Exploring thoracic kyphosis and incident fracture from vertebral morphology with high-intensity exercise in middle-aged and older men with osteopenia and osteoporosis: a secondary analysis of the LIFTMOR-M trial.

Our aim was to explore change in kyphosis and vertebral fracture incidence following 8 months of high-intensity resistance and impact training (HiRIT) or machine-based isometric axial compression (IAC) training in men with osteopenia and osteoporosis. HiRIT and IAC improved posture. HiRIT participants did not experience progression or incident vertebral fracture. IAC participants did experience progression and incident vertebral fracture. INTRODUCTION: The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of an eight-month, supervised, high-intensity progressive resistance and impact training (HiRIT) program compared with machine-based isometric axial compression (IAC) training in middle-aged and older men with low areal bone mineral density (aBMD). The primary purpose of the current work was to explore change in thoracic kyphosis and incident fracture from vertebral morphology following eight-months of HiRIT or IAC training. The secondary purpose was to explore change in clinical kyphosis measures for HiRIT, IAC and a non-randomized, matched control group. METHODS: Men (≥ 45 yrs), with low aBMD, were recruited and randomized to HiRIT or IAC, or designated control. Clinical measures of thoracic kyphosis with inclinometry were determined. Cobb angle of kyphosis and vertebral fracture assessment using the Genant semi-quantitative method were determined from lateral thoracolumbar DXA (Medix DR, Medilink, France). Per-protocol (n = 40) and intention-to-treat (n = 93) analyses were conducted. RESULTS: Forty participants (HiRIT n = 20, IAC n = 20; 66.1 ± 7.8 yrs.; lumbar spine T-score - 0.1 ± 0.8; femoral neck T-score - 1.5 ± 0.5) underwent clinical kyphosis measures and thoracolumbar DXA at baseline and follow-up. No between-group differences were detected in kyphosis change, however, within-group improvements in neutral (HiRIT - 2.3 ± 0.8°; IAC - 2.5 ± 0.8°) and 'standing tall' (HiRIT - 2.4 ± 0.8°; IAC - 2.0 ± 0.8°) postures were observed (p < 0.05). HiRIT improved Cobb angle (- 3.5 ± 1.5°, p = 0.027) from baseline. Over the 8 months, no incident vertebral fractures nor progression of prevalent vertebral fractures occurred for HiRIT participants. Five incident fractures of thoracic vertebrae occurred for IAC and one wedge fracture progressed. Ninety-three participants underwent clinical kyphosis measures at both time-points (HiRIT n = 34, IAC n = 33, control n = 26). HiRIT exhibited a reduction in 'standing tall' kyphosis compared to control (- 2.3 ± 0.6° versus 1.4 ± 0.7°, p < 0.05), but no other between-group differences were detected. CONCLUSIONS: Although there was no difference in change between intervention groups, thoracic kyphosis appeared to improve in both HiRIT and IAC with exercise exposure. HiRIT improved 'standing tall' posture in comparison to usual activities. HiRIT was not associated with vertebral fracture progression or incident vertebral fracture, but for some IAC participants there was evidence of progression of vertebral fracture severity and incident vertebral fractures, in our small sample. Larger trials are required to confirm the observations of the current work, which was exploratory in nature.

High-intensity exercise did not cause vertebral fractures and improves thoracic kyphosis in postmenopausal women with low to very low bone mass: the LIFTMOR trial.

