Mesophyll conductance in two cultivars of wheat grown in glacial to super-elevated CO2 concentrations.

Mesophyll conductance (gm) is an important factor limiting photosynthesis. However, gm response to long-term growth in variable [CO2] is not well understood, particularly in crop plants. Here, we grew two cultivars of wheat (Halberd and Cranbrook), known to differ in gm under current environmental conditions, in four [CO2] treatments: glacial (206 µmol mol-1), pre-industrial (344 µmol mol-1), current ambient (489 µmol mol-1), and super-elevated (1085 µmol mol-1), and two water treatments (well-watered and moderate water limitation), to develop an evolutionary and future climate perspective on gm control of photosynthesis and water-use efficiency (WUE). In the two wheat genotypes, gm increased with rising [CO2] from glacial to ambient [CO2], but declined at super-elevated [CO2]. The responses of gm to different growth [CO2] also depend on water stress; however, the specific mechanism of gm response to [CO2] remains unclear. Although gm and gm/gsc (mesophyll conductance/stomatal conductance) were strongly associated with the variability of photosynthetic rates (A) and WUE, we found that plants with higher gm may increase A without increasing gsc, which increased WUE. These results may be useful to inform plant breeding programmes and cultivar selection for Australian wheat under future environmental conditions.

Short-term liveweight changes of dairy cows measured by stationary and walk-over weighing scales.

Monitoring and detecting individual cows' liveweight (LW) and liveweight change (LWC) are important for estimation of nutritional requirements and health management, and could be useful to measure short-term feed intake, water consumption, defecation, and urination. Walk-over weighing (WOW) systems can facilitate measurements of LW for these purposes, providing automated LW recorded at different times of the day. We conducted a field study to (1) quantify the contribution of feed and water intake, as well as urine and feces excretions, to short-term LWC and (2) determine the feasibility of stationary and WOW scales to detect subtle changes in LW as a result of feed and water intake, urination, and defecation. In this experiment, 10 cows walked through a WOW system and then stood individually on a stationary scale collecting weights at 10 and 3.3 Hz, respectively. Cows were offered 4 kg of feed and 10 kg of water on the stationary scale. For each animal, LW before and after eating and drinking was then calculated using different approaches. Liveweight change was calculated as the difference between the initial and final LW before and after eating and drinking for each statistical measure. The weights of feed intake, water consumption, urination, and defecation were measured and used as predictors of LWC. Urine and feces were collected from individual cows while the cow was on the scale, using a container, and weighed separately. The agreement between LWC measured using either stationary or WOW scales was assessed to determine the sensitivity of the scales to detect subtle changes in LW using the coefficient of determination (R2), Lin's concordance correlation coefficient (CCC), and mean bias. The prediction model showed that most of the regression coefficients were not significantly different from +1.0 for feed and water, or -1.0 for urine and feces. The R2 and CCC values demonstrated a satisfactory agreement between calculated and stationary LWC and values ranged from 0.60 to 0.92 and 0.71 to 0.94, respectively. A moderate agreement was achieved between calculated and automated LWC with R2 and Lin's CCC values of 0.45 to 0.63 and 0.60 to 0.74, respectively. Therefore, results demonstrated that new algorithms and data processing methods need to be continuously explored and improved to obtain accurate measurements of LW to measure changes in LW, especially from WOW scales.

Ferumoxytol MR Angiography versus Duplex US for Vascular Mapping before Arteriovenous Fistula Surgery for Hemodialysis.

