Effects of routine treatment with nonsteroidal anti-inflammatory drugs at calving and when lame on the future probability of lameness and culling in dairy cows: A randomized controlled trial.

Claw horn lesions (CHL) are reported as the most common cause of lameness in intensive dairy systems. Despite their prevalence, the underlying pathological mechanisms and preventive strategies for CHL remain poorly understood. Recent advances have pointed to the role of inflammation in disease aetiopathogenesis. Moderating inflammation from first calving may lead to long-term benefits and a viable intervention for treating and preventing disease. We conducted a 34-mo randomized controlled trial to investigate the effects of routine treatment with the nonsteroidal anti-inflammatory drug ketoprofen at calving and during treatment for lameness, on the future probability of lameness and culling, caused by exposure to normal farm conditions. A cohort of dairy heifers were recruited from a single, commercial dairy herd between January 8, 2018, and June 22, 2020, and randomly allocated to one of 4 treatment groups before first calving. The lactating herd was lameness scored every 2 wk on a 0 to 3 scale, to identify animals that became lame (single score ≥2a) and hence required treatment. Animals in group 1 received a therapeutic trim and a hoof block on the sound claw (if deemed necessary) every time they were treated for lameness. Animals in group 2 received the same treatment as group 1 with the addition of a 3-d course of ketoprofen (single dose daily) every time they were treated for lameness. Animals in group 3 received the same treatment as group 2 with the addition of a 3-d course of ketoprofen (single dose daily) starting 24 to 36 h after each calving. Animals in group 4 received a 3-d course of ketoprofen (single dose daily) every time they were identified with lameness. No therapeutic trim was administered to this group, unless they were identified as severely lame (a single score ≥3a). Animals were followed for the duration of the study (ending October 23, 2020). Probability of lameness was assessed by a lameness outcome score collected every 14 d. Data on culling was extracted from farm records. One hundred thirty-two animals were recruited to each group, with data from 438 animals included in the final analysis (111 in group 1, 117 in group 2, 100 in group 3, and 110 in group 4). Mixed effect logistic regression models were used to evaluate the effect of treatment group on the ongoing probability of lameness. Compared with the control group (group 1), animals in group 3 were less likely to become lame (odds ratio: 0.66) and severely lame (odds ratio: 0.28). A Cox proportional hazards survival model was used to investigate the effect of treatment group on time to culling. Compared with group 1, animals in groups 2 and 3 were at reduced risk of culling (hazard ratios: 0.55 and 0.56, respectively). The lameness effect size we identified was large and indicated that treating a cohort of animals with the group 3 protocol, would lead to an absolute reduction in population lameness prevalence of approximately 10% and severe lameness prevalence of 3%, compared with animals treated in accordance with conventional best practice (group 1).

The American College of Surgeons as an advocate for global surgery awareness.

The American College of Surgeons (ACS), founded in 1913, is the one of the oldest surgical professional organizations in the United States. Originally founded to foster surgical professional excellence and collaboration among surgeons in North America, the ACS has now expanded to over 80,000 members worldwide with programs delivering a rich portfolio of professional services in the domains of surgical education, clinical surgery and global surgery, surgical quality and leadership, surgical research, member services. ACS international programs initially focused on international professional exchange and hosting of young surgeons from around the world in US based surgical centers to develop scholarly and clinical collaborations. Over the last 20 years, with the founding of the ACS-Operation Giving Back (OGB) Program, the ACS has broadened its international perspective to support surgical care in emerging nations and to develop collaborative programs with host institutions in emerging nations to support surgical care capacity growth through on site partnerships, and educational and policy initiatives. To that end, in recent years, OGB has developed global surgical programs in the COSECSA region of sub-Saharan Africa creating opportunities to participate in Global Surgical Training Hubs. After developing a pilot hub project in Hawassa, Ethiopia, OGB is now in the process of scaling up two additional sites. In this manuscript, we will describe ACS's rich history of activities promoting international surgical collaboration and scholarship and discuss the process of creating the global surgical training hub model in Hawassa.

Seasonal abundance of the stable fly Stomoxys calcitrans in southwest England.

