An acute case of Pimelea elongata toxicity in cattle in western New South Wales.

In May 2019, 96 cattle died from Pimelea toxicity in a period of 19 days after potential exposure, with the first deaths occurring within 5 days. After examining the circumstances, we suspect that several factors contributed to the deaths. These included that recently purchased stock and transported had access to flooded land containing Pimelea elongata. This weed species contains simplexin and 18 other compounds. Roots, flowers and seeds are significantly more toxic than the stem, branches and leaves. We suspect that thirsty and hungry stock consumed seed and roots from flooded pastures and consumed lethal doses of simplexin. Blood tests were not good indicators of the conditions. Management strategies are suggested.

Non-Invasive Positive airway Pressure thErapy to Reduce Postoperative Lung complications following Upper abdominal Surgery (NIPPER PLUS): a pilot randomised control trial.

OBJECTIVES: Postoperative pulmonary complications (PPCs) are a common serious complication following upper abdominal surgery. Postoperatively, physiotherapy-led non-invasive ventilation (NIV) may be a promising method to reduce PPC incidence. The objectives of this pilot trial were to examine preliminary effectiveness, feasibility and safety of additional intermittent physiotherapy-led NIV compared to continuous high-flow nasal cannula oxygen therapy (HFNC) alone. DESIGN: Single-centre, assessor-blinded, parallel-group, pilot randomised control trial. SETTING: Primary-referral hospital in Australia. PARTICIPANTS: 130 high-risk patients undergoing upper abdominal surgery. INTERVENTIONS: Continuous HFNC for 48-hours following surgical extubation, or HFNC plus five 30-minute physiotherapy-led NIV sessions. OUTCOMES: PPC incidence, trial feasibility and safety. RESULTS: PPC incidence was similar between groups (HFNC alone 12/65 (18%) vs HFNC plus NIV 10/64 (16%) adjusted HR 0.95; 95% CI 0.40-2.29). Delivery of HFNC as per-protocol was achieved in 81% (n = 105) of all participants. Physiotherapy-led NIV initiated within four-hours of surgical extubation was achieved in 81% (n = 52) of intervention group participants, with a mean 4.2 (SD 1.3) total number of NIV sessions delivered in the first two postoperative days. NIV was delivered as per-protocol in 52% of this cohort. Two episodes of severe hypotension during NIV requiring medical intervention were reported. CONCLUSION: Delivery of continuous HFNC was feasible. Delivery of NIV within four-hours of extubation was achieved and delivered safely with< 1% adverse events. The planned NIV intervention of five sessions within two postoperative days was not feasible. The results of this pilot study have informed the decision not to proceed to a fully powered trial. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au ACTRN12617000269336. CONTRIBUTION OF THE PAPER.

Biomarker testing in oncology - Requirements for organizing external quality assessment programs to improve the performance of laboratory testing: revision of an expert opinion paper on behalf of IQNPath ABSL.

In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers.

A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle.

KEY POINTS: We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet.

Psychological wellbeing and use of alcohol and recreational drugs: results of the British HIV Association (BHIVA) national audit 2017.

OBJECTIVES: The aim of this national audit was to assess adherence of services providing HIV care in the UK to national standards and guidelines regarding psychological support and the assessment of alcohol and recreational drug use (including chemsex drugs) in people living with HIV (PLWH). METHODS: Participating sites completed a survey of their services' care pathways relating to psychological support and substance use. They performed a case-note review of up to 40 adult PLWH per service, reviewing sociodemographic and clinical information and assessment of psychological wellbeing, drug use and alcohol use. The surveys and case notes were assessed against relevant British HIV Association (BHIVA) guidelines and standards. RESULTS: The survey was completed by 112 services. Of these, 73%, 82% and 73% had formal annual processes for assessing the psychological wellbeing, alcohol use and drug use, respectively, of PLWH. Case-note data were provided for 4486 PLWH from 119 sites. Audited rates of assessment of PLWH were 66.0% for psychological wellbeing, 68.0% for alcohol use, 58.4% for recreational drug use and 16.8% for chemsex drug use. Variation between clinical services was wide, with ranges from < 10% to 100% routinely assessing PLWH for each of these domains. Services using assessment tools performed better. CONCLUSIONS: Assessment of PLWH for psychological wellbeing and alcohol and recreational drug use is variable in UK clinics, with a significant minority of services not documenting that they assessed these factors routinely. Wider adoption of assessment tools or proformas to assess PLWH in these areas is likely to improve surveillance for psychological morbidity and problematic alcohol or drug use.