Background Duplex US is performed routinely for vascular mapping prior to arteriovenous fistula (AVF) creation for hemodialysis but cannot demonstrate the central vasculature. Ferumoxytol, an iron oxide nanoparticle, provides an alternative to gadolinium contrast material for MR angiography for safe use in chronic kidney disease (CKD). Purpose To assess the clinical utility of ferumoxytol-enhanced MR angiography compared with duplex US for vascular mapping before upper limb AVF creation in participants with CKD. Materials and Methods In a prospective comparative study (ClinicalTrials.gov: NCT02997046) from December 2016 to August 2018, participants with CKD underwent ferumoxytol-enhanced MR angiography and duplex US. Two independent readers evaluated vessels for diameter, stenosis or occlusion, arterial disease, and central stenosis. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess intra- and interreader variability. On the basis of accepted standards for AVF creation, an algorithm was developed to predict AVF outcome based on imaging findings. Multivariable regression models used AVF success as the dependent variable and age, sex, and duplex US or ferumoxytol-enhanced MR angiography findings as independent variables. Results Fifty-nine participants with CKD (mean age, 59 years ± 13 [standard deviation]; 30 women) were evaluated. A total of 51 fistulas were created, of which 24 (47%) were successful. Ferumoxytol-enhanced MR angiography showed excellent inter- and intrareader repeatability (ICC, 0.84-0.99) for all variables assessed. In addition to revealing 15 central vasculature stenoses, ferumoxytol-enhanced MR angiography resulted in characterization of 88 of 236 (37%) of the arterial sections examined as unsuitable for AVF creation compared with 61 of 236 (26%) sections with duplex US (P = .01). Ferumoxytol-enhanced MR angiography independently predicted AVF success in models including (odds ratio, 6.5; 95% confidence interval: 1.7, 25; P = .006) and those excluding (odds ratio, 4.6; 95% confidence interval: 1.3, 17; P = .02) the central vasculature. Conclusion In addition to enabling identification of central vessel pathologic features, ferumoxytol-enhanced MR angiography revealed peripheral arterial disease not recognized with duplex US and was more predictive than duplex US of the outcome of arteriovenous fistula surgery. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Finn in this issue.

The effects of inbreeding on covering success, gestation length and foal sex ratio in Australian thoroughbred horses.

BACKGROUND: Horses produce only one foal from an eleven-month gestation period, making the maintenance of high reproductive rates essential. Genetic bottlenecks and inbreeding can increase the frequency of deleterious variants, resulting in reduced reproductive levels in a population. In this study we examined the influence of inbreeding levels on foaling rate, gestation length and secondary sex ratio in Australian Thoroughbred mares. We also investigated the genetic change in these traits throughout the history of the breed. Phenotypic data were obtained from 27,262 breeding records of Thoroughbred mares provided by three Australian stud farms. Inbreeding was estimated using the pedigree of each individual dating back to the foundation of the breed in the eighteenth century. RESULTS: While both gestation length and foaling rate were heritable, no measurable effect of inbreeding on either trait was found. However, we did find that the genetic value for both traits had decreased within recent generations. A number of environmental factors also had significant effects on foaling rate and gestation length. Secondary sex ratio had only an extremely small paternal heritable effect and was not susceptible to environmental influences. CONCLUSIONS: In contrast to racing performance, inbreeding had no measurable effect on foaling rate or gestation length in Australian Thoroughbred horses. This could be because the level of inbreeding in the population examined is not high enough to show a discernible effect on reproductive traits. Populations that experience higher levels of inbreeding due to use of artificial reproductive technologies or extremely small population sizes may show a more pronounced reduction in natural foaling rate or gestation length. It is also possible that the intensive management techniques used in the Thoroughbred population masks any negative effects of inbreeding. The decrease in the genetic value of foaling rate is likely to be because horses with unfavourable genetic potential have not yet been selected out of the population. The change in genetic value of gestation length may be due to selective breeding favouring horses with shorter pregnancies. We also found that prioritising the mating of older mares, and avoiding out of season mating could lead to an increased breeding success.

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish renal registry.

BACKGROUND: Infection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland. METHODS: Study design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed. RESULTS: During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. CONCLUSION: The rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection.

Analysis of variation in growth and spline-based growth models for Marecha and Lassi dromedary camels.

Camel is an important domestic animal that is well adapted to extremely harsh environments. Due to its multi-purpose role, the camel is gaining importance, particularly as a meat producer. Body weights at different ages and growth curves have been extensively studied in several livestock species. However, the information on the camel is very limited. We investigate patterns of variation in birth weight and weaning weight of two prominent breeds of camels in Pakistan, namely Marecha and Lassi. A further objective is not only to develop growth models which will account for systematic differences due to breed and sex but also to allow for individual variation in growth, by the application of appropriate statistical models. Birth weight, weaning, and monthly weights for a period of up to 48 months were recorded for each camel. Growth records of 137 camels consisting of 108 Marecha and 29 Lassi were obtained. Differences were detected between the two breeds, Marecha and Lassi, as well as differences between sexes, but only after 2 years of age. Beyond that, female Marecha camels had slower growth than males, whereas Lassi (mostly females) had faster growth than female Marechas. In addition, there is a sizable variation between individuals within the same breed-sex combination. The results of the present study will be of use to explore the potential of the camel as a meat producer in Pakistan.