The stable fly Stomoxys calcitrans (L.) is a cosmopolitan biting fly of both economic and welfare concern, primarily as a result of its painful bite, which can cause blood loss, discomfort and loss of productivity in livestock. Between June and November in 2016 and May and December in 2017, Alsynite sticky-traps were deployed at four Donkey Sanctuary sites in southwest England, which experience recurrent seasonal biting fly problems. The aim was to evaluate the seasonal dynamics of the stable fly populations and the risk factors associated with abundance. In total, 19 835 S. calcitrans were trapped during the study period. In both years, abundance increased gradually over summer months, peaking in late August/September. There were no relationships between seasonally detrended abundance and any climatic factors. Fly abundance was significantly different between sites and population size was consistent between years at three of the four sites. The median chronological age, as determined by pteridine analysis of flies caught live when blood-feeding, was 4.67 days (interquartile range 3.8-6.2 days) in males and 6.79 days (interquartile range 4.8-10.4 days) in females; there was no significant, consistent change in age or age structure over time, suggesting that adult flies emerge continuously over the summer, rather than in discrete age-related cohorts. The data suggest that flies are more abundant in the vicinity of active animal facilities, although the strong behavioural association between flies and their hosts means that they are less likely to be caught on traps where host availability is high. The implications of these results for fly management are discussed.

Interobserver agreement of digital dermatitis M-scores for photographs of the hind feet of standing dairy cattle.

Digital dermatitis (DD) is the leading infectious cause of lameness in dairy cattle, and it affects their welfare and productivity worldwide. At the herd level, DD is often assessed while cows are standing in a milking parlor, and lesions are most commonly evaluated using the M-score. The objective of this study was to examine the interobserver agreement for M-scores of the feet of standing cattle, based on digital color photographs of dairy cattle hind feet. A total of 88 photographs and written descriptors of the M-score were sent to 11 scorers working at 10 different institutions in 5 countries. The scorers received no formal training immediately before scoring the photographs; however, all regularly used the M-score to score DD. The answers for 36 photographs were excluded from the analysis because the photograph either had more than 1 M-stage as mode or not all scorers assigned an M-score to it. The M-scores of the 11 scorers from 52 photographs were available for analysis. Interobserver agreement was tested using Gwet's agreement coefficient (AC1) and the mode was assumed correct. Overall, moderate agreement emerged for the M-score (AC1 = 0.48). For the individual M-stages, almost perfect agreement existed for M0 (AC1 = 0.99), M1 (AC1 = 0.92), and M3 (AC1 = 0.82), and substantial agreement for M2 (AC1 = 0.61), M4 (AC1 = 0.65), and M4.1 (AC1 = 0.71). This outcome indicates the degree of individual variation in M-scoring in this context by unstandardized, experienced European observers, particularly for the M2, M4, and M4.1 stages. Standardized training is likely to improve the consistency of M-scoring and thus the generalizability of future DD research results on this important endemic disease.

Use of novel sensors combining local positioning and acceleration to measure feeding behavior differences associated with lameness in dairy cattle.

Time constraints for dairy farmers are an important factor contributing to the under-detection of lameness, resulting in delayed or missed treatment of lame cows within many commercial dairy herds. Hence, a need exists for flexible and affordable cow-based sensor systems capable of monitoring behaviors such as time spent feeding, which may be affected by the onset of lameness. In this study a novel neck-mounted mobile sensor system that combines local positioning and activity (acceleration) was tested and validated on a commercial UK dairy farm. Position and activity data were collected over 5 consecutive days for 19 high-yield dairy cows (10 lame, 9 nonlame) that formed a subset of a larger (120 cow) management group housed in a freestall barn. A decision tree algorithm that included sensor-recorded position and accelerometer data was developed to classify a cow as doing 1 of 3 categories of behavior: (1) feeding, (2) not feeding, and (3) out of pen for milking. For each classified behavior the mean number of bouts, the mean bout duration, and the mean total duration across all bouts was determined on a daily basis, and also separately for the time periods in between milking (morning = 0630-1300 h; afternoon = 1430-2100 h; night = 2230-0500 h). A comparative analysis of the classified cow behaviors was undertaken using a Welch t-test with Benjamini-Hochberg post-hoc correction under the null hypothesis of no differences in the number or duration of behavioral bouts between the 2 test groups of lame and nonlame cows. Analysis showed that mean total daily feeding duration was significantly lower for lame cows compared with non-lame cows. Behavior was also affected by time of day with significantly lower mean total duration of feeding and higher total duration of nonfeeding in the afternoons for lame cows compared with nonlame cows. The results demonstrate how sensors that measure both position and acceleration are capable of detecting differences in feeding behavior that may be associated with lameness. Such behavioral differences could be used in the development of predictive algorithms for the prompt detection of lameness as part of a commercially viable automated behavioral monitoring system.

