Central serous chorioretinopathy secondary to intramuscular testosterone therapy.

Summary: A patient treated with intramuscular testosterone replacement therapy for primary hypogonadism developed blurred vision shortly after receiving his testosterone injection. The symptom resolved over subsequent weeks and recurred after his next injection. A diagnosis of central serous chorioretinopathy (CSR) was confirmed following ophthalmology review. A decision was made to change the patient's testosterone regime from this 12-weekly intramuscular injection to a daily topical testosterone gel, given the possibility that peak blood levels of testosterone following intramuscular injection were causing his ocular complaint. His CSR did not recur after this change in treatment. CSR secondary to testosterone therapy is a rare finding but has been reported previously in the literature. Learning Points: Blurred vision in patients treated with testosterone replacement therapy (TRT) should prompt an ophthalmology review. The potential for reduced risk of central serous chorioretinopathy (CSR) with daily transdermal testosterone remains a matter of conjecture. CSR is a rare potential side effect of TRT.

Adapting lean methodology towards surgical tray rationalisation in inguinoscrotal day case surgery in the republic of Ireland.

INTRODUCTION: Lean methodologies have been used successfully in both industry and healthcare to reduce waste. The operating room (OR) and central supplies department (CSD) are areas associated with high hospital costs. The aim of this study was to employ Lean methodologies to support the rationalisation of surgical trays in paediatric inguinoscrotal surgery in order to reduce instrument wastage, processing times and overall costs in a European setting. METHODS: This was a prospective, pilot observation and implementation study using Lean methodology including DMAIC (Define, Measure, Analyse, Improve and Control) cycles. Relevant tray set-up included trays for boys ≥12 months age undergoing open elective inguinoscrotal surgery. A comparative analysis of two phases, pre and post-standardization was then carried out with respect to operating times, instrument set-up times, tray weights, and costs. Instruments that were used <40% of the time were eliminated from the surgical tray. RESULTS: Rationalization of the inguinoscrotal tray led to a 34.7% reduction in tray size, with a concomitant time-reduction of >2 min per case. The average overall instrument utilisation rate increased from 56% to 80% across users. Cost savings were projected at €5380.40 per annum based on current changes. There were no differences in operative time, or adverse outcomes. DISCUSSION: At the hospital level, the reduction in variation, and rationalisation of this single surgical tray could lead to both operational (Tray assembly process; Operating rooms; Ergonomic functionality) as well as economic (Sterilisation; Instrument repair; Purchases) financial and ergonomic improvements for the healthcare system. The reduction in time taken to count and sterilise instruments can lead to a potential manpower saving involving a redistribution of activities to other areas which may require them. CONCLUSION: Surgical tray rationalisation is emerging Lean concept with overlap across a number of specialities, and represents a technique by which to manage costs, and improve supply chain efficiency without any adverse effect in patient healthcare outcomes.

Comparison of Three Anaesthetic Options to Reduce Acute Pain Response in Kid Goats.

Three options for anesthetizing the skin around the horn bud of dairy goat kids were explored. Forty-five <10-day-old Saanen goat kids from were randomly split into five treatment groups (topical anesthetic cream (TA), vapocoolant spray (VS), local anesthetic applied by jet injector (JI), control - no treatment but painful stimulus applied (C), sham - no treatment and touching sites with a finger. The painful stimulus was multiple needle pricks on the skin around the horn bud. The outcome variables measured were heart rate movement, and vocalization during treatment application and administration of a painful stimulus around the horn bud. Heart rates were greater during application of a VS compared to TA.Neither the TA nor the VS appeared to have any effect on the response to the painful stimulus. Kids in the JI group had a 96% reduced odds of expressing a marked pain response in comparison to TA group and an 83% reduction in the odds of a high movement grade during a painful procedure in comparison to the combined results of the other three treatment groups.

A blockchain-based framework to support pharmacogenetic data sharing.

The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.

Suckling behavior of calves in seasonally calving pasture-based dairy systems, and possible environmental and management factors affecting suckling behaviors.

