Characterization of spaC-type Erysipelothrix sp. isolates causing systemic disease in ornamental fish.

Since 2012, low-to-moderate mortality associated with an Erysipelothrix sp. bacterium has been reported in ornamental fish. Histological findings have included facial cellulitis, necrotizing dermatitis and myositis, and disseminated coelomitis with abundant intralesional Gram-positive bacterial colonies. Sixteen Erysipelothrix sp. isolates identified phenotypically as E. rhusiopathiae were recovered from diseased cyprinid and characid fish. Similar clinical and histological changes were also observed in zebrafish, Danio rerio, challenged by intracoelomic injection. The Erysipelothrix sp. isolates from ornamental fish were compared phenotypically and genetically to E. rhusiopathiae and E. tonsillarum isolates recovered from aquatic and terrestrial animals from multiple facilities. Results demonstrated that isolates from diseased fish were largely clonal and divergent from E. rhusiopathiae and E. tonsillarum isolates from normal fish skin, marine mammals and terrestrial animals. All ornamental fish isolates were PCR positive for spaC, with marked genetic divergence (<92% similarity at gyrB, <60% similarity by rep-PCR) between the ornamental fish isolates and other Erysipelothrix spp. isolates. This study supports previous work citing the genetic variability of Erysipelothrix spp. spa types and suggests isolates from diseased ornamental fish may represent a genetically distinct species.

New host record and molecular characterization of Dicauda atherinoidi Hoffman & Walker (Bivalvulida: Myxobolidae): a parasite of the emerald shiner Notropis atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865.

Updated morphological and histopathological descriptions for Dicauda atherinoidi (Bivalvulida:Myxobolidae) and an expanded host range are supplemented with the first molecular data and phylogenetic analyses of the genus. Plasmodia were located on the head, ventrum/body and fins of infected emerald shiner Notropis atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865, a new host species. Myxospores were spherical, ranging 9.3-11.4 µm (10.5 ± 0.4) in length, 9.0-11.0 µm (9.7 ± 0.4) in width and 6.6-7.0 µm (6.8 ± 0.2) thick in sutural view, and possessed 2-3 caudal processes (5.3-68.3 µm, 31.1 ± 13.6) connected to the spore body at the sutural groove, all of which are consistent with the genus Dicauda. In the absence of available Dicauda sequence data, the 18S rDNA sequences from Michigan isolates were most similar to Myxobolus spp. Phylogenetic analyses clustered these isolates with myxobolid species from cyprinid fish, suggesting these parasites may represent an underpopulated group of cyprinid-infecting myxozoans. Histopathology revealed thin-walled plasmodial pseudocysts in the dermis and associated connective tissue, where granulomatous inflammation and focal scale atrophy were also present. Further sampling/sequencing of myxobolids from Notropis spp. should expand these underrepresented myxozoans and offer further insight into Myxobolidae host family tropisms.

Far-infrared observations of a massive cluster forming in the Monoceros R2 filament hub⋆.

We present far-infrared observations of Monoceros R2 (a giant molecular cloud at approximately 830 pc distance, containing several sites of active star formation), as observed at 70 µm, 160 µm, 250 µm, 350 µm, and 500 µm by the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) instruments on the Herschel Space Observatory as part of the Herschel imaging survey of OB young stellar objects (HOBYS) Key programme. The Herschel data are complemented by SCUBA-2 data in the submillimetre range, and WISE and Spitzer data in the mid-infrared. In addition, C18O data from the IRAM 30-m Telescope are presented, and used for kinematic information. Sources were extracted from the maps with getsources, and from the fluxes measured, spectral energy distributions were constructed, allowing measurements of source mass and dust temperature. Of 177 Herschel sources robustly detected in the region (a detection with high signal-to-noise and low axis ratio at multiple wavelengths), including protostars and starless cores, 29 are found in a filamentary hub at the centre of the region (a little over 1% of the observed area). These objects are on average smaller, more massive, and more luminous than those in the surrounding regions (which together suggest that they are at a later stage of evolution), a result that cannot be explained entirely by selection effects. These results suggest a picture in which the hub may have begun star formation at a point significantly earlier than the outer regions, possibly forming as a result of feedback from earlier star formation. Furthermore, the hub may be sustaining its star formation by accreting material from the surrounding filaments.

