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Correct diagnosis of cause of death is necessary to suggest the most effective management interventions to reduce perinatal lamb mortality. Haemorrhage on the surface of the brain has been used as a field diagnostic tool to allocate lambs to a cause of death category, but the usefulness of this method was unclear. This study aimed to evaluate whether gross pathology was related to neuronal death and whether haemorrhage of the central nervous system (CNS) was distinct between differing causes of death, enabling indicators to be used in field diagnoses. Lambs dying from natural causes (n = 64) and from euthanasia (n = 7) underwent postmortem examination, then the brain and spinal cord were extracted and examined histologically. Histological changes consistent with neuronal death were not detected in any lamb. Haemorrhage of the meninges and/or parenchyma of the CNS occurred in all lambs. The age of the haemorrhage indicated that it occurred near the time of death in most lambs. Dilation of blood vessels varied in severity but appeared to be unrelated to causal diagnosis, severity of subcutaneous oedema, breathing or milk status. Moderate or severe dilation of blood vessels and haemorrhage of the CNS did not occur in all lambs with alternative clear indicators of dystocia and occurred in all death classifications, so it could not be used as diagnostic indicators for classification of cause of death. Dilation and haemorrhage were unrelated to neuronal damage and may have been artefactual. In conclusion, haemorrhage of the CNS was not indicative of neuronal damage and could not be used to distinguish between lambs with clear indicators of differing causes of death, so it is not recommended as a field diagnostic tool.
Although lignin has been negatively correlated with neutral-detergent fibre (NDF) digestibility (NDFD) in ruminants and used to predict potential extent of NDF digestion of forages, selection of an analysis, Klason lignin (KL) or acid-detergent lignin (ADL), to describe that the nutritionally relevant lignin has not been resolved. Dismissed as an artifact is the difference between KL and ADL (ΔL). A question is whether ΔL influences NDFD. We evaluated the relationships of ΔL, KL and ADL with NDFD in order to determine the nutritionally homogeneous or heterogeneous nature of KL. Data sets from two laboratories (DS1 and DS2) were used that included ADL, KL and in vitro NDFD at 48 h (NDFD48). DS1 contained seven C3 grasses, seventeen C4 maize forages and nineteen alfalfas, and DS2 had fifteen C3 grasses, eight C4 forages and six alfalfas. Mean ΔL was greater than ADL in C3 and C4 samples and less in alfalfas. Within forage type and laboratory, ΔL was not correlated with NDFD48 (r −0·34–0·49; all P > 0·17). ADL was more consistently correlated with NDFD48 (r −0·47–−0·95; P < 0·01–0·21) than with KL (r 0·03–−0·91; P < 0·01–0·94). ΔL as a proportion of KL was correlated with NDFD48 in C3 and C4 samples (r 0·44–0·76; P < 0·01–0·08). The differing behaviours of ΔL and ADL relative to NDFD48 indicate that KL is a nutritionally heterogeneous fraction, the behaviour of which may vary by forage type and ratios of ADL and ΔL present.
Prolactin (PRL) data from adolescents treated with olanzapine are presented.
Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.
Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.
Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.
The changes in metabolic parameters in olanzapine-treated adolescents were examined.
Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.
Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).
Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.
With one in ten young people being affected by ill mental health and stigma regularly cited as a factor affecting access to early intervention services, focussing resources on school based stigma reduction strategies seems prudent. ‘Headucate’, a student society, designed a 50 minute workshop which aims to increase mental health literacy and decrease stigma.
Repeated, cross sectional surveys were carried out at three time points; 1) immediately before (n=77), 2) Immediately after (n=81) and 3) three months post workshop (n=73). The surveys were paper based versions of the Reported Intended Behaviours Score (RIBS) and Mental Health Knowledge Scale (MAKS) utilising a social distance scale.
Four year 10 classed (pupils aged 14-15) were recruited. Post hoc t-tests were carried out when one-way ANOVAS were significant.
Disorder knowledge (from MAKS) and intended contact (from RIBS) significantly increased between time points one and two (p<0.01 and <0.004 respectively) but then decreased.
Analysis of the question pertaining to knowing where to access help showed a statistically significant increase (p<0.001) between time points one and two and then a decrease at time three, albeit to a higher value than at time point one (3.45 compared to 3.13, P=0.088).
Headucate workshops offer a low resource option which is well accepted by students. Like other school based stigma reduction strategies, a dramatic increase was seen between immediately before and after indicating that the workshop resonates with the pupils, but there was little sustained change in attitudes.
Against a backdrop of poor mental health education in UK schools a group of students from Norwich Medical School have formed a student society called ‘Headucate’ in order to create, deliver and evaluate an educational intervention for adolescents, initially to be delivered in Norfolk schools.