In recent years, interest has been increasing in whether farmed animals are able to live a reasonably natural life, with one particular area of concern being calf-dam separation. The objectives of this study were to monitor the timing and frequency of suckling behavior of calves left on pasture to suckle their dams for up to 24 h (interquartile range 4.0-15.5 h) and to investigate possible risk factors that may contribute to any variability seen. Over 2 yr, a convenience sample of 8 farms (4 in the North Island, 4 in the South Island of New Zealand) were involved in an observational study where cows and calves were observed for 24 h a day over a 2-wk-long period per farm. During the observation period, farmers continued to remove calves at the same frequency they normally did (which ranged from once a day to 4 times a day). Cows (between 2 and 12 yr old) and calves were observed from a scissor lift in or beside the calving paddock. Cows had numbers written on them, and observers used binoculars and spotlights. Observers recorded the length of stage 2 labor, time of birth, standing, and first suckling, number of suckling events, time of calf removal from the dam, temperature where the cows were grazing, and size of the grazing area they were calving in. Dams were body condition scored before calving, and their age was extracted from farm records. A total of 697 calves were observed during the study. A total of 444 of 697 calves [63.7%; 95% confidence interval (CI) = 60.0-67.3%] suckled in the calving paddock (farm range 40.0% to 90.2%). Of the 444 calves that suckled in the calving paddock, 407 (58.4%; 95% CI 54.6-62.1%) suckled within the first 6 h after birth (farm range 33.0% to 83.6%). Individual risk factors associated with the hazard rate ratio (HR) for time to first suckling event were time to standing (calves who took more than 1.3 h to stand had a longer time from birth to first suckle) and age of the dam [compared with calves that were born from dams >7 years of age, calves born to dams that were 2-3 and 4-7 yr of age had a 1.49 (95% CI 1.07-2.06) and 1.19 (95% CI 0.89-1.60) HR, respectively, for time from birth to first suckle in the calving paddock]. Farm risk factors associated with the HR of suckling were frequency of calf collection [calves that were born on farms that collected calves once a day suckled earlier than calves on farms that removed calves more than once a day (HR 1.52; 95% CI 1.25-1.84)] and temperature [a minimum temperature of <10°C within 6 h of a calf being born was associated with a 0.69 (95% CI 0.53-0.89) hazard of suckling in the calving paddock]. We observed very large farm variability that urgently requires further investigation if pasture-based farms are ever to adopt a system where calves remain with their dams for longer than 24 h.

Epidemic disease risks and implications for Veterinary Services.

Growth in the livestock sector is associated with heightened risk for epidemic diseases. The increasing spillover of new diseases from wildlife is being driven by wide-scale anthropogenic changes allowing for more frequent and closer wildlife-human and wildlife-livestock contacts. An increasing number of epidemics in livestock are associated with rapid transition of livestock systems from extensive to intensive, and local to global movement of livestock and their products through value chain networks with weak biosecurity. Major livestock epidemics in the past two decades have had substantial economic impacts, and the COVID-19 pandemic highlights the devastating socio-economic consequences that spillovers can have when not identified and controlled early in the process of emergence. This highlights the importance of Veterinary Services to integrated, whole-of-society efforts to control infectious diseases in animals. Emphasis within Veterinary Services must be placed on prevention and preparedness. The authors suggest four areas for continued improvement in Veterinary Services to meet this challenge. These are a) continued development of staff capacity for risk assessment and value chain analysis, together with improved policies and communication, b) appropriate adaptation of approaches to prevention and control in resource-poor settings, c) improved multi-sectoral and transboundary cooperation, which enables the sharing of resources and expertise, and d) systematic approaches that enable Veterinary Services to influence decisionmaking for trade, markets, business, public health, and livelihood development at the national and regional levels.