A prospective cohort study of digital cushion and corium thickness. Part 2: Does thinning of the digital cushion and corium lead to lameness and claw horn disruption lesions?

The aim of this study was to determine whether a decrease in thickness of the sole soft tissues (SST) beneath the flexor tuberosity of the distal phalanx (i.e., the digital cushion and corium) predisposed a claw to develop claw horn disruption lesions (CHDL) or a leg to lameness. Data were analyzed from a longitudinal study of 179 cows, which had been examined at 5 assessment points -8, +1, +9, +17, and +29 wk relative to their first, second, third, or fourth calving. At each assessment point, SST were measured using ultrasonography. Additional assessment point data included sole lesions and back fat thickness (BFT), and cows had been locomotion scored every 2 wk from calving. One hundred fifty-eight cows completed the study. Separate logistic regression survival analyses were constructed to assess the outcomes, either lameness on a leg or CHDL on a claw; combinations of lameness and lesions were tested as outcomes. Cow level variables tested included farm and lactation number. Variables were tested describing previous SST thickness, minimum previous SST thickness, BFT, and change in either variable between prior assessment points. Prior lesions/lameness strongly predicted repeat cases and the final models had the outcome first lesion or lameness on a claw or leg. In the reported lameness models, lameness was defined as a leg being recorded as lame twice within 3 consecutive scores, and in the reported lesion models, lesion was defined as the first presence of either a sole ulcer or a severe sole hemorrhage on a claw. Thin SST increased the likelihood of lesion occurrence; thin SST on the lateral claw predicted subsequent lameness on a leg. Thin BFT and thinning of BFT between previous assessment points increased the likelihood of future lesion occurrence. Thin SST and thinning of BFT had additional effects on the likelihood of lesion occurrence, suggesting that BFT and sole SST had independent effects on lesion occurrence. However, change in SST thickness between assessment points did not influence the likelihood of future lesions or lameness. This suggests that thin SST were not simply a result of depletion of body fat and challenges the theory that thinning of the digital cushion with body fat mobilization leads to CHDL. Other possible mechanisms by which SST become thin are discussed and could include changes in integrity of the suspensory apparatus with physiological events.

A prospective cohort study of digital cushion and corium thickness. Part 1: Associations with body condition, lesion incidence, and proximity to calving.

