Site Directed Gene Disruption of rpfA in Xylella fastidiosa : Non-Biofilm Producing Mutants as an Approach to Eradication of Pierce\u27s Disease in Grapevine

Xylella fastidious a, a gram-negative, rod shaped bacterium, causes disease in many economically important plants including citrus, coffee, and grapevine. Xylella fastidiosa is xylem limited and is dependent on insect vectors for transmission. Pierce’s Disease of Vitis vinifere grape, transmitted by an insect vector, poses a serious threat to California vineyards today. The glassy-winged sharp-shooter, Homalodisca coagulata, has caused millions of dollars of damage to the California wine industry in just a few years. There is evidence that Xylella fastidiosa may share the molecular mechanisms through which the bacterium establishes infection with a closely related species, Xanthomonas campestris. A cluster of genes designated as regulation of pathogenicity factors are responsible for extracellular polysaccharide production and have been found in the genome of Xanthanomonas campestris and Xylella fastidiosa. Site-directed disruption of regulation of pathogenicity factor A, using homologous recombination in the Xylella fastidiosa strains Temecula and Napa, exhibited a decrease in extracellular polysaccharide that resulted in the inhibition of biofilm formation

Spatial-temporal analysis of breast cancer in upper Cape Cod, Massachusetts

INTRODUCTION. The reasons for elevated breast cancer rates in the upper Cape Cod area of Massachusetts remain unknown despite several epidemiological studies that investigated possible environmental risk factors. Data from two of these population-based case-control studies provide geocoded residential histories and information on confounders, creating an invaluable dataset for spatial-temporal analysis of participants' residency over five decades. METHODS. The combination of statistical modeling and mapping is a powerful tool for visualizing disease risk in a spatial-temporal analysis. Advances in geographic information systems (GIS) enable spatial analytic techniques in public health studies previously not feasible. Generalized additive models (GAMs) are an effective approach for modeling spatial and temporal distributions of data, combining a number of desirable features including smoothing of geographical location, residency duration, or calendar years; the ability to estimate odds ratios (ORs) while adjusting for confounders; selection of optimum degree of smoothing (span size); hypothesis testing; and use of standard software. We conducted a spatial-temporal analysis of breast cancer case-control data using GAMs and GIS to determine the association between participants' residential history during 1947–1993 and the risk of breast cancer diagnosis during 1983–1993. We considered geographic location alone in a two-dimensional space-only analysis. Calendar year, represented by the earliest year a participant lived in the study area, and residency duration in the study area were modeled individually in one-dimensional time-only analyses, and together in a two-dimensional time-only analysis. We also analyzed space and time together by applying a two-dimensional GAM for location to datasets of overlapping calendar years. The resulting series of maps created a movie which allowed us to visualize changes in magnitude, geographic size, and location of elevated breast cancer risk for the 40 years of residential history that was smoothed over space and time. RESULTS. The space-only analysis showed statistically significant increased areas of breast cancer risk in the northern part of upper Cape Cod and decreased areas of breast cancer risk in the southern part (p-value = 0.04; ORs: 0.90–1.40). There was also a significant association between breast cancer risk and calendar year (p-value = 0.05; ORs: 0.53–1.38), with earlier calendar years resulting in higher risk. The results of the one-dimensional analysis of residency duration and the two-dimensional analysis of calendar year and duration showed that the risk of breast cancer increased with increasing residency duration, but results were not statistically significant. When we considered space and time together, the maps showed a large area of statistically significant elevated risk for breast cancer near the Massachusetts Military Reservation (p-value range:0.02–0.05; ORs range: 0.25–2.5). This increased risk began with residences in the late 1940s and remained consistent in size and location through the late 1950s. CONCLUSION. Spatial-temporal analysis of the breast cancer data may help identify new exposure hypotheses that warrant future epidemiologic investigations with detailed exposure models. Our methods allow us to visualize breast cancer risk, adjust for known confounders including age at diagnosis or index year, family history of breast cancer, parity and age at first live- or stillbirth, and test for the statistical significance of location and time. Despite the advantages of GAMs, analyses are for exploratory purposes and there are still methodological issues that warrant further research. This paper illustrates that GAM methods are a suitable alternative to widely-used cluster detection methods and may be preferable when residential histories from existing epidemiological studies are available.National Cancer Institute (5R03CA119703-02); National Institute of Enviornmental Health (5P42ES007381

