High frequency UV-Vis sensors estimate error in riverine dissolved organic carbon load estimates from grab sampling.

High frequency ultraviolet - visible (UV-VIS) sensors offer a way of improving dissolved organic carbon (DOC) load estimates in rivers as they can be calibrated to DOC concentration. This is an improvement on periodic grab sampling, or the use of pumped sampling systems which store samples in-field before collection. We hypothesised that the move to high frequency measurements would increase the load estimate based on grab sampling due to systemic under-sampling of high flows. To test our hypotheses, we calibrated two sensors in contrasting catchments (Exe and Bow Brook, UK) against weekly grab sampled DOC measurements and then created an hourly time series of DOC for the two sites. Taking this measurement as a 'true' value of DOC load, we simulated 1,000 grab sampling campaigns at weekly, fortnightly and monthly frequency to understand the likely distribution of load and error estimates. We also performed an analysis of daily grab samples collected using a pumped storage sampling system with weekly collection. Our results show that: a) grab sampling systemically underestimates DOC loads and gives positively skewed distributions of results, b) this under-estimation and positive skew decreases with increasing sampling frequency, c) commonly used estimates of error in the load value are also systemically lowered by the oversampling of low, stable flows due to their dependence on the variance in the flow-weighted mean concentration, and d) that pumped storage systems may lead to under-estimation of DOC and over estimation of specific ultra-violet absorbance (SUVA), a proxy for aromaticity, due to biodegradation during storage.

A model of gross primary productivity based on satellite data suggests formerly afforested peatlands undergoing restoration regain full photosynthesis capacity after five to ten years.

Peatlands are an important terrestrial carbon store, but disturbance has resulted in the degradation of many peatland ecosystems and caused them to act as a net carbon source. Restoration work is being undertaken but monitoring the success of these schemes can be difficult and costly using traditional field-based methods. A landscape-scale alternative is to use satellite data to assess the condition of peatlands and to estimate gaseous carbon fluxes. In this study we used Moderate Resolution Imaging Spectroradiometer (MODIS) products to model Gross Primary Productivity (GPP) over peatland sites at various stages of restoration. We found that the MOD17A2H GPP product overestimates GPP modelled from data collected by eddy covariance towers situated at two ex-forestry sites undergoing restoration towards blanket bog at the Forsinard Flows RSPB reserve, Scotland, UK (one full year of data), and a near-natural Atlantic blanket bog site in Glencar, Ireland (ten-year data series). We calibrated a Temperature and Greenness (TG) model for the Forsinard sites and found it to be more accurate than the MODIS GPP product at local scale. We also found that inclusion of a wetness factor using the Normalised Difference Water Index (NDWI) improved inter-annual accuracy of the model. This TGWa (annual Temperature, Greenness and Wetness) model was then applied to six control sites comprising near-natural bog across the reserve, and to six sites on which restoration began between 1998 and 2006. GPP from 2005 to 2016 was estimated for each site using the model. The resulting modelled trends are positive at all six restored sites, increasing by approximately 5.5 g C/m2/yr every year since restoration began in the Forsinard Flows reserve. The results suggest that peatland sites undergoing restoration at Forsinard Flows reach the carbon assimilation potential of near-natural bog sites between 5 and 10 years after restoration was begun.

RNA interference validation of detoxification genes involved in ivermectin tolerance in Drosophila melanogaster.

Previously, we observed increased transcription levels of specific cytochrome P450 monooxygenase (P450) and adenosine triphosphate binding cassette (ABC) transporter genes in human body lice, Pediculus humanus humanus, following exposure to ivermectin using the non-invasive induction assay, which resulted in tolerance. To confirm the roles of these genes in induction and tolerance, the robust genetic model insect Drosophila melanogaster was chosen. Orthologous genes corresponding to the body louse P450 (Cyp9f2, Cyp6g2 and Cyp9h1) and ABC transporter (Mrp1, GC1824 as an ABCB type and CG3327 as an ABCG type) genes were selected for in vivo bioassay. Following a brief treatment with a sublethal dose of ivermectin, the mortality response was significantly slower, indicating the presence of tolerance. Concurrently, the transcription levels of Cyp9f2 and Mrp1 at 3 h and those of Cyp6g2, Cyp9h1, Mrp1, CG1824 and CG3327 at 6 h post-treatment were upregulated, indicating gene induction. In behavioural bioassay using GAL4/UAS-RNA interference transgenic fly lines, increased susceptibility to ivermectin was observed following heat shock in the Cyp9f2 , Cyp6g2 , Cyp9h1 , Mrp1 or CG3327-knockdown flies. Considering that these five genes are orthologous to those which had the largest over-expression level following ivermectin-induced tolerance in the body louse, the current results suggest that they are also associated with ivermectin detoxification in D. melanogaster and that body lice and D. melanogaster are likely to share, in part, similar mechanisms of tolerance to ivermectin.

Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus.

We previously observed that ivermectin-induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non-invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [3 H]-9-(2-phosphonomethoxyethyl) adenine ([3 H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors. Efflux was also determined to be ATP-dependent. Using a variety of insecticides in a competition assay, only co-injection of ivermectin and dichlorodiphenyltrichloroethane led to decreased efflux of [3 H]-PMEA. PhABCC4-expressing oocytes also directly effluxed [3 H]-ivermectin, which increased over time. In addition, ivermectin appeared to be oxidatively metabolized and/or sequestered, although at low levels, following functional expression of CYP6CJ1 along with cytochrome P450 reductase in Sf9 cells. Our study suggests that PhABCC4 and perhaps CYP6CJ1 are involved in the Phase III and Phase I xenobiotic metabolism of ivermectin, respectively, and may play an important role in the evolution of ivermectin resistance in lice and other insects as field selection occurs.

The unusual reproductive system of head and body lice (Pediculus humanus).

Insect reproduction is extremely variable, but the implications of alternative genetic systems are often overlooked in studies on the evolution of insecticide resistance. Both ecotypes of Pediculus humanus (Phthiraptera: Pediculidae), the human head and body lice, are human ectoparasites, the control of which is challenged by the recent spread of resistance alleles. The present study conclusively establishes for the first time that both head and body lice reproduce through paternal genome elimination (PGE), an unusual genetic system in which males transmit only their maternally derived chromosomes. Here, we investigate inheritance patterns of parental genomes using a genotyping approach across families of both ecotypes and show that heterozygous males exclusively or preferentially pass on one allele only, whereas females transmit both in a Mendelian fashion. We do however observe occasional transmission of paternal chromosomes through males, representing the first known case of PGE in which whole-genome meiotic drive is incomplete. Finally, we discuss the potential implications of this finding for the evolution of resistance and invite the development of new theoretical models of how this knowledge might contribute to increasing the success of pediculicide-based management schemes.

Comparison of the proliferation and excretion of Bartonella quintana between body and head lice following oral challenge.

Human body and head lice are highly related haematophagous ectoparasites but only the body louse has been shown to transmit Bartonella quintana, the causative agent of trench fever. The mechanisms by which body lice became a vector for B. quintana, however, are poorly understood. Following oral challenge, green fluorescent protein-expressing B. quintana proliferated over 9 days postchallenge with the number of bacteria being significantly higher in whole body vs. head lice. The numbers of B. quintana detected in faeces from infected lice, however, were approximately the same in both lice. Nevertheless, the viability of B. quintana was significantly higher in body louse faeces. Comparison of immune responses in alimentary tract tissues revealed that basal transcription levels of peptidoglycan recognition protein and defensins were lower in body lice and the transcription of defensin 1 was up-regulated by oral challenge with wild-type B. quintana in head but not in body lice. In addition, the level of cytotoxic reactive oxygen species generated by epithelial cells was significantly lower in body lice. Although speculative at this time, the reduced immune response is consistent with the higher vector competence seen in body vs. head lice in terms of B. quintana infection.

The natural course of spinal cord injury: changes over 40 years among those with exceptional survival.

OBJECTIVES: To identify 40-year longitudinal changes in health, activity, employment, life satisfaction and self-rated adjustment after spinal cord injury. STUDY DESIGN: Longitudinal, mailed self-report. METHODS: Participants were identified from outpatient records of a Midwestern USA university hospital in 1973. Follow-ups were conducted in 1984 and approximate 10-year intervals thereafter. A total of 49 participants completed each of the five assessments. Data were reviewed and analyzed by research team members and a research associate with experience in biostatistics at a medical university in Southeastern USA. Life Situation Questionnaire included the following: (1) demographic and injury characteristics, (2) educational status and employment, (3) community participation, (4) life satisfaction, (5) adjustment, and (6) recent medical history. RESULTS: Proportion of individuals with 10+ non-routine physician visits increased from consistently <10% to >40% during the 40 years. Proportion who spent a week or more in hospital increased from a low of 10% at 20-year follow-up to 43% at 40-year follow-up. Percentage employed and average hours employed initially improved over time but decreased substantially during the last two times of measurement. Satisfaction with health, sex life and social life declined over time, whereas satisfaction with employment improved initially and was maintained over time. Self-rated current adjustment remained stable, whereas predicted future adjustment declined steadily over 40 years. CONCLUSIONS: Age-related declines were apparent for need of physician visits and hospitalizations, with notable declines in satisfaction with sex life, social life and health. However, not all indices declined over time. Participants appeared to maintain stability when rating their own adjustment.

