Using the results of routine laboratory workplace surveillance activities to assess compliance with recommended biosafety guidelines

The biological safety profession has historically functioned within an environment based on recommended practices rather than regulations, so summary data on compliance or noncompliance with recommended practices is largely absent from the professional literature. The absence of safety performance outcome data is unfortunate since the concept of biosafety containment is based on a combination of facility based controls and workplace practices, and persistent failures in either type of controls could ultimately result in injury or death. In addition, the number of laboratories requiring biosafety containment is likely to grow significantly in the coming years in the wake of the terrorist events of 2001. In this study, the outcomes of 768 biosafety level 2 (BSL-2) safety surveys were analyzed for commonalities and trends. Items of non-compliance noted were classified as facility related or practice related. The most frequent item of noncompliance encountered was the failure to re-certify biosafety cabinetry. Not surprisingly, the preponderance of the other frequent items of non-compliance encountered were practice related, such as general housekeeping orderly, changes in compliance levels, as well as establish trends in the elements of items of non-compliance during the sequential survey period. The findings described in this study are significant because, for the first time, the outcomes of compliance with recommended biosafety practices can be characterized and thus used as the basis for focused interventions. Since biosafety is heavily reliant on adherence to specific safety practices, the ability to focus interventions on objectively identified practice-related items of non-compliance can assist in the reduction of worker risk in this area experiencing tremendous growth. The information described is also of heighten importance given the number of workplaces expected to involve potentially infectious agents in the coming years. ^

The role of workplace absence as an organizational mechanism in predicting employee alcohol and drug disorders

Background. EAP programs for airline pilots in companies with a well developed recovery management program are known to reduce pilot absenteeism following treatment. Given the costs and safety consequences to society, it is important to identify pilots who may be experiencing an AOD disorder to get them into treatment. ^ Hypotheses. This study investigated the predictive power of workplace absenteeism in identifying alcohol or drug disorders (AOD). The first hypothesis was that higher absenteeism in a 12-month period is associated with higher risk that an employee is experiencing AOD. The second hypothesis was that AOD treatment would reduce subsequent absence rates and the costs of replacing pilots on missed flights. ^ Methods. A case control design using eight years (time period) of monthly archival absence data (53,000 pay records) was conducted with a sample of (N = 76) employees having an AOD diagnosis (cases) matched 1:4 with (N = 304) non-diagnosed employees (controls) of the same profession and company (male commercial airline pilots). Cases and controls were matched on the variables age, rank and date of hire. Absence rate was defined as sick time hours used over the sum of the minimum guarantee pay hours annualized using the months the pilot worked for the year. Conditional logistic regression was used to determine if absence predicts employees experiencing an AOD disorder, starting 3 years prior to the cases receiving the AOD diagnosis. A repeated measures ANOVA, t tests and rate ratios (with 95% confidence intervals) were conducted to determine differences between cases and controls in absence usage for 3 years pre and 5 years post treatment. Mean replacement costs were calculated for sick leave usage 3 years pre and 5 years post treatment to estimate the cost of sick leave from the perspective of the company. ^ Results. Sick leave, as measured by absence rate, predicted the risk of being diagnosed with an AOD disorder (OR 1.10, 95% CI = 1.06, 1.15) during the 12 months prior to receiving the diagnosis. Mean absence rates for diagnosed employees increased over the three years before treatment, particularly in the year before treatment, whereas the controls’ did not (three years, x = 6.80 vs. 5.52; two years, x = 7.81 vs. 6.30, and one year, x = 11.00cases vs. 5.51controls. In the first year post treatment compared to the year prior to treatment, rate ratios indicated a significant (60%) post treatment reduction in absence rates (OR = 0.40, CI = 0.28, 0.57). Absence rates for cases remained lower than controls for the first three years after completion of treatment. Upon discharge from the FAA and company’s three year AOD monitoring program, case’s absence rates increased slightly during the fourth year (controls, x = 0.09, SD = 0.14, cases, x = 0.12, SD = 0.21). However, the following year, their mean absence rates were again below those of the controls (controls, x = 0.08, SD = 0.12, cases, x¯ = 0.06, SD = 0.07). Significant reductions in costs associated with replacing pilots calling in sick, were found to be 60% less, between the year of diagnosis for the cases and the first year after returning to work. A reduction in replacement costs continued over the next two years for the treated employees. ^ Conclusions. This research demonstrates the potential for workplace absences as an active organizational surveillance mechanism to assist managers and supervisors in identifying employees who may be experiencing or at risk of experiencing an alcohol/drug disorder. Currently, many workplaces use only performance problems and ignore the employee’s absence record. A referral to an EAP or alcohol/drug evaluation based on the employee’s absence/sick leave record as incorporated into company policy can provide another useful indicator that may also carry less stigma, thus reducing barriers to seeking help. This research also confirms two conclusions heretofore based only on cross-sectional studies: (1) higher absence rates are associated with employees experiencing an AOD disorder; (2) treatment is associated with lower costs for replacing absent pilots. Due to the uniqueness of the employee population studied (commercial airline pilots) and the organizational documentation of absence, the generalizability of this study to other professions and occupations should be considered limited. ^ Transition to Practice. The odds ratios for the relationship between absence rates and an AOD diagnosis are precise; the OR for year of diagnosis indicates the likelihood of being diagnosed increases 10% for every hour change in sick leave taken. In practice, however, a pilot uses approximately 20 hours of sick leave for one trip, because the replacement will have to be paid the guaranteed minimum of 20 hour. Thus, the rate based on hourly changes is precise but not practical. ^ To provide the organization with practical recommendations the yearly mean absence rates were used. A pilot flies on average, 90 hours a month, 1080 annually. Cases used almost twice the mean rate of sick time the year prior to diagnosis (T-1) compared to controls (cases, x = .11, controls, x = .06). Cases are expected to use on average 119 hours annually (total annual hours*mean annual absence rate), while controls will use 60 hours. The cases’ 60 hours could translate to 3 trips of 20 hours each. Management could use a standard of 80 hours or more of sick time claimed in a year as the threshold for unacceptable absence, a 25% increase over the controls (a cost to the company of approximately of $4000). At the 80-hour mark, the Chief Pilot would be able to call the pilot in for a routine check as to the nature of the pilot’s excessive absence. This management action would be based on a company standard, rather than a behavioral or performance issue. Using absence data in this fashion would make it an active surveillance mechanism. ^