Claw horn disruption lesions (CHDL) are a major cause of lameness in dairy cattle and are likely a result of excessive forces being applied to the germinal epithelium that produces the claw horn. The digital cushion is a connective tissue structure, containing depots of adipose tissue, that sits beneath the distal phalanx and has been shown to be thicker in fatter cows. Body condition score (BCS) loss is a risk factor for CHDL, and one possible explanation is that fat is mobilized from the digital cushion during negative energy balance, causing the digital cushion to thin and lose force-dissipating capacity, leading to disruption of claw horn growth. This prospective cohort study investigated the association between measures of body fat and sole soft tissue (SST) thickness (a combined measure of the corium and digital cushion beneath the distal phalanx) in a longitudinal manner. The SST of 179 cows in 2 high-yielding dairy herds were measured at 5 assessment points between 8 wk before and 35 wk postcalving. The BCS, back fat thickness (BFT), and lesion incidence were recorded. Data were analyzed in a 4-level mixed effects regression model, with the outcome being SST thickness beneath the flexor tuberosity of the distal phalanx. Data from 827 assessment points were available for analysis. The overall mean of SST was 4.99 mm (standard deviation: 0.95). The SST was thickest 8 wk before calving (5.22 mm, standard deviation: 0.91) and thinnest 1 wk postcalving (4.68 mm, standard deviation: 0.87), suggesting an effect of calving on SST. The BFT was positively correlated with SST in the model with a small effect size (a 10 mm decrease in BFT corresponded with a 0.13 mm decrease in SST), yet the nadir of BFT was 11.0 mm at 9 to 17 wk postcalving (when SST was ∼4.95 mm), rather than occurring with the nadir of SST immediately after calving. The SST also varied with other variables [e.g., cows that developed a sole ulcer or severe sole hemorrhage during the study had thinner SST (-0.24 mm)], except when a sole ulcer was present, when it was thicker (+0.53 mm). Cows that developed lesions had a thinner digital cushion before the lesion occurrence, which became thickened with sole ulcer presence, perhaps representing inflammation. Furthermore, although BFT was correlated with SST over time, SST may also have been influenced by other factors such as integrity of the suspensory apparatus, which could have a major effect on CHDL. Measures of body fat likely contributed to having thin SST, but other factors including calving, herd, and lesion presence also had an effect.

Isotope-filtered nD NMR spectroscopy of complex mixtures to unravel the molecular structures of phenolic compounds in tagged soil organic matter.

Unravelling structures of molecules contained in complex, chromatographically inseparable mixtures is a challenging task. Due to the number of overlapping resonances in NMR spectra of these mixtures, unambiguous chemical shift correlations attributable to individual molecules cannot be achieved and thus their structure determination is elusive by this technique. Placing a tag carrying an NMR active nucleus onto a subset of molecules enables (i) to eliminate signals from the non-tagged molecules, and (ii) to obtain a set of correlated chemical shifts and coupling constants belonging to a single molecular type. This approach provides an opportunity for structure determination without the need for compound separation. Focusing on the most abundant functional groups of natural organic matter molecules, the carboxyl and hydroxyl groups were converted into esters and ethers, respectively by introducing (13)CH3O groups. A set of (13)C-filtered nD NMR experiments was designed yielding structures/structural motives of tagged molecules. The relative sensitivity of these experiments was compared and a step-by-step guide how to use these experiments to analyse the structures of methylated phenolics is provided. The methods are illustrated using an operational fraction of soil organic matter, fulvic acid isolated from a Scottish peat bog. Analysis of 33 structures identified in this sample revealed a correlation between the position of the methoxy cross-peaks in the (1)H, (13)C HSQC spectra and the compound type. This information enables profiling of phenolic compounds in natural organic matter without the need to acquire a full set of experiments described here or access to high field cryoprobe NMR spectrometers.

Linking bone development on the caudal aspect of the distal phalanx with lameness during life.

Claw horn disruption lesions (CHDL; sole hemorrhage, sole ulcer, and white line disease) cause a large proportion of lameness in dairy cattle, yet their etiopathogenesis remains poorly understood. Untreated CHDL may be associated with damage to the internal anatomy of the foot, including to the caudal aspect of the distal phalanx upon which bone developments have been reported with age and with sole ulcers at slaughter. The primary aim of this study was to assess whether bone development was associated with poor locomotion and occurrence of CHDL during a cow's life. A retrospective cohort study imaged 282 hind claws from 72 Holstein-Friesian dairy cows culled from a research herd using X-ray micro-computed tomography (µ-CT; resolution: 0.11mm). Four measures of bone development were taken from the caudal aspect of each distal phalanx, in caudal, ventral, and dorsal directions, and combined within each claw. Cow-level variables were constructed to quantify the average bone development on all hind feet (BD-Ave) and bone development on the most severely affected claw (BD-Max). Weekly locomotion scores (1-5 scale) were available from first calving. The variables BD-Ave and BD-Max were used as outcomes in linear regression models; the explanatory variables included locomotion score during life, age, binary variables denoting lifetime occurrence of CHDL and of infectious causes of lameness, and other cow variables. Both BD-Max and BD-Ave increased with age, CHDL occurrence, and an increasing proportion of locomotion scores at which a cow was lame (score 4 or 5). The models estimated that BD-Max would be 9.8mm (SE 3.9) greater in cows that had been lame at >50% of scores within the 12mo before slaughter (compared with cows that had been assigned no lame scores during the same period), or 7.0mm (SE 2.2) greater if the cow had been treated for a CHDL during life (compared with cows that had not). Additionally, histology demonstrated that new bone development was osteoma, also termed "exostosis." Age explained much of the variation in bone development. The association between bone development and locomotion score during life is a novel finding, and bone development appears specific to CHDL. Bone development on the most severely affected foot was the best explained outcome and would seem most likely to influence locomotion score. To stop irreparable anatomical damage within the foot, early identification of CHDL and effective treatment could be critical.