To create an educational intervention that:
Is the length of a standard lesson
Is age appropriate and acceptable
Contains appropriate signposting
Contains content that challenges common myths and replaces them with knowledge
Contains content that encourages empathy and understanding towards those with mental illnesses
Is easily delivered in the same way each time so that its effectiveness can be evaluated
To create an intervention effective at tackling stigma and empowering adolescents to recognise signs of poor mental health and access services appropriately.
Lesson plan created after consultation with psychiatrists, a psychologist, a GP, a university outreach professional, a teacher and secondary school age children, then trialled and revised.
Interactive workshop produced with 5 sections.
1) Myth vs Fact activity that dispels prevalent myths
2) Scenario based activity to demonstrate that mental health is a spectrum
3) An interactive presentation covering the most common mental illnesses and their symptoms
4) An activity focusing on talking to those with mental illnesses, furthering the scenario from the previous activity
5) A question and answer session. Every student leaves with a leaflet containing appropriate signposting.
We have created an educational intervention ready to be delivered and evaluated.
GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).
To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.
To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).
Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.
Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.
GXR was effective and well tolerated in children and adolescents with ADHD.
Placebo-adjusted difference in LS mean change from baseline in ADHD-RS-IV total score (95% Cl, p-value; effect size)
−8.9 (−11.9, −5.8, p<0.001; 0.76)
−3.8 (−6.8, −0.7, p<0.05; 0.32)
Difference in improvement from placebo for CGI-I (95% Cl, p-value)
23.7% (11.1, 36.4; p<0.001)
12.1% (−0.9, 25.1; p<0.05)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; learning and school domain score (95%CI, p-value; effect size)
−0.22 (−0.36, −0.08, p<0.01; 0.42)
−0.16 (−0.31, −0.02, p<0.05; 0.32)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; family domain score (95%CI, p-value; effect size)
Mental health education is not compulsory in the UK therefore adolescents have very varied experiences despite half of people with mental health illnesses reporting having experienced symptoms by 14 years old. University students are ideal for delivering a relaxed, educational intervention aimed at this age group, providing an opportunity to for them to learn necessary tools for recognising signs of poor mental health and tackle associated stigma.
To expand Headucate's membership, including other disciplines within the University of East Anglia (UEA) and provide core training enabling members to deliver a school-based educational intervention
Recruitment of members has been a multifaceted approach utilising social media sites such as Facebook and the Headucate website, and oncampus events and ‘awareness campaigns’ including several successful evening talks and lectures.
Three training sessions, which include ‘Introduction to Mental Health’, ‘Workshop run-through’ and ‘Child Protection’, have been developed for all members wishing to partake in the delivery of workshops.
We have recruited approximately 300 members since summer 2012; 70 fully paid members in 2012/13 academic year and currently 45 paid members for 2013/14.
A total of 18 members are fully trained and ready to deliver workshops within schools and 17 other members have just one training session remaining.
We are looking forward to delivering our first workshops in October and building on a successful first year. We are confident we can provide workshops for approximately 600 children per year.
The symptoms of many mental illnesses often begin during high school. Interventions to improve mental health awareness amongst adolescents may lead to improved outcomes. in the UK unfortunately many schools do not fulfil this need and mental health education is not a compulsory part of the curriculum.
To develop and measure the effectiveness of and educational intervention designed to raise awareness and empower adolescents to recognise signs of poor mental health and access services appropriately.
Evaluate the effectiveness of the intervention through baseline and follow up surveys.
Students at Norwich Medical School collaborated with teachers, psychiatrists and general practitioners to design an educational intervention that aims to tackle stigma and raise awareness of mental health conditions among 13-14 year olds in the hope that they can access services when needed, support those around them and look after their mental health. To evaluate effectiveness of the intervention, a knowledge, attitudes and practices survey that utilises a social distance scale that has been adapted for this age group and will be used to gather baseline and follow up data after six months.
We have developed a one-hour educational intervention delivered by medical students, that uses a variety of teaching techniques to raise awareness of mental health issues. We will start implementation in January 2013 so will have baseline effectiveness results shortly after.
Headucate has the potential to fill an important gap in effectively raising awareness of mental health issues in schools.
GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children.
To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial.
To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145).
Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs.
Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis.
GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.
In this commentary, we offer an additional function of rationalization. Namely, in certain social contexts, the proximal and ultimate function of beliefs and desires is social inclusion. In such contexts, rationalization often facilitates distortion of rather than approximation to truth. Understanding the role of social identity is not only timely and important, but also critical to fully understand the function(s) of rationalization.