The Crosslinking Degree Controls The Mechanical, Rheological, And Swelling Properties Of Hyaluronic Acid Microparticles.

Viscosupplements, used for treating joint and cartilage diseases, restore the rheological properties of synovial fluid, regulate joint homeostasis and act as scaffolds for cell growth and tissue regeneration. Most viscosupplements are hydrogels composed of hyaluronic acid (HA) microparticles suspended in fluid HA. These microparticles are crosslinked with chemicals to assure their stability against enzyme degradation and to prolong the action of the viscosupplement. However, the crosslinking also modifies the mechanical, swelling and rheological properties of the HA microparticle hydrogels, with consequences on the effectiveness of the application. The aim of this study is to correlate the crosslinking degree (CD) with these properties to achieve modulation of HA/DVS microparticles through CD control. Because divinyl sulfone (DVS) is the usual crosslinker of HA in viscosupplements, we examined the effects of CD by preparing HA microparticles at 1:1, 2:1, 3:1, and 5:1 HA/DVS mass ratios. The CD was calculated from inductively coupled plasma spectrometry data. HA microparticles were previously sized to a mean diameter of 87.5 µm. Higher CD increased the viscoelasticity and the extrusion force and reduced the swelling of the HA microparticle hydrogels, which also showed Newtonian pseudoplastic behavior and were classified as covalent weak. The hydrogels were not cytotoxic to fibroblasts according to an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.

Metabolic Memory Of ß-cells Controls Insulin Secretion And Is Mediated By Camkii.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of metabolic memory, just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects. Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and Ca(2+)-dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information.

Hypothalamic S1p/s1pr1 Axis Controls Energy Homeostasis.

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

Environmental Controls In The Water Use Patterns Of A Tropical Cloud Forest Tree Species, Drimys Brasiliensis (winteraceae).

Trees from tropical montane cloud forest (TMCF) display very dynamic patterns of water use. They are capable of downwards water transport towards the soil during leaf-wetting events, likely a consequence of foliar water uptake (FWU), as well as high rates of night-time transpiration (Enight) during drier nights. These two processes might represent important sources of water losses and gains to the plant, but little is known about the environmental factors controlling these water fluxes. We evaluated how contrasting atmospheric and soil water conditions control diurnal, nocturnal and seasonal dynamics of sap flow in Drimys brasiliensis (Miers), a common Neotropical cloud forest species. We monitored the seasonal variation of soil water content, micrometeorological conditions and sap flow of D. brasiliensis trees in the field during wet and dry seasons. We also conducted a greenhouse experiment exposing D. brasiliensis saplings under contrasting soil water conditions to deuterium-labelled fog water. We found that during the night D. brasiliensis possesses heightened stomatal sensitivity to soil drought and vapour pressure deficit, which reduces night-time water loss. Leaf-wetting events had a strong suppressive effect on tree transpiration (E). Foliar water uptake increased in magnitude with drier soil and during longer leaf-wetting events. The difference between diurnal and nocturnal stomatal behaviour in D. brasiliensis could be attributed to an optimization of carbon gain when leaves are dry, as well as minimization of nocturnal water loss. The leaf-wetting events on the other hand seem important to D. brasiliensis water balance, especially during soil droughts, both by suppressing tree transpiration (E) and as a small additional water supply through FWU. Our results suggest that decreases in leaf-wetting events in TMCF might increase D. brasiliensis water loss and decrease its water gains, which could compromise its ecophysiological performance and survival during dry periods.