Achieving assessor accuracy on the International Standards for Neurological Classification of Spinal Cord Injury.

STUDY DESIGN: A retrospective audit of assessor accuracy using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) in three multicentre randomised controlled trials (SCIPA: Spinal Cord Injury and Physical Activity) spanning 2010-2014 with standards revised in 2011. OBJECTIVES: To investigate assessor accuracy of neurological classification after spinal cord injury. SETTING: Australia and New Zealand. METHODS: ISNCSCI examinations were undertaken by trained clinicians prior to randomisation. Data were recorded manually and ISNCSCI worksheets circulated to panels, consensus reached and worksheets corrected. An audit team used a 2014 computerised ISNCSCI algorithm to check manual worksheets. A second audit team assessed whether the 2014 computerised algorithm accurately reflected pre- and post-2011 ISNCSCI standards. RESULTS: Of the 208 ISNCSCI worksheets, 24 were excluded. Of the remaining 184 worksheets, 47 (25.5%) were consistent with the 2014 computerised algorithm and 137 (74.5%) contained one or more errors. Errors were in motor (30.1%) or sensory (12.4%) levels, zone of partial preservation (24.0%), motor/sensory scoring (21.5%), ASIA Impairment Scale (AIS, 8.3%) and complete/incomplete classification (0.8%). Other difficulties included classification when anal contraction/sensation was omitted, incorrect neurological levels and violation of the 'motor follows sensory rule in non-testable myotomes' (7.4%). Panel errors comprised corrections that were incorrect or missed or incorrect changes to correct worksheets. CONCLUSION: Given inaccuracies in the manual ISNCSCI worksheets in this long-term clinical trial setting, continued training and a computerised algorithm are essential to ensure accurate scoring, scaling and classification of the ISNCSCI and confidence in clinical trials.

Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical isolator.

PURPOSE: The occupational risk associated with handling of cytotoxic anticancer drugs is well documented and, in many countries, pharmaceutical isolators are used to contain cytotoxic residues during preparation of cytotoxic infusions. Isolators are difficult to clean leading to concerns that cytotoxic contamination from the work area could be transferred to surfaces of products leaving the isolator. This study investigated the surface contamination arising from the preparation of five anticancer drug infusions (Epirubicin, Fluorouracil, Cisplatin, Oxaliplatin and Carboplatin) in a pharmaceutical isolator and compared use of a conventional syringe and needle technique with a closed-system drug transfer device (CSDTD). METHODS: Wipe samples were taken over 1 week from pre-defined areas in the isolator, gloves, preparation mats, and also from the surfaces of prepared cytotoxic infusion bags and pre-filled syringes to obtain baseline surface contamination data. Following operator familiarisation, the CSDTD was then introduced and sampling repeated for a further week (intervention period). The samples obtained were analysed using validated HPLC-UV, HPLC-FL and ICP-MS techniques, as appropriate. RESULTS: All surfaces sampled during baseline, including external surfaces of infusions and syringes, were contaminated with each marker drug. During the intervention phase, isolator surfaces were free from detectable contamination and the contamination measured on gloves, preparation mats and surface of infusions was markedly reduced. The frequency of contamination on syringe and infusion surfaces was also lower. CONCLUSION: Surface contamination from cytotoxic infusion preparation in a pharmaceutical isolator was significant and could transmit cytotoxic residues to patient and public areas via infusion surfaces. The frequency and amount of contamination were reduced by the CSDTD.

Pain medication misuse among participants with spinal cord injury.