La croissance du secteur de l'élevage est associée à un risque accru de maladies épidémiques. Les changements anthropiques à grande échelle sont à l'origine du nombre croissant de maladies émergentes atteignant de nouvelles espèces réceptives (spillover) à partir de réservoirs sauvages, à la faveur de contacts plus fréquents et plus rapprochés entre la faune sauvage et les humains, d'une part, et entre la faune sauvage et les animaux domestiques, d'autre part. On considère qu'un nombre croissant d'épidémies affectant le bétail sont dues à la transition rapide des systèmes d'élevage extensif vers des systèmes intensifs, et aux mouvements du bétail et des produits de l'élevage de l'échelle locale à l'échelle mondiale par le biais de réseaux de chaînes de valeur dotés d'un faible niveau de biosécurité. Au cours des deux dernières décennies, d'importantes épidémies affectant le bétail ont eu un impact économique considérable ; en outre, la pandémie de COVID-19 a mis en évidence les conséquences socio-économiques dévastatrices des atteintes de nouvelles espèces réceptives par des agents pathogènes, lorsque ces maladies ne sont pas détectées et maîtrisées dès le processus d'émergence. Cela souligne l'importance cruciale des Services vétérinaires dans les efforts de lutte contre les maladies infectieuses chez les animaux, qui doivent être intégrés et mobiliser la société entière. Les Services vétérinaires doivent mettre un accent particulier sur la prévention et la préparation. Les auteurs proposent quatre aspects d'amélioration continue pour que les Services vétérinaires puissent relever ce défi. Il s'agit : a) du développement permanent des compétences des personnels vétérinaires en matière d'évaluation du risque et d'analyse des chaînes de valeur, et leur articulation avec de meilleures politiques et une communication plus performante ; b) une adaptation adéquate des méthodes de prévention et de contrôle dans les configurations faiblement dotées en ressources ; c) une meilleure coopération multisectorielle et transfrontalière afin de partager les ressources et les compétences ; d) des dispositifs systémiques permettant aux Services vétérinaires d'influencer les prises de décision en matière d'échanges internationaux, de marchés, de commerce, de santé publique et de développement des moyens de subsistance, à l'échelle nationale et régionale.

El crecimiento del sector pecuario está condicionado por la existencia de un mayor riesgo de enfermedades epidémicas. La creciente diseminación de nuevas enfermedades a partir de animales silvestres es consecuencia de transformaciones antrópicas a gran escala que posibilitan un contacto más frecuente y estrecho de la fauna silvestre con el ser humano y el ganado. Cada vez son más las epidemias del ganado que tienen que ver con la rápida transición de los sistemas pecuarios de un régimen de producción extensiva a otro de producción intensiva y con el paso de la dimensión local a la mundial de la circulación de animales y sus derivados a través de redes de cadenas de valor que presentan una endeble seguridad biológica. En los últimos dos decenios ha habido grandes epidemias que han afectado al ganado y tenido importantes consecuencias económicas. La pandemia de COVID-19 es un elocuente ejemplo de los devastadores efectos socioeconómicos que puede tener la extensión de un patógeno cuando no se detecta y controla en un momento lo bastante precoz del proceso de emergencia. Ello pone de relieve la importancia que revisten los Servicios Veterinarios para que toda la sociedad pueda reaccionar de forma integrada a la hora de combatir las enfermedades infecciosas de los animales. Dentro de los Servicios Veterinarios, conviene poner el acento en la prevención y la preparación. Para lograr este objetivo los autores señalan cuatro ámbitos que exigen una constante mejora: a) el desarrollo continuo de la capacidad del personal en materia de determinación de riesgos y análisis de cadenas de valor, ligado a la mejora de las políticas y la comunicación; b) la adecuada adaptación de los métodos de prevención y control en contextos de escasos recursos; c) una mejor cooperación multisectorial y transfronteriza, que permita poner en común recursos y competencias técnicas; y d) enfoques sistemáticos que hagan posible que los Servicios Veterinarios influyan en los procesos decisorios relativos al desarrollo del comercio, los mercados, las empresas, la salud pública y los medios de sustento a escala tanto nacional como regional.

Acute diabetic neuropathy following improved glycaemic control: a case series and review.