A comparison of lower limb EMG and ground reaction forces between barefoot and shod gait in participants with diabetic neuropathic and healthy controls

Background: It is known that when barefoot, gait biomechanics of diabetic neuropathic patients differ from nondiabetic individuals. However, it is still unknown whether these biomechanical changes are also present during shod gait which is clinically advised for these patients. This study investigated the effect of the participants own shoes on gait biomechanics in diabetic neuropathic individuals compared to barefoot gait patterns and healthy controls. Methods: Ground reaction forces and lower limb EMG activities were analyzed in 21 non-diabetic adults (50.9 +/- 7.3 yr, 24.3 +/- 2.6 kg/m(2)) and 24 diabetic neuropathic participants (55.2 +/- 7.9 yr, 27.0 +/- 4.4 kg/m(2)). EMG patterns of vastus lateralis, lateral gastrocnemius and tibialis anterior, along with the vertical and antero-posterior ground reaction forces were studied during shod and barefoot gait. Results: Regardless of the disease, walking with shoes promoted an increase in the first peak vertical force and the peak horizontal propulsive force. Diabetic individuals had a delay in the lateral gastrocnemius EMG activity with no delay in the vastus lateralis. They also demonstrated a higher peak horizontal braking force walking with shoes compared to barefoot. Diabetic participants also had a smaller second peak vertical force in shod gait and a delay in the vastus lateralis EMG activity in barefoot gait compared to controls. Conclusions: The change in plantar sensory information that occurs when wearing shoes revealed a different motor strategy in diabetic individuals. Walking with shoes did not attenuate vertical forces in either group. Though changes in motor strategy were apparent, the biomechanical did not support the argument that the use of shoes contributes to altered motor responses during gait.

Psychogenetics of Turner syndrome: an investigation of 28 subjects and respective controls using the Bender test and Piagetian scales

Piagetian scales and the Bender visual motor gestalt test (BT) were applied to 28 subjects with universal 45, X Turner syndrome (TS), and their respective controls, in order to investigate their cognitive performance. Dermatoglyphics were also analyzed to obtain clues concerning embryological changes that may have appeared during development of the nervous system and could be associated with cognitive performance of TS patients. Dermatoglyphic pattern distribution was similar to that reported in previous studies of TS individuals: ulnar loops in the digital patterns and finger ridge, a-b, and A'-d counts were more frequent, while arch and whorl patterns were less frequent compared to controls. However, we did not find higher frequencies of hypothenar pattern, maximum atd angle, and ulnarity index in our TS subjects, unlike other investigations. Furthermore, we found significant differences between TS and control T line index values. The BT scores were also lower in probands, as has been previously reported, revealing a neurocognitive deficit of visual motor perception in TS individuals, which could be due to an absence of, or deficiency in, cerebral hemispheric lateralization. However, TS subjects seemed to improve their performance on BT with age. Cognitive performance of the TS subjects was not significantly different from that of controls, confirming a previous study in which TS performance was found to be similar to that of the normal Brazilian population. There were significant correlations between BT scores and Piagetian scale levels with dermatoglyphic parameters. This association could be explained by changes in the common ectodermal origin of the epidermis and the central nervous system. TS subjects seem to succeed in compensating their spatial impairments in adapting their cognitive and social contacts. We concluded that genetic counseling should consider cognitive and psychosocial difficulties presented by TS subjects, providing appropriate treatment and orientation for them and their families.

The Essential Nucleolar Yeast Protein Nop8p Controls the Exosome Function during 60S Ribosomal Subunit Maturation

The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxyl-terminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Dnop8/GAL:NOP8. Interestingly, Nop8p mediates association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control the exosome function during pre-rRNA processing.