STUDY DESIGN: Self-reported survey. OBJECTIVE: Our purpose was to identify the predictors of pain medication misuse (PMM) among participants with spinal cord injury (SCI). SETTING: A medical university in the southeastern United States. METHODS: A total of 919 adults with impairment from traumatic SCI of at least 1-year duration, who reported at least one painful condition and were taking prescription medication to treat pain, were included in this study. PMM was measured by the Pain Medication Questionnaire (PMQ). RESULTS: The average PMQ score was 19.7, with 25.8% of participants scoring at or above the cutoff of 25, which is indicative of PMM. A three-stage logistic regression analysis was conducted by sequentially adding three sets of predictors to the equation: (1) demographic and injury characteristics; (2) pain characteristics and (3) frequency of pain medication use. Age and education level were protective of PMM, whereas pain intensity, pain interference and pain medication use were risk factors. Number of painful days was not significant in the final model. CONCLUSION: PMM must be of concern after SCI, given its high prevalence among those with at least one painful condition and its relationship with pain indicators.

Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study.

AIMS: To examine the associations of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase (GGT) with diabetes risk and to determine whether associations differ by race and/or gender. We hypothesized that all liver enzymes would be associated with diabetes risk and that associations would differ by race and gender. METHODS: Prospective cohort of 7495 white and 1842 black participants without diabetes in the Atherosclerosis Risk in Communities Study. Poisson and Cox models adjusted for demographic, socio-behavioural, and metabolic and health-related factors were used. RESULTS: During a median of 12 years of follow-up, 2182 incident cases of diabetes occurred. Higher liver enzyme levels were independently associated with diabetes risk: adjusted hazard ratios (95% confidence intervals) were 1.68 (1.49-1.89), 1.16 (1.02-1.31) and 1.95 (1.70-2.24) comparing the highest with the lowest quartiles of ALT, AST, and GGT, respectively. Gamma-Glutamyl transferase was most strongly related to diabetes risk, even at levels considered within the normal range (≤ 60 U/l) in clinical practice. Adjusted incidence rates by quartiles of liver enzymes were similar by gender but higher in black versus white participants. Nonetheless, relative associations of ALT, AST, and GGT with diabetes were similar by race (P for interactions > 0.05). CONCLUSIONS: Compared with ALT and AST, GGT was more strongly associated with diabetes risk. Our findings suggest that abnormalities in liver enzymes precede the diagnosis of diabetes by many years and that individuals with elevated liver enzymes, even within the normal range as defined in clinical practice, are at high risk for diabetes.

External validation of the Oldham composite Covid-19 associated mortality model (OCCAM), a prognostic model for death in patients hospitalised with Covid-19.

OBJECTIVE: External validation of the Oldham Composite Covid-19 associated Mortality Model (OCCAM), a prognostic model for Covid-19 mortality in hospitalised patients comprised of age, history of hypertension, current or previous malignancy, admission platelet count < 150 × 103/µL, admission CRP ≥ 100 µg/mL, acute kidney injury (AKI), and radiographic evidence of > 50% total lung field infiltrates. PATIENTS AND METHODS: Retrospective study assessing discrimination (c-statistic) and calibration of OCCAM for death in hospital or within 30 days of discharge. 300 adults admitted to six district general and teaching hospitals in North West England for treatment of Covid-19 between September 2020 and February 2021 were included. RESULTS: Two hundred and ninety-seven patients were included in the validation cohort analysis, with a mortality rate of 32.8%. The c-statistic was 0.794 (95% confidence interval 0.742-0.847) vs. 0.805 (95% confidence interval 0.766 - 0.844) in the development cohort. Visual inspection of calibration plots demonstrate excellent calibration across risk groups, with a calibration slope for the external validation cohort of 0.963. CONCLUSION: The OCCAM model is an effective prognostic tool that can be utilised at the time of initial patient assessment to aid decisions around admission and discharge, use of therapeutics, and shared decision-making with patients. Clinicians should remain aware of the need for ongoing validation of all Covid-19 prognostic models in light of changes in host immunity and emerging variants.

Comparison of the transcriptional profiles of head and body lice.

Head and body lice are both blood-feeding parasites of humans although only the body louse is a potent disease vector. In spite of numerous morphological and life history differences, head and body lice have recently been hypothesized to be ecotypes of the same species. We took a comparative genomics approach to measure nucleotide diversity by comparing expressed sequence tag data sets from head and body lice. A total of 10 771 body louse and 10 770 head louse transcripts were predicted from a combined assembly of Roche 454 and Illumina sequenced cDNAs from whole body tissues collected at all life stages and during pesticide exposure and bacterial infection treatments. Illumina reads mapped to the 10 775 draft body louse gene models from the whole genome assembly predicted nine presence/absence differences, but PCR confirmation resulted in a single gene difference. Read per million base pair estimates indicated that 14 genes showed significant differential expression between head and body lice under our treatment conditions. One novel microRNA was predicted in both lice species and 99% of the 544 transcripts from Candidatus riesia indicate that they share the same endosymbiont. Overall, few differences exist, which supports the hypothesis that these two organisms are ecotypes of the same species.

