Developing a tool to assess the health-related quality of life in calves with respiratory disease: content validation.

Bovine respiratory disease (BRD) is a major welfare and productivity issue for calves. Despite the extensive negative impacts on calf welfare and performance, BRD remains challenging to detect and treat effectively. However, the clinical signs of disease are only one aspect of the disease that is experienced by the individual. The assessment of emotional experience in animals is not straightforward, but it is increasingly recognised that the quality of behaviour and demeanour of an individual is a reflection of their internal emotional state. The aim of the present study was to complete the content validation stage of the development process for a health-related quality of life (HRQOL) tool. This was based around indicators from an existing conceptual framework containing twenty-three indicators in two domains (clinical signs and behavioural expression). The content validation stage involves engaging with key stakeholders. For this study, this took the form of a survey and discussions with focus groups, which are standard methods in this field. A survey and stakeholder focus groups were conducted to assess the usefulness of each indicator and its relevance for inclusion within a HRQOL tool. In the survey, participants were asked to rate the usefulness of each of the indicators using a 4-point scale which were then dichotomised into 'useful' and 'less useful'. Based on the 'useful' result, each indicator within the domains was ranked. A similar approach was taken with the responses from the focus groups. Focus group participants were asked to select indicators that they felt were of use and the result of this was used to rank each of the indicators. The ranks of the indicators from both the survey and the focus groups along with the transcripts from the focus groups were used to determine the indicators from each domain to include within the HRQOL tool. Indicators within the clinical signs domain that were included were nasal discharge, cough, respiratory effort, ocular appearance (discharge and vibrancy), body and head posture and ear carriage. For the domain of behavioural expression, the indicators included were movement to feed, responsiveness, spatial proximity, volume of feed intake, motivation at feed and vigour. The next stage will be to validate the construction of the HRQOL tool through its use in practice. The inclusion of indicators that allow the experiential aspects of disease to be recorded in health assessments will likely increase the ability of farmers and others to detect respiratory disease in calves.

Early prediction of respiratory disease in preweaning dairy calves using feeding and activity behaviors.

Bovine respiratory disease (BRD) represents one of the major disease challenges affecting preweaning dairy-bred calves. Previous studies have shown that differences in feeding and activity behaviors exist between healthy and diseased calves affected by BRD. The aim of this study was to develop and assess the accuracy of models designed to predict BRD from feeding and activity behaviors. Feeding and activity behaviors were recorded for 100 male preweaning calves between ~8 to 42 d of age. Calves were group housed with ad libitum access to milk via automatic milk feeders, water, starter diet, and straw. Activity was monitored via a leg-mounted accelerometer. Health status of individual calves was monitored daily using an adapted version of the Wisconsin Scoring System to identify BRD. Three models were created to predict disease: (1) deviation from normal lying time based on moving averages (MA); (2) random forest (RF), a machine learning technique based on feeding and activity variables; and (3) a combination of RF and MA output. For the MA model, lying time was predicted based on behavior over previous days (3- and 7-d MA) and the expected value for the current day (based on calf age; measured using accelerometers). Data were not split into training and test data sets. Occasions when the actual lying time increased >9% of predicted lying time were classified as a deviation from normal and a disease alert was provided. Both feeding and activity behaviors were included within the RF model. Data were split into training (70%) and test (30%) data sets based on disease events. Events were classified as 2 d before, the day(s) of the disease event, and 2 d after the event. Accuracy of models was assessed using sensitivity, specificity, balanced accuracy, and Matthews correlation coefficient (MCC). If a positive disease prediction agreed with an actual disease event within a 3-d rolling window, it was classified as a true positive. Stand-alone models (RF; MA) showed high specificity (0.95; 0.97), moderate sensitivity (0.35; 0.43), balanced accuracy (0.65; 0.64), and MCC (0.25; 0.29). Combining outputs increased accuracy (specificity = 0.95, sensitivity = 0.54, balanced accuracy = 0.75, MCC = 0.36). The work presented is the first to demonstrate the use of modeling data derived from precision livestock farming techniques that monitor feeding and activity behaviors for early detection of BRD in preweaning calves, offering a significant advance in health management of youngstock.

