Miracle-dz/UniFAR-FTUs huggingface dataset:
Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs

ABSTRACT It is the mature gametocytes of Plasmodium that are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes of Plasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio of Plasmodium falciparum (∼3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns.
Risk factors for chronic mucus hypersecretion in individuals with and without COPD: influence of smoking and job exposure on CMH

Background Chronic mucus hypersecretion (CMH) is highly prevalent in smokers and associated with an accelerated lung function decline and chronic obstructive pulmonary disease (COPD). Several risk factors contribute to CMH and to COPD. It is, however, unknown if risk factors for CMH are similar in persons with and without COPD. Methods 1479 persons with and 8529 without COPD, participating in the general population-based LifeLines cohort, completed questionnaires and underwent spirometry. Occupational exposure was assessed using the ALOHA+ job exposure matrix. Analyses were performed using multiple logistic regression models. Results In COPD, a significantly higher risk for CMH was associated with higher pack-years smoking (per 10 pack-years) (OR=1.28; 1.12 to 1.46) and environmental tobacco smoke (ETS) (OR=2.06; 1.33 to 3.19). In non-COPD; male gender (OR=1.91; 1.51 to 2.41), higher Body Mass Index (OR=1.04; 1.01 to 1.06), higher pack-years smoking (OR=1.28; 1.14 to 1.44), current smoking (OR=1.50; 1.04 to 2.18), low and high exposure to mineral dust (OR=1.39; 1.04 to 1.87 and OR=1.60; 1.02 to 2.52), high exposure to gases & fumes (OR=2.19; 1.49 to 3.22). Significant interactions were found between COPD and exposure to gases & fumes (p=0.018) and aromatic solvents (p=0.038). Conclusions A higher risk for CMH was associated with higher pack-years smoking regardless of COPD status. However, a higher risk for CMH was associated with high occupational exposure to gases & fumes in individuals without COPD only.
The new organization of the health care delivery system.

The U.S. health care system is restructuring at a dizzying pace. In many parts of the country, managed care has moved into third-generation models emphasizing capitated payment for enrolled lives and, in the process, turning most providers and institutions into cost centers to be managed rather than generators of revenue. While the full impact of the new managed care models remains to be seen, most evidence to date suggests that it tends to reduce inpatient use, may be associated with greater use of physician services and preventive care, and appears to result in no net differences either positive or negative with regard to quality or outcomes of care in comparison with fee-for-service plans. Some patients, however, tend to be somewhat less satisfied with scheduling of appointments and the amount of time spent with providers. There is no persuasive evidence that managed care lowers the rate of growth in overall health care costs within a given market. Further, managed care performance varies considerably across the country, and the factors influencing managed care performance are not well understood. Organized delivery systems are a somewhat more recent phenomenon representing various forms of ownership and strategic alliances among hospitals, physicians, and insurers designed to provide more cost-effective care to defined populations by achieving desired levels of functional, physician-system, and clinical integration. Early evidence suggests that organized delivery systems that are more integrated have the potential to provide more accessible coordinated care across the continuum, and appear to be associated with higher levels of inpatient productivity, greater total system revenue, greater total system cash flow, and greater total system operating margin than less integrated delivery forms. Some key success factors for developing organized delivery systems have been identified. Important roles are played by organizational culture, information systems, internal incentives, total quality management, physician leadership, and the growth of group practices. This chapter describes the growth and evolution of managed care and organized delivery systems, the research evidence regarding managed care and organized delivery systems, and the likely future organization of the health system in light of recent trends and evidence. It also highlights some of the more important public policy implications of the new health care infrastructure.
Tumor necrosis factor mediates lung antibacterial host defense in murine Klebsiella pneumonia