SUMMARY: We present three cases of acute diabetic neuropathy and highlight a potentially underappreciated link between tightening of glycaemic control and acute neuropathies in patients with diabetes. Case 1: A 56-year-old male with poorly controlled type 2 diabetes (T2DM) was commenced on basal-bolus insulin. He presented 6 weeks later with a diffuse painful sensory neuropathy and postural hypotension. He was diagnosed with treatment-induced neuropathy (TIN, insulin neuritis) and obtained symptomatic relief from pregabalin. Case 2: A 67-year-old male with T2DM and chronic hyperglycaemia presented with left lower limb pain, weakness and weight loss shortly after achieving target glycaemia with oral anti-hyperglycaemics. Neurological examination and neuro-electrophysiological studies suggested diabetic lumbosacral radiculo-plexus neuropathy (DLPRN, diabetic amyotrophy). Pain and weakness resolved over time. Case 3: A 58-year-old male was admitted with blurred vision diplopia and complete ptosis of the right eye, with intact pupillary reflexes, shortly after intensification of glucose-lowering treatment with an SGLT2 inhibitor as adjunct to metformin. He was diagnosed with a pupil-sparing third nerve palsy secondary to diabetic mononeuritis which improved over time. While all three acute neuropathies have been previously well described, all are rare and require a high index of clinical suspicion as they are essentially a diagnosis of exclusion. Interestingly, all three of our cases are linked by the development of acute neuropathy following a significant improvement in glycaemic control. This phenomenon is well described in TIN, but not previously highlighted in other acute neuropathies. LEARNING POINTS: A link between acute tightening of glycaemic control and acute neuropathies has not been well described in literature. Clinicians caring for patients with diabetes who develop otherwise unexplained neurologic symptoms following a tightening of glycaemic control should consider the possibility of an acute diabetic neuropathy. Early recognition of these neuropathies can obviate the need for detailed and expensive investigations and allow for early institution of appropriate pain-relieving medications.

Effects of a topically applied anaesthetic on the behaviour, pain sensitivity and weight gain of dairy calves following thermocautery disbudding with a local anaesthetic.

Aims: To compare the effect of a topically applied anaesthetic to no pain relief or meloxicam on the behavioural responses, pain sensitivity and weight gain of calves following disbudding with or without sedation. Methods: A total of 364, 2-6 week-old calves from three commercial farms were systematically allocated to one of six treatment groups. All calves received a cornual nerve block prior to disbudding, with half restrained in a crate and half sedated with xylazine. Within these groups one third received no further treatment (control), one third were treated with meloxicam >10 minutes prior to disbudding and one third received a topical anaesthetic applied to the horn bud wounds following disbudding. The frequency of ear flicks, head shakes, head scratches and pain sensitivity of the wound were recorded on up to eight occasions over 24 hours after disbudding. Calves were weighed before, and 7 and 28 days after, disbudding to determine average daily weight gain (ADG). Results: Compared to calves in the crate-control group, all other groups had reduced ear flicks at all times following disbudding (p < 0.01). Treatment with meloxicam and topical anaesthesia in addition to sedation reduced head scratches compared to calves in the crate-control group (p ≤ 0.013). At 22 hours after disbudding head shakes were reduced in sedated calves treated with topical anaesthetic compared to calves in the crate-control group (p < 0.001). Pain sensitivity was lower in all sedated calves than unsedated calves (p < 0.001). The ADG between Days 0-7 was 0.14 (95% CI = 0.015-0.274) kg/day greater in sedated calves treated with meloxicam than calves in the crate-control group (p = 0.03), and the ADG between Days 0-28 tended to be 0.06 (95% CI=-0.01-0.13) kg/day greater in sedated calves treated with topical anaesthetic than calves in the crate-control group (p = 0.09). Conclusion and clinical relevance: Sedation of calves for disbudding reduced the pain experienced in the following 24 hours. There was a benefit to providing calves with topical anaesthetic following disbudding on behavioural responses and pain sensitivity, which was similar to that of treating calves with meloxicam.

Detection of hepatitis C virus in an exhumed body identified the origin of a nosocomial transmission that caused multiple fatal diseases.