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

Edwardsiella ictaluri infection in Pangasius catfish imported from West Bengal into the Southern Caribbean.

In response to a mortality event, seven Pangasius catfish (Pangasianodon hypophthalmus) were submitted to the University of the West Indies, School of Veterinary Medicine, Trinidad and Tobago, for diagnostic evaluation. These fish were part of a consignment that arrived from Kolkata two weeks earlier. Fish presented with perianal haemorrhage and blister-like swellings on the skin which ruptured to leave ulcers. Edwardsiella ictaluri was consistently recovered from the brain and skin. Repetitive sequence-mediated PCR analysis revealed genetic fingerprints consistent with E. ictaluri isolates from farm-raised channel catfish in Mississippi, USA. Plasmid analysis of the case isolates identified two unique plasmids that differ slightly in conformation and content from the pEI1 and pEI2 plasmids described for E. ictaluri from other fish hosts. The case isolates were also PCR negative for several E. ictaluri virulence factors. The biological implications of these genetic differences are unclear and warrant further study. This is the first report and documentation of E. ictaluri infection in Trinidad and Tobago, suggesting the pathogen may have been introduced concurrently with the importation of fish. This report emphasizes the importance of adequate health screenings of imported lots to minimize the threat of introducing E. ictaluri to non-endemic areas.

Detection of Salmonella enterica Serovar Montevideo and Newport in Free-ranging Sea Turtles and Beach Sand in the Caribbean and Persistence in Sand and Seawater Microcosms.

Salmonellae are Gram-negative zoonotic bacteria that are frequently part of the normal reptilian gastrointestinal flora. The main objective of this project was to estimate the prevalence of non-typhoidal Salmonella enterica in the nesting and foraging populations of sea turtles on St. Kitts and in sand from known nesting beaches. Results suggest a higher prevalence of Salmonella in nesting leatherback sea turtles compared with foraging green and hawksbill sea turtles. Salmonella was cultured from 2/9 and identified by molecular diagnostic methods in 3/9 leatherback sea turtle samples. Salmonella DNA was detected in one hawksbill turtle, but viable isolates were not recovered from any hawksbill sea turtles. No Salmonella was detected in green sea turtles. In samples collected from nesting beaches, Salmonella was only recovered from a single dry sand sample. All recovered isolates were positive for the wzx gene, consistent with the O:7 serogroup. Further serotyping characterized serovars Montevideo and Newport present in cloacal and sand samples. Repetitive-element palindromic PCR (rep-PCR) fingerprint analysis and pulsed-field gel electrophoresis of the 2014 isolates from turtles and sand as well as archived Salmonella isolates recovered from leatherback sea turtles in 2012 and 2013, identified two distinct genotypes and four different pulsotypes, respectively. The genotyping and serotyping were directly correlated. To determine the persistence of representative strains of each serotype/genotype in these environments, laboratory-controlled microcosm studies were performed in water and sand (dry and wet) incubated at 25 or 35°C. Isolates persisted for at least 32 days in most microcosms, although there were significant decreases in culturable bacteria in several microcosms, with the greatest reduction in dry sand incubated at 35°C. This information provides a better understanding of the epizootiology of Salmonella in free-ranging marine reptiles and the potential public health risks associated with human interactions with these animals in the Caribbean.

Comparison of Edwardsiella ictaluri isolates from different hosts and geographic origins.