Evaluation of treatments for claw horn lesions in dairy cows in a randomized controlled trial.

Lameness is one of the most significant endemic disease problems facing the dairy industry. Claw horn lesions (principally sole hemorrhage, sole ulcer, and white line disease) are some of the most prevalent conditions. Despite the fact that thousands of animals are treated for these conditions every year, experimental evidence is limited on the most effective treatment protocols. A randomized, positively controlled clinical trial was conducted to test the recovery of newly lame cows with claw horn lesions. Animals on 5 farms were locomotion scored every 2wk. Cows were eligible for recruitment if they had 2 nonlame scores followed by a lame score and had a claw horn lesion on a single claw of a single foot. Following a therapeutic trim, enrolled cows were randomly allocated to 1 of 4 treatments: treatment 1-no further treatment (positive control; TRM), treatment 2-trim plus a block on the sound claw (TB), treatment 3-trim plus a 3-d course of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (TN), treatment 4-trim plus a block plus ketoprofen (TBN). The primary outcome measure was locomotion score 35d after treatment, by an observer blind to treatment group. Descriptive statistics suggested that treatment groups were balanced at the time of enrollment, that is, randomization was successful. Based on a sound locomotion score (score 0) 35d after treatment, the number of cures was 11 of 45 (24.4%) for TRM, 14 of 39 (35.9%) for TB, 12 of 42 (28.6%) for TN, and 23 of 41 (56.1%) for TBN. The difference between TBN and TRM was significant. To test for confounding imbalances between treatment groups, logistic regression models were built with 2 outcomes, either sound (score 0) or nonlame (score 0 or 1) 35d after treatment. Compared with TRM, animals that received TBN were significantly more likely to cure to a sound outcome. Farm, treatment season, lesion diagnosis, limb affected, treatment operator, and stage of lactation were included in the final models. Our work suggests that lameness cure is maximized with NSAID treatment in addition to the common practices of therapeutic trimming and elevation of the diseased claw using a block when cows are newly and predominantly mildly lame.

Evaluating an intervention to reduce lameness in dairy cattle.

Lameness in dairy cattle remains a significant welfare concern for the UK dairy industry. Farms were recruited into a 3-yr study evaluating novel intervention approaches designed to encourage farmers to implement husbandry changes targeted toward reducing lameness. All farms completing the study were visited at least annually and received either monitoring only (MO, n=72) or monitoring and additional support (MS, n = 117) from the research team. The additional support included traditional technical advice on farm-specific solutions, facilitation techniques to encourage farmer participation, and application of social marketing principles to promote implementation of change. Lameness prevalence was lower in the MO (27.0 ± 1.94 SEM) and MS (21.4 ± 1.28) farms at the final visit compared with the same MO (38.9 ± 2.06) and MS (33.3 ± 1.76) farms on the initial visit. After accounting for initial lameness, intervention group status, and year of visit within a multilevel model, we observed an interaction between year and provision of support, with the reduction in lameness over time being greater in the MS group compared with the MO group. Farms in the MS group made a greater number of changes to their husbandry practices over the duration of the project (8.2 ± 0.39) compared with those farms in the MO group (6.5 ± 0.54). Because the lameness prevalence was lower in the MS group than the MO group at the start of the study, the contribution of the additional support was difficult to define. Lameness can be reduced on UK dairy farms although further work is needed to identify the optimum approaches.

