Comparison between Ormeloxifene and Norethisterone in reducing menorrhagia in dysfunctional uterine bleeding

Background: Dysfunctional Uterine Bleeding (DUB) is a condition that affects nearly every woman at some point in her life. This study aims to compare the efficacy of Ormeloxifene and Norethisterone in reducing menorrhagia in such patients.Methods: This prospective study was done on 100 women presenting with dysfunctional uterine bleeding, of 20-50 years of age, who were ready for follow-up and were allocated into two equal groups, one was given Ormeloxifene and the other was given Norethisterone for a period of 3 months. Haemoglobin levels, endometrial thickness on ultrasound and Pictorial Blood loss Assessment Chart (PBAC) scores were assessed before and after the treatment.Results: It was found that both Ormeloxifene and Norethisterone reduced menorrhagia, with a significant difference in PBAC scores (p value <0.05). There was a notable reduction in PBAC scores in Ormeloxifene group (66.53% change from pretreatment mean value) as compared to Norethisterone group (31.38% change from pretreatment mean value); and same holds true for the change in haemoglobin levels as well as endometrial thickness. Ormeloxifene was found to have a greater effect on heavy menstrual bleeding in comparison to Norethisterone.Conclusions: Ormeloxifene is a new modality and is found to be a better option in reducing menorrhagia in DUB in respect to a greater success rate, better compliance and cost effectiveness

Rentabilidad financiera y la sostenibilidad empresarial en la Consultora Silfersystem de Lima Cercado

En la presente indagación se tuvo como objetivo determinar la relación entre la rentabilidad financiera y la sostenibilidad empresarial en la Consultora Silfersystem de Lima Cercado. Para el desarrollo del estudio se utilizó una metodología correspondiente al enfoque cuantitativo, de tipo básica, de diseño no experimental, de alcance explicativo causal; para el cual, participaron como muestra 50 trabajadores pertenecientes a la consultoría Silfersystem S.A.C. La recolección de información se realizó utilizando como técnica la encuesta y como instrumentos un cuestionario sobre la variable en estudio. Planteando como conclusión que se observa que las variables rentabilidad financiera y sostenibilidad empresarial poseen relación, ya que mediante la aplicación en el estudio del Rho de Spearman se pudo obtener el dato de 0,852; el cual es un resultado que evidencia la relación alta entre las variables. Asimismo, observando el nivel de significancia 0,00 < 0,05, por el cual se aceptó la hipótesis planteada por el investigador, La rentabilidad financiera se relaciona con la sostenibilidad empresarial en la Consultora Silfersystem de Lima Cercado

Factors affecting the initiation of a shared decision making program in obstetric practices

As healthcare systems progress toward initiatives that increase patient engagement, stake-holder hopes are that shared decision making (SDM) will become routine practice. Yet, there is limited empirical evidence to guide such SDM program implementations, particularly in obstetric practices. The first stage of any project implementation is the “initiation stage”, in which project leaders define a project’s purpose and stakeholders and structures are put in place to support the new initiative. Our study’s objective was to identify factors affecting the initiation stage of an SDM program implementation project for TOLAC, trial of labor after Cesarean. We conducted a multiple-case study of an SDM program implementation in three obstetric settings in Washington State. The research design and analysis were guided by implementation science frameworks and project management literature. Data sources included interviews with key informants from the State, SDM tool vendors, and three project sites, as well as implementation documents. The study results provide insight into how the identified project implementation factors provide an essential foundation for informing project planning, execution, and reflection/evaluation. In this study, the State’s decision aid certification program pressured the project sites to shape the project purpose and engage stakeholders that would meet immediate project requirements (specifically, state require-ments). The study reveals that external demands may not be in perfect alignment with the internal necessities required for an SDM program’s long-term viability and sustainability. Findings may be used by implementers and researchers to model and strategize the early stages of SDM program implementation projects, particularly in the obstetric setting

