An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet.

Broad absorption signatures from alkali metals, such as the sodium (Na I) and potassium (K I) resonance doublets, have long been predicted in the optical atmospheric spectra of cloud-free irradiated gas giant exoplanets1-3. However, observations have revealed only the narrow cores of these features rather than the full pressure-broadened profiles4-6. Cloud and haze opacity at the day-night planetary terminator are considered to be responsible for obscuring the absorption-line wings, which hinders constraints on absolute atmospheric abundances7-9. Here we report an optical transmission spectrum for the 'hot Saturn' exoplanet WASP-96b obtained with the Very Large Telescope, which exhibits the complete pressure-broadened profile of the sodium absorption feature. The spectrum is in excellent agreement with cloud-free, solar-abundance models assuming chemical equilibrium. We are able to measure a precise, absolute sodium abundance of logεNa = [Formula: see text], and use it as a proxy for the planet's atmospheric metallicity relative to the solar value (Zp/Zʘ = [Formula: see text]). This result is consistent with the mass-metallicity trend observed for Solar System planets and exoplanets10-12.

Less absorbed solar energy and more internal heat for Jupiter.

The radiant energy budget and internal heat are fundamental properties of giant planets, but precise determination of these properties remains a challenge. Here, we report measurements of Jupiter's radiant energy budget and internal heat based on Cassini multi-instrument observations. Our findings reveal that Jupiter's Bond albedo and internal heat, 0.503 ± 0.012 and 7.485 ± 0.160 W m-2 respectively, are significantly larger than 0.343 ± 0.032 and 5.444 ± 0.425 Wm-2, the previous best estimates. The new results help constrain and improve the current evolutionary theories and models for Jupiter. Furthermore, the significant wavelength dependency of Jupiter's albedo implies that the radiant energy budgets and internal heat of the other giant planets in our solar system should be re-examined. Finally, the data sets of Jupiter's characteristics of reflective solar spectral irradiance provide an observational basis for the models of giant exoplanets.

VEGF-induced phosphorylation of Bcl-2 influences B lineage leukemic cell response to apoptotic stimuli.

Post-translational modification of Bcl-2 protein has been described in a variety of cell models with effects varying from enhanced to abrogated function. In this study, we demonstrated that Bcl-2 was constitutively phosphorylated in several hematopoietic tumor cell lines and in primary ALL cells. Increased phosphorylation of Bcl-2 protein in the JM1 ALL cell line, achieved by expression of the phosphomimetic Bcl-2 construct S70E, enhanced JM1 cell chemoresistance. In contrast, initiation of JM1 cell apoptosis was coincident with dephosphorylation of Bcl-2 and elevated protein phosphatase 2A activity. S70E expression also diminished tBid-mediated cytochrome c release and blunted chemotherapy-induced activation of caspases-9 and -3 in JM1 cells. To determine whether soluble factors produced by stromal cells in the bone marrow influence phosphorylation of Bcl-2 protein, a panel of recombinant cytokines was evaluated. Of those tested, vascular endothelial growth factor (VEGF) induced phosphorylation of Bcl-2 protein and blunted cytochrome c release during chemotherapy or tBid treatment of ALL cells. In contrast, JM1 cells transfected with S70A, resulting in expression of Bcl-2 protein that cannot be phosphorylated, were not efficiently rescued from apoptosis by VEGF. These observations suggest that optimal protection of leukemic cells by VEGF may require activation of a pathway that includes Bcl-2 phosphorylation.

ON THE COMPOSITION OF YOUNG, DIRECTLY IMAGED GIANT PLANETS.

The past decade has seen significant progress on the direct detection and characterization of young, self-luminous giant planets at wide orbital separations from their host stars. Some of these planets show evidence for disequilibrium processes like transport-induced quenching in their atmospheres; photochemistry may also be important, despite the large orbital distances. These disequilibrium chemical processes can alter the expected composition, spectral behavior, thermal structure, and cooling history of the planets, and can potentially confuse determinations of bulk elemental ratios, which provide important insights into planet-formation mechanisms. Using a thermo/photochemical kinetics and transport model, we investigate the extent to which disequilibrium chemistry affects the composition and spectra of directly imaged giant exoplanets. Results for specific "young Jupiters" such as HR 8799 b and 51 Eri b are presented, as are general trends as a function of planetary effective temperature, surface gravity, incident ultraviolet flux, and strength of deep atmospheric convection. We find that quenching is very important on young Jupiters, leading to CO/CH4 and N2/NH3 ratios much greater than, and H2O mixing ratios a factor of a few less than, chemical-equilibrium predictions. Photochemistry can also be important on such planets, with CO2 and HCN being key photochemical products. Carbon dioxide becomes a major constituent when stratospheric temperatures are low and recycling of water via the H2 + OH reaction becomes kinetically stifled. Young Jupiters with effective temperatures ≲700 K are in a particularly interesting photochemical regime that differs from both transiting hot Jupiters and our own solar-system giant planets.