Oral bisphosphonates are associated with reduced mortality after hip fracture.

UNLABELLED: Intravenous bisphosphonates reduce mortality following hip fracture. We determined whether new use of oral bisphosphonates was also associated with reductions in mortality in 209 hip fracture patients. Oral bisphosphonate exposure led to relative reduction of 8% per month of use (p = 0.001) or about a 60% reduction in mortality per year of use. INTRODUCTION: Intravenous bisphosphonates reduce mortality following hip fracture. Using prospectively collected long-term data from a randomized trial of osteoporosis quality improvement for hip fracture, we determined whether new use of oral bisphosphonates was associated with reductions in mortality or the composite outcome of death or new fracture. METHODS: Originally, 220 hip fracture patients were randomized to case manager (n = 110) or usual care followed by facilitated bone mineral density (BMD) testing (n = 110) interventions. All were eligible for bisphosphonate treatment. Post-randomization, we followed patients for 3 years and ascertained bisphosphonate treatment, medication adherence and persistence, all-cause mortality, and new clinical fractures. Proportional hazards analyses with time-varying treatment status were undertaken. RESULTS: The final study cohort included 209 patients: 136 (65%) females, 104 (50%) older than 75 years, 90 (43%) with poor self-reported health, and 38 (18%) underweight. Of these, 76 (36%) had a previous fracture before hip fracture and 132 (81%) had low BMD. A total of 101 (46%) patients started oral bisphosphonates and 65 (64%) remained on treatment at the final evaluation. Overall, 24 (11%) patients died, 19 (9%) had new fractures, and 42 (20%) reached the composite outcome of death or fracture. Compared to no treatment, bisphosphonate exposure was independently associated with reduced mortality (17[16%] vs. 7[7%]; adjusted hazard ratio (aHR) = 0.92 per month treated; 95%CI, 0.88-0.97) and composite endpoints (28[26%] vs. 5[15%]; aHR = 0.94 per month treated; 95%CI, 0.91-0.97). CONCLUSION: Like intravenous bisphosphonates after hip fracture, our study suggests that oral bisphosphonates may be associated with reductions in all-cause mortality.

Review of preventative behavioural interventions for dermal and respiratory hazards.

BACKGROUND: No previous systematic review of the evidence base has been undertaken to help occupational health professionals understand how to reliably lower the instance of occupational ill-health through reducing risk-taking behaviour. AIMS: To evaluate the effectiveness and processes of occupational-based behavioural interventions for workers exposed to dermal and respiratory hazards. METHODS: A systematic review was conducted. Sixteen electronic databases were searched using key words. Bibliography, health and safety websites and hand searches of key journals were also undertaken. Articles were included if they evaluated an intervention targeting workers' behavioural compliance, addressed dermal or respiratory hazards, used before and after measures with a control group comparison and used behaviour-related exposure indicators such as airborne exposure, health effects, behaviour observations and self-reported work practices. Data were extracted according to potential sources of bias, impact and behavioural change processes used. RESULTS: Ten of 550 articles identified as potentially relevant were included. A predominance of small effect sizes, particularly for larger samples, demonstrated limited but positive impact upon exposure. Studies contained too much heterogeneity for reliable meta-analysis. None of the studies covered the full range of behaviour change components necessary for reducing exposure risk. CONCLUSIONS: We conclude that future interventions could enhance their effectiveness through improving design quality, reporting and basing their content upon evidence-based behavioural change approaches. Using a comprehensive range of evidence-informed behaviour change ingredients should improve occupational health professional's ability to reliably reduce occupational ill-health where exposure cannot totally be designed out of the workplace.

A macrophage migration inhibitory factor-like tautomerase from Teladorsagia circumcincta (Nematoda: Strongylida).