Management impacts on the dissolved organic carbon release from deadwood, ground vegetation and the forest floor in a temperate Oak woodland.

The forest floor is often considered the most important source of dissolved organic carbon (DOC) in forest soils, yet little is known about the relative contribution from different forest floor layers, understorey vegetation and deadwood. Here, we determine the carbon stocks and potential DOC production from forest materials: deadwood, ground vegetation, leaf litter, the fermentation layer and top mineral soil (Ah horizon), and further assess the impact of management. Our research is based on long-term monitoring plots in a temperate deciduous woodland, with one set of plots actively managed by thinning, understorey scrub and deadwood removal, and another set that were not managed in 23 years. We examined long-term data and a spatial survey of forest materials to estimate the relative carbon stocks and concentrations and fluxes of DOC released from these different pools. Long-term soil water monitoring revealed a large difference in median DOC concentrations between the unmanaged (43.8 mg L-1) and managed (18.4 mg L-1) sets of plots at 10 cm depth over six years, with the median DOC concentration over twice as high in the unmanaged plots. In our spatial survey, a significantly larger cumulative flux of DOC was released from the unmanaged than the managed site, with 295.5 and 230.3 g m-2, respectively. Whilst deadwood and leaf litter released the greatest amount of DOC per unit mass, when volume of the material was considered, leaf litter contributed most to DOC flux, with deadwood contributing least. Likewise, there were significant differences in the carbon stocks held by different forest materials that were dependent on site. Vegetation and the fermentation layer held more carbon in the managed site than unmanaged, whilst the opposite occurred in deadwood and the Ah horizon. These findings indicate that management affects the allocation of carbon stored and DOC released between different forest materials.

Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance.

Transcriptional profiling results, using our non-invasive induction assay {short exposure intervals (2-5 h) to sublethal amounts of insecticides [< lethal concentration 3% (LC(3)) at 24 h] administered by stress-reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present [~lethal concentration 90% (LC(90)) in 2-4 h]}, showed that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin. Injection of double-stranded RNAs (dsRNAs) against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increased sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance.

Extensive gene duplication of acetylcholinesterase associated with organophosphate resistance in the two-spotted spider mite.

Monocrotophos-resistant two-spotted spider mites (TSSMs), Tetranychus urticae, are known to possess three mutations on the acetylcholinesterase (AChE) gene (Tuace) that are involved in target site insensitivity. Cross-strain comparison of three strains (highly resistant AD, moderately resistant PyriF and susceptible UD strains) revealed that resistant strains have relatively more Tuace copies than the UD strain and that the levels of transcript were directly proportional to copy numbers. AChEs from the AD and PyriF strains had similar V(max) values to those of AChE from the UD strain but increased K(m) and reduced k(cat) constants, suggesting that the mutated, resistant form of AChE may carry a fitness cost. Relative copy numbers of Tuace in field populations varied from 2.4 to 6.1, correlating well with their levels of resistance (r(2)= 0.895). These results are suggestive of the involvement of Tuace gene duplication in resistance. Thus, monocrotophos resistance in TSSMs appears to have evolved through a combination of mutation accumulation and extensive gene duplication.

A point mutation in a glutamate-gated chloride channel confers abamectin resistance in the two-spotted spider mite, Tetranychus urticae Koch.

The molecular mechanisms and genetics of abamectin resistance mediated by target site insensitivity in the two-spotted spider mite, Tetranychus urticae, were investigated by comparing two isogenic abamectin-susceptible (AbaS) and abamectin-resistant (AbaR) strains. Cloning and sequencing of full-length cDNA fragments of gamma-amino butyric acid (GABA)-gated chloride channel genes revealed no polymorphisms between the two strains. However, sequence comparison of the full-length cDNA fragment of a T. urticae glutamate-gated chloride channel gene (TuGluCl) identified a G323D point mutation as being tentatively related with abamectin resistance. In individual F(2) progenies obtained by backcrossing, the G323D genotype was confirmed to correlate with abamectin resistance. Bioassays using progeny from reciprocal crossings revealed that the abamectin resistance trait resulting from TuGluCl insensitivity is incompletely recessive.

Decreased detoxification genes and genome size make the human body louse an efficient model to study xenobiotic metabolism.