Feeding behaviour and activity as early indicators of disease in pre-weaned dairy calves.

Across the industry, there is large variation in health status of dairy calves and as a result, disease incidence and antibiotic use is high. This has significant implications for animal welfare, productivity and profitability of dairy and dairy-beef production systems. Technology-based early detection systems could alleviate these issues; however, methods of early detection of disease in dairy calves have not been widely explored. This study aimed to determine whether changes in activity and feeding behaviour can be used as early warning indicators of respiratory disease in calves. In total, 100 pre-weaned male Holstein calves (age: ~8-42 days) were used. Calves were group-housed and provided with starter diet, straw bedding and ad libitum water. Calves were fed milk replacer ad libitum through an automatic calf feeder, and each calf was fitted with a leg-mounted activity monitor. Daily activity and feeding behaviour variables were calculated for each calf. Each calf was assessed daily using a modified version of the Wisconsin Scoring System to assess respiratory disease status. Calves were classed as 'Diseased', 'Intermediate' or 'Healthy' based on their cumulative health score. The peak day of the most extreme illness event was identified for each calf. Data from Diseased and Healthy calves were paired for analysis based on age and BW. Data were compared for the day of peak illness, and for the 3 days previous and post. Compared to healthy calves, diseased calves lay for longer and tended to have longer lying bouts (daily lying: 17.6 ±â€¯0.3 vs 16.7 ±â€¯0.2 h, P < 0.01; bout length: 74.8 ±â€¯10.6 vs 56.0 ±â€¯3.7 min, P = 0.09 for diseased and healthy calves, respectively). Diseased calves fed for a shorter time and had fewer feeder visits (with intake) each day compared to healthy calves (feeding time (min): 19.3 ±â€¯1.4 vs 22.8 ±â€¯1.5; P < 0.05; visits: 2.1 ±â€¯0.2 vs 3.2 ±â€¯0.4; P < 0.05). Importantly, differences between diseased and healthy calves were evident in both activity and feeding behaviour on the days prior to the peak day of disease. Lying bout length was greater in diseased calves for the 2 days prior to the peak day (P < 0.05), lying time was longer on day -1 (P < 0.05) and feeder visits with milk intake were less frequent on day -3 (P < 0.05). Thus, measurement of feeding and activity using precision technology within early detection systems could facilitate early intervention and optimized treatment.

The first case of HIV-2 in Scotland.

HIV-1 infects an estimated 37 million people worldwide, while the rarer HIV-2 infects 1-2 million worldwide. HIV-2 is mainly restricted to West African countries. The majority of patients in Scotland are diagnosed with HIV-1, but in 2013 the West of Scotland Specialist Virology Centre (WoSSVC) diagnosed Scotland's first HIV-2 positive case in a patient from Côte d'Ivoire. HIV-2 differs from HIV-1 in terms of structural viral proteins, viral transmissibility, prolonged period of latency, intrinsic resistance to certain antivirals and how to monitor the effectiveness of treatment. Over the course of 5 years the patient has required several changes in treatment due to both side effects and pill burden. This case highlights the complexity of HIV-2 patient management over time.

Comparison of thermal imaging and rectal temperature in the diagnosis of pyrexia in pre-weaned calves using on farm conditions.