Karyotypic analysis of adult pluripotent stem cells.

Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.

Habitable evaporated cores: transforming mini-Neptunes into super-Earths in the habitable zones of M dwarfs.

We show that photoevaporation of small gaseous exoplanets ("mini-Neptunes") in the habitable zones of M dwarfs can remove several Earth masses of hydrogen and helium from these planets and transform them into potentially habitable worlds. We couple X-ray/extreme ultraviolet (XUV)-driven escape, thermal evolution, tidal evolution, and orbital migration to explore the types of systems that may harbor such "habitable evaporated cores" (HECs). We find that HECs are most likely to form from planets with ∼1 M⊕ solid cores with up to about 50% H/He by mass, though whether or not a given mini-Neptune forms a HEC is highly dependent on the early XUV evolution of the host star. As terrestrial planet formation around M dwarfs by accumulation of local material is likely to form planets that are small and dry, evaporation of small migrating mini-Neptunes could be one of the dominant formation mechanisms for volatile-rich Earths around these stars.

Discovery and spectroscopy of the young jovian planet 51 Eri b with the Gemini Planet Imager.

Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the Gemini Planet Imager, we discovered a planet orbiting the ~20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 × 10(-6) and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter.

Earnings changes for depressed individuals treated by mental health specialists.

OBJECTIVE: It is unclear whether the additional benefits of receiving depression treatment from mental health specialists in routine care pays for the additional costs, compared with treatment delivered by general medical providers. This study examines the difference in lost earnings and the difference in treatment costs experienced by depressed individuals treated in these two sectors. METHOD: Representative community residents with depression were recruited and interviewed at baseline and at 6-month and 12-month follow-ups. Lost earnings were measured by lost workdays multiplied by subjects' wage rates. Treatment costs were approximated by charges abstracted from provider and insurance records. RESULTS: After controlling for sociodemographic variables, baseline severity, and baseline comorbidity, the authors found a net mean annual economic savings of $877 associated with depression treatment delivered in the mental health sector compared with the general medical sector. Sensitivity analyses in alternative scenarios indicated similar savings. CONCLUSIONS: Although it is the trend for primary care providers to provide mental health services, these analyses indicate a net economic savings if depression treatment is provided by mental health specialists, probably as a result of patients' greater functional improvement. As gatekeepers, especially in managed care, primary care providers have a unique responsibility to identify and detect patients with mental health problems. In the current structure, however, they may lack the necessary time to provide effective mental health services. Therefore, mental health specialists play a crucial role, with primary care providers' cooperation (i.e., detection, consultation, and referral), in providing the most cost-effective mental health services.

Expenditures for the treatment of major depression.

OBJECTIVE: Health policy makers lack accurate information about per capita spending for the treatment of major depression, the distribution of those expenditures, and the proportion of the health care dollar consumed by depression treatment. METHOD: The authors recruited and followed a community cohort of individuals with major depression; the 298 subjects were either enrolled in fee-for-service insurance plans or self-insured. Charges for all health care services received during the year following baseline were abstracted from medical and insurance records. RESULTS: Over the course of 1 year, 48.1% of the subjects received depression treatment. The per capita total expenditure for inpatient and outpatient depression treatment averaged $631, with a median of $152, for the treated subjects. Just 4.9% of the treated subjects consumed 45.0% of the outpatient expenditures. Depression treatment consumed only 8 cents of every health care dollar spent on the patients treated for depression. CONCLUSIONS: Studies are needed to examine how the level and distribution of expenditures for depression treatment change under managed care and to determine whether and how any differences affect outcomes in the afflicted population. Managed care attempts to contain costs by limiting outpatient care may not affect total health care expenditures dramatically, since depression treatment consumes such a minuscule portion of the health care dollar spent on this population.

Anesthesia for pediatric external beam radiation therapy.

