A Conceptual Framework for Studying the Sources of Variation in Program Effects

Evaluations of public programs in many fields reveal that (1) different types of programs (or different versions of the same program) vary in their effectiveness, (2) a program that is effective for one group of people might not be effective for other groups of people, and (3) a program that is effective in one set of circumstances may not be effective in other circumstances. This paper presents a conceptual framework for research on such variation in program effects and the sources of this variation. The framework is intended to help researchers -- both those who focus mainly on studying program implementation and those who focus mainly on estimating program effects -- see how their respective pieces fit together in a way that helps to identify factors that explain variation in program effects and thereby support more systematic data collection on these factors. The ultimate goal of the framework is to enable researchers to offer better guidance to policymakers and program operators on the conditions and practices that are associated with larger and more positive effects

Expression of Epstein–Barr Virus–Encoded Small RNA (by the EBER-1 Gene) in Liver Specimens from Transplant Recipients with Post-Transplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV)—associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1—positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1—positive cells (P<0.001), and such cells were rare. EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies. (N Engl J Med 1992;327:1710–4.), POST-TRANSPLANTATION lymphoproliferative disease (PTLD), either polyclonal or monoclonal, complicates the clinical course of 1 to 10 percent of organ-transplant recipients.123 Immunohistochemical studies have demonstrated that the lymphoid cells within the lesions of PTLD almost invariably contain Epstein–Barr virus (EBV), primarily in a state of latent infection.4,5 The EBER-1 gene is expressed early during latent EBV infection and codes for a small messenger RNA (mRNA) expressed at up to 107 copies per cell.6 We and others have previously demonstrated the value of the detection of EBER-1 RNA for identifying EBV-infected cells in formalin-fixed paraffin-embedded tissues.7,8 In the current investigation, we used… © 1992, Massachusetts Medical Society. All rights reserved

Convective intensification of magnetic fields in the quiet Sun

Kilogauss-strength magnetic fields are often observed in intergranular lanes at the photosphere in the quiet Sun. Such fields are stronger than the equipartition field B_e, corresponding to a magnetic energy density that matches the kinetic energy density of photospheric convection, and comparable with the field B_p that exerts a magnetic pressure equal to the ambient gas pressure. We present an idealised numerical model of three-dimensional compressible magnetoconvection at the photosphere, for a range of values of the magnetic Reynolds number. In the absence of a magnetic field, the convection is highly supercritical and is characterised by a pattern of vigorous, time-dependent, “granular” motions. When a weak magnetic field is imposed upon the convection, magnetic flux is swept into the convective downflows where it forms localised concentrations. Unless this process is significantly inhibited by magnetic diffusion, the resulting fields are often much greater than B_e, and the high magnetic pressure in these flux elements leads to their being partially evacuated. Some of these flux elements contain ultra-intense magnetic fields that are significantly greater than B_p. Such fields are contained by a combination of the thermal pressure of the gas and the dynamic pressure of the convective motion, and they are constantly evolving. These ultra-intense fields develop owing to nonlinear interactions between magnetic fields and convection; they cannot be explained in terms of “convective collapse” within a thin flux tube that remains in overall pressure equilibrium with its surroundings

Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study.

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child-Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = -0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction

Localised plumes in three-dimensional compressible magnetoconvection

Within the umbrae of sunspots, convection is generally inhibited by the presence of strong vertical magnetic fields. However, convection is not completely suppressed in these regions: bright features, known as umbral dots, are probably associated with weak, isolated convective plumes. Motivated by observations of umbral dots, we carry out numerical simulations of three-dimensional, compressible magnetoconvection. By following solution branches into the subcritical parameter regime (a region of parameter space in which the static solution is linearly stable to convective perturbations), we find that it is possible to generate a solution which is characterised by a single, isolated convective plume. This solution is analogous to the steady magnetohydrodynamic convectons that have previously been found in two-dimensional calculations. These results can be related, in a qualitative sense, to observations of umbral dots.Comment: submitted to MNRA

