MagneToRE: Mapping the 3-D Magnetic Structure of the Solar Wind Using a Large Constellation of Nanosatellites

Unlike the vast majority of astrophysical plasmas, the solar wind is accessible to spacecraft, which for decades have carried in-situ instruments for directly measuring its particles and fields. Though such measurements provide precise and detailed information, a single spacecraft on its own cannot disentangle spatial and temporal fluctuations. Even a modest constellation of in-situ spacecraft, though capable of characterizing fluctuations at one or more scales, cannot fully determine the plasma’s 3-D structure. We describe here a concept for a new mission, the Magnetic Topology Reconstruction Explorer (MagneToRE), that would comprise a large constellation of in-situ spacecraft and would, for the first time, enable 3-D maps to be reconstructed of the solar wind’s dynamic magnetic structure. Each of these nanosatellites would be based on the CubeSat form-factor and carry a compact fluxgate magnetometer. A larger spacecraft would deploy these smaller ones and also serve as their telemetry link to the ground and as a host for ancillary scientific instruments. Such an ambitious mission would be feasible under typical funding constraints thanks to advances in the miniaturization of spacecraft and instruments and breakthroughs in data science and machine learning

Impact of change in maternal age composition on the incidence of Caesarean section and low birth weight: analysis of delivery records at a tertiary hospital in Tanzania, 1999–2005

<p>Abstract</p> <p>Background</p> <p>Previous studies on change in maternal age composition in Tanzania do not indicate its impact on adverse pregnancy outcomes. We sought to establish temporal changes in maternal age composition and their impact on annual Caesarean section (CS) and low birth weight deliveries (LBWT) at Muhimbili National Hospital in Tanzania.</p> <p>Methods</p> <p>We conducted data analysis of 91,699 singleton deliveries that took place in the hospital between 1999 and 2005. The data were extracted from the obstetric data base. Annual proportions of individual age groups were calculated and their trends over the years studied. Multiple logistic analyses were conducted to ascertain trends in the risks of CS and LBWT. The impact of age composition changes on CS and LBWT was estimated by calculating annual numbers of these outcomes with and without the major changes in age composition, all others remaining equal. In all statistics, a p value < 0.05 was considered significant.</p> <p>Results</p> <p>The proportion of teenage mothers (12–19 years) progressively decreased over time while that of 30–34 years age group increased. From 1999, the risk of Caesarean delivery increased steadily to a maximum in 2005 [adjusted OR = 1.7; 95%CI (1.6–1.8)] whereas that of LBWT declined to a minimum in 2005 (adjusted OR = 0.76; 95% CI (0.71–0.82). The current major changes in age trend were responsible for shifts in the number of CS of up to206 cases per year. Likewise, the shift in LBWT was up to 158 cases per year, but the 30–34 years age group had no impact on this.</p> <p>Conclusion</p> <p>The population of mothers giving birth at MNH is progressively becoming older with substantial impact on the incidence of CS and LBWT. Further research is needed to estimate the health cost implications of this change.</p

Incidence of stillbirth and perinatal mortality and their associated factors among women delivering at Harare Maternity Hospital, Zimbabwe: a cross-sectional retrospective analysis

BACKGROUND: Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Infant mortality remains a challenge in the care of pregnant women worldwide, but particularly for developing countries and the need to understand contributory factors is crucial for addressing appropriate perinatal health. METHODS: Using information available in obstetric records for all deliveries (17,072 births) at Harare Maternity Hospital, Zimbabwe, we conducted a cross-sectional retrospective analysis of a one-year data, (1997–1998) to assess demographic and obstetric risk factors for stillbirth and early neonatal death. We estimated risk of stillbirth and early neonatal death for each potential risk factor. RESULTS: The annual frequency of stillbirth was 56 per 1,000 total births. Women delivering stillbirths and early neonatal deaths were less likely to receive prenatal care (adjusted relative risk [RR] = 2.54; 95% confidence intervals [CI] 2.19–2.94 and RR = 2.52; 95% CI 1.63–3.91), which for combined stillbirths and early neonatal deaths increased with increasing gestational age (Hazard Ratio [HR] = 3.98, HR = 7.49 at 28 and 40 weeks of gestation, respectively). Rural residence was associated with risk of infant dying in utero, (RR = 1.33; 95% CI 1.12–1.59), and the risk of death increased with increasing gestational age (HR = 1.04, HR = 1.69, at 28 and 40 weeks of gestation, respectively). Older maternal age was associated with risk of death (HR = 1.50; 95% CI 1.21–1.84). Stillbirths were less likely to be delivered by Cesarean section (RR = 0.64; 95% CI 0.51–0.79), but more likely to be delivered as breech (RR = 4.65; 95% CI 3.88–5.57, as were early neonatal deaths (RR = 3.38; 95% CI 1.64–6.96). CONCLUSION: The frequency of stillbirth, especially macerated, is high, 27 per 1000 total births. Early prenatal care could help reduce perinatal death linking the woman to the health care system, increasing the probability that she would seek timely emergency care that would reduce the likelihood of death of her infant in utero. Improved quality of obstetric care during labor and delivery may help reduce the number of fresh stillbirths and early neonatal deaths