The human body louse, Pediculus humanus humanus, has one of the smallest insect genomes, containing ∼10 775 annotated genes. Annotation of detoxification [cytochrome P450 monooxygenase (P450), glutathione-S-transferase (GST), esterase (Est) and ATP-binding cassette transporter (ABC transporter)] genes revealed that they are dramatically reduced in P. h. humanus compared to other insects except for Apis mellifera. There are 37 P450, 13 GST and 17 Est genes present in P. h. humanus, approximately half the number found in Drosophila melanogaster and Anopheles gambiae. The number of putatively functional ABC transporter genes in P. h. humanus and Ap. mellifera are the same (36) but both have fewer than An. gambiae (44) or Dr. melanogaster (65). The reduction of detoxification genes in P. h. humanus may be a result of this louse's simple life history, in which it does not encounter a wide variety of xenobiotics. Neuronal component genes are highly conserved across different insect species as expected because of their critical function. Although reduced in number, P. h. humanus still retains at least a minimum repertoire of genes known to confer metabolic or toxicokinetic resistance to xenobiotics (eg Cyp3 clade P450s, Delta GSTs, B clade Ests and B/C subfamily ABC transporters), suggestive of its high potential for resistance development.

Cardiac pacing in patients with a cervical spinal cord injury.

STUDY DESIGN: Retrospective medical record review. OBJECTIVES: To compare patients, admitted to an intensive care unit (ICU) with an acute cervical spinal cord injury (SCI) and documented motor deficit, who did, with those who did not, require a cardiac pacemaker. SETTING: South Australian Tertiary Referral Intensive Care and Spinal Injury Unit. METHODS: Retrospective medical record review and data set linkage. RESULTS: From 1995 to 2007, 465 patients sustained a cervical SCI. Of these, 30 (6.5%) were admitted to ICU with a clinically assessable motor deficit and 3 (0.6% of all patients, or 10% of those admitted to ICU) required a cardiac pacemaker. All three patients had a cervical SCI, C5 (American Spinal Injury Association A) tetraplegia, and required invasive mechanical respiratory and inotropic support and a tracheostomy for weaning. Two patients (66%) were discharged alive to rehabilitation. Patients requiring a pacemaker had bradycardic episodes over a longer period (11 vs 4 days, P=0.01), a trend towards a later onset of bradycardia (8 vs 1.5 days, P=0.05) and a longer ICU length of stay (37 vs 10 days, P=0.02). CONCLUSION: Patients with a cervical SCI requiring a cardiac pacemaker are characterized by a higher level of SCI injury and motor loss, require mechanical respiratory and inotropic support, a tracheostomy to wean, and bradycardic episodes of a later onset and over a longer period of time. These findings suggest that such patients should be managed at hospitals with specialized acute spinal injury, intensive care and cardiac pacemaker services.

Repeatability of subjective evaluation of lameness in horses.

REASONS FOR PERFORMING STUDY: Previous studies have suggested that agreement between equine veterinarians subjectively evaluating lameness in horses is low. These studies were limited to small numbers of horses, evaluating movement on the treadmill or to evaluating previously-recorded videotape. OBJECTIVES: To estimate agreement between equine practitioners performing lameness evaluations in horses in the live, over ground setting. METHODS: 131 mature horses were evaluated for lameness by 2-5 clinicians (mean 3.2) with a weighted-average of 18.7 years of experience. Clinicians graded each limb using the AAEP lameness scale by first watching the horse trot in a straight line only and then after full lameness evaluation. Agreement was estimated by calculation of Fleiss' (kappa). Evaluators agreed if they picked the same limb as lame or not lame regardless of the severity of perceived lameness. RESULTS: After only evaluating the horse trot in a straight line clinicians agreed whether a limb was lame or not 76.6% of the time (kappa= 0.44). After full lameness evaluation clinicians agreed whether a limb was lame or not 72.9% of the time (kappa= 0.45). Agreement on forelimb lameness was slightly higher than on hindlimb lameness. When the mean AAEP lameness score was >1.5 clinicians agreed whether or not a limb was lame 93.1% of the time (kappa= 0.86), but when the mean score was < or = 1.5 they agreed 61.9% (kappa= 0.23) of the time. When given the task of picking whether or not the horse was lame and picking the worst limb after full lameness evaluation, clinicians agreed 51.6% (kappa= 0.37) of the time. CONCLUSIONS: For horses with mild lameness subjective evaluation of lameness is not very reliable. POTENTIAL RELEVANCE: A search for and the development of more objective and reliable methods of lameness evaluation is justified and should be encouraged and supported.