A macrophage migration inhibitory factor (MIF)-like molecule, Tci-MIF-1, was isolated from Teladorsagia circumcincta and subjected to detailed characterization. A cDNA representing Tci-mif-1 was isolated following its identification in third-stage larvae (L3)-enriched cDNA population. Sequencing of the cDNA indicated a 348-bp open reading frame (ORF) with the closest orthologue being a MIF derived from the human hookworm Ancylostoma ceylanicum. Messenger RNA (mRNA) representing the Tci-MIF-1 transcript was detected in eggs, L3 and adult stages of T. circumcincta. The transcript was also present, but to a lesser extent in fourth-stage larvae (L4). Detection of Tci-MIF-1 protein in T. circumcincta developmental stages reflected the transcript levels identified by reverse transcriptase-PCR. Using immunohistochemistry, the Tci-MIF-1 protein was shown to have a diffuse distribution in L3 tissue, and in L4 and adult stages, the protein was localized to the nematode gut. A recombinant version of Tci-MIF-1 was produced, and enzymic assays indicated that this recombinant protein and a somatic extract of L3 possessed dopachrome tautomerase activity as has been observed previously in other MIF-like molecules. Neither native, purified Tci-MIF nor recombinant Tci-MIF-1 dramatically influenced the in vitro migration of sheep monocytes.

Sampling strategies for monitoring lameness in dairy cattle.

Evaluating the prevalence of lameness within herds of dairy cattle is important for management and certification purposes; however, sampling strategies that could reduce the time taken for an assessment would be valuable. The prevalence of lame and severely lame cows on 224 United Kingdom dairy farms was available for analysis. Presence of more than 1 severely lame cow on a farm was a useful indication of a lameness problem. The vast majority (80%) of the 182 farms that had > or = 1 severely lame cow present had an overall lameness prevalence >25%, whereas only 24% of the 42 farms that had no severely lame cows had an overall prevalence >25%. Information was available on individual milking order through the parlor on the day of the lameness assessment. On 37 farms where cows were housed in a group, lameness prevalence was 11.9% greater in the last third compared with the first third of the milking order. For 36 herds that were larger than 100 cows, sampling a maximum of 100 cows from the middle of the milking order produced an estimate of prevalence within 5% of the true prevalence on 83% of farms. A reasonable sampling strategy may, therefore, be to observe up to 100 cows from the middle of the milking order. Also, presence of severely lame cows at the end of milking may be useful for identifying those farms likely to benefit from further support.

Assessment of lameness prevalence and associated risk factors in dairy herds in England and Wales.

Visits were made to 205 dairy farms in England and Wales between October 2006 and May 2007 by 1 or more of 4 researchers. At each visit, all milking cows were locomotion scored (lameness scored) using a 4-point scale (0=sound locomotion, 1=imperfect locomotion, 2=lame, 3=severely lame). The mean prevalence of lameness (scores 2 and 3) across the study farms was 36.8% (range=0-79.2%). On each farm, the presence within the housing and grazing environments of commonly reported risks for increased lameness was recorded. Each farmer was interviewed to gauge the ability of the farm staff to detect and treat lameness. A multivariable linear regression model was fitted. Risk factors for increased lameness were the presence of damaged concrete in yards, cows pushing each other or turning sharply near the parlor entrance or exit, cattle grazing pasture also grazed by sheep, the use of automatic scrapers, not treating lame cows within 48h of detection, and cows being housed for 61 d or longer at the time they were locomotion scored by the visiting researcher. Having a herd consisting entirely of a breed or breeds other than Holstein-Friesian was associated with a reduction in lameness prevalence compared with having a herd consisting entirely of Holstein-Friesians.

First experimental evidence for a bis-ethene chromium(I) complex forming from an activated ethene oligomerization catalyst.

A bis-ethene chromium(I) species, which is the postulated key intermediate in the widely accepted metallacyclic mechanism for ethene oligomerization, is experimentally observed. This catalytic transformation is an important commercial route to linear α-olefins (primarily, 1-hexene and 1-octene), which act as comonomers for the production of polyethene. Here, electron paramagnetic resonance studies of a catalytic system based on [Cr(CO)4(PNP)][Al(OC(CF3)3)4] [PNP = Ph2PN(iPr)PPh2] activated with Et6Al2 provide the first unequivocal evidence for a chromium(I) bis-ethene complex. The concentration of this species is enhanced under ethene and isotope labeling studies that confirm its composition as containing [Cr(C2H4)2(CO)2(PNP)]+ These observations open a new route to mechanistic studies of selective ethene oligomerization.