Quantum phase transition of the sub-Ohmic rotor model

We investigate the behavior of an $N$-component quantum rotor coupled to a bosonic dissipative bath having a sub-Ohmic spectral density $J(\omega) \propto \omega^s$ with $s<1$. With increasing dissipation strength, this system undergoes a quantum phase transition from a delocalized phase to a localized phase. We determine the exact critical behavior of this transition in the large-$N$ limit. For $1>s>1/2$, we find nontrivial critical behavior corresponding to an interacting renormalization group fixed point while we find mean-field behavior for $s<1/2$. The results agree with those of the corresponding long-range interacting classical model. The quantum-to-classical mapping is therefore valid for the sub-Ohmic rotor model.Comment: 7 pages, final version as publishe

Neurobiological findings in posttraumatic stress disorder: a review

Since posttraumatic stress disorder (PTSD) was first recognized as a psychiatric disorder, it has generated a great deal of scientific interest. Recent studies on the neurobiology of PTSD provide evidence that PTSD is biologically distinct from other types of traumatic and nontraumatic stress responses. This paper reviews three important directions of neurobiological research in PTSD: noradrenergic axis changes and associated alterations in autonomic responsivity neuroendocrine changes involving the hypothalamic-pituitary-adrenocortical (HPA) axis, and neuroanatomy changes involving the hippocampus. Each section reviews the salient aspects of preclinical research on the biology of stress and their bearing on the understanding of PTSD, and summarizes prominent findings from clinical biological studies of PTSD, Tentative models that integrate current findings from the clinical study of PTSD are reviewed. To conclude, the important methodological and empirical issues that need to be addressed by future studies are indicated

Combined logical and data-driven models for linking signalling pathways to cellular response

Background Signalling pathways are the cornerstone on understanding cell function and predicting cell behavior. Recently, logical models of canonical pathways have been optimised with high-throughput phosphoproteomic data to construct cell-type specific pathways. However, less is known on how signalling pathways can be linked to a cellular response such as cell growth, death, cytokine secretion, or transcriptional activity. Results In this work, we measure the signalling activity (phosphorylation levels) and phenotypic behavior (cytokine secretion) of normal and cancer hepatocytes treated with a combination of cytokines and inhibitors. Using the two datasets, we construct "extended" pathways that integrate intracellular activity with cellular responses using a hybrid logical/data-driven computational approach. Boolean logic is used whenever a priori knowledge is accessible (i.e., construction of canonical pathways), whereas a data-driven approach is used for linking cellular behavior to signalling activity via non-canonical edges. The extended pathway is subsequently optimised to fit signalling and behavioural data using an Integer Linear Programming formulation. As a result, we are able to construct maps of primary and transformed hepatocytes downstream of 7 receptors that are capable of explaining the secretion of 22 cytokines. Conclusions We developed a method for constructing extended pathways that start at the receptor level and via a complex intracellular signalling pathway identify those mechanisms that drive cellular behaviour. Our results constitute a proof-of-principle for construction of "extended pathways" that are capable of linking pathway activity to diverse responses such as growth, death, differentiation, gene expression, or cytokine secretion.Marie Curie International Reintegration Grants (MIRG-14-CT-2007-046531)Vertex Pharmaceuticals IncorporatedBundesministerium für Wissenschaft und Forschung (HepatoSys)Massachusetts Institute of Technology (Rockwell International Career Development Professorship)Bundesministerium für Wissenschaft und Forschung (HepatoSys 0313081D

Perceptions of gender and tuberculosis in a south Indian urban community

Background: The Revised National Tuberculosis Control Programme (RNTCP) in India advocating Directly Observed Treatment-Short course (DOTS) detects nearly three times more male than female TB patients. The reasons for this difference are unclear. An understanding of the community’s health beliefs, perceptions on the disease and behaviour towards TB patients may throw some light on this issue. Material and Methods: A qualitative study using focus group discussions was conducted among men and women of younger and older age groups from lower income neighbourhoods. The information obtained was grouped into themes which included, understanding of TB, vulnerability, access to health care and social responses. Gender differences in community perceptions on TB seem to be critical in issues related to marriage. Results: The stigma of TB is more visible in women than men when it comes to marriage. Men and children were perceived to get preferential attention by their families during illness. While the younger age group, irrespective of gender, accessed care from private providers, the older group preferred a government facility. Awareness of TB was acceptable but it seemed more associated as a respiratory disease and the common symptom associated with TB was cough. Conclusion: This study highlights the need for gender specific intervention strategies to enhance better access of TB services