Observation errors in early historical upper-air observations

Upper-air observations are a fundamental data source for global atmospheric data products, but uncertainties, particularly in the early years, are not well known. Most of the early observations, which have now been digitized, are prone to a large variety of undocumented uncertainties (errors) that need to be quantified, e.g., for their assimilation in reanalysis projects. We apply a novel approach to estimate errors in upper-air temperature, geopotential height, and wind observations from the Comprehensive Historical Upper-Air Network for the time period from 1923 to 1966. We distinguish between random errors, biases, and a term that quantifies the representativity of the observations. The method is based on a comparison of neighboring observations and is hence independent of metadata, making it applicable to a wide scope of observational data sets. The estimated mean random errors for all observations within the study period are 1.5 K for air temperature, 1.3 hPa for pressure, 3.0 ms−1for wind speed, and 21.4° for wind direction. The estimates are compared to results of previous studies and analyzed with respect to their spatial and temporal variability.

Factors Associated with Early Versus Late Development of Breast and Ovarian Cancer in BRCA1 and BRCA2 Positive Women

Hereditary breast and ovarian cancer (HBOC) is caused by a mutation in the BRCA1 or BRCA2 genes. Women with a BRCA1/2 mutation are at increased risks for breast and ovarian cancer and often develop cancer at an earlier age than the general population. However, some women with a BRCA1/2 mutation do not develop breast or ovarian cancer under the age of 50 years. There have been no specific studies on BRCA positive women with no cancer prior to age 50, therefore this study sought to investigate factors within these women with no cancer under age 50 with respect to reproductive risk factors, BMI, tumor pathology, screening history, risk-reducing surgeries, and family history. 241 women were diagnosed with cancer prior to age 50, 92 with cancer at age 50 or older, and 20 women were over age 50 with no cancer. Data were stratified based on BRCA1 and BRCA2 mutation status. Within the cohorts we investigated differences between women who developed cancer prior to age 50 and those who developed cancer at age 50 or older. We also investigated the differences between women who developed cancer at age 50 or older and those who were age 50 or older with no cancer. Of the 92 women with a BRCA1/2 mutation who developed cancer at age 50 or older, 46 developed ovarian cancer first, 45 developed breast cancer, and one had breast and ovarian cancer diagnosed synchronously. BRCA2 carriers diagnosed age 50 or older were more likely to have ER/PR negative breast tumors when compared to BRCA2 carriers who were diagnosed before age 50. This is consistent with one other study that has been performed. Ashkenazi Jewish women with a BRCA1 mutation were more likely to be diagnosed age 50 or older than other ethnicities. Hispanic women with a BRCA2 mutation were more likely to be diagnosed prior to age 50 when compared to other ethnicities. No differences in reproductive factors or BMI were observed. Further characterization of BRCA positive women with no cancer prior to age 50 may aid in finding factors important in the development of breast or ovarian cancer.

Early Iron Age Kinneret – Early Aramaean or Just Late Canaanite? Remarks on the Material Culture of a Border Site in Northern Palestine at the Turn of an Era

In recent years, scholars have identified Early Iron Age Kinneret as belonging either to the kingdom of Geshur1 or at least as being part of an early Aramaean polity.2 It is the purpose of this paper to reexamine the archaeological evidence for such an assumption and to critically test the currently available data against this hypothesis.

Adolescent Sexual Behavior: Examining Data from Texas and the US

Background: The US has higher rates of teen births and sexually transmitted infections (STI) than other developed countries. Texas youth are disproportionately impacted. Purpose: To review local, state, and national data on teens’ engagement in sexual risk behaviors to inform policy and practice related to teen sexual health. Methods: 2009 middle school and high school Youth Risk Behavior Survey (YRBS) data, and data from All About Youth, a middle school study conducted in a large urban school district in Texas, were analyzed to assess the prevalence of sexual initiation, including the initiation of non-coital sex, and the prevalence of sexual risk behaviors among Texas and US youth. Results: A substantial proportion of middle and high school students are having sex. Sexual initiation begins as early as 6th grade and increases steadily through 12th grade with almost two-thirds of high school seniors being sexually experienced. Many teens are not protecting themselves from unintended pregnancy or STIs – nationally, 80% and 39% of high school students did not use birth control pills or a condom respectively the last time they had sex. Many middle and high school students are engaging in oral and anal sex, two behaviors which increase the risk of contracting an STI and HIV. In Texas, an estimated 689,512 out of 1,327,815 public high school students are sexually experienced – over half (52%) of the total high school population. Texas students surpass their US peers in several sexual risk behaviors including number of lifetime sexual partners, being currently sexually active, and not using effective methods of birth control or dual protection when having sex. They are also less likely to receive HIV/AIDS education in school. Conclusion: Changes in policy and practice, including implementation of evidence-based sex education programs in middle and high schools and increased access to integrated, teen-friendly sexual and reproductive health services, are urgently needed at the state and national levels to address these issues effectively.

