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Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

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All soils and rocks contain naturally occurring radioactive material (NORM). Many ores and raw materials contain relatively high levels of natural radionuclides, and processing such materials can further increase the concentrations of natural radionuclides, sometimes referred to as 'technologically enhanced naturally occurring radioactive material' (TENORM). Examples of NORM minerals include uranium ores, monazite (a source of rare earth minerals), and phosphate rock used to produce phosphate fertiliser. Such activities have the potential to result in above background radiation exposure to workers and the public. The objective of this paper is to review the sources and exposure from NORM in North American industries, and provide a perspective on the potential radiological hazards to workers and the environment. Proper consideration of NORM issues is important and needs to be integrated in the assessment of these projects. Concerns over radioactivity and radiation amongst non-governmental organisations and the local public have resulted in the cancellation of NORM mining and mineral extraction projects, as well as inhibition of the safe use of by-product materials from various NORM industries. This paper also briefly comments on the current regulatory framework for NORM (TENORM) in Canada and the USA, as well as the potential implications of the recent activities of the International Commission on Radiological Protection for NORM industries.

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Radiation weighting factors have long been employed to modify absorbed dose as part of the process of evaluating radiological impact to humans. Their use represents an acknowledgement of the fundamental difference in energy deposition patterns of charged and uncharged particles, and how this can translate into varying degrees of biological impact. Weighting factors used in human radiation protection are derived from a variety of endpoints taken from in-vitro experiments that include human and animal cell lines, as well as in-vivo experiments with animals. Nonetheless, the application of radiation weighting factors in the context of dose assessment of animals and plants is not without some controversy. Specifically, radiation protection of biota has largely focused on limiting deterministic effects, such as reduced reproductive fitness. Consequently, the application of conventional stochastic-based radiation weighting factors (when used for human protection) appears inappropriate. While based on research, radiation weighting factors represent the parsing of extensive laboratory studies on relative biological effectiveness. These studies demonstrate that the magnitude of a biological effect depends not just on dose, but also on other factors including the rate at which the dose is delivered, the type and energy of the radiation delivering the dose, and, most importantly, the endpoint under consideration. This article discusses the efforts taken to develop a logical, transparent, and defensible approach to establishing radiation weighting factors for use in assessing impact to non-human biota, and the challenges found in differentiating stochastic from deterministic impacts.

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Uranium and thorium series radionuclides are present in all soils and rocks. Thus, radon and thoron, the radioactive noble gases originating in the uranium ((238)U) and thorium ((232)Th) decay chains is ubiquitous and everyone is exposed to both radon and thoron gases and their particulate radioactive decay products. As described in UNSCEAR Annex E (2006), radon and its decay products have been recognised for many years as a hazard to underground miners. More recently, the risks from exposure to residential radon have been demonstrated through residential case-control epidemiological studies. However, as discussed by UNSCEAR, exposures to thoron and its decay products have often been relatively ignored. Moreover, unlike radon the effects of exposure to thoron and its decay products are not available from epidemiology and thus, a dosimetric approach is required to assess risks. UNSCEAR continues to recommend the use of a dose conversion factor for thoron decay products of 40 nSv (Bq h m(-3))(-1). UNSCEAR Annex E suggests there is an emerging problem, namely, that the contribution of (220)Rn (thoron) gas to the (222)Rn (radon) gas measurement signal is not well known. Until recently, this has largely been ignored. This is an important consideration as measurements at work and homes are the basis for investigating lung cancer exposure-response relationships. Based on UNSCEAR Annex E, this paper provides an overview of the sources and levels of thoron and its associated decay products at home and work. In addition, this paper provides an overview of the thoron dosimetry considered by UNSCEAR Annex E and some recent results.

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SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

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This paper describes the AACTG Adherence Instruments, which are comprised of two self-report questionnaires for use in clinical trials conducted by the Adult AIDS Clinical Trials Group (AACTG). The questionnaires were administered to 75 patients at ten AACTG sites in the USA. All patients were taking combination antiretroviral therapy (ART), including at least one protease inhibitor. Eleven per cent of patients reported missing at least one dose the day before the interview, and 17% reported missing at least one dose during the two days prior. The most common reasons for missing medications included 'simply forgot' (66%) and a number of factors often associated with improved health, including being busy (53%), away from home (57%) and changes in routine (51%). Less adherent patients reported lower adherence self-efficacy (p = 0.006) and were less sure of the link between non-adherence and the development of drug resistance (p = 0.009). They were also more likely to consume alcohol, to be employed outside the home for pay and to have enrolled in clinical trials to gain access to drugs (all p < 0.05). Twenty-two per cent of patients taking drugs requiring special instructions were unaware of these instructions. Each questionnaire took approximately ten minutes to complete. Responses to the questionnaires were favourable. These questionnaires have been included in six AACTG clinical trials to date and have been widely disseminated to investigators both in the USA and abroad.