Measuring core body temperature is used as part of the diagnostic process in assessing the health of animals. Typically in calves, this is carried out using a rectal thermometer which can be time consuming, stressful to the calf and is invasive by nature. A non-invasive technique that is gaining recognition is thermal imaging. This study investigated the use of thermal imaging as a technique to assess core body temperature in pre-weaned artificially reared calves. A total of 125 male and female calves had rectal temperatures measured daily from day 7 until day 40 of life, and at the same time had a thermal image taken of the area around the medial canthus of the eye. A weak correlation (r = 0.28) was found between calf rectal temperature and thermal image temperature. A multivariable predictive model for core body temperature increased the correlation (r = 0.32) when including the environmental parameters of air temperature (p < .001) and wind speed (p < .001) as well as reconstituted milk replacer consumption (p < .01). The effectiveness of a predictive model including these parameters for the detection of calves with a core body temperature ≥ 39.5 °C was examined and found to have a sensitivity of 0% and a specificity of 100%. The results of this study demonstrate the need to take thermal environmental parameters into consideration when using thermal imaging to assess body temperature. However, the results suggest that accurate measures of core body temperature using thermal imaging cannot be achieved under commercial farm conditions. Further research is needed to determine what other factors could be measured to increase predictive ability.

Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy.

SETTING: Glasgow, Scotland, UK. BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment. OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use. DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression. RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors. CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.

Missed opportunities for HIV diagnosis: a three-year audit in the West of Scotland.

BACKGROUND: National specialty guidelines for HIV testing aim to increase diagnosis and reduce late presentation. An audit of new HIV diagnoses in Glasgow was performed to assess local performance against these guidelines and estimate the proportion of patients presenting who had previous missed opportunities for diagnosis. METHODS: A retrospective case note review of 339 patients diagnosed from September 2008 to September 2011 was performed. Documented past medical history was assessed for HIV clinical indicator conditions prior to HIV diagnosis and prior review by medical services. RESULTS: Ninety (26%) individuals had at least one documented clinical indicator condition prior to HIV diagnosis, of whom 80 had prior contact with at least one speciality. This group also had a lower mean nadir CD4 count (258 cells/cmm versus 393 cells/cmm, p = <0.005) and were more likely to be severely immunocompromised at diagnosis, with a CD4 count below 50 cells/cmm (31% versus 9%, p = <0.005). AIDS-defining illnesses were also more common (31% versus 8%, p ≤ 0.005) as was HIV-related mortality (p ≤ 0.005). CONCLUSION: Additional support and training are required to increase adherence to HIV-testing guidelines within primary and secondary care in order to prevent ongoing late presentation with both individual clinical and public health implications.

The impact of dystocia on dairy calf health, welfare, performance and survival.

Up to one-third of dairy calves are born after dystocia and this is a major cause of calf mortality. This study investigated the neonatal physiology, survival, health and subsequent growth of dairy calves following dystocia and is the first longitudinal study to analyse multiple effects and to look beyond the perinatal period. A total of 455 live born Holstein calves (N: No assistance, n=360; FN: Farmer assistance but normally presented calf, n=82; FM: Farmer assistance of malpresented calf, n=13) were followed from birth to first service (heifers) or until leaving the farm (bulls). Compared to N calves, FN and FM animals had higher salivary cortisol concentrations at day 1 (P<0.001) and FN calves had lower passive immune transfer (P=0.03). Dystocia had no biologically significant impact on rectal temperature throughout the first 4 days (P>0.05). During the first 60 days, FM calves had a higher proportion of days with non-routine health treatments (P<0.05) and, by the time of weaning, mortality in FN and FM heifers was higher than in N calves (2.8×; P<0.01). However, in surviving calves, growth to first service was not affected by dystocia category (P>0.05). Calves which survive dystocia experience lower passive immunity transfer, higher mortality and higher indicators of physiological stress. Such calves have poorer welfare in the neonatal period and possibly beyond. Strategies need to be implemented to improve the subsequent health and welfare of such calves and to lower the incidence of dystocia.

Fever in the returning traveller.