The intraspecific variability of E. ictaluri isolates from different origins was investigated. Isolates were recovered from farm-raised catfish (Ictalurus punctatus) in Mississippi, USA, tilapia (Oreochromis niloticus) cultured in the Western Hemisphere and zebrafish (Danio rerio) propagated in Florida, USA. These isolates were phenotypically homologous and antimicrobial profiles were largely similar. Genetically, isolates possessed differences that could be exploited by repetitive-sequence-mediated PCR and gyrB sequence, which identified three distinct E. ictaluri genotypes: one associated with catfish, one from tilapia and a third from zebrafish. Plasmid profiles were also group specific and correlated with rep-PCR and gyrB sequences. The catfish isolates possessed profiles typical of those described for E. ictaluri isolates; however, plasmids from the zebrafish and tilapia isolates differed in both composition and arrangement. Furthermore, some zebrafish and tilapia isolates were PCR negative for several E. ictaluri virulence factors. Isolates were serologically heterogenous, as serum from a channel catfish exposed to a catfish isolate had reduced antibody activity to tilapia and zebrafish isolates. This work identifies three genetically distinct strains of E. ictaluri from different origins using rep-PCR, 16S, gyrB and plasmid sequencing, in addition to antimicrobial and serological profiling.

Myxobolus neurophilus Guilford 1963 (Myxosporea: Myxobolidae): a common parasite infecting yellow perch Perca flavescens (Mitchell, 1814) in Saskatchewan, Canada.

The goal of this study was to identify a myxosporidian parasite infecting the central nervous system of yellow perch Perca flavescens (Mitchell, 1814) observed while investigating a fish kill in Saskatchewan, Canada. Fish were collected from seven different lakes, from two distinct watersheds. Sixty-four per cent (54/86) of yellow perch contained myxozoan pseudocysts located throughout the spinal cord and brain. Myxospores measured 16.5 µm (range 16.2-16.8) long and 8.2 µm (range 7.9-8.4) wide and contained two pyriform, mildly dissymmetrical, polar capsules measuring 7.7 µm (range 7.3-8.1) long and 2.7 µm (range 2.4-3.0) wide. The polar capsules each contained a single polar filament, with 7-9 turns per polar filament coil. Sequencing of the 18S SSU rDNA gene demonstrated >99% similarity to Myxobolus neurophilus. In 60% of infected fish, there was a mild to moderate, non-suppurative myelitis or encephalitis, or both, associated with myxospores. Axonal degeneration was present in rare cases. These findings extend the geographical distribution of M. neurophilus and suggest it may be widespread in yellow perch populations in Saskatchewan.

Fatal septicemia caused by the zoonotic bacterium Streptococcus iniae during an outbreak in Caribbean reef fish.

An outbreak of Streptococcus iniae occurred in the early months of 2008 among wild reef fish in the waters of the Federation of St Kitts and Nevis, lasting almost 2 months. Moribund and dead fish were collected for gross, histological, bacteriological, and molecular analysis. Necropsy findings included diffuse fibrinous pericarditis, pale friable livers, and serosal petechiation. Cytological and histological analysis revealed granulocytic and granulomatous inflammation with abundant coccoid bacterial organisms forming long chains. Necrosis, inflammation, and vasculitis were most severe in the pericardium, meninges, liver, kidneys, and gills. Bacterial isolates revealed ß-hemolytic, Gram-positive coccoid bacteria identified as S. iniae by amplification and 16S ribosomal RNA gene sequencing. Results from biochemical and antimicrobial susceptibility analysis, together with repetitive element palindromic polymerase chain reaction fingerprinting, suggest that a single strain was responsible for the outbreak. The inciting cause for this S. iniae-associated cluster of mortalities is unknown.

Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide.