Development of micro-electrospray mass spectrometry for ultra high sensitivity and application in the study of drugs of abuse on endogenous \lbrack Met\rbrack $\sp5$-enkephalin release

A micro-electrospray interface was developed specifically for the neurobiological applications described in this dissertation. Incorporation of a unique nano-flow liquid chromatography micro-electrospray "needle" into the micro-electrospray interface (micro-ES/MS) increased the sensitivity of the mass spectrometric assay by $\sim$1000 fold and thus permitted the first analysis of specific neuroactive compounds in brain extracellular fluid collected by in vivo microdialysis (Md).^ Initial in vivo data presented deals with the pharmacodynamics of a novel GABA$\sb{\rm B}$ antagonist and the availability of the compound in its parent (unmetabolized) form to the brain of the anesthetized rat. Next, the first structurally specific endogenous release of (Met) $\sp5$-enkephalin was demonstrated in unanesthetized freely-moving animals (release of $\sim$6.5 fmole of (Met) $\sp5$-enkephalin into the dialysate by direct neuronal depolarization). The Md/micro-ES/MS system was used to test the acute effects of drugs of abuse on the endogenous release of (Met) $\sp5$-enkephalin from the globus pallidus/ventral pallidum brain region in rats. Four drugs known to be abused by man (morphine, cocaine, methamphetamine and diazepam) were tested. Morphine and cocaine both elicited a two-fold or more increase in the release of (Met) $\sp5$-enkephalin over vehicle controls. Diazepam elicited a small decrease in (Met) $\sp5$-enkephalin levels and methamphetamine showed no significant effect on (Met) $\sp5$-enkephalin. These results imply that (Met) $\sp5$-enkephalin may be involved in the reward pathway of certain drugs of abuse. ^

Rescue from apoptosis in early (CD34 selected) versus late (CD34 unselected) human hematopoietic cells by VLA-4 and VCAM-1 dependent adhesion to bone marrow stromal cells

The interaction of hematopoietic precursor cell with bone marrow stromal cells is assumed to be important to the survival of hematopoietic precursor cells during hematopoietic cell long-term culture. Early hematopoietic stem cells are preferentially found within the stromal adherent cell fraction in primary long-term bone marrow cultures. The purpose of this dissertation was to understand the molecular mechanisms that govern these interactions for the regulation of survival and proliferation of early versus late hematopoietic cells.^ Monoclonal antibodies to the VLA-4 recognize the alpha4 beta1 integrin receptor on human hematopoietic cells. This monoclonal antibody blocks the adhesion between early hematopoietic progenitor cells (CD34 selected cells) and stromal cells when added to cultures of these cells. Addition of the VLA-4 monoclonal antibody to cultures of stromal cells and CD34 selected cells was shown to induce apoptosis of CD34 selected cells in these CD34 selected cell/stromal cell cocultures, as measured by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling method. In contrast to these experiments with early hematopoietic progenitor cells (CD34+), the level of adhesion between more differentiated cells (unfractionated hematopoietic cells) and stromal cells was not significantly altered by addition of the anti-VLA-4 monoclonal antibody. Similarly, the level of apoptosis of unfractionated hematopoietic cells was not significantly increased by the addition of anti-VLA-4 monoclonal antibody to cultures of the latter cells with stromal cells. The binding of the unfractionated cells is less than that of the CD34 selected. Since there is no difference between the alpha4 beta1 integrin expression level of the early and late myeloid cells, there may be a difference in the functional state of the integrin between the early and late myeloid cells. We also show that CD34+ selected precursor cells proliferate at a higher rate when these cells are plated on recombinant VCAM-1 molecules. These data indicate that the alpha4beta1 integrin receptor (VLA-4) plays a central role in the apoptosis rescue function which results from the anchorage-dependent growth of the CD34 selected early hematopoietic cells on stromal cells. The data suggest that these apoptosis rescue pathways have less significance as the cells mature and become anchorage-independent in their growth. These data should assist in the design of systems for the ex vivo proliferation and transduction of early hematopoietic cells for genetic therapy. ^

Managing the risks of medical technology: Do hazard surveillance systems provide an early warning of medical device problems?