International travel is increasing and a significant number of travellers will develop a febrile illness during or shortly after their return from the tropics. The differential diagnosis is broad and a systematic approach to the management of these patients is required in order to establish the diagnosis and to initiate prompt and effective treatment. Fever may be due to infectious agents found only in tropical countries, or due to infections unrelated to travel and found worldwide. Important infections that should be considered in all returning travellers include malaria, dengue, enteric fever, rickettsial infections, and HIV seroconversion. Other diagnoses will be considered after a detailed history including countries visited with dates, activities undertaken and symptoms. At a minimum, all travellers from countries where there is malaria transmission should be tested repeatedly for malaria as well as having several sets of blood cultures taken. Many tropical infections are diagnosed serologically at specialist reference laboratories. Specialist advice on the investigation and management of returning travellers should be sought from infectious diseases physicians and microbiologists. Patients with malaria or enteric fever may deteriorate rapidly and travellers should be advised to seek prompt medical attention if they become unwell after travel to the tropics. This review will focus on some of the more important imported infections, diagnostic clues from the history, examination and investigations, and important considerations in their management.

State-resolved velocity map imaging of surface-scattered molecular flux.

This work describes a novel surface-scattering technique which combines resonance enhanced multiphoton ionization (REMPI) with velocity-map imaging (VMI) to yield quantum-state and 2D velocity component resolved distributions in the scattered molecular flux. As an initial test system, we explore hyperthermal scattering (E(inc) = 21(5) kcal mol(-1)) of jet cooled HCl from Au(111) on atomically flat mica surfaces at 500 K. The resulting images reveal 2D (v(in-plane) and v(out-of-plane)) velocity distributions dominated by two primary features: trapping/thermal-desorption (TD) and a hyperthermal, impulsively scattering (IS) distribution. In particular, the IS component is strongly forward scattered and largely resolved in the velocity map images, which allows us to probe correlations between rotational and translational degrees of freedom in the IS flux without any model dependent deconvolution from the TD fraction. These correlations reveal that HCl molecules which have undergone a large decrease in velocity parallel to scattering plane have actually gained the most rotational energy, reminiscent of a dynamical energy constraint between these two degrees of freedom. The data are reduced to a rotational energy map that correlates with velocity along and normal to the scattering plane, revealing that exchange occurs primarily between rotation and the in-plane kinetic energy component, with v(out-of-plane) playing a relatively minor role.

Intraoperative patellar kinematics following resection of the central one-third of the patellar tendon in the ovine stifle joint.

OBJECTIVES: The bone-patellar tendon-bone complex is routinely harvested for anterior cruciate ligament reconstruction in humans. Patella infera may ensue. However, the contribution from resection of the central one-third of the patellar tendon (PT) to potentially altered patellofemoral kinematics, in addition to those induced by a positional shift of the patella, are yet to be distinguished. Objectives of this study were to characterize changes in intraoperative patellar kinematics and PT length in nine sheep immediately following unilateral resection of the central one-third PT, and again at six, 12 and 24 weeks postoperatively. METHODS: Following implantation of bone-screws into the patella and tibia, electromagnetic receivers were anchored to these, and then passively-induced, unloaded patellar kinematics were captured. Patellar kinematics were referenced to the tibial coordinate frame and analysed using non-parametric tests (Wilcoxon Signed Rank Test). RESULTS: Resection alone did cause significant alteration in kinematics at the time of surgery (p <0.05). Postoperatively, a mean increase in PT length of 2.6 mm was detected in the operated stifles, reflected partly as a net 2.8 mm proximal patellar shift (p <0.001). This was accompanied by a mean net six degree medial shift in the patellar tilt pattern (p <0.001). Significant changes to patellar spin in the latter parts of flexion were also observed (p <0.005). Kinematic and length changes did not recover up to 24 weeks postoperatively. CLINICAL SIGNIFICANCE: The data obtained in this study suggests that both the patellar height and integrity of the PT are important determinants of patellar kinematics in the ovine stifle joint.

Population pharmacokinetics of sulfadoxine and pyrimethamine in Malawian children with malaria.

