Paper Session II-B - Space Shuttle-Solution to DoD Dual Access To Space

Now is the time to revisit the use of the Space Shuttle to implement the DoD policy of dual access to space. The Shuttle Program is in transition, improving its operational responsiveness and reducing its costs to satisfy customer requirements. Many key Shuttle Program management positions are held by people with DoD spacelift experience. NASA\u27s way of doing business is , being changed to make programs happen quicker, faster, and cheaper. Shuttle costs have been reduced by more than 25 percent since 1991. Further consolidation and streamlining of Shuttle operations can be implemented to reduce recurring costs to as low as $2.0 billion, down over$1.5 billion from today\u27s operations costs. Shuttle processing has been improved to the point that the current four Orbiter fleet could easily support twelve flights per year, up four over today\u27s flight manifest. The Shuttle provides the DoD with a backup launch capability for larger payloads which is much more reliable and less costly than the Titan IV. In addition, the Space Shuttle provides the DoD with many unique spacelift capabilities not available from the expendable launch vehicle fleet. The decision prior to the Challenger accident to move the preponderance of the payloads to Shuttle was just as incorrect as the decision after the Challenger accident to remove all DoD and commercial payloads from Shuttle. This paper will present how the Space Shuttle can become DoD\u27s cost effective solution to dual access to space and the benefits the DoD will accrue from .utilizing the Shuttle as a spacelift asset

Screening and diagnosing depression in women visiting GPs' drop in clinic in Primary Health Care

<p>Abstract</p> <p>Background</p> <p>Only half of all depressions are diagnosed in Primary Health Care (PHC). Depression can remain undetected for a long time and entail high costs for care and low quality of life for the individuals. Drop in clinic is a common form of organizing health care; however the visits are short and focus on solving the most urgent problems. The aim of this study was to investigate the prevalence and severity of depression among women visiting the GPs' drop in clinic and to identify possible clues for depression among women.</p> <p>Methods</p> <p>The two-stage screening method with "high risk feedback" was used. Beck's Depression Inventory (BDI) was used to screen 155 women visiting two GPs' drop in clinic. Women who screened positive (BDI score ≥10) were invited by the GP to a repeat visit. Major depression (MDD) was diagnosed according to DSM-IV criteria and the severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). Women with BDI score <10 constituted a control group. Demographic characteristics were obtained by questionnaire. Chart notations were examined with regard to symptoms mentioned at the index visit and were categorized as somatic or mental.</p> <p>Results</p> <p>The two-stage method worked well with a low rate of withdrawals in the second step, when the GP invited the women to a repeat visit. The prevalence of depression was 22.4% (95% CI 15.6–29.2). The severity was mild in 43%, moderate in 53% and severe in 3%. The depressed women mentioned mental symptoms significantly more often (69%) than the controls (15%) and were to a higher extent sick-listed for a longer period than 14 days. Nearly one third of the depressed women did not mention mental symptoms. The majority of the women who screened as false positive for depression had crisis reactions and needed further care from health professionals in PHC. Referrals to a psychiatrist were few and revealed often psychiatric co-morbidity.</p> <p>Conclusion</p> <p>The prevalence of previously undiagnosed depression among women visiting GPs' drop in clinic was high. Clues for depression were identified in the depressed women's symptom presentation; they often mention mental symptoms when they visit the GP for somatic reasons e.g. respiratory infections. We suggest that GPs do selective screening for depression when women mention mental symptoms and offer to schedule a repeat visit for follow-up rather than just recommending that the patient return if the mental symptoms do not disappear.</p

Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants

<div><p>Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.</p></div

Mutation of the SINV C:R interaction sites negatively affects incoming viral genomic RNA function.

<p><b>A</b>) The RNA decay profiles of the incoming viral genomic RNAs of the individual SINV C:R interaction site mutants and parental wild type virus were determined by qRT-PCR analysis as described in the materials and methods. Plotted is the relative abundance of the incoming viral genomic RNAs (y-axis) with regards to time (x-axis). Regression analysis was utilized to determine the RNA decay profile (as shown with the solid line) and the dashed lines represent the 95% confidence intervals of the aforementioned regression. <b>B</b>) The half-lives of the individual genomic RNAs as determined using the calculations reported in Dolken et al., as determined by the first point at which the relative abundance has reached 0.5. C) The levels of Nanoluciferase activity for wild type parental virus and the nt10100 and nt10400 C:R interaction site mutants were determined as reported in the materials and methods at the indicated times post infection. All quantitative data in this figure represents the mean of at least three independent biological replicates. Comparative analysis was performed using variable bootstrapping, as described in the materials and methods, with the error bar representing the standard deviation of the mean. Statistical significance, as indicated on the individual panels above, are the p-Values obtained from Student’s t-test.</p

Test-retest reliability of the PRIME-MD: limitations in diagnosing mental disorders in primary care

. CONCLUSION: The PRIME-MD is one of the few instruments in primary care that actually diagnoses specific mental disorders according to the DSM criteria. However, there was a failure to adequately classify sub-threshold disorders. Mental disorders, as seen in primary care, encompass important specific symptoms and clinical syndromes that vary in duration and severity over time, but they also encompass an admixture of somatic and psychological symptoms that do not match current diagnostic systems. This most likely resulted in methodological uncertainty about the level of agreement. Diagnostic criteria in psychiatry need to be operationalized for use in primary care and require further evaluatio

Proposed model of SINV C:R interaction site function.

<p>After receptor mediated endocytosis the acidification of the endosome resulting in release of the nucleocapsid core into the host cytoplasm. Disassembly of the nucleocapsid core occurs shortly after endosomal release; and SINV capsid protein remains bound to the C:R interaction sites following disassembly. Retention of Capsid:RNA binding at the C:R interaction sites enables evasion of the host RNA decay machinery and rapid assembly of the host translational machinery. Collectively, these interactions lead to the efficient establishment of viral infection, including but not limited to the modulation of the host innate immune response resulting in viral disease and pathogenesis. Disruption of the C:R interaction sites (lower pathway), leading to the ablation of Capsid:RNA interactions, results in RNA instability and a reduction of genomic RNA function early during infection.</p