Our aim was to assess risk of vertebral fracture during high-intensity resistance and impact training (HiRIT) for postmenopausal women with low bone mass. HiRIT did not induce vertebral fracture, as evidenced by a reduction in kyphosis following 8 months of training and a lack of change in vertebral morphology. INTRODUCTION: The LIFTMOR trial demonstrated a novel, HiRIT program notably improved bone mass in postmenopausal women with osteopenia and osteoporosis. While no clinical signs or symptoms of vertebral crush fracture were evident during the trial, anecdotal feedback suggests that concerns about safety of HiRIT in the osteoporosis demographic remain. The aim of the current work was to assess vertebral body morphology, Cobb angle, and clinical measures of thoracic kyphosis in participants in the LIFTMOR trial for evidence of vertebral fracture following 8 months of supervised HiRIT. METHODS: Participants were randomized to either 8 months of 30-min, twice-weekly, supervised HiRIT or unsupervised, low-intensity, home-based exercise (CON). Lateral thoracolumbar DXA scans (Medix DR, Medilink, France) were performed at baseline and follow-up. Cobb angle was determined, and vertebral fracture identification was performed using the semiquantitative Genant method. Clinical kyphosis measurements were performed in relaxed standing (neutral posture) and standing tall using an inclinometer and a flexicurve. RESULTS: The HiRIT group exhibited a reduction in inclinometer-determined standing tall thoracic kyphosis compared to CON (- 6.7 ± 8.2° vs - 1.6 ± 8.1°, p = 0.031). Both the HiRIT and CON groups exhibited within-group improvement in kyphosis in relaxed standing as measured by both inclinometer and flexicurve (p < 0.05). There were no changes in vertebral fracture classification in the HiRIT group post-intervention. A single, new, wedge deformity was observed for CON. CONCLUSIONS: Supervised HiRIT was not associated with an increased risk of vertebral fracture in postmenopausal women with low bone mass. Indeed, a clinically relevant improvement in thoracic kyphosis was observed following 8 months of supervised HiRIT, further supporting its efficacy as an osteoporosis intervention for postmenopausal women with low to very low bone mass.

Background levels of micro-organisms in the busy urban environment of transport hubs.

AIMS: We constantly interact with our surrounding microbiome, including the micro-organisms present in highly populated public places. However, data on everyday exposure to background levels of micro-organisms are limited. To address this, bacteria and fungi were collected and enumerated in settled dust from railway stations. METHODS AND RESULTS: Samples were collected weekly for 52 weeks, from up to three pre-determined surfaces in each of 17 railway stations in England and Scotland. Trained staff at each station took surface wipes, sending them to the laboratory for culture-based analysis for total bacteria and fungi. Maximum yields of bacteria at the stations were 107 -108 colony forming units (CFU) per cm2 , and 104 -105 CFU per cm2 for fungi. CONCLUSIONS: There was evidence of seasonal trends, with bacterial numbers rising from spring through to winter, while fungal numbers peaked in autumn. Microbial numbers were similar in samples taken at the same time at a given station. Influences on contamination levels were likely to be a combination of passenger numbers and station layout, with dust generated from construction work also contributing. SIGNIFICANCE AND IMPACT OF THE STUDY: A baseline of typical human exposure to micro-organisms in public transport hubs was established through the generation of a comprehensive database.

The Forteo Patient Registry linkage to multiple state cancer registries: study design and results from the first 8 years.

The Forteo Patient Registry (FPR) aims to estimate the incidence of osteosarcoma in US patients treated with teriparatide. Enrollment began in 2009 and will continue through 2019, with linkage planned through 2024. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. INTRODUCTION: The Forteo Patient Registry (FPR) was established in 2009 to estimate the incidence of osteosarcoma in US patients treated with teriparatide. The objective of this paper is to describe study methods, challenges encountered, and progress to date. METHODS: The FPR is a prospective US registry designed to link data from participants annually with state cancer registries. Patient enrollment is planned for 10 years (2009-2019) and annual linkage with US state cancer registries for 15 years (2010-2024). All US state cancer registries and DC were invited to participate. Patients are recruited using pre-enrollment materials included in teriparatide device packaging, kits, and brochures distributed by health-care providers; a toll-free number; and a study website. A linkage algorithm is used to match data from enrolled participants with cancer registry data. RESULTS: For the eighth annual linkage in 2017, information necessary for linkage with 63,270 patients in the FPR was submitted to each of the 42 participating registries. These patients contributed approximately 242,782 person-years of follow-up. A total of 5268 adult osteosarcoma cases diagnosed since January 1, 2009, were available for linkage from participating state cancer registries. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. CONCLUSIONS: Based on the estimated 242,782 person-years of observation as of the eighth annual linkage and projecting current enrollment rate to study end in 2024, it is anticipated that the completed study will be able to detect a fourfold increase in the risk of osteosarcoma if one exists.

Search for Cosmic-Ray Electron and Positron Anisotropies with Seven Years of Fermi Large Area Telescope Data.

The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.

Microplastic pollution in the Greenland Sea: Background levels and selective contamination of planktivorous diving seabirds.

