Post-Replication Repair Suppresses Duplication-Mediated Genome Instability

RAD6 is known to suppress duplication-mediated gross chromosomal rearrangements (GCRs) but not single-copy sequence mediated GCRs. Here, we found that the RAD6- and RAD18-dependent post-replication repair (PRR) and the RAD5-, MMS2-, UBC13-dependent error-free PRR branch acted in concert with the replication stress checkpoint to suppress duplication-mediated GCRs formed by homologous recombination (HR). The Rad5 helicase activity, but not its RING finger, was required to prevent duplication-mediated GCRs, although the function of Rad5 remained dependent upon modification of PCNA at Lys164. The SRS2, SGS1, and HCS1 encoded helicases appeared to interact with Rad5, and epistasis analysis suggested that Srs2 and Hcs1 act upstream of Rad5. In contrast, Sgs1 likely functions downstream of Rad5, potentially by resolving DNA structures formed by Rad5. Our analysis is consistent with models in which PRR prevents replication damage from becoming double strand breaks (DSBs) and/or regulates the activity of HR on DSBs

Contracting strategy formulation for production competition in major weapon systems acquisition.

Production competition has emerged as a major objective in major weapon systems acquisition. The complexity and length of the acquisition process, and the expense involved in major weapon systems requires that early and careful planning be conducted in order to achieve production competition. In this study, the researcher defines and identifies the characteristics and roles of the acquisition strategy, the acquisition plan, functional implementation plans, and the contracting strategy. The concept of production competition and the feasible methodologies for pursuing it are investigated. Contracting strategy formulation is studied in detail and program issues that are consistently encountered in contracting strategy formulation are presented. A methodology for identifying problem issues in contracting strategy formulation is developed and analyzed. The study concludes that the role of the contracting officer and the contracting strategy is not sufficiently recognized nor defined in the critical role of integrating functional requirements and objectives into an integrated acquisition plan.http://archive.org/details/contractingstrat00hayeLieutenant Commander, United States NavyApproved for public release; distribution is unlimited

Environmental Policy Factors in the Maritime Industry and Anticipated Regulatory Trends

Increased environmental regulatory policy has been put in place by the International Maritime Organization (IMO) in response to waterborne oil pollution events. We examine the IMO regulatory response to these incidences. This paper covers literature on the subject of environmental norms in the Maritime Industry. Starting with the Oil and Pollution Act of 1954 (OILPOL) and the International Convention for the Prevention of Pollution from Ships 1973/78 (MARPOL), there has been increased frequency of adoption and amending of environmental maritime treaties. Better practices in the form of policy are implemented to change behavior of IMO members. Using institutional theory as a framework with other consensus forming theories, we identify possible cycles in policy amendment and adoption. Data to be used includes (1) oil spill data from the International Tankers Owners Pollution Federation Limited (ITOPF), (2) IMO convention and amendment, (3) labor statistics from the Baltic and International Maritime Council (BIMCO) and International Shipping Federation (ISF), and (4) ages of the World Fleet collected from the yearly publication Review of Maritime Transportation. The linear regression model drawn identified a significant relationship between the severity and number of oil spill incidents to the length of time the policy was given to enter into force. This research concludes with a discussion of anticipating regulatory trends based on waterborne pollution events

Predictors of Natural and Unnatural Mortality among Patients with Personality Disorder:Evidence from a Large UK Case register

People with personality disorder have reduced life expectancy, yet, within this population, little is known about the clinical predictors of natural and unnatural deaths. We set out to investigate this, using a large cohort of secondary mental health patients with personality disorder.We identified patients with an ICD-10 diagnosis of personality disorder, aged ≥15 years in a large secondary mental healthcare case register. The case register was linked to national mortality tracing. Using Cox regression, we modelled the effect of a number of pre-specified clinical variables on all-cause, natural cause and unnatural cause mortality.2,440 patients were identified. Eighty-five deaths (3.5% of cohort) occurred over a 5-year observation period, of which over 50% were from natural causes. All-cause mortality was associated with alcohol or drug use (adjusted Hazard Ratio [aHR] 2.3; 95% CI 1.3-4.1), physical illness (aHR 1.9; 95% CI 1.0-3.6), and functional impairment (aHR 1.9; 95% CI 1.0-3.6). Natural cause mortality was associated with mild problems of alcohol or drug use (aHR 3.4; 95% CI 1.5-7.4), and physical illness (aHR 2.4; 95% CI 1.0-5.6). Unnatural cause mortality was associated only with severe alcohol or drug use (aHR 3.1; 95% CI 1.3-7.3).Alcohol and drug use, physical illness, and functional impairment are predictors of mortality in individuals with personality disorder. Clinicians should be aware of the existence of problems in these domains, even at mild levels, when assessing the needs of patients with personality disorder

Probing the Evolution of the Galaxy Interaction/Merger Rate Using Collisional Ring Galaxies