In addition to parasite resistance, inadequate levels of exposure to antimalarial drugs may contribute to treatment failure. We developed population pharmacokinetic (PK) models to describe the distribution of sulfadoxine (SDX) and pyrimethamine (PYM) in children with uncomplicated malaria in Malawi. The concentration levels of antimalarial drugs in whole blood were determined using high-performance liquid chromatography. We found no evidence of underdosing in children as compared with adults; the children had drug exposure levels similar to those described in adults. Treatment failure was more likely in children with lower PYM concentrations on day 14 (P = 0.024), and there was a trend for lower SDX concentrations on day 14 (P = 0.061). SDX and PYM concentrations at levels predictive of treatment failure have been identified at day 14. Less than one-third of the children displayed drug concentration levels above these thresholds after receiving the recommended SDX-pyrimethamine (SP) dose. Our findings suggest that PK factors contributed to the observed high rate of treatment failure, and we therefore recommend a higher SP dose for children under the age of 5 years.

Neurophysiological findings in patients 1 year after snake bite induced neurotoxicity in Sri Lanka.

Snake bite causes significant morbidity and mortality in Sri Lanka. Snake venoms contain neurotoxins that block neuromuscular junction transmission. Presynaptic neurotoxicity most commonly causes destruction of nerve terminals with recovery by regrowth, whilst postsynaptic neurotoxicity usually involves competition at the acetylcholine receptor. The aim of this study was to investigate whether there were long-term clinical or neurophysiological changes in snake bite survivors 1 year after their envenoming. Detailed neurophysiological tests and clinical examinations were performed on 26 snake bite victims who had presented with neurotoxicity 12 months previously, and their results were compared with controls recruited from the same communities. Significant differences were observed in some nerve conduction parameters in some snake bite victims compared with controls, predominantly in those thought to have elapid bites, including prolongation of sensory, motor and F-wave latencies and reduction of conduction velocities. There was no evidence of any residual deficits in neuromuscular junction transmission. These results suggest a possible demyelinating type polyneuropathy. None of the cases or controls had abnormalities on clinical examination. This is one of the few studies to report possible long-term neurological damage following systemic neurotoxicity after snake bite. The clinical significance of these neurophysiological abnormalities is uncertain and further studies are required to investigate whether the abnormalities persist and to see whether clinical consequences develop.

CT and MR imaging cochlear distance measurements may predict cochlear implant length required for a 360 degrees insertion.

BACKGROUND AND PURPOSE: A preoperative prediction of the 360 degrees point insertion depth would aid the planning of electric acoustic stimulation (EAS) implantation. The purpose of this study was to establish whether the distance between the round window and the opposite cochlear wall on CT or MR imaging may be used to predict the length of a cochlear implant electrode array required to be inserted to the 360 degrees point of the basal turn. MATERIALS AND METHODS: CT and MR imaging data were studied in 19 patients undergoing cochlear implantation. Distances were measured between the round window and the opposite outer cochlear wall on an oblique paracoronal reformatted image. Adjusted distance measurements were applied to a spiral function to estimate the length of an electrode array extending between the round window entry point and the 360 degrees point. This was compared with measurements of implant length to this insertion depth on postoperative CT. RESULTS: Intraobserver reproducibility for each of the 2 observers was r = 0.85/0.55 for CT and r = 0.87/0.67 for MR imaging. Interobserver reproducibility was r = 0.68 for CT and r = 0.84 for MR imaging. There was no bias between CT and MR imaging measurements, with a mean difference of less than 0.1 mm. CT and MR imaging estimates markedly correlated with the actual length of the electrode array extending to the 360 degrees insertion depth (SD between the estimated and actual length was 0.84 mm for CT and 0.87 mm for MR imaging). CONCLUSIONS: CT and MR imaging measures of cochlear distance (CD) were used to predict insertion depths to 360 degrees , and these were markedly concordant with the actual length of the electrode array required to reach this point. MR imaging measurements were more precise and similar in accuracy to those obtained with CT.

Simple measures are as effective as invasive techniques in the diagnosis of pulmonary tuberculosis in Malawi.

SETTING: Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings. OBJECTIVE: To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN: Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS: A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples. CONCLUSIONS: For countries such as Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using BAL after induced sputum is limited.