Tumor necrosis factor (TNF) is a proinflammatory cytokine which has recently been shown to have beneficial effects in the setting of acquired host immunity. However, the role of TNF in innate immune responses, as in the setting of bacterial pneumonia, has been incompletely characterized. To determine the role of TNF in gram-negative bacterial pneumonia, CBA/J mice were challenged with 10(2) CFU of Klebsiella pneumoniae intratracheally, resulting in the time-dependent expression of TNF MRNA and protein within the lung. Passive immunization of animals with a soluble TNF receptor-immunoglobulin (Ig) construct (sTNFR:Fc) intraperitoneally 2 h prior to K. pneumoniae inoculation resulted in a significant reduction in bronchoalveolar lavage neutrophils, but not macrophages, at 48 h, as compared with animals receiving control IgG1. Furthermore, treatment with sTNFR:Fc resulted in 19.6- and 13.5-fold increases in K. pneumoniae CFU in lung homogenates and plasma, respectively, as compared with animals receiving control IgG1. Finally, treatment of Klebsiella-infected mice with sTNFR:Fc markedly decreased both short- and long-term survival of these animals. In conclusion, our studies indicate that endogenous TNF is a critical component of antibacterial host defense in murine Klebsiella pneumonia.
Noninvasive cardiac output monitoring by aortic blood flow determination: evaluation of the Sometec Dynemo-3000 system.

OBJECTIVE The Sometec Dynemo-3000 system allows the permanent measurement of descending aorta diameter by an echographic (A-scan) device and the blood flow velocity by a pulse Doppler velocimeter. The Dynemo-3000 then furnishes a new hemodynamic parameter, i.e., descending aortic blood flow (ABF), which is a fraction of the cardiac output (CO). We evaluate the ability of this system to measure the aortic diameter and to accurately detect ABF changes. DESIGN A case study prospective trial. SETTING A 24-bed medical intensive care unit of a 1,100-bed university hospital. PATIENTS Twenty critically ill patients fully sedated, mechanically ventilated, and monitored by a pulmonary artery catheter. INTERVENTIONS CO values determined by conventional thermodilution method (TD-CO) and ABF were recorded during the study, which included two initial baseline periods, a dobutamine infusion (5 microg/kg/min) interval of 30 mins, and a third baseline period. To assess the accuracy of A-scan, aortic diameter was measured by transesophageal echocardiography. The difference between echocardiography and A-scan was used to determine bias and precision for aortic diameter measurements. TD-CO and ABF variations were analyzed using Kruskal-Wallis and Wilcoxon tests. Association between TD-CO and ABF values was determined by calculating the linear correlation coefficient. The ability of ABF to detect a TD-CO >6.0 L/min and its variations >13% was analyzed by determination of sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. MEASUREMENTS AND MAIN RESULTS Aortic diameter measurements by A-scan and bidimensional methods were 23.0+/-2.8 mm (SD) and 24.2+/-2.7 mm, respectively. Bias and precision were 1.1 mm and 1.4 mm (95% confidence interval: -1.9 to 3.7), respectively. During the course of dobutamine infusion, we observed a significant increase of TD-CO mean value from 6.65+/-1.53 L/min to 9.30+/-2.5 L/min (p=.0008), and a parallel and significant increase in ABF mean value from 4.34+/-1.18 L/min to 5.70+/-1.63 L/min (p= .0029). Absolute TD-CO and ABF values had a correlation coefficient of 0.80. For detection of an increased TD-CO, PPV and NPV were 87% and 86%, respectively. For detection of TD-CO changes >13%, PPV and NPV were 80% and 94%, respectively. CONCLUSIONS The Dynemo-3000 system is able to display the real aortic diameter, which is one of the most important components of this noninvasive ultrasonic technique. When compared with TD-CO, the ABF determination provided by this ultrasonic device constitutes a reliable noninvasive tool for estimating CO and tracking its changes.
Integration of Activating and Inhibitory Receptor Signaling by Regulated Phosphorylation of Vav1 in Immune Cells