Ventilation heterogeneity in children with well controlled asthma with normal spirometry indicates residual airways disease.

BACKGROUND: In adults with asthma, ventilation heterogeneity, independent of inflammation, has been hypothesised to be associated with airway remodelling. Bronchial biopsy in preschool children with wheeze demonstrates early structural changes. Ventilation heterogeneity is sensitive to airway disease in other paediatric respiratory conditions such as cystic fibrosis, so may be sensitive to early airway disease in asthma. An observational study was performed in which it was hypothesised that ventilation heterogeneity (lung clearance index (LCI) and phase III slope indices (S(cond) and S(acin))) were more sensitive than conventional measurements (forced expiratory volume in 1 s (FEV(1)) and exhaled nitric oxide (Feno)) for detecting residual airways disease in children with well controlled asthma. METHODS: In 31 children with asthma of mean age 10.6 years (range 5-15), FEV(1), LCI, S(cond) and S(acin) were measured at two separate visits, before and after blinded salbutamol or placebo, with Feno measured once. 29 healthy volunteers of mean age 11.2 years (range 5-16) completed measurements at one visit only. RESULTS: Baseline mean (SD) LCI was significantly higher in children with asthma than in controls (6.69 (0.91) vs 6.24 (0.47), p = 0.02). There were no significant differences in FEV(1) or median Feno. Following salbutamol there was a small significant change in mean (SD) FEV(1) (from -1.26 (1.25) to -0.93 (0.23), p = 0.03) but not in LCI, S(cond) or S(acin). Importantly, LCI remained significantly higher after bronchodilator in children with asthma than in controls (6.64 (0.69), p = 0.01). CONCLUSION: This study identifies the presence of residual ventilation heterogeneity in children with well controlled asthma and normal FEV(1). The role of LCI in measuring early airway disease in children with asthma requires further exploration, possibly as a surrogate of structural remodelling.

Calcitonin messenger RNA encodes multiple polypeptides in a single precursor.

Recombinant DNA techniques were used to analyze the structure of the messenger RNA encoding a precursor of calcitonin, a small calcium-regulating hormone of 32 amino acids. Analyses of the nucleotide sequences of cloned complementary DNA's comprising the entire coding sequence of the messenger RNA revealed that calcitonin is flanked at both its amino and carboxyl termini by peptide extensions linked to the hormone by short sequences of basic amino acids. The location of glycine next to the carboxyl terminal prolinamide of calcitonin is consistent with indications that glycine is required for the enzymatic amidation of proline to the prolinamide. During cellular biosynthesis, calcitonin arises from a large precursor protein by cleavages at both amino and carboxyl terminal residues of the hormone. These findings raise questions concerning the regulation of these cleavages and the potential biological functions of the precursor extensions derived from these cleavages.

The development, implementation and testing of a lameness control programme based on HACCP principles and designed for heifers on dairy farms.

This paper describes the development and testing of a lameness control programme (LCP) for heifers on dairy farms. The LCP, which is based on the analysis of hazards and critical control points (HACCP), was tested via a randomised intervention study on 60 farms. Tangible hazards for each farm were identified, allotted to 11 categories of proximate hazard and scored on each farm to quantify the risks presented by each hazard. Feet were inspected for signs of claw horn disease and infection, such as digital dermatitis. Intervention was generally ineffective, primarily through failure to implement the LCP. However, retrospective analysis was able to demonstrate highly significant associations between risks attached to proximate hazards and probabilities of lameness and foot lesions, allowing the severity of these hazards to be ranked. The most significant proximate hazards of environmental origin were prolonged standing on concrete, standing in wet slurry and factors that cause claw trauma. The most severe proximate hazards however were those associated with failures of management, especially poor claw condition and inadequate foot care. Overall farm risks (OFR) were estimated by summing the products of the generic severity for proximate hazards with on-farm risks. Changes in OFR were significantly related to changes in outcome (lameness and lesions).