The Food and Drug Administration (FDA) is responsible for risk assessment and risk management in the post-market surveillance of the U.S. medical device industry. One of the FDA regulatory mechanisms, the Medical Device Reporting System (MDR) is an adverse event reporting system intended to provide the FDA with advance warning of device problems. It includes voluntary reporting for individuals, and mandatory reporting for device manufacturers. ^ In a study of alleged breast implant safety problems, this research examines the organizational processes by which the FDA gathers data on adverse events and uses adverse event reporting systems to assess and manage risk. The research reviews the literature on problem recognition, risk perception, and organizational learning to understand the influence highly publicized events may have on adverse event reporting. Understanding the influence of an environmental factor, such as publicity, on adverse event reporting can provide insight into the question of whether the FDA's adverse event reporting system operates as an early warning system for medical device problems. ^ The research focuses on two main questions. The first question addresses the relationship between publicity and the voluntary and mandatory reporting of adverse events. The second question examines whether government agencies make use of these adverse event reports. ^ Using quantitative and qualitative methods, a longitudinal study was conducted of the number and content of adverse event reports regarding breast implants filed with the FDA's medical device reporting system during 1985–1991. To assess variation in publicity over time, the print media were analyzed to identify articles related to breast implant failures. ^ The exploratory findings suggest that an increase in media activity is related to an increase in voluntary reporting, especially following periods of intense media coverage of the FDA. However, a similar relationship was not found between media activity and manufacturers' mandatory adverse event reporting. A review of government committee and agency reports on the FDA published during 1976–1996 produced little evidence to suggest that publicity or MDR information contributed to problem recognition, agenda setting, or the formulation of policy recommendations. ^ The research findings suggest that the reporting of breast implant problems to FDA may reflect the perceptions and concerns of the reporting groups, a barometer of the volume and content of media attention. ^

CHROMOSOMAL ORIGIN OF DM-DNA

Double minutes (dm) are small chromatin particles of 0.3 microns diameter found only in the metaphase cells of human and murine tumors. Dm are unique cytogenetic structures since their numbers per cell show wide variation. At cell division, dm are retained despite the lack of centromeres. In squash preparations, dm show clustering often in association with chromosomes. Human carcinoma cell line SW613-S18 was found to have large numbers of dm and biological characteristics favorable for mitotic synchronization and chromosome isolation experiments.^ S18 cells were synchronized to mitosis with metabolic and mitotic blocking compounds. Mitotic cells were lysed to release chromosomes and dm from the mitotic spindle and the resulting suspensions were fractionated to enrich for dm. The DNA in enriched fractions was characterized. The reassociation kinetics of dm-DNA driven with placental human DNA was similar to the reassociation curve of labeled placental DNA under similar conditions. In situ hybridization of dm-DNA to tumor and normal metaphase cells showed grain localization over the entire karyotype. Dm-DNA was shown by pulse chase DNA replication experiments to replicate during early and mid S-phase of the cell cycle, but not in late S-phase. In addition, BrdUrd incorporation studies showed that dm-DNA replicates only once during the S-phase. Premature chromosome condensation studies suggest the basis of numerical heterogeneity of dm is nondisjunction, not anomalous or unscheduled DNA replication.^ These data and previous cytochemical banding studies of dm in SW613-S18 indicate that dm-DNA is chromosomal in origin. No evidence of gene amplification was found in the DNA reassociation data. It is likely that dm-DNA represents the pale-staining G-band regions of the human karyotype in this cell line. ^

Depression in early adulthood: prevalence and psychosocial correlates among young Swiss men

QUESTION UNDER STUDY Depression in young adults is common, but data from Switzerland are scarce. Our study gives a point prevalence estimate of depression in young Swiss men, and describes the association between depression and education, material and social resources, and job/school satisfaction. METHODS We used data from the cross-sectional Swiss Federal Surveys of Adolescents (ch-x) from 2010 to 2011 comprising 9,066 males aged between 18 and 25 years. Depression was assessed by means of self-reports using the Patient Health Questionnaire (PHQ-9). Persons were categorised into three groups: depression, subthreshold depression, and no depression. We assessed the relationship between depression and education, material and social resources, and satisfaction with job/school. Differences according to depression status were tested with chi-square tests for categorical variables and one-way analyses of variance for continuous variables. RESULTS Point prevalence of depression (3.60%) and subthreshold depression (3.62%) was high. Poor mental health was associated with lower education in young adults (p <0.001), and with their parents' education (p = 0.024). Social resources in persons with depression and subthreshold depression were substantially reduced (i.e., social support and satisfaction with social relations; both p <0.001). Young men with depression and subthreshold depression also reported a current lack of satisfaction with job/school (p <0.001). CONCLUSIONS Prevalence of (subthreshold) depression is high in young Swiss men. Depression at this age might result in a bad long-term prognosis owing to its association with low satisfaction with job/school and low self-efficacy. Interventions should especially consider the lower social resources of young men with depression.

