during the Miocene modified the geometry of the western end of the arc: the Internal Rif rotated anticlockwise to form the present north trending sector of the arc, and additional components of displacement produced by extension were transferred into the external thrust belt along a series of strike-slip faults and shear zones. These allowed the limbs of the arc to rotate and extend, tightening the arc, and creating variations in the amounts and directions of shortening around the arc. The Betic sector of the arc rotated clockwise by 25° during this process, and the southern Rif rotated anticlockwise by ∼55°. (3) Oblique convergence on the two limbs of the arc, dextral in the Betics and sinistral in the southern Rif, resulted in strongly noncoaxial deformation. This had three related effects: (1) large rotations of individual thrust sheets resulted from the oblique propagation of thrusts away from the thrust front, followed by pinning and rotation as the thrust sheets peeled off, (2) continued oblique convergence resulted in distributed shear, particularly in the rear of the thrust wedge, causing rotation of stacks of thrust sheets on the scale of a few tens of kilometers, and (3) distributed shear in the orogen resulted in the rotation of folds as they amplified, the hinges migrating through the rock body, and rotating at a slower rate than the rock. These rotations were substantially larger than the bulk rotations of the limbs of the arc, and they strongly modified the orientations of folds, thrust traces, and the structural indicators of fault slip directions

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

Relativistic effects and two-body currents in 2H(e⃗,e′p)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

Measurements of the ${^2}H(\vec{e},e^{\prime}p)n$ reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, $f_{LT}$ and $f_{LT}^{\prime}$, and the transverse-transverse, $f_{TT}$, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q$^2$=0.15 (GeV/c)$^2$. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

Meson Exchange Currents in (e,e'p) recoil polarization observables

A study of the effects of meson-exchange currents and isobar configurations in $A(\vec{e},e'\vec{p})B$ reactions is presented. We use a distorted wave impulse approximation (DWIA) model where final-state interactions are treated through a phenomenological optical potential. The model includes relativistic corrections in the kinematics and in the electromagnetic one- and two-body currents. The full set of polarized response functions is analyzed, as well as the transferred polarization asymmetry. Results are presented for proton knock-out from closed-shell nuclei, for moderate to high momentum transfer.Comment: 44 pages, 18 figures. Added physical arguments explaining the dominance of OB over MEC, and a summary of differences with previous MEC calculations. To be published in PR

BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network

Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2. However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis. Here we show that BMP2 induces DLX3, a homeodomain protein that activates Runx2 gene transcription. Small interfering RNA knockdown studies in osteoblasts validate that DLX3 is a potent regulator of Runx2. Furthermore in Runx2 null cells, DLX3 forced expression suffices to induce transcription of Runx2, osteocalcin, and alkaline phosphatase genes, thus defining DLX3 as an osteogenic regulator independent of RUNX2. Our studies further show regulation of the Runx2 gene by several homeodomain proteins: MSX2 and CDP/cut repress whereas DLX3 and DLX5 activate endogenous Runx2 expression and promoter activity in non-osseous cells and osteoblasts. These HD proteins exhibit distinct temporal expression profiles during osteoblast differentiation as well as selective association with Runx2 chromatin that is related to Runx2 transcriptional activity and recruitment of RNA polymerase II. Runx2 promoter mutagenesis shows that multiple HD elements control expression of Runx2 in relation to the stages of osteoblast maturation. Our studies establish mechanisms for commitment to the osteogenic lineage directly through BMP2 induction of HD proteins DLX3 and DLX5 that activate Runx2, thus delineating a transcriptional regulatory pathway mediating osteoblast differentiation. We propose that the three homeodomain proteins MSX2, DLX3, and DLX5 provide a key series of molecular switches that regulate expression of Runx2 throughout bone formation. <br/

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention