Methods to improve the translation of evidence-based interventions: A primer on dissemination and implementation science for occupational safety and health researchers and practitioners.

Objective: A limited focus on dissemination and implementation (D&I) science has hindered the uptake of evidence-based interventions (EBIs) that reduce workplace morbidity and mortality. D&I science methods can be used in the occupational safety and health (OSH) field to advance the adoption, implementation, and sustainment of EBIs for complex workplaces. These approaches should be responsive to contextual factors, including the needs of partners and beneficiaries (such as employers, employees, and intermediaries). Methods: By synthesizing seminal literature and texts and leveraging our collective knowledge as D&I science and/or OSH researchers, we developed a D&I science primer for OSH. First, we provide an overview of common D&I terminology and concepts. Second, we describe several key and evolving issues in D&I science: balancing adaptation with intervention fidelity and specifying implementation outcomes and strategies. Next, we review D&I theories, models, and frameworks and offer examples for applying these to OSH research. We also discuss widely used D&I research designs, methods, and measures. Finally, we discuss future directions for D&I science application to OSH and provide resources for further exploration. Results: We compiled a D&I science primer for OSH appropriate for practitioners and evaluators, especially those newer to the field. Conclusion: This article fills a gap in the OSH research by providing an overview of D&I science to enhance understanding of key concepts, issues, models, designs, methods and measures for the translation into practice of effective OSH interventions to advance the safety, health and well-being of workers.

Uptake and use of recommendations for the diagnosis, severity scoring and management of chronic GVHD: an international survey of the EBMT-NCI Chronic GVHD Task Force.

In 2005, the National Institutes of Health (NIH) consensus conference published a series of papers recommending methods to improve the conduct of clinical trials in chronic GVHD. Although the NIH recommendations were primarily aimed at strengthening research, several papers addressed issues relevant for clinical practice, particularly diagnosis, severity scoring, and ancillary and supportive care practices. We conducted an international survey to assess the uptake of these recommendations, identify barriers to greater use and document the use and perceived effectiveness of available treatments. The response rate for the American survey of 1387 practitioners was 21.8%, and it was 24.6% for 407 centers surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar with the NIH consensus recommendations (94-96%) and used them in practice. Multiple barriers to greater use were reported. Besides lack of time (55-62%), unfamiliarity with the recommendations, scarcity of evidence supporting the impact of recommendations on outcomes, insufficient training/experience in chronic GVHD management and inaccessibility of subspecialists were also endorsed. Systemic corticosteroids were reported to be the most effective treatment for chronic GVHD, but many others were perceived to have moderate or great success. Therapeutic management of steroid-refractory chronic GVHD was identified as the highest priority for research.

Relative effectiveness of different particles and energies in disrupting behavioral performance.

On exploratory class missions to other planets, astronauts will be exposed to varieties and doses of heavy particles, which are not experienced in low earth orbit. These particles can affect neurobehavioral function and potentially interfere with the ability of astronauts to successfully meet mission requirements. While a significant amount of research has been performed on the relative biological effectiveness (RBE) of different types of heavy particles on cytogenetic function, little research has been done on the effectiveness of different particles on central nervous system function and on cognitive/behavioral performance. The present paper reviews some recent research on the effects of exposure to different types and energies of heavy particles on the performance of two behavioral tasks which depend upon the integrity of the central dopaminergic system. This review indicates that the RBE of different particles for neurobehavioral dysfunction cannot be predicted only on the basis of the linear energy transfer of the specific particle.

Amphetamine-induced taste aversion learning in young and old F-344 rats following exposure to 56Fe particles.

Exposure to (56)Fe particles produces changes in dopaminergic function and in dopamine-dependent behaviors, including amphetamine-induced conditioned taste aversion (CTA) learning. Because many of these changes are characteristic of the changes that accompany the aging process, the present study was designed to determine whether or not there would be an interaction between age and exposure to (56)Fe particles in the disruption of an amphetamine-induced CTA. One hundred and forty F-344 male rats 2-, 7-, 12-, and 16-months old, were radiated with (56)Fe particles (0.25-2.00 Gy, 1 GeV/n) at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of radiation on the acquisition of a CTA produced by injection of amphetamine (3 mg/kg, i.p.). The main effect of age was to produce a significant decrease in conditioning day sucrose intake; there was no affect of age on the acquisition of the amphetamine-induced CTA. Exposing rats to (56)Fe particles disrupted the acquisition of the CTA produced by injection of amphetamine only in the 2-month-old rats. These results do not support the hypothesis of an interaction between age and exposure to (56)Fe particles in producing a disruption of amphetamine-induced CTA learning. As such, these results suggest that the aging produced by exposure to (56)Fe particles may be endpoint specific.

Medical and psychosocial outcome of patients with occupational contact dermatitis in Israel.

BACKGROUND: Although the medical, financial and prognostic factors of occupational contact dermatitis (OCD) have been addressed, studies on the social outcome of OCD are sparse. OBJECTIVE: To define the medical and psychosocial outcome of patients with OCD. METHODS: Workers with OCD were interviewed by telephone using a questionnaire that included questions about the occupation, dermatological disease, sick leave, present working status and disability claims, and questions related to the subjective perceptions of OCD in all areas of psychosocial functioning and quality of life. RESULTS: Seventy workers (64.3% males and 35.7% females) were interviewed. Forty per cent had stopped working and one-third had taken sick leave because of OCD. Forty-seven (67.1%) were currently working while 23 (32.8%) were unemployed. Disability compensation was claimed by only 41.4% and was received by 24.3%. Eight workers (11.4%) had persistent postoccupational dermatitis (PPOD). Loss of employment affected the occupational area of the workers' lives (100%), and also interpersonal relationships (45.7%), relationships within the family (18.6%), daily functioning (45.7%) and mental health (24.3%). CONCLUSIONS: Considerable working time is lost because of unemployment or sick leave due to OCD. Only a small proportion of eligible patients with OCD apply for disability compensation and an even smaller proportion receive it. Our study demonstrates the significance of OCD to the psychosocial aspects of workers' lives and emphasizes that the assessment of OCD outcome should relate not only to the medical but also to the psychosocial aspect of the disease.

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

Cognitive deficits induced by 56Fe radiation exposure.

Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle.

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.

Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing.

Splenic immune function is modulated by sympathetic innervation, which in turn is controlled by inputs from supraspinal regions. In the present study, the characterization of central circuits involved in the control of splenic function was accomplished by injecting pseudorabies virus (PRV), a retrograde transynaptic tracer, into the spleen and conducting a temporal analysis of the progression of the infection from 60 hours to 110 hours postinoculation. In addition, central noradrenergic cell groups involved in splenic innervation were characterized by dual immunohistochemical detection of dopamine-beta-hydroxylase and PRV. Infection in the CNS first appeared in the spinal cord. Splenic sympathetic preganglionic neurons, identified in rats injected with Fluoro-Gold i.p. prior to PRV inoculation of the spleen, were located in T(3)-T(12) bilaterally; numerous infected interneurons were also found in the thoracic spinal cord (T(1)-T(13)). Infected neurons in the brain were first observed in the A5 region, ventromedial medulla, rostral ventrolateral medulla, paraventricular hypothalamic nucleus, Barrington's nucleus, and caudal raphe. At intermediate survival times, the number of infected cells increased in previously infected areas, and infected neurons also appeared in lateral hypothalamus, A7 region, locus coeruleus, subcoeruleus region, nucleus of the solitary tract, and C3 cell group. At longer postinoculation intervals, infected neurons were found in additional hypothalamic areas, Edinger-Westphal nucleus, periaqueductal gray, pedunculopontine tegmental nucleus, caudal ventrolateral medulla, and area postrema. These results demonstrate that the sympathetic outflow to the spleen is controlled by a complex multisynaptic pathway that involves several brainstem and forebrain nuclei.

Identification of delta- and mu-type opioid receptors on human and murine dendritic cells.

The purpose of this study was to evaluate mu- and delta-opioid receptors (OR) on human and murine dendritic cells (DC). Expression of mu- and delta-OR mRNA on DC was demonstrated by RT-PCR. The immunocytochemical and Western blot analyses revealed the expression of OR protein in DC. Radioreceptor assay demonstrated the specific saturated temperature-dependent binding of [3H]-labeled opioid ligand on DC and B(max)=2.8+/-0.3 fmol/10(6) cells and K(D)=4.8+/-1.0 nM were calculated by a Scatchard analysis. Finally, OR ligands DADLE and DAGO dose-dependently modulated the capacity of DC to induce T cell proliferation in an MLR assay. Importantly, expression of functional OR on DC was significantly increased upon TNF-alpha-induced DC maturation. Thus, these data suggest a new mechanism of opioid-dependent neuroendocrine immunomodulation.

Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults.

Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance.

Psychological stress and antibody response to immunization: a critical review of the human literature.

OBJECTIVE: The objective of this review was to evaluate the evidence for the hypothesis that psychological stress influences antibody response to immunization in humans. METHODS: A critical review of the literature was conducted. RESULTS: The evidence supports an association between psychological stress and suppression of humoral immune (antibody) response to immunization. This association is convincing in the case of secondary immune response but weak for primary response. The lack of consistent evidence for a relation with primary response may be attributed to a failure to consider the critical points when stress needs to be elevated in the course of the production of antibody. Lower secondary antibody responses were found among patients with chronically high levels of stress (severe enduring problems or high levels of trait negative affect). These responses were found most consistently among older adults. Lower secondary responses were also found for those reporting acute stress or negative affect, but only in studies of secretory immunoglobulin A antibody in which psychological and antibody measures were linked very closely in time. Health practices did not mediate relations between stress and antibody responses; however, there were indications that elevated cortisol levels among stressed patients could play a role. Evidence also suggests the possible influences of dispositional stress-reactivity and low positive affect in the inhibition of antibody production. CONCLUSIONS: The literature supports a relationship between psychological stress and antibody responses to immunizations. The data are convincing in the case of secondary response but weak for primary response. More attention to the kinetics of stress and antibody response and their interrelations is needed in future research.

Effects of exposure to 56Fe particles on the acquisition of a conditioned place preference in rats.

Exposure to low doses of 56Fe particles produces changes in neural function and behavior. The present experiments were designed to examine the effects of irradiation on the acquisition of a dopamine-mediated conditioned place preference (CPP). In the CPP procedure, rats are given an injection of the dopamine agonist amphetamine in one distinctive compartment and a saline injection in a different compartment of a three-compartment apparatus. Control rats develop a preference for the amphetamine-paired compartment. In contrast, rats exposed to 1 Gy of 56Fe particles fail to develop a similar preference. The results of the experiment indicate that exposure to low doses of heavy particles can disrupt the neural mechanisms that mediate the reinforcement of behavior.

Role of locus coeruleus in foot shock-evoked Fos expression in rat brain.

The robust activation of locus coeruleus neurons in response to a variety of stressors, in conjunction with the widespread outputs of the locus coeruleus, suggest that the locus coeruleus may be important in mediating responses to stress. Previous studies in rats have demonstrated that exposure to foot shock elicits Fos expression, a marker of neuronal activation, in the locus coeruleus and other brain sites. In order to evaluate the involvement of the locus coeruleus in foot shock-induced activation of other brain sites, shock-induced Fos expression was examined in the locus coeruleus and other brain areas known to be activated by foot shock, following direct inhibition of the locus coeruleus by local infusion of muscimol, a GABA agonist, prior to foot shock. Control rats received infusions of artificial cerebrospinal fluid into the locus coeruleus or muscimol into areas outside of locus coeruleus. Rats infused with artificial cerebrospinal fluid and then exposed to foot shock had significant increases in Fos expression in several brain areas, including locus coeruleus, nucleus O, several subdivisions of the hypothalamus, subnuclei of amygdala, bed nucleus of the stria terminalis and cingulate cortex. Inhibition of the locus coeruleus prior to foot shock significantly inhibited Fos expression in the locus coeruleus, nucleus O, some subdivisions of the hypothalamus including the magnocellular and medial parvicellular paraventricular hypothalamic nucleus, subnuclei of amygdala, and cingulate cortex. In contrast, inhibition of the locus coeruleus did not affect shock-induced Fos expression in other areas, including certain subdivisions of the hypothalamus and bed nucleus of the stria terminalis. We suggest that foot shock may activate multiple pathways, with activation of certain discrete nuclei requiring input from the locus coeruleus and activation of others occurring independently of locus coeruleus input.

A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34.

Amyotrophic lateral sclerosis (ALS) denotes a heterogeneous group of neurodegenerative disorders affecting upper and lower motor neurons. ALS4 is a juvenile-onset, autosomal dominant form of ALS that is characterized by slow progression, distal limb weakness and amyotrophy, and pyramidal signs associated with severe loss of motor neurons in the brain and spinal cord. The ALS4 locus was recently mapped by linkage analysis to a large genetic interval on chromosome 9q34. By undertaking extensive genetic linkage analysis, we have significantly refined the ALS4 locus to a critical interval of less than 3 cM, flanked by D9S149 and D9S1198. Previous physical mapping in this region has indicated that this critical interval spans approximately 500 kb. Seventeen putative transcripts have been localized within this interval including 7 characterized genes, 2 partially characterized genes, and 8 "anonymous" expressed sequence tags . These are therefore positional candidate genes for the ALS4 locus. We have also undertaken mutation analysis and genetic mapping to investigate and exclude candidate genes, including RING3L/ORFX and RALGDS, from a pathogenic role in ALS4.

[Familiarizing medical students with hospital social worker's role].

Patient care in a general hospital is usually provided by a multi-professional team. Treatment is most effective when each professional understands the functions of the various other members of the team. Professional literature and research have highlighted differences in perception by social workers and physicians of the proper function of the medical social worker. Our social work department has developed a teaching program for medical students to enhance their knowledge with regard to this issue. It is presented at a single-session group meeting of an hour and a half, with structured content and goals.