Despite the global significance of the Leach’s Storm-petrel Hydrobates leucorhous colony on Baccalieu Island, Newfoundland and Labrador, Canada, the estimate of 3.36 million breeding pairs reported for 1984 by Sklepkovych and Montevecchi stands as the single published population estimate for the world’s largest colony. This study increases knowledge of this population by analysing data from additional independent surveys conducted in 1984 and 1985, and by updating the population status with a survey conducted in 2013. Population estimates were derived by extrapolating occupied burrow densities to the estimated occupied area of four main habitat types (heath, forest, grass and fern), which in turn were based on proportions of habitats observed in plots (1984 and 1985) or by using a Geographic Information System approach (2013). Based on these surveys, the Leach’s Storm-petrel breeding population size on Baccalieu Island was estimated at 5.12 ± 0.73 (SE) and 4.60 ± 0.42 (SE) million pairs in 1984 and 1985 respectively, representing estimates 37–51% greater than the original 1984 survey. While discrepancies among these estimates were largely driven by the way occupied areas were estimated, our study confirms that Baccalieu Island hosts the largest Leach’s Storm-petrel colony in the world. Results from the 2013 survey estimate the current breeding Leach’s Storm-petrel population at 1.95 ± 0.14 (SE) million pairs, representing a 42% decline over 29 years (-1.4% per year), relative to the original published estimate of 3.36 ± 0.12 (SE) million pairs. The most prominent change has occurred in the density of storm-petrel burrows found in forest habitat which dropped by 70% despite forest remaining the second most abundant habitat available to nesting storm-petrels on Baccalieu Island. The cause of this decline remains unknown and is likely multi-faceted. Future research focusing on demographic studies is required to understand what is driving the population decline of this internationally important colony.
Negative interactions between people and large carnivores are common and will probably increase as the human population and livestock production continue to expand. Livestock predation by wild carnivores can significantly affect the livelihoods of farmers, resulting in retaliatory killings and subsequent conflicts between local communities and conservationists. A better understanding of livestock predation patterns could help guide measures to improve both human relationships and coexistence with carnivores. Environmental variables can influence the intensity of livestock predation, are relatively easy to monitor, and could potentially provide a useful predictive framework for targeting mitigation. We chose lion predation of livestock as a model to test whether variations in environmental conditions trigger changes in predation. Analysing 6 years of incident reports for Pandamatenga village in Botswana, an area of high human–lion conflict, we used generalized linear models to show that significantly more attacks coincided with lower moonlight levels and temperatures, and attack severity increased significantly with extreme minimum temperatures. Furthermore, we found a delayed effect of rainfall: lower rainfall was followed by a significantly increased severity of attacks in the following month. Our results suggest that preventative measures, such as introducing deterrents or changing livestock management, could be implemented adaptively based on environmental conditions. This could be a starting point for investigating similar effects in other large carnivores, to reduce livestock attacks and work towards wider human–wildlife coexistence.
The likelihood that Palaeolithic artisans sometimes used natural objects as models for their image-making has long been suggested, yet well-contextualized and stratified examples have remained rare. This study examines a series of natural and fabricated items from the Natufian settlement of Wadi Hammeh 27 in Jordan (12,000–12,500 cal. bc) to propose that the site occupants collected a variety of found objects such as fossils, unusually shaped stones and animal bones, which they utilized as templates in the production of geometric art pieces. Natural and fabricated objects were woven into complex schemes of relation by Natufian artisans. Existing patterns were copied and applied to a variety of representational images. Found objects were sometimes subtly modified, whereas at other times they were transformed into finished artefacts. The scute pattern on the tortoise carapace, in particular, appears to have formed the basis of important ritual beliefs across the Natufian culture area. At Wadi Hammeh 27, it was evoked in various media and at various scales to form interrelating tableaux of representation.
In the autumn of 2018, an outbreak of cryptosporidiosis affected adult employees from the same company in Western Norway. The organism was Cryptosporidium parvum, GP60 subtype IIaA14G1R1. All those infected had drunk from the same container of self-pressed apple juice. Incubation period (1 week) and clinical signs were similar among those infected, although some experienced a more prolonged duration of symptoms (up to 2–3 weeks) than others. The infections resulted after consumption from only one of 40 containers of juice and not from any of the other containers. It seems that although Cryptosporidium oocysts were detected in a sample from another container, the contamination did not affect the whole batch. This is perhaps indicative of a restricted contamination event, either from contaminated ground in the orchard, or during collection of the fruit, or during processing. Although outbreaks of food-borne cryptosporidiosis have previously been associated with consumption of contaminated apple juice, most of the more recent outbreaks of food-borne cryptosporidiosis have been associated with salad vegetables or herbs. This outbreak, the first outside USA reported to be associated with apple juice, is a timely reminder that such juice is a suitable transmission vehicle for Cryptosporidium oocysts, and that appropriate hygienic measures are essential in the production of such juice, including artisanal (non-commercial) production.
Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)