A national study of autogenous arteriovenous access use and patency in a contemporary hemodialysis population.

OBJECTIVE: The predicted outcomes of autogenous arteriovenous (AV) hemodialysis access creation are predominantly based on historical data; however, both the hemodialysis population and clinical practices have changed significantly during the last decade. This study examined contemporary AV access clinical use and patencies. METHODS: A multicenter observational cohort study was performed of all new AV accesses created in Scotland in 2015. The primary end point was efficacy assessed by successful AV access use for a minimum of 30 days and primary, primary assisted, and secondary patency at 1 year. Data obtained included all interventions to maintain or to restore patency. Predictors of patency loss including demographics, comorbid conditions, dialysis status, AV access location, duplex ultrasound surveillance, procedures, prior access, and antiplatelets were assessed. Kaplan-Meier and competing risks analyses were performed to estimate the probability of AV access failure. All patients were followed up for at least 1 year or had a censoring event. RESULTS: A total of 582 AV accesses were created in 537 patients (mean age, 60 [standard deviation, 14] years; 60% men; 42% with diabetes) in nine adult renal centers. Mean follow-up was 11.8 (standard deviation, 7.6) months. By the end of the follow-up, 322 (55.3%) AV accesses were successfully used for dialysis. At 1 year, 48% (95% confidence interval [CI], 44-52) of AV accesses had primary patency, (95% CI, 63-71) had primary assisted patency, and 69% (95% CI, 65-73) had secondary patency. The leading cause of primary patency loss was primary failure (30%). An average of 0.48 intervention per patient-year was required to maintain patency. On multivariable analysis, patency was better for an upper arm than for a forearm AV access (1-year secondary patency of upper arm vs forearm AV accesses, 74% vs 58%). The cumulative hazard and incident functions for AV access failure were 31% (95% CI, 27-35) and 23% (95% CI, 20-27) at 1 year, respectively. CONCLUSIONS: Despite advances in recent years with preoperative vessel assessment and surveillance, patency rates have not improved, with primary failure remaining the major obstacle. Competing events should be taken into consideration; otherwise, biases may occur with overestimation of the probability of AV access failure.

Potential risk factors of ovarian cancer and analysis of CA125, a biomarker used for its monitoring and diagnosis.

Ovarian cancer (OC) is the fourth most common cancer among Pakistani, Scottish and Chinese women. The aim of the present study was to determine the association of potential risk factors with OC and analysis of Cancer Antigen 125 (CA125) in its monitoring and diagnosis. A total of 200 patients diagnosed with OC were included in this study. All the patients were interviewed and 54 OC patients (case group) and 35 age-matched healthy subjects (control group) gave their blood for analysis of CA125. The blood of case and control groups was subjected to an ELISA test for the evaluation of CA125 levels. Majority of the patients were of 40-50 years of age and most of the patients were diagnosed at this period of life. The majority of the patients experienced their first menarche and menopause at the age of 13-14 and 40-50 years respectively. There is no significant association between early menarche and OC family history, nor between late menopause and OC family history. There is a significant association between family history of breast cancer (BC) and age of menarche (P = 0.005). An OC patient with an age of menarche of 13 years or younger has 2.8 times the odds of having a family history of BC than those whose age of menarche is more than 13 years. Eleven percent of patients diagnosed with OC received no intervention. All other patients underwent treatment options including hysterectomy (69.5%), radiotherapy (39%) and chemotherapy (95%). The profiles of the patients showed that those who had a family history of OC were more likely to provide blood samples (OR = 3.87, P = 0.025), and similarly for those with a history of breast cancer (OR = 2.83, P = 0.022) in comparison to those who were not willing to provide blood for testing of biomarker. The distribution of CA125 for OC patients and control group showed that CA125 values were significantly higher (P = 0.034) in the case patients compared with the control group. The decrease in CA125 levels indicated the positive response to treatment, whereas increase in CA125 values showed resistant and disease progression. 52% of the patients with OC were correctly diagnosed as having OC (based on the optimal cut-point of CA125), while 83% of those without OC were also correctly diagnosed (with 48% of OC patients and 17% of non-OC patients incorrectly diagnosed). We concluded that there is significant association between family history of breast cancer and OC history and use of CA125 as a biomarker is not an ideal diagnostic and monitoring test as it has low sensitivity and high specificity.