BACKGROUND: Doxorubicin and cyclophosphamide (AC) therapy is an effective treatment for early-stage breast cancer. Doxorubicin is a substrate for ABCB1 and SLC22A16 transporters. Cyclophosphamide is a prodrug that requires oxidation to 4-hydroxycyclophosphamide, which yields a cytotoxic alkylating agent. The initial oxidation is catalysed by cytochrome P450 enzymes including CYP2B6, CYP2C9, CYP2C19 and CYP3A5. Polymorphic variants of the genes coding for these enzymes and transporters have been identified, which may influence the systemic pharmacology of the two drugs. It is not known whether this genetic variation has an impact on the efficacy or toxicity of AC therapy. METHODS: Germ line DNA samples from 230 patients with breast cancer on AC therapy were genotyped for the following SNPs: ABCB1 C1236T, G2677T/A and C3435T, SLC22A16 A146G, T312C, T755C and T1226C, CYP2B6*2, *8, *9, *3, *4 and *5, CYP2C9*2 and *3, CYP3A5*3 and CYP2C19*2. Clinical data on survival, toxicity, demographics and pathology were collated. RESULTS: A lower incidence of dose delay, indicative of less toxicity, was seen in carriers of the SLC22A16 A146G, T312C, T755C variants. In contrast, a higher incidence of dose delay was seen in carriers of the SLC22A16 1226C, CYP2B6*2 and CYP2B6*5 alleles. The ABCB1 2677A, CYP2B6*2, CYP 2B6*8, CYP 2B6*9, CYP 2B6*4 alleles were associated with a worse outcome. CONCLUSION: Variant alleles in the ABCB1, SLC22A16 and CYP2B6 genes are associated with response to AC therapy in the treatment of breast cancer.

A novel Henneguya species from channel catfish described by morphological, histological, and molecular characterization.

Channel catfish Ictalurus punctatus from a commercial farming operation in the Mississippi Delta were submitted for examination for the presence of infection by the trematode Bolbophorus damnificus. The fish were instead found to possess skin nodules suggestive of Henneguya pellis, a species previously described in the blue catfish I. furcatus. Despite the dermal location and distribution of lesions, morphological characteristics of the myxospores were inconsistent with H. pellis. Spores possessed a lanceolate spore body 15.4 +/- 1.5 microm (mean +/- SD; range = 12.2-19.3 microm) in length and 5.5 +/- 0.6 microm (range = 4.5-6.8 microm) in width in valvular view, and 4.7 +/- 0.2 microm (range = 4.2-5.0 microm) in width in sutural view. Polar capsules were pyriform and unequal in both length and width and contained polar filaments with six coils. Polar capsules measured 6.1 +/- 0.8 microm (range = 4.0-7.9 microm) long and 1.7 +/- 0.3 microm (range = 1.0-2.2 microm) wide. The caudal appendages were 50.5 +/- 8.3 microm (range = 34.8-71.4 micorm) long and the total length of the spore was 65.9 +/- 8.6 microm (range = 48.2-90.0 microm). The "blister like" plasmodia were round or ovoid, up to 2 mm in diameter, and randomly distributed throughout the epidermis of the fish. Histologically, plasmodia were confined to the dermis and elicited no inflammatory reaction from the fish. A blast search of the 18S small subunit rDNA sequence obtained by polymerase chain reaction amplification resulted in no identical sequence matches but indicated a close relationship to H. gurlei, H. ictaluri, and H. exilis. The unique host record, spore morphology, and novel genetic sequence derived from this isolate lead us to propose this isolate as a novel species, H. sutherlandi.

Discomfort from sinusoidal oscillation in the roll and lateral axes at frequencies between 0.2 and 1.6 Hz.

Discomfort caused by low frequency lateral and roll oscillations is often predicted from lateral acceleration in the plane of the seat, irrespective of whether it comes from horizontal motion or a component of gravity arising from roll. This study investigated discomfort from lateral and roll oscillation and whether acceleration in the plane of a seat predicts discomfort. Twelve subjects, sitting with and without backrest, used magnitude estimation to judge sinusoidal oscillations in the roll and lateral axes at ten frequencies between 0.2 and 1.6 Hz at magnitudes between 0.063 and 0.63 m s(-2) root mean square. The rate of growth of vibration discomfort with increasing magnitude reduced with increasing frequency, so the frequency-dependence of discomfort varied with magnitude. Acceleration in the plane of the seat predicted discomfort from both lateral and roll oscillation at frequencies less than 0.4 Hz. At higher frequencies, acceleration produced by roll oscillation resulted in greater discomfort than the same acceleration produced by lateral oscillation. At frequencies greater than 0.4 Hz, a full height backrest increased discomfort with both lateral and roll oscillation. The prediction of discomfort caused by low frequency lateral and roll oscillation requires that both components are measured and assessed according to their separate effects.