Microplastics have been reported everywhere around the globe. With very limited human activities, the Arctic is distant from major sources of microplastics. However, microplastic ingestions have been found in several Arctic marine predators, confirming their presence in this region. Nonetheless, existing information for this area remains scarce, thus there is an urgent need to quantify the contamination of Arctic marine waters. In this context, we studied microplastic abundance and composition within the zooplankton community off East Greenland. For the same area, we concurrently evaluated microplastic contamination of little auks (Alle alle), an Arctic seabird feeding on zooplankton while diving between 0 and 50 m. The study took place off East Greenland in July 2005 and 2014, under strongly contrasted sea-ice conditions. Among all samples, 97.2% of the debris found were filaments. Despite the remoteness of our study area, microplastic abundances were comparable to those of other oceans, with 0.99 ± 0.62 m-3 in the presence of sea-ice (2005), and 2.38 ± 1.11 m-3 in the nearby absence of sea-ice (2014). Microplastic rise between 2005 and 2014 might be linked to an increase in plastic production worldwide or to lower sea-ice extents in 2014, as sea-ice can represent a sink for microplastic particles, which are subsequently released to the water column upon melting. Crucially, all birds had eaten plastic filaments, and they collected high levels of microplastics compared to background levels with 9.99 and 8.99 pieces per chick meal in 2005 and 2014, respectively. Importantly, we also demonstrated that little auks took more often light colored microplastics, rather than darker ones, strongly suggesting an active contamination with birds mistaking microplastics for their natural prey. Overall, our study stresses the great vulnerability of Arctic marine species to microplastic pollution in a warming Arctic, where sea-ice melting is expected to release vast volumes of trapped debris.

The relationship between clinical and standardized tests for hand-arm vibration syndrome.

BACKGROUND: Standardized laboratory tests are undertaken to assist the diagnosis and staging of hand-arm vibration syndrome (HAVS), but the strength of the relationship between the tests and clinical stages of HAVS is unknown. AIMS: To assess the relationship between the results of thermal aesthesiometry (TA), vibrotactile (VT) thresholds and cold provocation (CP) tests with the modified Stockholm scales for HAVS and to determine whether the relationship is affected by finger skin temperature. METHODS: Consecutive records of workers referred to a Tier 5 HAVS assessment centre from 2006 to 2015 were identified. The diagnosis and staging of cases was undertaken from the clinical information contained in the records. Cases with alternative or mixed diagnoses were excluded and staging performed according to the modified Stockholm scale without knowledge of the results of the standardized laboratory tests. RESULTS: A total of 279 cases of HAVS were analysed. Although there was a significant trend for sensorineural (SN) and vascular scores to increase with clinical stage (P < 0.01), there was no significant difference in scores between 2SN early and 2SN late or between 2SN late and 3SN. There was moderate correlation between the TA and VT scores and the clinical SN stages (r = 0.6). This correlation did not change when subjects were divided into those with a finger skin temperature <30 and >30°C. CP scores distributed bimodally and correlated poorly with clinical staging (r = 0.2). CONCLUSIONS: Standardized SN tests distinguish between the lower Stockholm stages, but not above 2SN early. This has implications for health surveillance and UK policy.

The effect of an offset polar cap dipolar magnetic field on the modeling of the Vela pulsar's γ-ray light curves.

We performed geometric pulsar light curve modeling using static, retarded vacuum, and offset polar cap (PC) dipole B-fields (the latter is characterized by a parameter ε), in conjunction with standard two-pole caustic (TPC) and outer gap (OG) emission geometries. The offset-PC dipole B-field mimics deviations from the static dipole (which corresponds to ε = 0). In addition to constant-emissivity geometric models, we also considered a slot gap (SG) E-field associated with the offset-PC dipole B-field and found that its inclusion leads to qualitatively different light curves. Solving the particle transport equation shows that the particle energy only becomes large enough to yield significant curvature radiation at large altitudes above the stellar surface, given this relatively low E-field. Therefore, particles do not always attain the radiation-reaction limit. Our overall optimal light curve fit is for the retarded vacuum dipole field and OG model, at an inclination angle [Formula: see text] and observer angle [Formula: see text]. For this B-field, the TPC model is statistically disfavored compared to the OG model. For the static dipole field, neither model is significantly preferred. We found that smaller values of ε are favored for the offset-PC dipole field when assuming constant emissivity, and larger ε values favored for variable emissivity, but not significantly so. When multiplying the SG E-field by a factor of 100, we found improved light curve fits, with α and ζ being closer to best fits from independent studies, as well as curvature radiation reaction at lower altitudes.

In vivo ruminal degradation characteristics and apparent digestibility of low-quality prairie hay for steers consuming monensin and Optimase.