Associations between nutritional energy delivery, bioimpedance spectroscopy and functional outcomes in survivors of critical illness.

BACKGROUND: Patients who survive critical illness frequently develop muscle weakness that can impact on quality of life; nutrition is potentially a modifiable risk factor. The present study aimed to explore the associations between cumulative energy deficits (using indirect calorimetry and estimated requirements), nutritional and functional outcomes. METHODS: A prospective single-centre observational study of 60 intensive care unit (ICU) patients, who were mechanically ventilated for at least 48 h, was conducted. Cumulative energy deficit was determined from artificial nutrition delivery compared to targets. Measurements included: (i) at recruitment and ICU discharge, weight, fat-free mass (bioimpedance spectroscopy) and malnutrition (Subjective Global Assessment score B/C); (ii) at awakening and ICU discharge, physical function (Physical Function in Intensive Care Test-scored) and muscle strength (Medical Research Council sum-score (MRC-SS). ICU-acquired weakness was defined as a MRC-SS score of less than 48/60. RESULTS: The median (interquartile range) cumulative energy deficit compared to the estimated targets up to ICU day 12 was 3648 (2514-5650) kcal. Adjusting for body mass index, age and severity of illness, cumulative energy deficit (per 1000 kcal) was independently associated with greater odds of ICU-acquired weakness [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.4-3.3, P = 0.001] and malnutrition (OR = 1.9, 95% CI = 1.1-3.2, P = 0.02). In similar multivariable linear models, cumulative energy deficit was associated with reductions in fat-free mass (-1.3 kg; 95% CI = -2.4 to -0.2, P = 0.02) and physical function scores (-0.6 points; 95% CI = -0.9 to -0.3, P = 0.001). CONCLUSIONS: Cumulative energy deficit from artificial nutrition support was associated with reduced functional outcomes and greater loss of fat-free mass in ventilated ICU patients.

Implementing routine blood-borne virus testing for HCV, HBV and HIV at a London Emergency Department - uncovering the iceberg?

UK guidelines recommend routine HIV testing in high prevalence emergency departments (ED) and targeted testing for HBV and HCV. The 'Going Viral' campaign implemented opt-out blood-borne virus (BBV) testing in adults in a high prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current engagement in care, and severity of disease was established. LTC was defined as patient informed plus ⩾1 clinic visit. A total of 6211/24 981 ED attendees were tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%) required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged). 16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients requiring LTC had advanced disease (CD4 1, Fibroscan F3/F4 or liver cancer), including five with AIDS-defining conditions and three hepatocellular carcinomas. There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV patients. ED testing was valuable as one-third of those requiring LTC (new, disengaged or unknown status patients) had advanced disease.

Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case-control study.

OBJECTIVE: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). DESIGN: Case-control. SETTING: Three tertiary-care centres across the USA. POPULATION: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. METHODS: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P). MAIN OUTCOME MEASURES: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction). CONCLUSION: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P. TWEETABLE ABSTRACT: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment.

Sonographic evaluation of diaphragmatic function during breathing control.

OBJECTIVE: To investigate the effect of "breathing control" on sonographic diaphragmatic excursion. METHOD: A prospective, randomized, assessor-blinded study design involving 20 physiotherapy students; ten with knowledge of the breathing control technique (Group BC) and ten without (Group CON). All participants were asked to perform a Chester step test. Group BC performed BC, while Group CON adopted their own breathing pattern during recovery after the step test. Respiratory rate and sonographic parameters of the diaphragm including diaphragmatic excursion, speed of diaphragmatic contraction (slope of contraction), and inspiratory time were recorded before and after the step test. RESULTS: All baseline data were similar for both groups except age. Respiratory rate at 1 min post-step test was higher in Group CON (24.6±4.9 bpm) compared to Group BC (15.6 ± 3.8 bpm) (p < 0.001). Post-step test sonographic evaluation demonstrated an increase in diaphragmatic excursion with a significant time and group interaction (F(4,72) = 5.499, p = 0.005). Post hoc analysis revealed that the diaphragmatic excursion was significantly higher in Group BC compared to Group CON at first, second and third minute post-step test. Time and group interactions were not significant in inspiration time (F(4,72) = 2.459, p = 0.082) nor the slope of contraction (F(4,72) = 0.655, p = 0.582)]. CONCLUSION: Post-exercise diaphragmatic excursion was higher in participants applying BC. Non-invasive ultrasonography is able to promote objective evaluation of the relationship between breathing techniques and diaphragmatic function.