Acute effects of force and vibration on finger blood flow.

OBJECTIVES: To investigate the effects of contact force at the finger on acute changes in finger circulation during exposure to vibration. METHODS: Each of 10 subjects attended 11 sessions in which they experienced five successive experimental 5-minute periods: (i) no force and no vibration; (ii) force and no vibration; (iii) force and vibration; (iv) force and no vibration; (v) no force and no vibration. During periods (ii) to (iv), the intermediate phalanx of the right middle finger applied one of two forces (2 N or 5 N) on a platform that vibrated during period (iii) at one of two frequencies: 31.5 Hz (at 4 or 16 ms(-2) r.m.s.) or 125 Hz (at 16 or 64 ms(-2) r.m.s.). Finger blood flow was measured in the exposed right middle finger, the unexposed right little finger, and the unexposed left middle fingers throughout the 25 minutes of each session. RESULTS: The application of force alone caused a reduction in finger blood flow in the exposed finger, but not other fingers. There were additional reductions in finger blood flow caused by vibration, with greater reductions at the higher vibration magnitudes at both frequencies but no difference between the two frequencies when using unweighted acceleration. The vibration caused a similar vasoconstriction in vibrated and non-vibrated fingers. CONCLUSIONS: Modest levels of force applied by a finger can have a large effect on the finger blood flow, possibly due to the constriction of local blood vessels. The acute vascular effects of vibration cause additional reductions in finger blood flow that are not limited to the finger experiencing force and vibration. In all fingers (exposed and not exposed to vibration), the greater the magnitude of vibration, the greater the reduction in finger blood flow. In all fingers (exposed and not exposed to vibration), when the vibration was frequency weighted according to current standards, 125 Hz vibration caused greater reductions in finger blood flow than 31.5 Hz vibration.

Phase I study of temozolomide plus paclitaxel in patients with advanced malignant melanoma and associated in vitro investigations.

The purpose of this study was to determine activity of temozolomide combined with paclitaxel or epothilone B in vitro, and to investigate the combination of temozolomide with paclitaxel in a Phase I clinical trial. Melanoma cell lines A375P and DX3 were treated with temozolomide and either paclitaxel or epothilone B. Combination indices were determined to assess the degree of synergism. In a clinical study, 21 patients with malignant melanoma were treated with increasing doses of temozolomide (orally, days 1-5), in combination with a fixed dose of paclitaxel (i.v. infusion day 1), followed by dose escalation of the latter drug. Cycles of treatment were repeated every 3 weeks. Pharmacokinetics of both agents were determined on day 1, with temozolomide pharmacokinetics also assessed on day 5. All three compounds were active against the melanoma cell lines, with epothilone B being the most potent. There was a strong degree of synergism between temozolomide and either paclitaxel or epothilone B. In the clinical study, no pharmacokinetic interaction was observed between temozolomide and paclitaxel. Dose escalation of both drugs to clinically active doses was possible, with no dose-limiting toxicities observed at 200 mg m(-2) day(-1) temozolomide and 225 mg m(-2) day(-1) paclitaxel. There were two partial responses out of 15 evaluable patients. One patient remains alive and symptom-free at 4 years after treatment. Temozolomide and paclitaxel may be administered safely at clinically effective doses. Further evaluation of these combinations in melanoma is warranted.

Minimum health and safety requirements for workers exposed to hand-transmitted vibration and whole-body vibration in the European Union; a review.