Seven ruminally cannulated crossbred steers (BW = 720 ± 62 kg) were used in a randomized crossover design (4 periods, each 18 d) to evaluate in vivo rumen characteristics and apparent digestibility of steers consuming low-quality prairie hay and 1 of 4 isonitrogenous protein supplements. Treatments included 1) 40% CP (DM basis) cottonseed meal and wheat middlings-based supplement (Control), 2) a cottonseed meal and wheat middlings-based supplement with slow-release urea and a fibrolytic feed enzyme (Optimase; Alltech, Inc., Nicholasville, KY) designed to replace 30% of plant-based CP provided in the Control (OPT), 3) the Control plus 0.40 mg∙kg BW∙d monensin (Rumensin 90; Elanco Animal Health, Greenfield, IN; MON), and 4) the OPT plus 0.40 mg∙kg BW∙d monensin (COMBO). Steers were allowed ad libitum access to prairie hay (5.0% CP and 76% NDF) and were provided each respective supplement at 0800 h daily at a rate of 1.0 g/kg of BW. Steers were adapted to diets for 10 d before sample collection. Beginning on d 11, DMI was measured and samples were collected to determine apparent digestibility. On d 15 of the 18-d period, rumen fluid was collected 10 times over a 24-h period. Forage DMI was greater ( ≤ 0.02) for steers consuming the OPT compared with steers consuming the MON or COMBO, although forage DMI was not different ( = 0.10) among steers consuming the Control compared with steers consuming the OPT, MON, or COMBO. Steers fed the MON and COMBO had lower ( ≤ 0.05) passage rate compared with steers fed the Control and the OPT. The MON-fed steers had lower ( = 0.01) ruminal pH and increased ( = 0.03) propionate as a percentage of total VFA production. A time × treatment ( = 0.01) interaction was observed for ruminal NH-N due to a rapid (0 to 1 h after feeding) increase followed by a quick (1 to 4 h after feeding) decline in NH-N by steers consuming the OPT and COMBO that was not observed for steers consuming all other treatments. Apparent digestibility of DM ( = 0.01) and NDF ( = 0.03) were improved for steers fed the COMBO supplement compared with steers consuming all other experimental supplements. This work suggests that the OPT may be an effective replacement for a portion of supplemental degradable intake protein in low-quality forage. Further research is necessary to determine if the combination of monensin and the Optimase consistently improves low-quality forage utilization.

Limited efficacy of antimicrobial metaphylaxis in finishing pigs: A randomized clinical trial.

Pigs that die from pathogens associated with porcine respiratory disease complex (PRDC) in the late finishing period represent a significant economic wastage. While it is common to apply antimicrobial metaphylaxis (AM) to control PRDC, there are few studies exploring the potential cost-saving benefits of AM. In this study we examined the value of using AM in commercially reared, late finishing pigs, from farms with endemic PRDC. A total of 732 pigs from four AIAO wean to market sources, were blocked into 2 matching cohorts, based on enrollment body weight, sex, and rectal temperature. The cohorts received either control (C) or AM (Tulathromycin 2.5mg/kg IM, Zoetis, Florham Park, NJ, USA). Post treatment weight gain over the 21 day period was used as a measure of health and productivity. The AM treated pigs in the lowest weight quartile at enrollment, showed a significantly improved weight gain over controls (18.5 kg vs. 16.4 kg, mean difference=2.1 kg, CI 1.10-3.10, p=0.005) that was not evident in any other starting weight quartiles. These results indicate that the biological advantage and associated improvement in growth efficiency associated with the use of AM against PRDC, is only conferred to a specific sub-set of animals. The economic advantage of this strategy is therefore, only likely if the indicators of potential benefit (e.g., lighter weight cohort) can be reliably established. Further studies are needed to determine whether targeted AM could be effectively applied across the industry.

What are dental non-attenders' preferences for anxiety management techniques? A cross-sectional study based at a dental access centre.