The extent of phosphorylation of a guanine nucleotide exchange factor determines the cytotoxicity of natural killer cells. Deciding Cytotoxicity Natural killer (NK) cell activity depends on the interplay between activating and inhibitory receptors. Activating receptors stimulate the recruitment and phosphorylation of Vav1, a factor required to drive formation of the contact area between the NK cell and its target. Conversely, inhibitory receptor signaling results in the dephosphorylation of Vav1 to block activation. Mesecke et al. modeled multiple combinations of signaling events upstream of Vav1, classifying the input-output behaviors into different phenotypic classes. The authors used their models to predict that Vav1 occupied a central “decision-making” hub in the crosstalk between activating and inhibitory signals and that the phosphorylation of Vav1 depended on the physical association of activating receptors with Src family kinases. Further, the extent of phosphorylation of Vav1 correlated with the cytotoxic activity of NK cells. Validation of these predictions in NK cells suggests that this mathematical approach may prove useful in understanding the nonlinear integration of opposing signals in other systems. Natural killer (NK) cells are effector cells of the immune system whose activation is carefully regulated by the interplay of signals from activating and inhibitory receptors. Signals from activating receptors induce phosphorylation of the guanine nucleotide exchange factor Vav1, whereas those from inhibitory receptors lead to the dephosphorylation of Vav1 by the Src homology 2 domain–containing protein tyrosine phosphatase 1 (SHP-1). Here, we used mathematical modeling and experiments with NK cells to gain insight into this integration of positive and negative signals at a molecular level. Our data showed a switch-like regulation of Vav1 phosphorylation, the extent of which correlated with the cytotoxic activity of NK cells. Comparison of our experimental results with the predictions that we derived from an ensemble of 72 mathematical models showed that a physical association between Src family kinases and activating receptors on NK cells was essential to generate the cytotoxic response. Our data support a central role for Vav1 in determining the cytotoxic activity of NK cells and provide insight into the molecular mechanism of the integration of positive and negative signals during lymphocyte activation.
Clinical predictors of functional outcome of bipolar patients in remission.

OBJECTIVES A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample. METHODS The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome. RESULTS Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables-older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations-were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F = 12.54, df = 58, p < 0.001). CONCLUSIONS A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.
Just One Look, and Fractures and Death Can Be Predicted in Elderly Ambulatory Women

Background: The chronological age is clearly the strongest risk factor for fractures or death. Age as a concept can be described exactly as chronological age. Age in relative terms can be described as biological age. Objective: We postulated that, even without taking into account known or unknown comorbidity, an immediate and totally subjective evaluation of an individual’s biological age is predictive of forthcoming fractures and death. Methods: At baseline the biological age was estimated in 1,004 randomly recruited ambulatory 75-year-old women. All women were of the same ethnic background. Two independent observers estimated the biological age within 15 s of first sight of each woman. Based on this estimation of the biological age, the women were divided into tertiles. The women were then followed prospectively for a mean of 4.6 (range 3.0–6.5) years. All retrospective fractures and prospective fractures and deaths were registered. Results: When the tertile of the biologically oldest women was compared with all other women, their odds ratio for sustaining any type of prospective fracture was 1.71 (95% confidence interval 1.22–2.39), for hip fractures 2.69 (1.42–5.11), for clinical vertebral fractures 2.83 (1.57–5.11), and for multiple fractures 3.17 (1.64–6.10). Also, when retrospectively sustained fractures were included, the predictive ability for biological age remained. The death rate amongst the tertile of biologically oldest women was increased when compared with the rest of the women (odds ratio 4.33, CI 3.62–5.17). Conclusions: In ambulatory elderly women, without specific consideration of comorbidity, a subjective estimate of the biological age is predictive of future fractures and death. Subjective estimation of the biological age, in relation to the chronological age, is a valuable indicator of health, conveying additional information that merits its use in clinical practice.
Impact of Medicaid disenrollment in Tennessee on breast cancer stage at diagnosis and treatment

States routinely may consider rollbacks of Medicaid expansions to address statewide economic conditions. To the authors' knowledge, little is known regarding the effects of public insurance contractions on health outcomes. The current study examined the effects of the 2005 Medicaid disenrollment in Tennessee on breast cancer stage at the time of diagnosis and delays in treatment among nonelderly women.
The Professionalism Movement: Can We Pause?