Panic symptoms in transient loss of consciousness: Frequency and diagnostic value in psychogenic nonepileptic seizures, epilepsy and syncope.

PURPOSE: Previous studies suggest that ictal panic symptoms are common in patients with psychogenic nonepileptic seizures (PNES). This study investigates the frequency of panic symptoms in PNES and if panic symptoms, just before or during episodes, can help distinguish PNES from the other common causes of transient loss of consciousness (TLOC), syncope and epilepsy. METHODS: Patients with secure diagnoses of PNES (n=98), epilepsy (n=95) and syncope (n=100) were identified using clinical databases from three United Kingdom hospitals. Patients self-reported the frequency with which they experienced seven symptoms of panic disorder in association with their episodes. A composite panic symptom score was calculated on the basis of the frequency of symptoms. RESULTS: 8.2% of patients with PNES reported "never" experiencing any of the seven panic symptoms in their episodes of TLOC. Patients with PNES reported more frequent panic symptoms in their attacks than those with epilepsy (p<0.001) or syncope (p<0.001), however, patients with PNES were more likely "rarely" or "never" to report five of the seven-ictal panic symptoms than "frequently" or "always" (45-69% versus 13-29%). A receiver operating characteristic analysis demonstrated that the composite panic symptom score distinguished patients with PNES from the other groups (sensitivity 71.1%, specificity 71.2%), but not epilepsy from syncope. CONCLUSIONS: Patients with PNES report TLOC associated panic symptoms more commonly than those with epilepsy or syncope. Although panic symptoms are reported infrequently by most patients with PNES, a composite symptom score may contribute to the differentiation between PNES and the other two common causes of TLOC.

On compression and damage evolution in two thermoplastics.

The well-known Taylor cylinder impact test, which follows the impact of a flat-ended cylindrical rod onto a rigid stationary anvil, is conducted over a range of impact speeds for two polymers, polytetrafluoroethylene (PTFE) and polyetheretherketone (PEEK). In previous work, experiments and a model were developed to capture the deformation behaviour of the cylinder after impact. These works showed a region in which spatial and temporal variation of both longitudinal and radial deformation provided evidence of changes in phase within the material. In this further series of experiments, this region is imaged in a range of impacted targets at the Diamond synchrotron. Further techniques were fielded to resolve compressed regions within the recovered polymer cylinders that showed a fracture zone in the impact region. The combination of macroscopic high-speed photography and three-dimensional X-ray imaging has identified the development of failure with these polymers and shown that there is no abrupt transition in behaviours but rather a continuous range of responses to competing operating mechanisms. The behaviours noted in PEEK in these polymers show critical gaps in understanding of polymer high strain-rate response.

Dynamic damage in carbon-fibre composites.

The Taylor test is used to determine damage evolution in carbon-fibre composites across a range of strain rates. The hierarchy of damage across the scales is key in determining the suite of operating mechanisms and high-speed diagnostics are used to determine states during dynamic loading. Experiments record the test response as a function of the orientation of the cylinder cut from the engineered multi-ply composite with high-speed photography and post-mortem target examination. The ensuing damage occurs during the shock compression phase but three other tensile loading modes operate during the test and these are explored. Experiment has shown that ply orientations respond to two components of release; longitudinal and radial as well as the hoop stresses generated in inelastic flow at the impact surface. The test is a discriminant not only of damage thresholds but of local failure modes and their kinetics. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'.

Analysis of changes in maternal circulating angiogenic factors throughout pregnancy for the prediction of preeclampsia.