T-Cell activation: a queuing theory analysis at low agonist density

We analyze a simple linear triggering model of the T-cell receptor (TCR) within the framework of queuing theory, in which TCRs enter the queue upon full activation and exit by downregulation. We fit our model to four experimentally characterized threshold activation criteria and analyze their specificity and sensitivity: the initial calcium spike, cytotoxicity, immunological synapse formation, and cytokine secretion. Specificity characteristics improve as the time window for detection increases, saturating for time periods on the timescale of downregulation; thus, the calcium spike (30 s) has low specificity but a sensitivity to single-peptide MHC ligands, while the cytokine threshold (1 h) can distinguish ligands with a 30% variation in the complex lifetime. However, a robustness analysis shows that these properties are degraded when the queue parameters are subject to variation—for example, under stochasticity in the ligand number in the cell-cell interface and population variation in the cellular threshold. A time integration of the queue over a period of hours is shown to be able to control parameter noise efficiently for realistic parameter values when integrated over sufficiently long time periods (hours), the discrimination characteristics being determined by the TCR signal cascade kinetics (a kinetic proofreading scheme). Therefore, through a combination of thresholds and signal integration, a T cell can be responsive to low ligand density and specific to agonist quality. We suggest that multiple threshold mechanisms are employed to establish the conditions for efficient signal integration, i.e., coordinate the formation of a stable contact interface

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Outbreak of pandemic influenza A/H1N1 2009 in Nepal

<p>Abstract</p> <p>Background</p> <p>The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009.</p> <p>Results</p> <p>Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type.</p> <p>Conclusion</p> <p>The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.</p

Stochastic Models of Lymphocyte Proliferation and Death

Quantitative understanding of the kinetics of lymphocyte proliferation and death upon activation with an antigen is crucial for elucidating factors determining the magnitude, duration and efficiency of the immune response. Recent advances in quantitative experimental techniques, in particular intracellular labeling and multi-channel flow cytometry, allow one to measure the population structure of proliferating and dying lymphocytes for several generations with high precision. These new experimental techniques require novel quantitative methods of analysis. We review several recent mathematical approaches used to describe and analyze cell proliferation data. Using a rigorous mathematical framework, we show that two commonly used models that are based on the theories of age-structured cell populations and of branching processes, are mathematically identical. We provide several simple analytical solutions for a model in which the distribution of inter-division times follows a gamma distribution and show that this model can fit both simulated and experimental data. We also show that the estimates of some critical kinetic parameters, such as the average inter-division time, obtained by fitting models to data may depend on the assumed distribution of inter-division times, highlighting the challenges in quantitative understanding of cell kinetics

Migration of cytotoxic lymphocytes in cell cycle permits local MHC I–dependent control of division at sites of viral infection

Virus-specific cytotoxic CD8+ T cells are in cell cycle as they transit from lymphoid tissues to sites of infection

Epitope Density Influences CD8+ Memory T Cell Differentiation

The generation of long-lived memory T cells is critical for successful vaccination but the factors controlling their differentiation are still poorly defined. We tested the hypothesis that the strength of T cell receptor (TCR) signaling contributed to memory CD8(+) T cell generation.We manipulated the density of antigenic epitope presented by dendritic cells to mouse naïve CD8(+) T cells, without varying TCR affinity. Our results show that a two-fold decrease in antigen dose selectively affects memory CD8(+) T cell generation without influencing T cell expansion and acquisition of effector functions. Moreover, we show that low antigen dose alters the duration of the interaction between T cells and dendritic cells and finely tunes the expression level of the transcription factors Eomes and Bcl6. Furthermore, we demonstrate that priming with higher epitope density results in a 2-fold decrease in the expression of Neuron-derived orphan nuclear receptor 1 (Nor-1) and this correlates with a lower level of conversion of Bcl-2 into a pro-apoptotic molecule and an increased number of memory T cells.Our results show that the amount of antigen encountered by naïve CD8(+) T cells following immunization with dendritic cells does not influence the generation of functional effector CD8(+) T cells but rather the number of CD8(+) memory T cells that persist in the host. Our data support a model where antigenic epitope density sensed by CD8(+) T cells at priming influences memory generation by modulating Bcl6, Eomes and Nor-1 expression

Reconstruction of cell population dynamics using CFSE

Background: Quantifying cell division and death is central to many studies in the biological sciences. The fluorescent dye CFSE allows the tracking of cell division in vitro and in vivo and provides a rich source of information with which to test models of cell kinetics. Cell division and death have a stochastic component at the single-cell level, and the probabilities of these occurring in any given time interval may also undergo systematic variation at a population level. This gives rise to heterogeneity in proliferating cell populations. Branching processes provide a natural means of describing this behaviour. Results: We present a likelihood-based method for estimating the parameters of branching process models of cell kinetics using CFSE-labeling experiments, and demonstrate its validity using synthetic and experimental datasets. Performing inference and model comparison with real CFSE data presents some statistical problems and we suggest methods of dealing with them. Conclusion: The approach we describe here can be used to recover the (potentially variable) division and death rates of any cell population for which division tracking information is available