In 2002, the Parliament and Commission of the European Community agreed "minimum health and safety requirements" for the exposure of workers to the risks arising from vibration. The Directive defines qualitative requirements and also quantitative requirements in the form of "exposure action values" and "exposure limit values". The quantitative guidance is based on, but appears to conflict with, the guidance in International Standards for hand-transmitted vibration (ISO 5349) and whole-body vibration (ISO 2631). There is a large internal inconsistency within the Directive for short duration exposures to whole-body vibration: the two alternative methods give very different values. It would appear prudent to base actions on the qualitative guidance (i.e. reducing risk to a minimum) and only refer to the quantitative guidance where there is no other reasonable basis for the identification of risk (i.e. similar exposures are not a suspected cause of injury). Health surveillance and other precautions will be appropriate wherever there is reason to suspect a risk and will not be restricted to conditions where the exposure action value is exceeded.

Cigarette smoking, occupational exposure to noise, and self reported hearing difficulties.

AIMS: To explore the interaction of smoking and occupational exposure to noise as risk factors for hearing difficulty in the general population. METHODS: A questionnaire was mailed to 21 201 adults of working age, selected at random from the age-sex registers of 34 British general practices, and to 993 members of the armed services, randomly selected from pay records. Questions were asked about smoking habits, years spent in a noisy occupation, difficulty in hearing conversation, and wearing of a hearing aid. Associations of hearing difficulty with smoking habit were examined by logistic regression and compared across strata of noise exposure, with adjustment for potential confounders. RESULTS: Around half of the respondents had ever smoked, and half of these still smoked. Among 10 418 who provided details on hearing, 348 were classed as having moderate and 311 as having severe hearing difficulty. Risk of hearing difficulty was 3-5-fold higher in those employed for >5 years in noisy work compared with those never employed in a noisy job. Within strata of noise exposure (including those who had never worked in a noisy job), ex- and current smokers had a higher risk of hearing difficulty than lifetime non-smokers. The additional risks were small compared with those of long term noise exposure, and the combination of effects was more consistent with an additive than a multiplicative interaction. CONCLUSIONS: Smoking may adversely affect hearing, and workers should be encouraged to refrain from both smoking and exposure to noise. However, the extra risk to hearing incurred by smoking in high ambient noise levels is small relative to that from the noise itself, which should be the main target for preventive measures.

The relative importance of whole body vibration and occupational lifting as risk factors for low-back pain.

AIMS: To explore the impact of occupational exposure to whole body vibration (WBV) on low back pain (LBP) in the general population and to estimate the burden of LBP attributable to occupational WBV in comparison with that due to occupational lifting. METHODS: A questionnaire including sections on WBV at work, LBP, and potential risk factors was mailed to a community sample of 22 194 men and women of working age. Sources and durations of exposure to occupational WBV were ascertained for the past week and personal vibration doses (eVDV) were estimated. Analysis was confined to subjects reporting exposures in the past week as typical of their work. Associations of LBP with eVDV, driving industrial vehicles, and occupational lifting were explored by logistic regression and attributable numbers were calculated. RESULTS: Significant associations were found between daily lifting of weights greater than 10 kg at work and LBP, troublesome LBP (which made it difficult to put on hosiery), and sciatica (prevalence ratios 1.3 to 1.7); but the risk of these outcomes in both sexes varied little by eVDV and only weak associations were found with riding on industrial vehicles. Assuming causal associations, the numbers of cases of LBP in Britain attributable to occupational WBV were estimated to be 444 000 in men and 95 000 in women. This compared with an estimated 940 000 male cases and 370 000 female cases of LBP from occupational lifting. CONCLUSIONS: The burden of LBP in Britain from occupational exposure to WBV is smaller than that attributable to lifting at work.

Dose-response patterns for vibration-induced white finger.