The first 365 days on haemodialysis: variation in the haemodialysis access journey and its associated burden.

Background: The modality by which haemodialysis (HD) is delivered [arteriovenous fistula (AVF), arteriovenous graft (AVG) or central venous catheter (CVC)] varies widely and is influenced by clinical evidence, patient factors and the prevailing service configuration. The aim of this study was to determine the outcome and impact of access strategy on patient outcome by mapping out the HD journey in a cohort of incident patients. Methods: A 2-year cohort of consecutive incident HD patients from the point of referral for first dialysis access to completion of the first 365 days of HD was prospectively reviewed. Data were sought on access type; radiological, surgical and other access-related activity; bacteraemic events; admission rates and cumulative financial cost. Results: A total of 144 patients started RRT for the first time with HD over the 2-year period. All were followed up to 1 year after starting HD, generating a total of 47 753 observed HD days. Activity prior to starting HD for the full cohort was found to average 0.92 arteriovenous (AV) access creation procedures, 0.40 CVC insertions, 0.14 interventional radiology procedures and 0.41 ultrasound examinations per patient. The small number of patients who started on an AVG had a tendency towards higher pre-HD surgical and imaging activity than those who started on an AVF or CVC. Activity after starting HD varied greatly with the access type used at the start of HD, with AVF patients experiencing less hospitalization, procedure and imaging activity and financial costs compared with those who start HD with a CVC. Patients who started on an AVG had a tendency towards lower surgical activity rates and financial costs than those who started on a CVC. Conclusions: Providing, maintaining and dealing with the complications of HD vascular access places a significant burden of activity that is shared across nephrology, surgery and imaging services. A well-functioning AVF is associated with the lowest burden, whereas a failed AVF or CVC access is associated with the highest burden. Patient journeys are shaped by the vascular access that they use and we suggest that the contemporary pursuit of HD access should focus on delivering personalized access solutions.

Quantification of plasma corticosterone in juvenile farmed saltwater crocodiles (Crocodylus porosus) using current Australian Code of Practice guidelines.

Saltwater crocodiles (Crocodylus porosus) across three size categories (hatchlings, grower and harvest-size) were repeatedly blood sampled on two farms in the Northern Territory, Australia to determine reference plasma corticosterone (CORT; crocodilian stress hormone) levels. The mean CORT values for hatchlings (<1 year old), growers (1-3 years) and harvest-size individuals (2 + years) were 1.65 ±â€¯0.15 ng/ml, 2.73 ±â€¯0.21 ng/ml and 2.19 ±â€¯0.16 ng/ml, respectively. No inter-farm differences within the hatchling or harvest-size crocodiles were detected, but growers on Farm 2 had significantly lower plasma CORT than those on Farm 1. However, the grower growth rate coefficients were the same across both farms so the repeated blood sampling design most likely contributed to the difference in CORT values rather than any management procedures. Plasma corticosterone levels significantly increased with time of day. Substantial variation in plasma CORT was observed at each sampling which is not unprecedented in the literature but requires further elucidation. Irrespective, as CORT values were generally low, our results suggest that the farming environment and husbandry practices, as implemented under the Australian industry Code of Practice, are effective as baseline animal welfare measures although they should be viewed as a foundation for further welfare research and not considered static.

Short communication: The effect of temperature-humidity index on milk yield and milking frequency of dairy cows in pasture-based automatic milking systems.