Learning enjoyment in early adolescence

There is empirical evidence showing that positive emotional and motivational factors in formal learning contexts decrease at the stage of young adolescence. According to Stage-Environment-Fit Theory and Self-Determination Theory, this change should be explained by a non-fulfilment of students' needs. By combining two different methods (questionnaires and day-to-day diaries) and applying a longitudinal design, this study aimed to explore the change in and the determinants of habitual and actual learning enjoyment. The sample consisted of 356 students. Quantitative results indicated that learning enjoyment and classroom practices decreased between Grades 6 and 7. Path analyses revealed that classroom practices are the source of students' learning enjoyment, while self-efficacy functions as a partial mediator. Data from students' diaries showed that a teacher's neglect of students' needs for competence and relatedness were significant sources of impeded learning enjoyment. Practical implications suggest the relevance of adjusting learning conditions to the needs of young adolescents in order to provide a facilitating basis for learning enjoyment.

Ar-40/Ar-39 Evidence for Middle Proterozoic (1300-1500 Ma) Slow Cooling of the Southern Black Hills, South Dakota, Midcontinent, North America: Implications for Early Proterozoic P-T Evolution and Posttectonic Magmatism

Ar-40/Ar-39 total gas and plateau dates from muscovite and biotite in the southern Black Hills, South Dakota, provide evidence for a period of Middle Proterozoic slow cooling. Early Proterozoic (1600-1650 Ma) mica dates were obtained from metasedimentary rocks located in a synformal structure between the Harney Peak and Bear Mountain domes and also south of Bear Mountain. Metamorphic rocks from the dome areas and undeformed samples of the similar to 1710 Ma Harney Peak Granite (HPG) yield Middle Proterozoic mica dates (similar to 1270-1500 Ma). Two samples collected between the synform and Bear Mountain dome yield intermediate total gas mica dates of similar to 1550 Ma. We suggest two end-member interpretations to explain the map pattern of cooling ages: (1) subhorizontal slow cooling of an area which exhibits variation in mica Ar retention intervals or (2) mild folding of a Middle Proterozoic (similar to 1500 Ma) similar to 300 degrees C isotherm. According to the second interpretation, the preservation of older dates between the domes may reflect reactivation of a preexisting synformal structure (and downwarping of relatively cold rocks) during a period of approximately east-west contraction and slow uplift during the Middle Proterozoic. The mica data, together with hornblende data from the Black Hills published elsewhere, indicate that the ambient country-rock temperature at the 3-4 kbar depth of emplacement of the HPG was between 350 degrees C and 500 degrees C, suggesting that the average upper crustal geothermal gradient was 25 degrees-40 degrees C/km prior to intrusion. The thermochronologic data suggest HPG emplacement was followed by a similar to 200 m.y. period of stability and tectonic quiescence with little uplift. We propose that crust thickened during the Early Proterozoic was uplifted and erosionally(?) thinned prior to similar to 1710 Ma and that the HPG magma was emplaced into isostatically stable crust of relatively normal thickness. We speculate that uplift and crustal thinning prior to HPG intrusion was the result of differential thinning of the subcrustal lithosphere beneath the Black Hills. If so, this process would have also caused an increase in mantle heat flux across the Moho and triggered vapor-absent melting of biotite to produce the HPG magma. This scenario for posttectonic granite generation is supported, in part, by the fact that in the whole of the Black Hills, the HPG is spatially associated with the deepest exposed Early Proterozoic country rock.

The effect of abrupt climatic warming on biogeochemical cycling and N2O emissions in a terrestrial ecosystem