AIMS: To investigate alternative relations between cumulative exposures to hand-transmitted vibration (taking account of vibration magnitude, lifetime exposure duration, and frequency of vibration) and the development of white finger (Raynaud's phenomenon). METHODS: Three previous studies have been combined to provide a group of 1557 users of powered vibratory tools in seven occupational subgroups: stone grinders, stone carvers, quarry drillers, dockyard caulkers, dockyard boilermakers, dockyard painters, and forest workers. The estimated total operating duration in hours was thus obtained for each subject, for each tool, and for all tools combined. From the vibration magnitudes and exposure durations, seven alternative measurements of cumulative exposure were calculated for each subject, using expressions of the form: dose = summation operator a(m)(i)t(i), where a(i) is the acceleration magnitude on tool i, t(i) is the lifetime exposure duration for tool i, and m = 0, 1, 2, or 4. RESULTS: For all seven alternative dose measures, an increase in dose was associated with a significant increase in the occurrence of vibration-induced white finger, after adjustment for age and smoking. However, dose measures with high powers of acceleration (m > 1) faired less well than measures in which the weighted or unweighted acceleration, and lifetime exposure duration, were given equal weight (m = 1). Dose determined solely by the lifetime exposure duration (without consideration of the vibration magnitude) gave better predictions than measures with m greater than unity. All measures of dose calculated from the unweighted acceleration gave better predictions than the equivalent dose measures using acceleration frequency-weighted according to current standards. CONCLUSIONS: Since the total duration of exposure does not discriminate between exposures accumulated over the day and those accumulated over years, a linear relation between vibration magnitude and exposure duration seems appropriate for predicting the occurrence of vibration-induced white finger. Poorer predictions were obtained when the currently recommended frequency weighting was employed than when accelerations at all frequencies were given equal weight. Findings suggest that improvements are possible to both the frequency weighting and the time dependency used to predict the development of vibration-induced white finger in current standards.

Occupational exposure to noise and the attributable burden of hearing difficulties in Great Britain.

AIMS: To determine the prevalence of self reported hearing difficulties and tinnitus in working aged people from the general population, and to estimate the risks from occupational exposure to noise and the number of attributable cases nationally. METHODS: A questionnaire was mailed to 22 194 adults of working age selected at random from the age-sex registers of 34 British general practices (21 201 subjects) and from the central pay records of the British armed services (993 subjects). Information was collected on years of employment in a noisy job; and whether the respondent wore a hearing aid, had difficulty in hearing conversation, or had experienced persistent tinnitus over the past year. Associations of hearing difficulty and tinnitus with noise exposure were examined by logistic regression, with adjustment for age, sex, smoking habits, and frequent complaints of headaches, tiredness, or stress. The findings were expressed as prevalence ratios (PRs) with associated 95% confidence intervals (CIs). Attributable numbers were calculated from the relevant PRs and an estimate of the prevalence of occupational exposure to noise nationally. RESULTS: Some 2% of subjects reported severe hearing difficulties (wearing a hearing aid or having great difficulty in both ears in hearing conversation in a quiet room). In men, the prevalence of this outcome rose steeply with age, from below 1% in those aged 16-24 years to 8% in those aged 55-64. The pattern was similar in women, but severe hearing loss was only about half as prevalent in the oldest age band. Tinnitus was far more common in subjects with hearing difficulties. In both sexes, after adjustment for age, the risk of severe hearing difficulty and persistent tinnitus rose with years spent in a noisy job. In men older than 35 years with 10 or more years of exposure, the PR for severe hearing difficulty was 3.8 (95% CI 2.4 to 6.2) and that for persistent tinnitus 2.6 (95% CI 2.0 to 3.4) in comparison with those who had never had a noisy job. Nationally, some 153 000 men and 26 000 women aged 35-64 years were estimated to have severe hearing difficulties attributable to noise at work. For persistent tinnitus the corresponding numbers were 266 000 and 84 000. CONCLUSIONS: Significant hearing difficulties and tinnitus are quite common in men from the older working age range. Both are strongly associated with years spent in a noisy occupation--a predominantly male exposure. The national burden of hearing difficulties attributable to noise at work is substantial.