Hot weather is known to negatively affect cow performance primarily through reduced feed intake and milk yield. However, little information is available on how it affects cow milk yield and milking frequency in automatic milking systems (AMS). Milking data were collected from 6 pasture-based AMS farms in Australia to assess the effect of temperature-humidity index (THI) on milk yield and milking frequency. Daily measures of average milk yield per cow and average milking frequency per cow during December to February (Australian summer) were assessed for associations with maximum, minimum, and average THI from d 0, -1, -2, and -3 in relation to the milking data. Average daily milk yield per cow was negatively associated with an increasing maximum, minimum, and average THI (-0.11, -0.08, and -0.15 kg/THI unit increase, respectively) on the collection day and up to 3 d prior. The average daily milking frequency was negatively associated with maximum THI on 1 d (-0.003/THI unit increase) and 2 d (-0.003/THI unit increase) before collection. Our results show that high THI conditions were negatively associated with milking frequency and milk yield in a pasture-based AMS and that research into management and infrastructure (cow cooling) in these systems is warranted to reduce production losses.

Characterising infant and young child feeding practices and the consumption of poultry products in rural Tanzania: A mixed methods approach.

Suboptimal breastfeeding practices, early initiation of complementary feeding, and monotonous cereal-based diets have been implicated as contributors to continuing high rates of child undernutrition in sub-Saharan Africa. Nutrition-sensitive interventions, including agricultural programs that increase access to nutrient-rich vegetables, legumes, and animal-source foods, have the potential to achieve sustainable improvements in children's diets. In the quest to evaluate the efficacy of such programs in improving growth and development in the first 2 years of life, there is a role for mixed methods research to better understand existing infant and young child feeding practices. This analysis forms part of a longitudinal study assessing the impact of improvements to poultry health and crop production on diets and growth of 503 randomly selected children from eight rural communities in Manyoni District in central Tanzania. Using an explanatory sequential design, the quantitative phase of data collection was conducted between May 2014 and May 2016, comprising six monthly structured questionnaires, four monthly household-level documentation of chicken and egg consumption, and fortnightly records of children's breastfeeding status. The subsequent qualitative phase involved in-depth interviews with a subset of 39 mothers in October 2016. Breastfeeding was almost universal (96.8%) and of long duration (mean = 21.7 months, SD = 3.6), but early initiation of complementary feeding was also common (74.4%; mean = 4.0 months, SD = 1.8), overwhelmingly driven by maternal perceptions of insufficient milk supply (95.0%). Chicken and eggs were infrequently eaten, but close associations between maternal and child consumption patterns (p < .001) suggest the potential for strategies that increase household-level consumption to bring nutritional benefits to young children.

A novel multiplex PCR assay for simultaneous detection of nine clinically significant bacterial pathogens associated with bovine mastitis.

For rapid and simultaneous detection of nine bovine mastitic pathogens, a sensitive and specific multiplex PCR assay was developed. The assay was standardized using reference strains and validated on mastitic milk cultures which were identified to species level based on 16S rRNA sequencing. Multiplex PCR assay also efficiently detected the target bacterial strains directly from milk. The detection limit of the assay was up to 50 pg for DNA isolated from pure cultures and 104 CFU/ml for spiked milk samples. As estimated by latent class analysis, the assay was sensitive up to 88% and specific up to 98% for targeted mastitic pathogens, compared with the bacterial culture method and the 16S rRNA sequence analysis. This novel molecular assay could be useful for monitoring and maintaining the bovine udder health, ensuring the bacteriological safety of milk, and conducting epidemiological studies.

Risk factors and outcome of stroke in renal transplant recipients.

Stroke incidence is high in end-stage renal disease, and risk factors differ between the dialysis and general populations. However, risk factors and outcomes following renal transplantation remain unclear. We analyzed all adult patients with a functioning renal transplant from 01/01/2007 to 12/31/2012. Data were extracted from the electronic patient record. Variables associated with stroke were identified by survival analyses; demographic, clinical, and imaging and laboratory variables were assessed and case fatality determined. Follow-up was until 05/12/2013. A total of 956 patients were identified (median age 40.1 years, 59.9% male). Atrial fibrillation (AF) prevalence was 9.2%, and 38.2% received a transplant during follow-up. A total of 26 (2.7%) experienced a stroke during 4409 patient-years of follow-up (84.6% ischemic). Stroke incidence was 5.96/1000 patient-years. Factors associated with stroke on regression analysis were prior stroke, diabetes, age, systolic hypertension, and hemoglobin. Atrial fibrillation was associated with time to stroke (P<0.001). Warfarin did not associate with ischemic stroke risk in those with AF. Fatality was 19.2% at 7, 23.1% at 28, and 42.3% at 365 days after stroke. Patients with a functioning renal transplant have a high stroke incidence and case fatality. Unlike those on hemodialysis, risk factors are similar to the general population. We did not demonstrate benefit from warfarin use in those with AF.