The topic of developing professionalism dominated the content of many academic medicine publications and conference agendas during the past decade. Calls to address the development of professionalism among medical students and residents have come from professional societies, accrediting agencies, and a host of educators in the biomedical sciences. The language of the professionalism movement is now a given among those in academic medicine. We raise serious concerns about the professionalism discourse and how the specialized language of academic medicine disciplines has defined, organized, contained, and made seemingly immutable a group of attitudes, values, and behaviors subsumed under the label of "professionalism. " In particular, we argue that the professionalism discourse needs to pay more attention to the academic environment in which students are educated, that it should articulate specific positive behaviors, that the theory of professionalism must be constructed from a dialogue with those we are educating, and that this theoretical and practical discourse must aim at a deeper understanding of social justice and the role of medicine within a just society.
Validity and Rater Reliability of Peer and Self Assessments for Urban Middle School Students

This project studied the validity and reliability of self and peer assessments used for group work. The targeted population is middle school students in urban schools. The sample includes 45 sixth graders selected from a public middle school in a large Midwestern metropolitan area. The students worked in groups to complete a classroom project. Self and peer assessment forms were used to rate each member's contribution to the group work. A Generalizability Theory design was used to evaluate the reliability of self and peer assessments. The validity of student ratings was assessed by comparing them to those assigned by the teacher. Results of this study indicate that peer ratings were not significantly different from teacher scores, but self-assessment scores were significantly higher than teacher scores. Acceptable rater reliability was achieved only when self-assessment scores were excluded.
Using genetic algorithms for optimal design of trusses

The paper presents a method for optimizing the design of plane and space trusses subject to a specified set of constraints. The method is based upon a search technique using genetic algorithms. Traditional structural optimization techniques consider it continuous search space, and consequently lead to unrealistic solutions because structural members are not available in continuously varying sizes. A practical method should consider only the discrete values associated with commonly available materials. On the other hand, most modern structural optimization techniques, even when they consider a discrete search space, suffer a lack of generality, and tend to be limited to a certain kind of structure. Genetic algorithms remedy these two problems since they can deal with discrete search spaces and they are general enough to be easily extended to any kind of structure without substantial modifications. Our results show the genetic algorithm can provide very good solutions, often surpassing other complex and specialized techniques. <<ETX>>
Local Dynamics and the Emergence of Social Inequality in Iron Age Botswana

Since the earliest class-based societies, social leveling mechanisms have limited, actively as well as unconsciously, social stratification. Understanding how such power structures have operated in the past and present requires the integration of social dimensions to the political economy in a way that does not assume that elites and/or urban centers drive the course of history. Here, the Middle and Late Iron Age in southern Africa (AD 900–1650) highlight the importance of these local dynamics in tandem with broader regional changes. At a time when protoglobal trade links Africa to the Middle East and Asia, cities emerged up to 1,000 km inland along with the material evidence for hereditary inequality. Yet the population at the trade center of Bosutswe at the eastern edge of the Kalahari responded flexibly to environmental and social variables, which, perhaps unintentionally, limited the consolidation of power in the hands of the elite. The following case study of Khubu la Dintša, a small agropastoral site near Bosutswe, reminds us that, even as hegemony exists, an emphasis on the social networks that tie together local and disparate groups results in not just daily patterns of behavior but also significant social change.
Jets in the magnetosheath: IMF control of where they occur

Abstract. Magnetosheath jets are localized regions of plasma that move faster towards the Earth than the surrounding magnetosheath plasma. Due to their high velocities, they can cause indentations when colliding into the magnetopause and trigger processes such as magnetic reconnection and magnetopause surface waves. We statistically study the occurrence of these jets in the subsolar magnetosheath using measurements from the five Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft and OMNI solar wind data from 2008 to 2011. We present the observations in the BIMF–vSW plane and study the spatial distribution of jets during different interplanetary magnetic field (IMF) orientations. Jets occur downstream of the quasi-parallel bow shock approximately 9 times as often as downstream of the quasi-perpendicular shock, suggesting that foreshock processes are responsible for most jets. For an oblique IMF, with 30–60∘ cone angle, the occurrence increases monotonically from the quasi-perpendicular side to the quasi-parallel side. This study offers predictability for the numbers, locations, and magnetopause impact rates of jets observed during different IMF orientations, allowing us to better forecast the formation of these jets and their impact on the magnetosphere.