BACKGROUND: Medico-legal conflicts arise when it is difficult to prove the cause of nosocomial infections. AIM: To report an outbreak of patient-to-patient transmission of hepatitis C virus (HCV) through the repeated use of a multi-dose saline flask during the rinsing of central venous catheters. METHODS: Blood samples were taken from each patient for the comparative analysis of their HCV RNA strains. No samples were available for one patient who died before the investigation started. Despite the known lability of HCV RNA, the body was exhumed four months after burial and postmortem samples were collected. HCV RNA was extracted successfully from liver and spleen samples. Genotyping of all the HCV strains was performed by sequence analysis of the 5'NC untranslated region, the E1 core conserved region and the E1/E2 hypervariable region. FINDINGS: Forensic investigators retraced the route used by two ward nurses, when saline catheter flushes were given to 14 patients with each nurse administering to seven patients. The comparative phylogenetic analysis of all case strains identified the deceased patient as the source of contamination to five patients. CONCLUSIONS: This study highlights the value of sequence analysis as a tool for solving medico-legal conflicts. The High Court of Justice found that a health worker's re-use of a contaminated needle resulted in the nosocomial transmission of HCV.

Bubbles and Dust: Experimental Results of Dissolution Rates of Metal Salts and Glasses From Volcanic Ash Deposits in Terms of Surface Area, Chemistry, and Human Health Impacts.

Explosive volcanic eruptions lead to ash deposition and subsequent leaching of contaminants into soils or surface water, impacting flora and fauna, including human health. This study determined the control of ash surface area and chemical composition on ash dissolution rates. Fresh, unhydrated ash samples from four contrasting volcanoes were analyzed in the laboratory. Column leachate tests were used to compare leaching rates over a range of basaltic to andesitic ashes as a function of time and surface area, to analyze the effects of ash deposition. It was found that surface area, measured both geometrically and by multipoint Brunauer-Emmett-Teller analysis, generally increases for a short time, gradually decreases, then increases over the rest of the leaching experiment, due to area to mass ratio fluctuations. After the column leachate tests, postleaching water analyses for elemental compositions were conducted by inductively coupled plasma-mass spectrometry and ion chromatography. Steady state dissolution rates initially decayed rapidly due to the smallest size fraction of ash (dust), which provides a large area of fresh leachable surfaces as well as the rapid dissolution of highly soluble metal salts. Some of the dissolved concentrations of elements relevant to human and ecosystem health such as F, Cd, Se, As, and Cr rose above World Health Organization (WHO) drinking water standards within an hour of experimental leaching. In nature, however, safe consumption standards are further dependent upon bioaccumulation and chronic exposure. As such, individual and recurring ash deposition events have applications to emergency response and preparedness in volcanic regions.

Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy.

HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity. KRM-II-81 was active against electroshock-induced convulsions in mice, pentylenetetrazole (PTZ)-induced convulsions in rats, elevations in PTZ-seizure thresholds, and amygdala-kindled seizures in rats with efficacies greater than that of diazepam. KRM-II-81 was also active in the 6 Hz seizure model in mice. Structural analogs of KRM-II-81 but not the ester, HZ-166, were active in all models in which they were evaluated. We further evaluated KRM-II-81 in human cortical epileptic tissue where it was found to significantly-attenuate picrotoxin- and AP-4-induced increases in firing rate across an electrode array. These molecules generally had a wider margin of separation in potencies to produce anticonvulsant effects vs. motor impairment on an inverted screen test than did diazepam. Ester bioisosters of HZ-166 are thus presented as novel agents for the potential treatment of epilepsy acting via selective positive allosteric amplification of GABAA signaling through α2/α3-containing GABA receptors. The in vivo data from the present study can serve as a guide to dosing parameters that predict engagement of central GABAA receptors.

Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth.

The PI3K-AKT signalling cascade has a highly conserved role in a variety of processes including cell growth and glucose homoeostasis. Variants affecting this pathway can lead to one of several segmental overgrowth disorders. These conditions are genetically heterogeneous and require tailored, multidisciplinary involvement throughout life. Hypoglycaemia is common in other overgrowth syndromes but has been described only sporadically in association with PIK3CA and CCND2 variants. We report a cohort of 6 children with megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes who developed clinically significant hypoglycaemia. Based on our findings, we suggest that segmental overgrowth patients should be screened for low blood glucose levels during childhood and there should be early specialist endocrine review in any children who develop hypoglycaemia.