Unexpected lower testosterone in faster growing farmed saltwater crocodile (Crocodylus porosus) hatchlings.

Agricultural production of the saltwater crocodile (Crocodylus porosus) is an emergent industry in northern Australia with many of the factors affecting production remaining unknown. In this study, we sought to expand upon our previous findings of reference corticosterone and immune function by reporting baseline sex hormone levels [testosterone (TEST) and estradiol (ESTR)] and their association with growth. This was achieved by sampling 253 hatchling crocodiles repeatedly at 3, 6, and 9months of age. Sampling age had a significant effect on both TEST (p<0.001) and ESTR (p<0.001) suggesting climatic/abiotic factors have an influence even in prepubescent crocodiles. Stress, as measured by plasma corticosterone, had no detectable effect on plasma ESTR or TEST levels. Unexpectedly however, TEST was higher in slower-growing crocodiles, which is contrary to what has been reported for the American alligator. ESTR was not associated with growth.

Canine atopic dermatitis: breed risk in Australia and evidence for a susceptible clade.

BACKGROUND: Genetic studies on canine atopic dermatitis (CAD) indicate that large populations from one geographical location are preferred for the identification of relevant susceptibility genes. Australian dogs are relatively isolated; studies on CAD in this population are limited. HYPOTHESIS/OBJECTIVES: To identify breeds at risk in the Australian dog population and to compare with worldwide breed predisposition. ANIMALS: Case records (n = 23,000) from University Veterinary Teaching Hospital (UVTH) dogs, including 722 with CAD. METHODS: The breed proportion of CAD and odds risk (OR) were calculated. A systematic review of 13 previous studies (1971-2010) was performed and compared to the study results by implementing an atopic dermatitis (AD)-to-reference population ratio (ADRPR). RESULTS: Eleven dog breeds with significant increased OR (≥1.0) were identified; all with breed CAD cases proportionally higher than their base hospital population. Gender risk in males from the pug dog breed (P = 0.007) was detected and the bichon frise breed had a similar trend (P = 0.05). Sixteen predisposed dog breeds were identified by systematic review. All breeds with significant increased OR in UVTH had ADRPR > 1.4; five (boxer, bulldog, Labrador retriever, pug, West Highland white terrier) were recognized as predisposed worldwide. One clade of breeds with common ancestry was highly represented in CAD cases worldwide and in Australia (81% of the significant OR cases). CONCLUSION AND CLINICAL IMPORTANCE: The use of a large population from one geographical location and ADRPR provided an objective comparison between worldwide AD studies; it identified one common clade of susceptible breeds. Breed genetics and related clinical presentation may help CAD diagnosis and treatment.

Manifestation of neuronal ceroid lipofuscinosis in Australian Merino sheep: observations on altered behaviour and growth.