OBJECTIVE: Dental anxiety is a barrier to attendance. Dental non-attenders may seek emergency care and may prefer to receive anxiety management measures for treatment required. Little is known about the preferences of these dental non-attenders for different anxiety management techniques. Understanding such preferences may inform management pathways, improve experiences, alleviate anxieties and encourage a more regular attendance pattern. As such, the aim of this study was to gain a greater understanding of the dental anxiety of patients attending a dental access centre for emergency dental treatment and to ascertain preferences for different anxiety management techniques. DESIGN: Cross-sectional study involving self-completed questionnaires and clinical observation. SETTING: NHS Dental Access Centre, York, UK. SUBJECTS AND METHODS: Two hundred participants not registered with a general dental practitioner, aged 18 years or over, experiencing pain and self-referred were recruited on a consecutive sampling basis. Participants completed a questionnaire eliciting demographic and dental history details, dental anxiety and preferences for dental anxiety management options. MAIN OUTCOME MEASURES: Correlation of the modified dental anxiety scale with preference for different dental anxiety management techniques. RESULTS: No significant predictive factors were found that explained preferring local anaesthetic to sedation, or general anaesthesia for restorations or extractions. Those highly anxious were less likely to consider tell-show-do techniques (p=0.001) or watching explanatory videos (p=0.004) to be helpful for overcoming their anxieties than the low or moderate anxiety groups. CONCLUSIONS: People attending access centres may represent a group who are unwilling to explore non-pharmacological methods to overcome their anxieties. This supports the need for sedation to provide treatment. Future work may include exploring in more depth the thoughts and opinions of this group of patients to improve understanding of their complex dental attitudes. From this, more effective strategies may be developed to encourage regular dental attendance.

Zinc transporter 8 autoantibodies: what is their clinical relevance in gestational diabetes?

AIMS: To investigate the prevalence, clinical significance and antepartum to postpartum trajectory of zinc transporter 8 autoantibodies, a novel marker of islet autoimmunity, in women with gestational diabetes mellitus. METHODS: A total of 302 consecutive women attending a multi-ethnic Australian gestational diabetes clinic were prospectively studied. Zinc transporter 8 autoantibodies were measured at gestational diabetes diagnosis and 3 months postpartum using an enzyme-linked immunosorbent assay, and were correlated with maternal phenotype, antepartum and postpartum glucose tolerance, treatment and perinatal outcomes. RESULTS: Of the 302 women, 30 (9.9%) were positive for one islet autoantibody antepartum. No participant had multiple islet autoantibodies. Zinc transporter 8 autoantibodies were the most prevalent autoantibody [zinc transporter 8 autoantibodies: 13/271 women (4.8%); glutamic acid decarboxylase 7/302 women (2.3%); insulinoma-associated antigen-2: 6/302 women (2.0%); insulin: 4/302 women (1.3%)]. Zinc transporter 8 autoantibody positivity was associated with a higher fasting glucose level on the antepartum oral glucose tolerance test, but not with BMI, insulin use, perinatal outcomes or postpartum glucose intolerance. Five of the six women who tested positive for zinc transporter 8 autoantibodies antepartum were negative for zinc transporter 8 autoantibodies postpartum, which corresponded to a significant decline in titre antepartum to postpartum (26.5 to 3.8 U/ml; P=0.03). This was in contrast to the antepartum to postpartum trajectory of the other islet autoantibodies, which remained unchanged. CONCLUSIONS: Zinc transporter 8 autoantibodies were the most common islet autoantibody in gestational diabetes. Zinc transporter 8 autoantibody positivity was associated with slightly higher fasting glucose levels and, unlike other islet autoantibodies, titres declined postpartum. Zinc transporter 8 autoantibodies may be a marker for islet autoimmunity in a proportion of women with gestational diabetes, but the clinical relevance of zinc transporter 8 autoantibodies in pregnancy and gestational diabetes requires further investigation.

Mannose-6-phosphate facilitates early peripheral nerve regeneration in thy-1-YFP-H mice.

The formation of scar tissue following nerve injury has been shown to adversely affect nerve regeneration and evidence suggests that mannose-6-phosphate (M6P), a potential scar reducing agent that affects transforming growth factor (TGF)-ß activation, may enhance nerve regeneration. In this study we utilized thy-1-YFP-H mice - a transgenic strain expressing yellow fluorescent protein (YFP) within a subset of axons - to enable visual analysis of axons regenerating through a nerve graft. Using this strain of mouse we have developed analysis techniques to visualize and quantify regeneration of individual axons across the injury site following the application of either M6P or vehicle to the site of nerve injury. No significant differences were found in the proportion of axons regenerating through the graft between M6P- and vehicle-treated grafts at any point along the graft length. Maximal sprouting occurred at 1.0mm from the proximal graft ending in both groups. The maximum change in sprouting levels for both treatment groups occurred between the graft start and 0.5-mm interval for both treatment groups. The difference between repair groups was significant at this point with a greater increase seen in the vehicle group than the M6P group. The average length of axons regenerating across the initial graft entry was significantly shorter in M6P- than in vehicle-treated grafts, indicating that they encountered less impedance. Application of M6P appears to reduce the disruption of regenerating axons and may therefore facilitate quicker recovery; this is likely to result from altered scar tissue formation in M6P grafts in the early stages of recovery. This study also establishes the usefulness of our methods of analysis using the thy-1-YFP-H mouse strain to visualize and quantify regeneration at the level of the individual axon.