The TBR1-related autistic-spectrum-disorder phenotype and its clinical spectrum.

A diverse range of genetic aberrations can lead to Autistic Spectrum Disorder (ASD) and many of these have been identified via Next Generation Sequencing (NGS) as part of large scale consortium studies. ASD is a phenotypically variable disorder and detailed clinical descriptions are essential to appreciate genotype-phenotype relationships. In this report, we provide a comprehensive clinical description of a child with ASD in whom a TBR1 variant was identified. We review this case in the context of the current TBR1 literature and highlight the variable spectrum of disease associated with this gene. The phenotypic information outlined within the literature is incomplete, exemplifying the limitations of massively-parallel sequencing studies with regards to clinical annotation. We suggest that future reporting of ASD variants should include standardised phenotypic descriptions. This would develop a more thorough understanding of genotype-phenotype relationship, so allowing us to better counsel and support our patients.

Calf and replacement heifer mortality from birth until weaning in pasture-based dairy herds in New Zealand.

The aims of this study were to (1) estimate the perinatal (birth to 24 h) and postnatal (∼24 h to the mean weaning age of 13 wk) mortality risk in pasture-based dairy calves until weaning, and (2) identify associated risk factors in the 2015 calving season. A prospective survey of 32 seasonal calving dairy farms was undertaken. Farmers recorded (daily) the number and sex of the calves alive or dead in the paddocks where cows calved. All daily animal movements in and out of the calf rearing facilities, including death and euthanasia, and the identification of the animals (if applicable) were recorded, and a survey of the farm management practices was undertaken. Individual and farm-level risk factors for perinatal mortality were modeled separately using generalized logistic mixed models with a random effect fitted for herd. Postnatal mortality incidence risk was calculated using time at risk for each calf from 24 h of age, collapsed into weeks, and multiplying the incidence risk by the mean weaning age of the study population. Farm-level risk factors contributing to postnatal mortality in the first week of life were assessed using a multivariable logistic mixed regression model. The mean perinatal mortality risk was 5.7% (95% confidence interval 5.4 to 6.1%) with a range from 2.2 to 8.6% (18,437 calves, 30 farms). Perinatal calf mortality was greater for male relative to female calves (odds ratio 1.39; 95% confidence interval 1.22 to 1.59), calves born in the first week of the calving period in comparison to wk 2 to 11 (odds ratio 0.32 to 0.66), and those born on days with greater rainfall (odds ratio 1.01 per 1 mm increase; 95% confidence interval 1.00 to 1.02). At the farm level, perinatal mortality increased for every extra week of calving period length (odds ratio 1.12; 95% confidence interval 1.06 to 1.17). The mean postnatal mortality risk was 4.1% (95% confidence interval 3.6 to 4.6%) with a range of 0 to 11% between farms. Farm-level risk factors contributing to mortality in the first week of life included farmer-reported disease problems in calves (odds ratio 2.2; 95% confidence interval 1.62 to 2.96), or calves hand-fed colostrum in the first 12 h of life (odds ratio 1.66; 95% confidence interval 1.26 to 2.19), which was assumed to be associated with poor colostrum quality and bacterial contamination. Regional differences were also observed in both perinatal and postnatal mortality risks, indicating that weather conditions, herd size, and management variations contribute to mortality incidence. In summary, the mortality risk of perinatal calves and postnatal calves until weaning on pasture-based farms is comparable with data published from other dairying systems despite the notable management differences. Several risk factors were identified that could be managed to reduce mortality incidence of dairy calves.

Prevalence and calf-level risk factors for failure of passive transfer in dairy calves in New Zealand.