BACKGROUND: For very young patients, anesthesia is often required for radiotherapy. This results in multiple exposures to anesthetic agents over a short period of time. We report a consecutive series of children anesthetized for external beam radiation therapy (EBRT). METHODS: Five hundred twelve children < or = 16 years old received EBRT from January 1983 to February 1996. Patient demographics, diagnosis, anesthesia techniques, monitoring, airway management, complications, and outcome were recorded for the patients requiring anesthesia. RESULTS: One hundred twenty-three of the 512 children (24%) required 141 courses of EBRT with anesthesia. Anesthetized patients ranged in age from 20 days to 11 years (mean 2.6 +/- 1.8 ). The frequency of a child receiving EBRT and requiring anesthesia by age cohort was: < or = 1 year (96%), 1-2 years (93%), 2-3 years (80%), 3-4 years (51%), 4-5 years (36%), 5-6 years (13%), 6-7 years (11%), and 7-16 years (0.7%). Diagnoses included: primary CNS tumor (28%), retinoblastoma (27%), neuroblastoma (20%), acute leukemia (9%), rhabdomyosarcoma (6%), and Wilms' tumor (4%). Sixty-three percent of the patients had been exposed to chemotherapy prior to EBRT. The mean number of anesthesia sessions per patient was 22 +/- 16. Seventy-eight percent of the treatment courses were once daily and 22% were twice daily. Anesthesia techniques included: short-acting barbiturate induction + inhalation maintenance (21%), inhalation only (20%), ketamine (19%), propofol only (12%), propofol induction + inhalation maintenance (7%), ketamine induction + inhalation maintenance (6%), ketamine or short-acting barbiturate induction + inhalation maintenance (6%). Monitoring techniques included: EKG (95%), O2 saturation (93%), fraction of inspired O2 (57%), and end-tidal CO2 (55%). Sixty-four percent of patients had central venous access. Eleven of the 74 children with a central line developed sepsis (15%): 6 of the 11 were anesthetized with propofol (55%), 4 with a short-acting barbiturate induction plus inhalation maintenance (36%), and 1 with inhalation alone (9%). Eight of the 11 (73%) received prior chemotherapy. CONCLUSION: Anesthesia was generally necessary at < or = 3 years, and rarely required at > 5 years of age. Sepsis associated with frequent use of the central venous access line was seen in 15% of the patients with these lines.

Alteration of nuclear factor-kappaB (NF-kappaB) expression in bone marrow stromal cells treated with etoposide.

Bone marrow stromal cells are an essential regulatory component in the hematopoietic microenvironment. Regulation of hematopoietic cell development is mediated, in part, through interaction of progenitor cells with stromal cell vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 expression has been shown to be driven primarily by binding of nuclear factor-kappaB (NF-kappaB) to two consensus binding sites in the promoter region. In this study, we show that down-regulation of VCAM-1 by the chemotherapeutic agent etoposide (VP-16) is associated with altered cellular localization of NF-kappaB. We demonstrated that VCAM-1 was diminished at the transcriptional level following treatment of stromal cells with VP-16, without alteration of VCAM-1 stability. Culture of bone marrow stromal cells in VP-16 resulted in reduced nuclear RelA (p65), a modest increase in nuclear NF-kappaB1 (p50), and reduced NF-kappaB binding to its DNA consensus sequence. Total levels of the NF-kappaB inhibitor Ikappa-Balpha were reduced during exposure to VP-16. Following removal of VP-16 from the culture, p65 and p50 nuclear profiles approximated those of untreated stromal cells, and VCAM-1 protein expression was restored. The current study indicates that NF-kappaB is a target molecule that is responsive to VP-16-induced damage in bone marrow stromal cells. As the primary transcription factor that promotes VCAM-1 expression, the observed changes in p65 and p50 cellular localization during treatment have a direct consequence for stromal cell function. The myriad of genes regulated by NF-kappaB, including both adhesion molecules and cytokines that contribute to stromal cell function, make chemotherapy-induced disruption of NF-kappaB biologically significant. Alterations in NF-kappaB activity may provide one measure by which the effects of aggressive treatment strategies on the bone marrow microenvironment can be evaluated.

Reproductive epidemiologic research in developing countries.