The large, rapid increase in atmospheric N2O concentrations that occurred concurrent with the abrupt warming at the end of the Last Glacial period might have been the result of a reorganization in global biogeochemical cycles. To explore the sensitivity of nitrogen cycling in terrestrial ecosystems to abrupt warming, we combined a scenario of climate and vegetation composition change based on multiproxy data for the Oldest Dryas–Bølling abrupt warming event at Gerzensee, Switzerland, with a biogeochemical model that simulates terrestrial N uptake and release, including N2O emissions. As for many central European sites, the pollen record at the Gerzensee is remarkable for the abundant presence of the symbiotic nitrogen fixer Hippophaë rhamnoides (L.) during the abrupt warming that also marks the beginning of primary succession on immature glacial soils. Here we show that without additional nitrogen fixation, climate change results in a significant increase of N2O emissions of approximately factor 3.4 (from 6.4 ± 1.9 to 21.6 ± 5.9 mg N2O–N m− 2 yr− 1). Each additional 1000 mg m− 2 yr− 1 of nitrogen added to the ecosystem through N-fixation results in additional N2O emissions of 1.6 mg N2O–N m− 2 yr− 1 for the time with maximum H. rhamnoides coverage. Our results suggest that local reactions of emissions to abrupt climate change could have been considerably faster than the overall atmospheric concentration changes observed in polar ice. Nitrogen enrichment of soils due to the presence of symbiotic N-fixers during early primary succession not only facilitates the establishment of vegetation on soils in their initial stage of development, but can also have considerable influence on biogeochemical cycles and the release of reactive nitrogen trace gases to the atmosphere.

Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis

BACKGROUND Bacterial meningitis is characterized by an intense inflammatory reaction contributing to neuronal damage. The aim of this study was to obtain a comparative analysis of cytokines and chemokines in patients with pneumococcal (PM) and meningococcal meningitis (MM) considering that a clear difference between the immune response induced by these pathogens remains unclear. METHODS The cyto/chemokines, IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-10, IL-1Ra, CXCL8/IL-8, CCL2/MCP-1, CLL3/MIP-1alpha, CCL4/MIP-1gamma and G-CSF, were measured in cerebrospinal fluid (CSF) samples from patients with PM and MM. Additionally, a literature review about the expression of cytokines in CSF samples of patients with MB was made. RESULTS Concerning cytokines levels, only IFN-gamma was significantly higher in patients with Streptococcus pneumoniae compared to those with Neisseria meningitidis, regardless of the time when the lumbar puncture (LP) was made. Furthermore, when samples were compared considering the timing of the LP, higher levels of TNF-alpha (P <0.05) were observed in MM patients whose LP was made within 48 h from the initial symptoms of disease. We also observed that the index of release of cyto/chemokines per cell was significantly higher in PM. From the literature review, it was observed that TNF-alpha, IL-1beta and IL-6 are the best studied cytokines, while reports describing the concentration of the cytokine IL-2, IL-1Ra, G-CSF and CCL4/MIP-1beta in CSF samples of patients with bacterial meningitis were not found. CONCLUSION The data obtained in this study and the previously published data show a similar profile of cytokine expression during PM and MM. Nevertheless, the high levels of IFN-gamma and the ability to release high levels of cytokines with a low number of cells are important factors to be considered in the pathogenesis of PM and thereby should be further investigated. Moreover, differences in the early response induced by the pathogens were observed. However, the differences observed are not sufficient to trigger changes in the current therapy of corticosteroids adopted in both the PM and MM.

An Early-Warning System for Hypo-/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models

Introduction: Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia / hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy. Methods: The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) auto-regressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models′ outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS. Results: The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms. Conclusion: Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.

Dispersal Modeling of Fish Early Life Stages: Sensitivity with Application to Atlantic Cod in the Western Gulf of Maine

As an initial step in establishing mechanistic relationships between environmental variability and recruitment in Atlantic cod Gadhus morhua along the coast of the western Gulf of Maine, we assessed transport success of larvae from major spawning grounds to nursery areas with particle tracking using the unstructured grid model FVCOM (finite volume coastal ocean model). In coastal areas, dispersal of early planktonic life stages of fish and invertebrate species is highly dependent on the regional dynamics and its variability, which has to be captured by our models. With state-of-the-art forcing for the year 1995, we evaluate the sensitivity of particle dispersal to the timing and location of spawning, the spatial and temporal resolution of the model, and the vertical mixing scheme. A 3 d frequency for the release of particles is necessary to capture the effect of the circulation variability into an averaged dispersal pattern of the spawning season. The analysis of sensitivity to model setup showed that a higher resolution mesh, tidal forcing, and current variability do not change the general pattern of connectivity, but do tend to increase within-site retention. Our results indicate strong downstream connectivity among spawning grounds and higher chances for successful transport from spawning areas closer to the coast. The model run for January egg release indicates 1 to 19 % within-spawning ground retention of initial particles, which may be sufficient to sustain local populations. A systematic sensitivity analysis still needs to be conducted to determine the minimum mesh and forcing resolution that adequately resolves the complex dynamics of the western Gulf of Maine. Other sources of variability, i.e. large-scale upstream forcing and the biological environment, also need to be considered in future studies of the interannual variability in transport and survival of the early life stages of cod.