Neuronal ceroid lipofuscinoses (NCL) is an inherited neurodegenerative disorder in children. Presently there is no effective treatment and the disorder is lethal. NCL occur in a variety of non-human species including sheep, which are recognised as valuable large animal models for NCL. This experiment investigated the progressive postural, behavioural and liveweight changes in NCL-affected lambs, to establish practical, non-invasive biomarkers of disease progression for future preclinical trials in a CLN6 Merino sheep model. A flock of eight lambs at pasture was studied, with the observer blind to the disorder status. Three genotypes were compared: homozygous affected NCL; n = 4), clinically normal heterozygous (Carrier; n = 2) and homozygous normal (non-carrier control (Normal); n = 2). Direct observation during daylight and continuous accelerometer measurements over 72 h were used to quantify lamb posture and behaviour in 11 sessions between 26-60 weeks of age, conducted at 3-5 week intervals. There was a Genotype (G) × Age (A) interaction (P = 0.001) for liveweight of the lambs in the experiment, with NCL, Carrier and Normal lambs gaining 11.8, 16.5 and 23.4 kg, respectively, between 26 and 60 weeks of age. G×A interactions were also found for walking behaviour (means for NCL, Carrier and Normal genotype groups at 26 and 60 weeks, were 1.7 and 7.9%, 3.3 and 3.1%, and 2.5 and 1.9% of observations, P = 0.008) and a composite variable of key behaviours identified in the principal components analysis (P < 0.001), with mean values for NCL lambs increasing three-fold compared to non-affected lambs as age increased. Similarly, NCL lambs became less responsive to visual and auditory stimuli as they aged. Mean responsiveness scores (out of 3) to visual stimuli for the NCL, Carrier and Normal genotypes at 26 and 60 weeks of age were 2.7 and 1.4, 2.8 and 2.9, and 3.0 and 3.0, respectively (G × A, P < 0.001). Changes in response to auditory stimuli were similar to visual stimuli. NCL lambs took more (P = 0.015) steps per 24 h than Carrier and Normal genotype lambs, but there was no G × A interaction. At 26 and 60 weeks of age respectively, NCL lambs took 2724 and 4121 steps per 24 h, compared to Carrier (1708 and 3105 steps) and Normal genotype lambs (2109 and 3506 steps). NCL lambs also performed less (P = 0.018) grazing behaviour than Carrier and Normal genotype lambs (66.5, 72.3 and 72.5% of observations for NCL, Carrier and Normal lambs, respectively). A number of behavioural changes identified in the experiment could form the basis for a protocol for monitoring and evaluation of disease progression.

In-patient hospital mortality patterns by day of the week: an analysis of admissions to a regional renal unit.

BACKGROUND AND AIMS: Higher mortality rates have been reported for patients admitted at a weekend compared to a weekday. Our aim was to assess in-patient mortality patterns by day of the week, in a tertiary renal unit. METHOD AND RESULTS: Mortality related to day of admission and day of death was analysed over a two-year period at Glasgow Western Infirmary renal unit. Typical caseload was also assessed over two random four-week periods. As a proportion of admissions, 30-day mortality was 46/540 (8.5%) on a weekend day compared with a weekday 107/2013 (5.3%) (RR1.60, p = 0.005). Thirty-day mortality rate was 46/208 = 0.22 deaths/weekend day of admission compared with 107/523 = 0.20 deaths/weekday of admission (incident rate ratio = 1.08, p = 0.67). There was no significant increased risk of death on a weekend day compared to a weekday (RR1.23, p = 0.23). A higher proportion of weekend admissions were from other hospitals. Acute kidney injury and haemodialysis patients formed a higher percentage of admissions. CONCLUSION: Admission day mortality expressed as a death rate/day does not differ between weekend/weekday admissions. Admission day mortality expressed as a proportion of total admissions was significantly higher at weekends. This suggests admission case-mix/workload differs at weekends with fewer 'well' patients admitted. In-patient mortality patterns are complex and any conclusions made should take into account case mix and workload.

Risk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis.

BACKGROUND AND PURPOSE: End-stage renal disease (ESRD) requiring hemodialysis carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge on risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. METHODS: All adult patients receiving hemodialysis for ESRD from January 1, 2007, to December 31, 2012, were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging, and dialysis-related variables were assessed, and case-fatality was determined. Follow-up was until December 31, 2013. RESULTS: A total of 1382 patients were identified (mean age, 60.5 years; 58.5% men). The prevalence of atrial fibrillation was 21.2%, and 59.4% were incident hemodialysis patients. One hundred and sixty patients (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident hemodialysis patients. Factors associated with stroke on regression analysis were prior stroke, diabetes mellitus, and age at starting renal replacement therapy. Atrial fibrillation was not significantly associated with stroke, and warfarin did not affect stroke risk in warfarin-treated patients. Fatality was 18.8% at 7 days, 26.9% at 28 days, and 56.3% at 365 days after stroke. CONCLUSIONS: Incidence of stroke is high in patients with ESRD on hemodialysis with high case-fatality. Incident hemodialysis patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving hemodialysis.