The influence of resuscitation preferences on obstetrical management of periviable deliveries

Objective Determine the relative influence of patient's resuscitation preferences on periviable delivery management. Methods Surveyed 295 obstetrician-gynecologists about managing periviable preterm premature rupture of membranes. Across 10 vignettes, we systematically varied gestational age; occupation; method of conception; and resuscitation preference. Physicians rated their likelihood (0-10) of proceeding with induction, steroids, and cesarean. Data were analyzed via conjoint analysis. Results 205 physician responses were included. Median ratings for management decisions were: induction 1.89; steroids 5.00; cesarean for labor 3.89; cesarean for distress 4.11. Gestational age had the greatest influence on physician ratings across all decisions (importance values ranging from 72.6-86.6), followed by patient's resuscitation preference (range= 9.3-21.4). Conclusion Gestational age is weighted more heavily than patients’ resuscitation preferences in obstetricians’ decision-making for periviable delivery management. Misalignment of antenatal management with parental resuscitation preferences may adversely affect periviable outcomes. Interventions are needed to facilitate more patient-centered decision-making in periviable care

Urban form, infrastructure, and spatial organization in the Roman Empire

Although there has been considerable interest in the nature of ancient cities, it has been difficult to identify and explore quantitative patterns in their design and amenities. In this article, we offer a model for the relationship between the size and infrastructure of settlements, before testing it against measures of the urban form of cities in the Roman Empire. This allows us to advocate a more consistent approach to investigating settlements that is capable of not only incorporating sites with divergent experiences into the same model, but also exposing their similarities and differences

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

Background: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.Methods and Results: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.Conclusions: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.<br/

Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy

Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapyinduced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.Steven Ngo, Ethan P. Oxley, Margherita Ghisi, Maximilian M. Garwood, Mark D. McKenzie, Helen L. Mitchell, Peter Kanellakis, Olivia Susanto, Michael J. Hickey, Andrew C. Perkins, Benjamin T. Kile, Ross A. Dickin

Population dynamics of a pathogen: the conundrum of vivax malaria

Building a mathematical model of population dynamics of pathogens within their host involves considerations of factors similar to those in ecology, as pathogens can prey on cells in the host. But within the multicellular host, attacked cell types are integrated with other cellular systems, which in turn intervene in the infection. For example, immune responses attempt to sense and then eliminate or contain pathogens, and homeostatic mechanisms try to compensate for cell loss. This review focuses on modeling applied to malarias, diseases caused by single-cell eukaryote parasites that infect red blood cells, with special concern given to vivax malaria, a disease often thought to be benign (if sometimes incapacitating) because the parasite only attacks a small proportion of red blood cells, the very youngest ones. However, I will use mathematical modeling to argue that depletion of this pool of red blood cells can be disastrous to the host if growth of the parasite is not vigorously check by host immune responses. Also, modeling can elucidate aspects of new field observations that indicate that vivax malaria is more dangerous than previously thought

Predictive factors of adherence to frequency and duration components in home exercise programs for neck and low back pain: an observational study

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that to facilitate physical activity sedentary people may adhere to one component of exercise prescriptions (intensity, duration or frequency) without adhering to other components. Some experts have provided evidence for determinants of adherence to different components among healthy people. However, our understanding remains scarce in this area for patients with neck or low back pain. The aims of this study are to determine whether patients with neck or low back pain have different rates of adherence to exercise components of frequency per week and duration per session when prescribed with a home exercise program, and to identify if adherence to both exercise components have distinct predictive factors.</p> <p>Methods</p> <p>A cohort of one hundred eighty-four patients with chronic neck or low back pain who attended physiotherapy in eight primary care centers were studied prospectively one month after intervention. The study had three measurement periods: at baseline (measuring characteristics of patients and pain), at the end of physiotherapy intervention (measuring characteristics of the home exercise program) and a month later (measuring professional behaviors during clinical encounters, environmental factors and self-efficacy, and adherence behavior).</p> <p>Results</p> <p>Adherence to duration per session (70.9% ± 7.1) was more probable than adherence to frequency per week (60.7% ± 7.0). Self-efficacy was a relevant factor for both exercise components (p < 0.05). The total number of exercises prescribed was predictive of frequency adherence (p < 0.05). Professional behaviors have a distinct influence on exercise components. Frequency adherence is more probable if patients received clarification of their doubts (adjusted OR: 4.1; p < 0.05), and duration adherence is more probable if they are supervised during the learning of exercises (adjusted OR: 3.3; p < 0.05).</p> <p>Conclusion</p> <p>We have shown in a clinic-based study that adherence to exercise prescription frequency and duration components have distinct levels and predictive factors. We recommend additional study, and advise that differential attention be given in clinical practice to each exercise component for improving adherence.</p

Posttraumatic stress disorder among female street-based sex workers in the greater Sydney area, Australia

BACKGROUND: This paper examines rates of exposure to work-related violence and other trauma, and the prevalence of lifetime and current posttraumatic stress disorder (PTSD) among female street-based sex workers. It also investigates associations between current PTSD symptoms and: demographic characteristics, psychiatric comorbidity, injecting and sex risk behaviours, and trauma history. METHODS: Cross sectional data collected from 72 women via face to face structured interviews. The interview included structured diagnostic assessment of DSM-IV PTSD; drug dependence; depression; experience of childhood trauma; and an assessment of sex working history. RESULTS: All but one of the women interviewed reported experiencing trauma, with the majority reporting multiple traumas that typically began in early childhood. Child sexual abuse, adult sexual assault and work related violence were commonly reported. Just under half of the women met DSM-IV criteria for PTSD and approximately one-third reported current PTSD symptoms. Adult sexual assault was associated with current PTSD symptoms. Depression and drug dependence were also highly prevalent; cocaine dependence in particular was associated with elevated rates of injecting risk and sexual risk behaviours. CONCLUSION: These women reported complex trauma histories and despite ongoing opportunities for clinical intervention, they continued to experience problems, suggesting that current models of treatment may not be appropriate. More targeted interventions, and integrated mental health and drug treatment services are needed to address the problems these women are experiencing. Outreach services to these women remain a priority. Education strategies to reduce risky injecting and sexual behaviours among sex workers should also remain a priority

Tissue-Specific Target Analysis of Disease-Associated MicroRNAs in Human Signaling Pathways

MicroRNAs are a large class of post-transcriptional regulators that bind to the 3′ untranslated region of messenger RNAs. They play a critical role in many cellular processes and have been linked to the control of signal transduction pathways. Recent studies indicate that microRNAs can function as tumor suppressors or even as oncogenes when aberrantly expressed. For more general insights of disease-associated microRNAs, we analyzed their impact on human signaling pathways from two perspectives. On a global scale, we found a core set of signaling pathways with enriched tissue-specific microRNA targets across diseases. The function of these pathways reflects the affinity of microRNAs to regulate cellular processes associated with apoptosis, proliferation or development. Comparing cancer and non-cancer related microRNAs, we found no significant differences between both groups. To unveil the interaction and regulation of microRNAs on signaling pathways locally, we analyzed the cellular location and process type of disease-associated microRNA targets and proteins. While disease-associated proteins are highly enriched in extracellular components of the pathway, microRNA targets are preferentially located in the nucleus. Moreover, targets of disease-associated microRNAs preferentially exhibit an inhibitory effect within the pathways in contrast to disease proteins. Our analysis provides systematic insights into the interaction of disease-associated microRNAs and signaling pathways and uncovers differences in cellular locations and process types of microRNA targets and disease-associated proteins