Accidental injury, risk-taking behaviour and the social circumstances in which young people (aged 12-24) live: a systematic review

In industrialised countries such as England and Wales, unintended injury (which ranges from sprains in sport to hospitalisation and death due to drugs or transport crashes) is the leading cause of death in children aged 0 to 14 years, and a major cause of death in young adults aged 15 to 24. It is also a major cause of ill health and disability in these age groups. There is a large body of research on young people and their perceived propensity to take risks. Common sense suggests that an increased willingness to place oneself at risk will result an increased likelihood of physical injury. However, given that pathways to injury are complex and not always well understood, the UK Department of Health commissioned a large systematic review to examine this multifaceted issue. Drug use • The review found that the use of drugs is associated with an increased risk of accidental death among young people and that 12–24 year olds are less at risk than those immediately older. However, risk of death increases with length of drug use, so there is value in targeting interventions at this age group. • Many more young men than women die from drug overdoses, because more men take drugs, but those women who do use drugs are at higher risk. Certain other groups of young people are more at risk than others. These include young people in deprived areas and men who have recently been released from prison. • There was a clear disjunction of views between young people who used drugs and those who did not. The young people who did not take drugs regarded them as risky and stated that media images about possible negative consequences dissuaded them from trying them, while those who did tended not to believe ‘official’ messages about possible harms and did not perceive taking drugs as being dangerous. Cannabis in particular was singled out as possibly being good for you, with some young people believing it to be cheaper than alcohol. The recent reclassification of cannabis and the subsequent debate may have helped to reinforce this view. • The burden of the more serious injuries – as demonstrated by the mortality statistics – is carried by young people in the lower socio-economic groups. • In road injuries, drugs are found in the bloodstream of more young fatal accident victims than older age groups; however, it is difficult to assess whether drugs actually contributed to the accident. • Driving on cannabis was thought to be more acceptable than drink-driving and not thought to be dangerous. Alcohol use • Almost everyone admitted to hospital for alcohol poisoning is aged between 11 and 17. After a sharp peak among 14 and 15 year olds, hospital admissions for injuries with alcohol involvement decline slowly between the ages of 16 and 30. • Correlational studies have shown that alcohol puts the drinker at an increased risk of injury, that young people are more likely to have injuries than older people, and that young men are more at risk than young women. In the one study that examined ethnicity, minority ethnic status did not increase alcohol-related injuries, and may in fact have had a protective association. • Views studies found that young people say that they do not commonly mix alcohol and other drugs. Most young people reported that drinking places them at greater risk of injury, though some did not. The younger teenagers – 14 and 15 year olds – felt most in danger of injury when drinking. Young people felt that they learned to manage their drinking through experience and that unsupervised, outdoor drinking was the most dangerous and was more common among younger teenagers (with injuries being considered less common in licensed venues). Peers encourage both drinking and drunken pranks, but also protect one another when they have become more vulnerable as a result of drink. Young people felt that drinking reduces their perceptions of danger and some stated that injury as a result was inevitable. Most young people were cautious about getting very drunk, though being sick as a result of drinking is common and not regarded as serious. Bad experiences – whether to self or someone else – might change behaviour in the short- but not long-term. • One study which examined attempts to reduce alcohol-related injuries found some evidence that motivational interviews in A&E departments are more effective than information handouts. Drink-driving • Drink-driving was generally considered dangerous and not socially acceptable, whereas driving on cannabis was more acceptable and not thought to be dangerous. Some young people stated that a lack of public transport (or alternatives, such as taxis) made it more likely that they would drink and drive. • Interventions based on models of behaviour change to reduce drink-driving are ineffective or have a negative effect. Combining different approaches has more effect than using a single approach. Education or skills training has either negative or no effects on driver behaviour and subsequent accidents, possibly because these approaches lead to over-confidence or early licensing. • Legislation and enforcement on reducing drink-driving has been found to be effective