The P450 oxidoreductase, RedA, controls development beyond the mound stage in Dictyostelium discoideum

Background: NADPH-cytochrome- P450 oxidoreductase (CPR) is a ubiquitous enzyme that belongs to a family of diflavin oxidoreductases and is required for activity of the microsomal cytochrome-P450 monooxygenase system. CPR gene-disruption experiments have demonstrated that absence of this enzyme causes developmental defects both in mouse and insect. Results: Annotation of the sequenced genome of D. discoideum revealed the presence of three genes (redA, redB and redC) that encode putative members of the diflavin oxidoreductase protein family. redA transcripts are present during growth and early development but then decline, reaching undetectable levels after the mound stage. redB transcripts are present in the same levels during growth and development while redC expression was detected only in vegetative growing cells. We isolated a mutant strain of Dictyostelium discoideum following restriction enzyme-mediated integration (REMI) mutagenesis in which redA was disrupted. This mutant develops only to the mound stage and accumulates a bright yellow pigment. The mound-arrest phenotype is cell-autonomous suggesting that the defect occurs within the cells rather than in intercellular signaling. Conclusion: The developmental arrest due to disruption of redA implicates CPR in the metabolism of compounds that control cell differentiation.

Physical controls on carbon dioxide transfer velocity and flux in low-gradient river systems and implications for regional carbon budgets

Outgassing of carbon dioxide (CO(2)) from rivers and streams to the atmosphere is a major loss term in the coupled terrestrial-aquatic carbon cycle of major low-gradient river systems (the term ""river system"" encompasses the rivers and streams of all sizes that compose the drainage network in a river basin). However, the magnitude and controls on this important carbon flux are not well quantified. We measured carbon dioxide flux rates (F(CO2)), gas transfer velocity (k), and partial pressures (p(CO2)) in rivers and streams of the Amazon and Mekong river systems in South America and Southeast Asia, respectively. F(CO2) and k values were significantly higher in small rivers and streams (channels <100 m wide) than in large rivers (channels >100 m wide). Small rivers and streams also had substantially higher variability in k values than large rivers. Observed F(CO2) and k values suggest that previous estimates of basinwide CO(2) evasion from tropical rivers and wetlands have been conservative and are likely to be revised upward substantially in the future. Data from the present study combined with data compiled from the literature collectively suggest that the physical control of gas exchange velocities and fluxes in low-gradient river systems makes a transition from the dominance of wind control at the largest spatial scales (in estuaries and river mainstems) toward increasing importance of water current velocity and depth at progressively smaller channel dimensions upstream. These results highlight the importance of incorporating scale-appropriate k values into basinwide models of whole ecosystem carbon balance.

Propofol-induced sleep: Polysomnographic evaluation of patients with obstructive sleep apnea and controls

OBJECTIVE: The localization of upper airway obstruction in patients with obstructive sleep apnea (OSA) may optimize treatment. Nasoendoscopy during propofol sedation allows such an evaluation, but the effect of this drug on respiratory patterns and muscle relaxation is unknown. The objective of the present study was to determine through polysomnography whether propofol would change sleep parameters. STUDY DESIGN: Prospective study of subjects submitted to polysomnography under sedation with propofol. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Fifteen non-obese subjects (4 controls/11 OSA patients) were submitted to two diurnal polysomnograms (90-120 minutes of sleep), with and without the use of propofol. The parameters presence of snoring, apnea-hypopnea index (AHI), oxygen desaturation, and sleep architecture were compared. RESULTS: The use of propofol did not induce snoring in the control subjects, whereas 100 percent of the OSA patients snored. AHI and mean oxygen saturation (SaO(2)) did not differ significantly between examinations with and without sedation. However, minimum SaO(2) differed significantly (P < 0.05) with sedation, being lower during propofol sedation. Propofol also significantly changed the sleep architecture, with a significant increase in N3 sleep (P < 0.005) and total abolishment of rapid eye movement sleep (P < 0.0005) during propofol sedation. CONCLUSIONS: These preliminary results allow us to infer that sedation with propofol changes sleep architecture but permits respiratory evaluation, because the main respiratory parameters evaluated in OSA are maintained. These preliminary results support the view that nasoendoscopy under propofol sedation is a promising examination for management of this disease. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

A Fault-Tolerant Manipulator Robot Based on H(2), H(infinity), and Mixed H(2)/H(infinity) Markovian Controls

This paper develops a Markovian jump model to describe the fault occurrence in a manipulator robot of three joints. This model includes the changes of operation points and the probability that a fault occurs in an actuator. After a fault, the robot works as a manipulator with free joints. Based on the developed model, a comparative study among three Markovian controllers, H(2), H(infinity), and mixed H(2)/H(infinity) is presented, applied in an actual manipulator robot subject to one and two consecutive faults.

Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42`s expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis. (C) 2009 Elsevier Inc. All rights reserved.

Environmental Risk Factors for Parkinson's Disease

Parkinson’s disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study’s results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.