This paper discusses the scientific rationale for carrying out reproductive epidemiologic research in developing countries, and the generalizability of results of research done in developed countries to developing countries. Practical problems encountered in doing research in developing countries include limited resources, overcommitted researchers, cost, and study monitoring. Cultural differences that affect the design and conduct of research activities in developing countries are also discussed.

Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy.

The interaction between leukemic cells and stromal cells of the bone marrow microenvironment has been shown to enhance leukemic cell survival during exposure to chemotherapeutic agents. In the current study we investigated whether association of B lineage acute lymphoblastic leukemic cells with human bone marrow stromal cells altered caspase activation during chemotherapy treatment. Following treatment with Ara-C or VP-16 in vitro, caspase 3 activity in leukemic cells was consistently reduced by co-culture of leukemic cells with human bone marrow stromal cell layers. These observations suggest that the protective effect of the bone marrow microenvironment on leukemic cells may be due, in part, to regulation of caspase 3 activity.

Plasma antioxidant depletion after cardiopulmonary bypass in operations for congenital heart disease.

We describe the use of two in vitro tests to characterize plasma antioxidant capacity at the time of cardiac bypass in operations for congenital heart disease in 30 patients aged 3 days to 16 years (average 4.4 +/- 0.9 years [standard error]). Bypass and crossclamp time, circuit volume, and type of operation were recorded for each patient. First, a test of plasma radical antioxidant power measured chain breaking (secondary) antioxidant capacity of plasma to prevent oxidation of linoleic acid in vitro. Second, overall ability of plasma to prevent lipid peroxidation was assessed by a classic test of plasma inhibition of malondialdehyde formation in a beef brain homogenate. Plasma total radical antioxidant power level at baseline was 0.74 +/- 0.03 mumol/ml plasma, which decreased to 0.15 +/- 0.05 mumol/ml plasma after bypass (p < 0.001) and 0.26 +/- 0.08 mumol/ml plasma with recovery (n = 18, p < 0.001). Analysis of variance of postbypass total radical antioxidant power value showed age (p = 0.0002, r = 0.63) and bypass time (p = 0.009, r = 0.4677) to be significant factors. Pump prime volume in milliliters per kilogram and preoperative hemoglobin value were not significant factors. Beef brain malondialdehyde formation in vitro was limited 92% +/- 3% by normal plasma before operation versus 53% +/- 5% after operation (p < 0.001) and 51% +/- 5% at recovery after arrival in the pediatric intensive care unit (p < 0.001). Analysis of variance of the changes from before to after operation showed age p = 0.0015, r = 0.55) and bypass time (p = 0.033, r = 0.39) to be significant factors. Thus antioxidant capacity of plasma is significantly diminished after cardiopulmonary bypass in children. Young patient age and long duration of cardiopulmonary bypass are identified as factors that correlate positively with depletion of antioxidant capacity with bypass.

Selective screening for cervical neoplasia: an approach for resource-poor settings.

BACKGROUND: Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. METHODS: To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. RESULTS: Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. CONCLUSION: Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit.

A comparison of two cause-of-death classification systems for deaths among women of reproductive age in Menoufia, Egypt.

Mortality data ascertained from sources other than a death registration system can validate the accuracy of the system, but this information is rarely obtained. Data on 1979 deaths among reproductive age women were collected in the 1981-1983 Reproductive Age Mortality Survey (RAMOS) in the governorate of Menoufia, Egypt, and compared with data on these deaths as recorded by the Egyptian death registration system. Although the distribution of the causes of death were similar, there were substantial differences between classification systems for deaths due to particular causes. Over half of the deaths classified differently by the systems were those assigned to circulatory disease on the death certificate. In contrast, there was a high rate of agreement between systems in the classification of trauma deaths. About half (52.4%) of cancer deaths had the same site-specific cancer diagnosis assigned by RAMOS. The percentage of deaths assigned to maternal causes was three times higher in RAMOS (19.2%) than on death certificates (6.1%). Reported mortality rates for this often-preventable cause of death have been substantially underestimated in national death registration systems. Such underreporting masks the need for additional prenatal care and maternal health programmes.

Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica.

The relationship between cervical cancer and the use of depot-medroxyprogesterone acetate (DMPA) was examined in a nationwide case-control study in Costa Rica. Cases were women ages 25-58 years of age with invasive squamous cell cancer (N = 149) or carcinoma in situ (CIS, N = 415) reported by the National Tumor Registry during 1982-84. Controls (N = 764) were randomly selected during a nationwide household survey. Using logistic regression, we adjusted for known risk factors for cervical cancer. DMPA use was associated with a risk of CIS of 1.1 (95% confidence interval 0.6-1.8) and a risk of invasive cancer of 1.4 (95% confidence interval 0.6-3.1). The slightly elevated risks observed may be the result of chance or a detection bias. One limitation of this study is that few women had used DMPA for longer than two years.