Investigation of gastrointestinal effects of organophosphate and carbamate pesticide residues on young children.

This prospective study was designed to investigate whether there is any association between gastrointestinal effects and pesticide residue exposure (as measured by metabolite levels in urine and faecal samples) in young children and to describe background levels of pesticide residues in samples from healthy children in the UK. Children (N=136) between the ages of 1.0 and 4.2 years were recruited. Of these, 107 provided background baseline samples and 26 provided samples when suffering from gastrointestinal symptoms. Urine samples (from all populations) were positive for (non-specific) carbaryl metabolite (urine 19/78, faeces 9/99), organophosphate metabolites (urine 103/135, faeces 47/111) and pirimicarb metabolite (urine 72/175, faeces 45/135). There were no statistically significant differences between samples from children when healthy or unwell. The urinary 95th percentile values for the healthy population of young children in this study were 31 nmol/l (carbaryl metabolite), 2156 nmol/l (total organophosphate metabolites) and 139 nmol/l (pirimicarb metabolite). In this study, samples from children suffering gastrointestinal symptoms were no more associated with anti-cholinergic pesticide metabolite levels or rotaviral infection than samples from healthy children. Background levels of anti-cholinergic pesticide metabolites in healthy UK children were in agreement with previously reported levels from the US and Germany.

Agreement between specially trained and accredited optometrists and glaucoma specialist consultant ophthalmologists in their management of glaucoma patients.

AIMS: Optometrists are becoming increasingly involved in the co-management of glaucoma patients as the burden on the Hospital Eye Service continues to escalate. The aim of this study was to assess the agreement between specially trained optometrists and glaucoma-specialist consultant ophthalmologists in their management of glaucoma patients. METHODS: Four optometrists examined 23-25 patients each and the clinical findings, up to the point of dilation, were documented in the hospital records. The optometrist, and one of two consultant ophthalmologists, then independently examined and documented the optic-disc appearance before recording their decisions regarding the stability and management of the patient on a specially designed proforma. Percentage agreement was calculated together with kappa or weighted kappa statistics, where appropriate. RESULTS: Agreement between consultants and optometrists in evaluating glaucoma stability was 68.5% (kappa (κ)=0.42-0.50) for visual fields, 64.5% (weighted κ=0.17-0.31) for optic discs, and 84.5% (weighted κ=0.55-0.60) for intraocular pressures. Agreement regarding medical management was 96.5% (κ=0.73-0.81) and for other glaucoma management decisions, including timing of follow-up, referral to a consultant ophthalmologist, and discharge, was 72% (weighted κ=0.65). This agreement increased to 90% following a retrospective independent then consensus review between the two consultants and when qualified agreements were included. Of the 47 glaucoma and non-glaucoma queries generated during the study, 42 resulted in a change of management. CONCLUSION: Confirming the ability of optometrists to make appropriate decisions regarding the stability and management of glaucoma patients is essential if their involvement is to continue to develop to meet the demand of an aging population.

Mortality and cancer incidence among British agricultural pesticide users.