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Aquatic biota in the Rhone River downstream of the Marcoule nuclear complex in France are exposed to natural sources of radiation and to radioactivity released from the Marcoule complex. A simple conservative screening level model was used to estimate the range of concentrations in aquatic media (water, sediments, and aquatic organisms) of both artificial and natural radionuclides and the consequent absorbed (whole body) dose rates for aquatic organisms. Five categories of aquatic organisms were studied, namely, submerged aquatic plants (phanerogam), non-bottom-feeding fish, bottom-feeding fish, mollusca, and fish-eating birds. The analysis was based on the radionuclide concentrations reported in four consecutive annual radioecological monitoring reports published by French agencies with nuclear regulatory responsibilities. The results of this assessment were used to determine, qualitatively, the magnitude of any potential health impacts on each of the five categories of aquatic organisms studied. The range of dose rate estimates ranged over three orders of magnitude, with maximum dose rates estimated to be in the order of 1 to 10 microGy h(-1). These maximum dose rates are a factor 40 or more below the international guideline intended to ensure the protection of aquatic populations (about 400 microGy h(-1)), and a factor ten or more below the level which may trigger the need for a more detailed evaluation of potential ecological consequences to the exposed populations (about 100 microGy h(-1)). As a result, chronic levels of radioactivity, artificial and natural, measured in aquatic media downstream of Marcoule are unlikely to result in adverse health impacts on the categories and species of aquatic organisms studied. Thus, based on the screening level analysis discussed in this paper, a more detailed evaluation of the dose rates does not appear to be warranted.

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Little is known about the use of cancer-screening services in homeless women and their attitudes about early detection programs. Face-to-face interviews were conducted with homeless women in San Francisco to determine rates of clinical breast exams, mammograms, and Pap smears. A total of 105 women were randomly selected from two homeless shelters. By self-report, 51 percent were current on clinical breast exams, 47 percent on mammograms, and 54 percent on Pap smears. These women had very positive attitudes toward receiving cancer-screening exams. In multivariate analyses, discussion about cancer prevention with a health care provider predicted current clinical breast exams and mammograms. More medical visits predicted being current on mammograms and Pap smears. Although homeless women represent a unique group of the urban poor, they are accessing cancer-screening exams at rates comparable to the general population.

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We conducted a longitudinal study of participants in phase I and II HIV vaccine safety and immunogenicity trials to examine changes in sexual risk behavior that are associated with risk of HIV transmission. The participants were 48 HIV-negative men and women enrolled in one of two placebo-controlled HIV vaccine trials conducted at San Francisco General Hospital. There was a significant increase in insertive unprotected anal intercourse (UAI) from 9% at baseline (trial entry), to 13% at the month 6 assessment, to 20% at the month 12 assessment (p = .02). The primary predictor of either insertive or receptive UAI during the vaccine trials was having engaged in this behavior prior to entry (p = .001). Higher-risk behavior was also seen among participants who were younger and had multiple sexual partners (each, p = .06) and who indicated that one of their reasons for participation in the vaccine trial was hope of protection from HIV infection (p = .07). These findings indicate that despite instructions otherwise, participants with a history of high-risk behavior or who express hope of protection from HIV infection by enrolling in vaccine trials may be candidates for more intensive risk-behavior counseling prior to and during their participation.

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This study explores the relationship of immune dysfunction to the neuropsychological performance of i.v. drug users (IVDUs) infected with HIV-1. Ninety-seven HIV-positive and 45 HIV-negative former IVDUs on methadone maintenance were evaluated using neuropsychological measures, physical examinations, and measures of immune function, including absolute CD4 counts and beta 2 microglobulin (beta 2-M). There were no significant differences between the HIV-positive and HIV-negative subjects on any single neuropsychological domain. There was, however, a significant group difference on a composite indicator of neuropsychological impairment, with 32% of HIV-positive subjects demonstrating some degree of overall impairment compared with only 13% of HIV-negative subjects. HIV-positive subjects were then stratified according to the Centers for Disease Control (CDC) symptom groupings: group II, asymptomatic, n = 29; group III, lymphadenopathy, n = 30; and group IV A or C-2, symptomatic, non-AIDS, n = 38. There were no significant neuropsychological differences among the three CDC groups. The HIV-positive subjects were also stratified on absolute CD4 counts (< or = 200, 201-400, and > 400) and beta 2-M (> or = 5, 3-5, and < 3). Individuals with greater immune compromise (CD4, < 200, beta 2-M, > or = 5) were more impaired on measures of motor functioning. beta 2-M was found to be a better predictor than CD4 count of impaired neuropsychological performance. Furthermore, individuals with beta 2-M values > or = 5 have more than a threefold increase in the incidence of neuropsychological impairment than those with beta 2-M values < 3.0. These results suggest that beta 2-M may serve as a useful clinical marker for the development of neuropsychological impairment and that the risk of such impairment increases as the immune system weakens.