AIM To determine the prevalence of failure of passive transfer (FPT) in dairy calves in New Zealand and to assess a range of potential calf-level risk factors for their association with FPT. METHOD Between July and September 2015, 107 dairy farms in nine regions across New Zealand were visited on three occasions: before 20% of cows had calved, when ∼50% of cows had calved, and when the last 10-20% of cows were calving. Farms were randomly selected from the client list of participating veterinary practices. On each farm, blood samples were collected from 10-20 calves between 24 hours and 8 days old and concentrations of total protein (TP) in serum determined. Calf identification, date of birth, dam's age and breed, details of colostrum feeding and the farmer's health assessment of the calf on arrival at the calf rearing facility were recorded. Concentrations of TP in serum ≤52 g/L were used to define FPT. RESULTS Of 3,819 calves sampled, 1,263 (33 (95% CI=31.6-34.6)%) were diagnosed with FPT, and the prevalence within farms ranged from 5-83%. Calf-level risk factors that were associated with increased odds of FPT were increasing age of dam (OR=1.12; 95% CI=1.08-1.16), calves recorded as unhealthy compared to healthy upon arrival at the calf rearing facility (OR=2.59; 95% CI=1.60-4.19), calves sampled on farms in Otago (OR=2.85; 95% CI=1.42-5.74) and Southland (OR 2.31; 95% CI=1.15-4.67) compared to the Far North, and calves sampled in the middle compared to the early calving period (OR=1.24; 95% CI=1.03-1.51). CONCLUSION On the farms visited FPT was diagnosed in one third of dairy calves. Calf-level risk factors for FPT included age of dam, health status of calf, region, and time of the calving period. Further investigations are required to establish why these are associated with increased odds of FPT. CLINICAL RELEVANCE These results provide a baseline for benchmarking, which, alongside the reported calf-level risk factors, can be used by veterinarians to improve colostrum management.

Heart Failure and MEF2 Transcriptome Dynamics in Response to ß-Blockers.

Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of ß-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without ß-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 "sensor" mouse model (6 weeks) was followed by four weeks of ß-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed. AT treatment resulted in an overall improvement in cardiac function of TAC mice and repression of MEF2 activity. RNA-seq identified 65 differentially expressed genes (DEGs) due to TAC treatment with enriched GO clusters including the inflammatory system, cell migration and apoptosis. These genes were mapped against DEGs in cardiomyocytes in which MEF2A expression was suppressed. Of the 65 TAC mediated DEGs, AT reversed the expression of 28 mRNAs. Rarres2 was identified as a novel MEF2 target gene that is upregulated with TAC in vivo and isoproterenol treatment in vitro which may have implications in cardiomyocyte apoptosis and hypertrophy. These studies identify a cohort of genes with vast potential for disease diagnosis and therapeutic intervention in heart failure.

Case study: failure of superior capsular reconstruction using dermal allograft.

Superior capsular reconstruction (SCR) is a novel technique for treating irreparable rotator cuff tears in younger patients in whom a reverse total shoulder arthroplasty is not the optimal treatment choice. This case study describes a middle-aged male with a recurrent, massive, irreparable rotator cuff tear treated with SCR that subsequently failed at the glenoid attachment. The patient underwent successful arthroscopic revision of the SCR. The case illustrates the MRI and arthroscopic correlations of the failed dermal allograft reconstruction, which to our knowledge has not been previously shown in the radiology literature.

Sibling recurrence of total anomalous pulmonary venous drainage.

Many childhood syndromic disorders are associated with congenital heart defects, but few present specifically with total anomalous pulmonary venous drainage (TAPVD). Here, we report two siblings presenting with TAPVD, tracheo-oesophageal fistula and dysmorphic features in the neonatal period. Careful examination of the mother revealed subtle facial asymmetry and a pre-auricular tag, suggesting a potential variable expression of a dominant disorder. Whole exome sequencing identified a pathogenic heterozygous mutation in EFTUD2, a gene, normally associated with mandibulofacial dystosis Guion-Almedia type (MFDGA), in both siblings and the mother. This is the first report of TAPVD occurring as part of the MFDGA phenotype. It serves to highlight the importance of modern sequencing panels in identifying causative mutations for heterogeneous syndromes such as MFDGA and familial congenital heart defects whilst emphasising the relevance of variable expression when counselling parents.