BACKGROUND: Although the acute effects of pesticides in humans are well known, uncertainty still exists about the health effects of chronic low-level exposure to pesticides. AIMS: To compare mortality and cancer incidence experienced by a cohort of British pesticide users to that of the Great Britain (GB) population. METHODS: The Pesticide Users Health Study (PUHS) comprises users of agricultural pesticides who have Certificates of Competence under the Control of Pesticides Regulations 1986. Participants were followed up between 1987 and 2004 (cancer incidence) or 2005 (mortality). Standardized mortality ratios (SMRs) and Standardized incidence ratios (SIRs) were estimated for outcomes of interest identified from the literature. RESULTS: Altogether, 62,960 pesticide users were followed up for 829,709 person-years (to 31 December 2005). Most participants were male (94%) and based in England (86%). All-cause mortality was lower for both men [SMR 0.58, 95% confidence interval (CI) 0.55-0.60] and women (SMR 0.71, 95% CI 0.52-0.98) compared to the GB population. Mortality and incidence were below those expected for all cancers combined among men (SMR 0.71, 95% CI 0.66-0.77; SIR 0.85, 95% CI 0.81-0.90), particularly for cancers of the lip, oral cavity and pharynx, digestive organs and respiratory system. The incidence of testicular cancer, non-melanoma skin cancer and multiple myeloma were above expected. Mortality from injury by machinery was significantly above expected for men (SMR 4.21, 95% CI 2.11-8.42). CONCLUSIONS: This study suggests that pesticide users in the PUHS are generally healthier than the national population but may have excesses of non-melanoma skin cancer, testicular cancer and multiple myeloma.

pKa prediction from an ab initio bond length: part 2--phenols.

The prediction of pK(a) continues to attract much attention with ongoing investigations into new ways to predict pK(a) accurately, where predicted pK(a) values deviate less than 0.50 log units from experiment. We show that a single descriptor, i.e. an ab initio bond length, can predict pK(a). The emphasis was placed on model simplicity and a demonstration that more accurate predictions emerge from single-bond-length models. A data set of 171 phenols was studied. The carbon-oxygen bond length, connecting the OH to the phenyl ring, consistently provided accurate predictions. The pK(a) of meta- and para-substituted phenols is predicted here by a single-bond-length model within 0.50 log units. However, accurate prediction of the pK(a) of ortho-substituted phenols necessitated their splitting into groups called high-correlation subsets in which the pK(a) of the compounds strongly correlated with a single bond-length. The highly compound-specific single-bond-length models produced better predictions than models constructed with more compounds and more bond lengths. Outliers were easily identified using single-bond-length models and in most cases we were able to determine the reason for the outlier discrepancy. Furthermore, the single-bond-length models showed better cross-validation statistics than the PLS models constructed using more than one bond length. For all of the single-bond-length models, RMSEE was less than 0.50. For the majority of the models, RMSEP was less than 0.50. The results support the use of multiple high-correlation subsets and a single bond-length to predict pK(a). Six one-term linear equations are listed as a starting point for the construction of a more comprehensive list covering a larger variety of compound classes.

pKa prediction from an ab initio bond length: part 3--benzoic acids and anilines.

The prediction of pK(a) from a single ab initio bond length has been extended to provide equations for benzoic acids and anilines. The HF/6-31G(d) level of theory is used for all geometry optimisations. Similarly to phenols (Part 2 of this series of publications), the meta-/para-substituted benzoic acids can be predicted from a single model constructed from one bond length. This model had an impressive RMSEP of 0.13 pK(a) units. The prediction of ortho-substituted benzoic acids required the identification of high-correlation subsets, where the compounds in the same subset have at least one of the same (e.g. halogens, hydroxy) ortho substituent. Two pK(a) equations are provided for o-halogen benzoic acids and o-hydroxybenzoic acids, where the RMSEP values are 0.19 and 0.15 pK(a) units, respectively. Interestingly, the bond length that provided the best model differed between these two high-correlation subsets. This demonstrates the importance of investigating the most predictive bond length, which is not necessarily the bond involving the acid hydrogen. Three high-correlation subsets were identified for the ortho-substituted anilines. These were o-halogen, o-nitro and o-alkyl-substituted aniline high-correlation subsets, where the RMSEP ranged from 0.23 to 0.44 pK(a) units. The RMSEP for the meta-/para-substituted aniline model was 0.54 pK(a) units. This value exceeded our threshold of 0.50 pK(a) units and was higher than both the m-/p-benzoic acids in this work and the m-/p-phenols (RMSEP = 0.43) of Part 2. Constructing two separate models for the meta- and para- substituted anilines, where RMSEP values of 0.63 and 0.33 pK(a) units were obtained respectively, revealed it was the meta-substituted anilines that caused the large RMSEP value. For unknown reasons the RMSEP value increased with the addition of a further twenty meta-substituted anilines to this model. The C-N bond always produced the best correlations with pK(a) for all the high-correlation subsets. A higher level of theory and an ammonia probe improved the statistics only marginally for the hydroxybenzoic acid high-correlation subsets.