We present the results from our program to determine the evolution of the galaxy interaction/merger rate with redshift using the unique star-forming characteristics of collisional ring galaxies. We have identified 25 distant collisional ring galaxy candidates (CRGCs) in a total of 162 deep Hubble Space Telescope Wide Field/Planetary Camera-2 images obtained from the HST Archives. Based on measured and estimated redshifts, these 25 CRGCs all lie in the redshift interval of 0.1 < z < 1. Using the local collisional ring galaxy volume density and the new ``standard'' cosmology, we find that in order to account for the number of identified CRGCs in our surveyed fields, the galaxy interaction/merger rate, parameterized as (1 + z)^m, must increase steeply with redshift.We determine a minimum value of m = 5.2 $\pm$ 0.7, though m could be as high as 7 or 8. We can rule out a non-evolving (m = 0) and weakly evolving (m = 1-2) galaxy interaction/merger rate at greater than the 4 sigma level of confidence.Comment: Accepted in the Astrophysical Journal (11 pages, 4 figures). Higher resolution version of the figures is available at http://www.astro.cornell.edu/~vassilis/papers

The Drought Monitor

There is a need for improved drought monitoring and assessment methods in the United States. Drought is the most costly natural disaster [Federal Emergency Management Agancy (FEMA 1995; Wilhite 2000)], but it is often neglected by developers of assessment and forecast products. Drought is more nebulous than other disasters and does not lend itself to traditional assessments or forecast methods. Its relatively slow onset and the complexity of its impacts are reasons for the new assessment methodology. Improvements in drought monitoring and forecasting techniques will allow for better preparation, lead to better management practices, and reduce the vulnerability of society to drought and its subsequent impacts. The Drought Monitor (additional information available online at http://drought.unl/edu/dm) was created with the goal of tracking and displaying the magnitude and spatial extent of drought and its impacts across the United States. The Drought Monitor is produced weekly and classifies drought severity into four major categories, with a fifth category threshold assigned to locations on a map are determined from a number of indicators, or tools, blended with subjective interpretation

The long-term impact of the MEMA kwa Vijana adolescent sexual and reproductive health intervention: effect of dose and time since intervention exposure.

BACKGROUND: Despite recent decreases in HIV incidence in many sub-Saharan African countries, there is little evidence that specific behavioural interventions have led to a reduction in HIV among young people. Further and wider-scale decreases in HIV require better understanding of when behaviour change occurs and why. The MEMA kwa Vijana adolescent sexual and reproductive health intervention has been implemented in rural Mwanza, Tanzania since 1999. A long-term evaluation in 2007/8 found that the intervention improved knowledge, attitudes to sex and some reported risk behaviours, but not HIV or HSV2 prevalence. The aim of this paper was to assess the differential impact of the intervention according to gender, age, marital status, number of years of exposure and time since last exposure to the intervention. METHODS: In 2007, a cross-sectional survey was conducted in the 20 trial communities among 13,814 young people (15-30 yrs) who had attended intervention or comparison schools between 1999 and 2002. Outcomes for which the intervention had an impact in 2001 or 2007 were included in this subgroup analysis. Data were analysed using cluster-level methods for stratified cluster-randomised trials, using interaction tests to determine if intervention impact differed by subgroup. RESULTS: Taking into account multiplicity of testing, concurrence with a priori hypotheses and consistency within the results no strong effect-modifiers emerged. Impact on pregnancy knowledge and reported attitudes to sex increased with years of exposure to high-quality intervention. CONCLUSIONS: The desirable long-term impact of the MEMA kwa Vijana intervention did not vary greatly according to the subgroups examined. This suggests that the intervention can have an impact on a broad cross-section of young people in rural Mwanza. TRIAL REGISTRATION: ClinicalTrials.gov NCT00248469

A cohort study on mental disorders, stage of cancer at diagnosis and subsequent survival.

OBJECTIVES: To assess the stage at cancer diagnosis and survival after cancer diagnosis among people served by secondary mental health services, compared with other local people. SETTING: Using the anonymised linkage between a regional monopoly secondary mental health service provider in southeast London of four London boroughs, Croydon, Lambeth, Lewisham and Southwark, and a population-based cancer register, a historical cohort study was constructed. PARTICIPANTS: A total of 28 477 cancer cases aged 15+ years with stage of cancer recorded at diagnosis were identified. Among these, 2206 participants had been previously assessed or treated in secondary mental healthcare before their cancer diagnosis and 125 for severe mental illness (schizophrenia, schizoaffective or bipolar disorders). PRIMARY AND SECONDARY OUTCOME MEASURES: Stage when cancer was diagnosed and all-cause mortality after cancer diagnosis among cancer cases registered in the geographical area of southeast London. RESULTS: Comparisons between people with and without specific psychiatric diagnosis in the same residence area for risks of advanced stage of cancer at diagnosis and general survival after cancer diagnosed were analysed using logistic and Cox models. No associations were found between specific mental disorder diagnoses and beyond local spread of cancer at presentation. However, people with severe mental disorders, depression, dementia and substance use disorders had significantly worse survival after cancer diagnosis, independent of cancer stage at diagnosis and other potential confounders. CONCLUSIONS: Previous findings of associations between mental disorders and cancer mortality are more likely to be accounted for by differences in survival after cancer diagnosis rather than by delayed diagnosis