PIP: A nationwide case-control study was conducted in Costa Rica in 1984-85 to examine the association between depot-medroxyprogesterone acetate (DMPA) and cervical cancer. Cases, restricted to women 25-58 years of age at the time of diagnosis, were women with invasive squamous cell cancer (n = 149) or carcinoma in situ (CIS, n=415) reported by the National Tumor Registry during 1982-84. The 764 controls were randomly selected during a nationwide household survey. On average, the CIS cases were younger than controls; the invasive cases were older than controls. Both case groups were more likely than controls to be of low socioeconomic status, to have become sexually active at a young age, to report a history of a sexually transmitted disease or pelvic inflammatory disease, and to report having 3 or more partners in their lifetime. Ever users of DMPA had a risk of CIS of 1.1 when compared with never users. Women who 1st used DMPA before age 30 had a CIS risk of 0.6 whereas users who began use after age 39 had a risk of 2.0. Both of these risk estimates were based on small numbers of users. Ever users of DMPA had a risk of invasive cancer of 1.4 when compared with never users, but all estimates for invasive cancer were based on only 10 cases who reported use of DMPA. Few of the women had used DMPA for longer than 2 years.

Efficacy of external cephalic version: a review.

OBJECTIVE: To assess the efficacy of external cephalic version, including safety, cost-benefit analysis, and impact on the cesarean delivery rate. DATA SOURCES: A MEDLINE search was conducted to identify all articles published in English between 1980-1991 on external cephalic version. References were also cross-checked for all reports. METHODS OF STUDY SELECTION: We reviewed only those articles providing sufficiently detailed data to determine actual numbers of subjects. In cases of duplicate results, only the latest publication was used. Rates of successful version, cesarean delivery, and fetal and maternal complications were presented. DATA EXTRACTION AND SYNTHESIS: Among the United States trials, the success rate was approximately 65% (range 48-77%), and once version succeeded, almost all the fetuses stayed in the vertex position until birth. Among those in whom external version was performed, the mean cesarean delivery rate was 37%, compared with 83% in controls (P < .001). External version would also save 12.3% of the costs of delivering breech patients overall. CONCLUSION: External cephalic version is safe and cost-effective. It substantially reduces the cesarean delivery rate among breech presentations, decreases the risk related to breech delivery, and avoids cesarean delivery in subsequent pregnancies. However, external version will not have a major impact on the high overall cesarean birth rate.

Provider choice and utility loss due to selective contracting in rural and urban areas.

An econometric model estimated the disutility of traveling long distances for depression treatment, and simulations calculated the utility loss associated with selective contracting in rural and urban areas. A representative sample of depression patients (n = 106) and all practicing providers (n = 3,710) in Arkansas were identified and the distances between them were calculated. Using discrete choice analysis, patient preferences for provider type and travel distance were estimated. Simulations calculated the utility loss associated with alternative scenarios of selective contracting. Provider type and distance were significant predictors of provider choice. To equate the utility loss associated with selective contracting in rural and urban areas, a slightly higher proportion of rural physicians and a substantially higher proportion of rural mental health specialists must be contracted. To avoid further reductions in geographic access, managed care organizations should contract with a higher proportion of rural providers than urban providers.

Persistently poor outcomes of undetected major depression in primary care.

Despite its relevance for quality care initiatives, the field of psychiatry has little scientific knowledge regarding the course of current major depression when primary care patients with the disorder remain undetected. Using statewide telephone screening, we identified and followed 98 adults with current major depression who made one or more visits to a primary care physician during the 6 months following baseline. Thirty-two percent of primary care patients with current major depression remained undetected for up to 1 year. Almost half of undetected patients developed suicidal ideation. Less than one-third of undetected patients made a visit during the month they reported their worst symptoms. Fifty-three percent of undetected patients reported five or more current symptoms at 1 year follow-up. Primary care patients with undetected major depression report persistently poor outcomes. Comparison of outcomes with detected patients suggests that quality improvement efforts directed at improving detection without improving management of detected patients may not improve outcomes.