Generalized Descent Methods for Asymmetric Systems of Equations and Variational Inequalities

We consider generalizations of the steepest descent algorithm for solving asymmetric systems of equations. We first show that if the system is linear and is defined by a matrix M, then the method converges if M2 is positive definite. We also establish easy to verify conditions on the matrix M that ensure that M is positive definite, and develop a scaling procedure that extends the class of matrices that satisfy the convergence conditions. In addition, we establish a local convergence result for nonlinear systems defined by uniformly monotone maps, and discuss a class of general descent methods. Finally, we show that a variant of the Frank-Wolfe method will solve a certain class of variational inequality problems. All of the methods that we consider reduce to standard nonlinear programming algorithms for equivalent optimization problems when the Jacobian of the underlying problem map is symmetric. We interpret the convergence conditions for the generalized steepest descent algorithms as restricting the degree of asymmetry of the problem map

BMP receptor 1b is required for axon guidance and cell survival in the developing retina

AbstractPrevious work has documented the importance of BMPs in eye development. Loss-of-function studies in mice, with targeted deletions in either the Bmp7 or Bmp4 genes, have shown that these molecules are critical for early eye development. On the basis of the asymmetry in the dorsal–ventral expression patterns of several members of this family, it has been proposed that these molecules are critical for some aspect of dorsal–ventral patterning in the eye; however, it has been difficult to test this hypothesis because of the early requirement for BMPs in eye development. We have therefore examined the effects of loss of one of the BMP receptors, the BmprIb, on the development of the eye by using targeted deletion. We have found that BmprIb is expressed exclusively in the ventral retina during embryonic development and is required for normal ventral ganglion cell axon targeting to the optic nerve head. In mice with a targeted deletion of the BmprIb gene, many axons arising from the ventrally located ganglion cells fail to enter the optic nerve head, and instead, make abrupt turns in this region. A second phenotype in these mice is a significantly elevated inner retinal apoptosis during a distinct phase of postnatal development, at the end of neurogenesis. Our results therefore show two distinct requirements for BmprIb in mammalian retinal development

Cognitive realism in online authentic learning environments

The development of virtual reality and advanced computer applications have meant that realistic creations of simulated environments are now possible. Such simulations have been used with to great effect in training in the military, air force, and in medical training. But how realistic do problems need to be in education for effective learning to occur? Some authors and researchers argue that problems should be real, or that simulations should have ultra-realistic physical similarity to an actual context. This paper proposes that physical verisimilitude to real situations is of less importance in learning than \u27cognitive realism\u27, provided by immersing students in engaging and complex tasks. The paper presents a description of the theory and research that provide the foundations for this approach. Examples of courses employing cognitive, rather than physical, realism will be presented together with the views of teachers, authors and instructional designers

Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

Sexual Health

Health Issue: Much attention is devoted to women's reproductive health, but the formative and mature stages of women's sexual lives are often overlooked. We have analyzed cross-sectional data from the Sexual Behaviour module of the 2000/2001 Canadian Community Health Survey (CCHS), and reviewed the literature and available indicators of the sexual health of Canadian women. Key Findings: Contemporary Canadian adolescents are becoming sexually active at younger ages than in previous generations. The gender gap between young males and females in age at first intercourse has virtually disappeared. The mean age at first intercourse for CCHS respondents aged 15–24 years was between 16 and 17. Canadian-born respondents are significantly younger at first intercourse than those who were born outside of Canada. Few adolescents recognize important risks to their sexual health. Older Canadians are sexually active, and continue to fin