OBJECTIVE: To assess whether changes in maternal angiogenic factors throughout pregnancy predict the development of preeclampsia. STUDY DESIGN: Placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 receptor (sFlt-1) were measured in 2355 women at 10, 18, 26 and 35 weeks gestation. Receiver operator characteristic analysis was used to calculate test characteristics for changes in analytes between time points. Linear mixed-effects models generated slopes of analytes throughout pregnancy, which in turn were used as predictors in adjusted logistic regression models. RESULT: Changes in analytes yielded positive predictive values of 9 to 19% and negative predictive values of 93 to 97%. Individuals with lowest quartile slopes in PlGF had sixfold greater odds (95% confidence interval (CI): 3.5, 10.2) of preeclampsia compared with individuals in the highest quartile. With respect to sFlt-1, the highest quartile had 5.1 times greater odds (95% CI: 3.1, 8.4) than the lowest quartile. CONCLUSION: Measuring the trend in PlGF and sFlt-1 across pregnancy segregates women at increased risk of preeclampsia. However, changes in these factors throughout pregnancy lack clinically useful predictive power.

Deterioration in physical activity and function differs according to treatment type in non-small cell lung cancer - future directions for physiotherapy management.

OBJECTIVES: To investigate in non-surgically and surgically treated non-small cell lung cancer (NSCLC): (1) changes in physical activity, function, health-related quality of life (HRQoL) and symptoms after diagnosis; and (2) the association between physical activity and outcomes. DESIGN: Prospective observational study. SETTING: Three acute tertiary hospitals. PARTICIPANTS: Sixty-nine individuals (43 male, median [IQR] age 68 [61 to 74] years) with stage I-IV NSCLC. MAIN OUTCOME MEASURES: The primary outcome (Physical Activity Scale for the Elderly) and secondary outcome (six-minute walk test and questionnaires assessing HRQoL, function, symptoms, mood) were measured at diagnosis (pre-treatment), and eight to ten weeks post-diagnosis (post-operative and/or during chemotherapy/radiotherapy). RESULTS: Individuals treated surgically (n=27) experienced a deterioration in physical activity levels (baseline median [IQR]=74 [51 to 135]; follow-up median [IQR]=29 [24 to 73]; median difference=45, effect size=0.3). At follow-up physical activity was inversely related to depression, pain and appetite loss (rho>0.5, p<0.05). In contrast non-surgical individuals (n=42) did not experience a change in physical activity, however did experience deterioration in function, functional capacity, global HRQoL, fatigue and dyspnoea. Physical activity levels were low in this group and at follow-up the strongest relationships with physical activity levels were global HRQoL, function, fatigue and mood (inverse, rho>0.5, p<0.05). CONCLUSIONS: Surgically treated individuals experienced a reduction in physical activity levels after diagnosis, which was not seen in the non-surgical group. Lower physical activity levels were associated with poorer outcomes, particularly in non-surgically treated individuals. Further research is required to establish the optimal intervention to improve physical activity levels in these cohorts.

Macrosomia has its roots in early placental development.

INTRODUCTION: We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. METHODS: We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). RESULTS: The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). CONCLUSIONS: Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development.

A survey of the management of transient loss of consciousness in the emergency department.

UNLABELLED: Transient loss of consciousness (TLoC) is a common presentation to the emergency department (ED). We sought to evaluate current practice in the management of patients with TLoC presenting to a large, city centre ED, against national standards. METHODS: The ED admissions database was searched to identify all patients attending with TLoC during October 2012. The clinical record of the attendance was reviewed to determine if the initial assessment met national standards. RESULTS: Ninety-one patients had a primary presentation with TLoC, representing 0.95% of ED attendances. Documentation of before/during/after the clinical event and clinical examination were done well. Notable aspects done less well included lying and standing blood pressure and recording of driving status. No patient was discharged from the ED with a copy of their 12-lead electrocardiogram (ECG). Sixty-five patients (71%) were discharged from the ED, with follow-up arranged for 11 (16%). Additional follow-up would have been appropriate in a further 15 cases (28%). CONCLUSION: Several aspects of the initial assessment of TLoC were done well. Areas for improvement include driving status documentation and advice, recording of postural blood pressures and ECG provision on discharge.