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This study explores the relationship of immune dysfunction to the neuropsychological performance of individuals infected with HIV-1. Fifty-five HIV-positive homosexual men and 37 negative homosexual controls were evaluated using neuropsychological measures, physical exams, and measures of immune functioning. There were no significant differences favoring HIV-negative subjects over HIV-positive subjects. HIV-positive subjects, in fact, performed slightly better on attention and memory procedures. The HIV-positive subjects were then stratified according to the Centers for Disease Control symptom groupings (Group II, asymptomatic, n = 19; Group III, lymphadenopathy, n = 17; and Group IVA or C-2, symptomatic, non-AIDS, (n = 19). There were no significant neuropsychological differences among the three CDC groups. The HIV-positive subjects were also stratified on two measures of immune functioning: absolute CD4 counts (< 200, 201-400, > 400) and beta 2-microglobulin (beta 2M) (> or = 5.0, 3.0-5.0, < 3.0). Individuals with greater immune compromise, as measured by beta 2M, were more impaired on measures of attention and memory and had greater overall neuropsychological impairment (p < 0.05). Furthermore, 57% of the subjects who were abnormal on beta 2M were also impaired on measures of attention and memory, whereas only 14% of those with normal beta 2M were impaired on these same measures (p < 0.05). These results suggest that HIV-positive asymptomatics without evidence of immune compromise do not appear to be at greater risk of cognitive impairment than HIV-negative controls. However, for those HIV-positive individuals who are immune-compromised (even while asymptomatic), there is increased risk of neuropsychological impairment. These results also suggest that knowledge of serostatus and the use of the CDC classification system alone are insufficient in exploring the development of neuropsychiatric changes in HIV-1 infection.

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OBJECTIVE: To explore the relationship of immune dysfunction to neurophysiological measures of brain-stem conduction time. DESIGN: Three-year longitudinal prospective cohort study; results of time 1 analyses reported. SETTING: San Francisco (California) General Hospital, Departments of Psychiatry and Epidemiology. PATIENTS: Volunteer sample of 55 human immunodeficiency virus (HIV)-positive and 37 HIV-negative homosexual men recruited from a larger cohort of homosexual men followed up since 1983 at San Francisco General Hospital as part of an ongoing study of the natural history and course of HIV type 1 infection. INTERVENTION: None. MAIN OUTCOME MEASURES: Auditory brain-stem responses and somatosensory evoked potentials for subjects stratified separately on HIV serostatus, Centers for Disease Control and Prevention symptom groupings, and absolute CD4 counts. RESULTS: The HIV-positive subjects had an increased wave III-V interpeak latency of the right ear auditory brain-stem response compared with the HIV-negative subjects (t test, P < .05). There were no significant differences among the three Centers for Disease Control and Prevention groupings on any evoked potential measure. When HIV-positive subjects were stratified on a measure of immune functioning, ie, CD4 counts, individuals with greater immune suppression were more impaired on speed of auditory brain-stem conduction time (Mann-Whitney U test, P < .05). Furthermore, 85% of subjects impaired on this evoked potential measure had CD4 counts of less than 0.40 x 10(9)/L (400/microL), whereas only 15% of those impaired on this measure had CD4 counts of greater than 0.40 x 10(9)/L. CONCLUSIONS: Asymptomatic HIV-positive subjects who do not have evidence of immune suppression do not appear to be at greater risk for neurophysiological impairment than HIV-negative subjects. The HIV-positive individuals who are immune suppressed (even while asymptomatic) appear to have an increased likelihood of central conduction time slowing as measured by evoked potential procedures.

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This article describes the development, implementation, and evaluation of a computer-based tutorial for a master's level course titled "Introduction to Nursing Research." The five parts of the paper include: related literature, background and rationale for the selection of the tutorial content, structure of the tutorial, an overview of the authoring language used to develop the tutorials, and the current evaluation activities.

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This study examined the contextual effects of the educational environment on faculty productivity (N = 241) from 25 nursing doctoral programs. There was a modest contextual effect upon faculty productivity after removing the contributions of individual characteristics. Highly productive programs were characterized by faculty of senior rank who had extensive teaching experience and who worked in highly productive environments. In addition, faculty who perceived their environment positively were more productive. There was also a significant individual effect upon faculty productivity after removing the contributions of the environment. Highly productive faculty were characterized by having higher academic rank, being older, and reporting a higher percentage of time spent on research activity. The significance of the contextual effects of working in a productive environment, perceiving the environment positively, and time spent on research activity are discussed.

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A methodology is presented for assessing the risk from Canadian uranium mill tailings piles. The methodology is based on the "set of triplets" concept and uses an event tree to identify various scenarios representing the performance of a pile over its 1,000-year design life. Compartment-type mathematical models are used to quantify the movement of hazardous substances through the environment. Numerical examples are given of both "level 1" (straight probabilistic) and "level 2" (probability of frequency) type analyses.

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