The joint influence of marital status, interpregnancy interval, and neighborhood on small for gestational age birth: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Interpregnancy interval (IPI), marital status, and neighborhood are independently associated with birth outcomes. The joint contribution of these exposures has not been evaluated. We tested for effect modification between IPI and marriage, controlling for neighborhood.</p> <p>Methods</p> <p>We analyzed a cohort of 98,330 live births in Montréal, Canada from 1997–2001 to assess IPI and marital status in relation to small for gestational age (SGA) birth. Births were categorized as subsequent-born with <it>short </it>(<12 months), <it>intermediate </it>(12–35 months), or <it>long </it>(36+ months) IPI, or as firstborn. The data had a 2-level hierarchical structure, with births nested in 49 neighborhoods. We used multilevel logistic regression to obtain adjusted effect estimates.</p> <p>Results</p> <p>Marital status modified the association between IPI and SGA birth. Being unmarried relative to married was associated with SGA birth for all IPI categories, particularly for subsequent births with <it>short </it>(odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31–1.95) and <it>intermediate </it>(OR 1.48, 95% CI 1.26–1.74) IPIs. Subsequent births had a lower likelihood of SGA birth than firstborns. <it>Intermediate </it>IPIs were more protective for married (OR 0.50, 95% CI 0.47–0.54) than unmarried mothers (OR 0.65, 95% CI 0.56–0.76).</p> <p>Conclusion</p> <p>Being unmarried increases the likelihood of SGA birth as the IPI shortens, and the protective effect of <it>intermediate </it>IPIs is reduced in unmarried mothers. Marital status should be considered in recommending particular IPIs as an intervention to improve birth outcomes.</p

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

BACKGROUND: For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg/kg) are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg) is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. METHODS: Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL) were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus), meningoencephalitis (S. pneumoniae), and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis). RESULTS: The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm(3)). Profound neutropenia (≤10 neutrophils/mm(3)) was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. CONCLUSION: A CPM total dose of 250 mg/kg is sufficient to induce profound and sustained neutropenia (<10 neutrophils/mm(3)) at least during 3 days in outbred mice, is simpler than previously described methods, and allows successful induction of infection in a variety of experimental models

Between life and death: exploring the sociocultural context of antenatal mental distress in rural Ethiopia

The high prevalence of antenatal common mental disorders in sub-Saharan Africa compared to high-income countries is poorly understood. This qualitative study explored the sociocultural context of antenatal mental distress in a rural Ethiopian community. Five focus group discussions and 25 in-depth interviews were conducted with purposively sampled community stakeholders. Inductive analysis was used to develop final themes. Worry about forthcoming delivery and fears for the woman’s survival were prominent concerns of all participants, but only rarely perceived to be pathological in intensity. Sociocultural practices such as continuing physical labour, dietary restriction, prayer and rituals to protect against supernatural attack were geared towards safe delivery and managing vulnerability. Despite strong cultural norms to celebrate pregnancy, participants emphasised that many pregnancies were unwanted and an additional burden on top of pre-existing economic and marital difficulties. Short birth interval and pregnancy out of wedlock were both seen as shameful and potent sources of mental distress. The notion that pregnancy in traditional societies is uniformly a time of joy and happiness is misplaced. Although antenatal mental distress may be self-limiting for many women, in those with enduring life difficulties, including poverty and abusive relationships, poor maternal mental health may persist

A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens

Understanding the mechanisms by which plants trigger host defenses in response to viruses has been a challenging problem owing to the multiplicity of factors and complexity of interactions involved. The advent of genomic techniques, however, has opened the possibility to grasp a global picture of the interaction. Here, we used Arabidopsis thaliana to identify and compare genes that are differentially regulated upon infection with seven distinct (+)ssRNA and one ssDNA plant viruses. In the first approach, we established lists of genes differentially affected by each virus and compared their involvement in biological functions and metabolic processes. We found that phylogenetically related viruses significantly alter the expression of similar genes and that viruses naturally infecting Brassicaceae display a greater overlap in the plant response. In the second approach, virus-regulated genes were contextualized using models of transcriptional and protein-protein interaction networks of A. thaliana. Our results confirm that host cells undergo significant reprogramming of their transcriptome during infection, which is possibly a central requirement for the mounting of host defenses. We uncovered a general mode of action in which perturbations preferentially affect genes that are highly connected, central and organized in modules. © 2012 Rodrigo et al.This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) grants BFU2009-06993 (S. F. E.) and BIO2006-13107 (C. L.) and by Generalitat Valenciana grant PROMETEO2010/016 (S. F. E.). G. R. is supported by a graduate fellowship from the Generalitat Valenciana (BFPI2007-160) and J.C. by a contract from MICINN grant TIN2006-12860. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Rodrigo Tarrega, G.; Carrera Montesinos, J.; Ruiz-Ferrer, V.; Del Toro, F.; Llave, C.; Voinnet, O.; Elena Fito, SF. (2012). A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens. PLoS ONE. 7(7):40526-40526. https://doi.org/10.1371/journal.pone.0040526S405264052677Peng, X., Chan, E. Y., Li, Y., Diamond, D. L., Korth, M. J., & Katze, M. G. (2009). Virus–host interactions: from systems biology to translational research. Current Opinion in Microbiology, 12(4), 432-438. doi:10.1016/j.mib.2009.06.003Dodds, P. N., & Rathjen, J. P. (2010). Plant immunity: towards an integrated view of plant–pathogen interactions. Nature Reviews Genetics, 11(8), 539-548. doi:10.1038/nrg2812Maule, A., Leh, V., & Lederer, C. (2002). The dialogue between viruses and hosts in compatible interactions. 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Cervical Mucus Properties Stratify Risk for Preterm Birth

Background: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. Methods and Findings: To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Conclusions: Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.Massachusetts Institute of Technology. Charles E. Reed Faculty Initiative FundBurroughs Wellcome Fund (Preterm Birth Research Grant)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. DISCUSSION: The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia

Experimental Evolution of an Oncolytic Vesicular Stomatitis Virus with Increased Selectivity for p53-Deficient Cells

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53−/− MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53−/− cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy