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The incompressibility constraint for fluid flow was imposed by Lagrange in the so-called Lagrangian variable description using his method of multipliers in the Lagrangian (variational) formulation. An alternative is the imposition of incompressibility in the Eulerian variable description by a generalization of Dirac’s constraint method using noncanonical Poisson brackets. Here it is shown how to impose the incompressibility constraint using Dirac’s method in terms of both the canonical Poisson brackets in the Lagrangian variable description and the noncanonical Poisson brackets in the Eulerian description, allowing for the advection of density. Both cases give the dynamics of infinite-dimensional geodesic flow on the group of volume preserving diffeomorphisms and explicit expressions for this dynamics in terms of the constraints and original variables is given. Because Lagrangian and Eulerian conservation laws are not identical, comparison of the various methods is made.
The European Prediction of Psychosis Study (EPOS) aimed to study a large sample of young patients who are at risk of psychosis and to estimate their conversion rate to psychosis during 18 months follow-up. This presentation describes quality of life and its changes in patients at risk of psychosis.
In six European centres, 16 to 35 year old psychiatric patients were examined. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Quality of life (QoL), measured by the Modular System for Quality of Life, was assessed at baseline and at 9 and 18 months’ follow-ups. Psychiatric patients without prodromal symptoms and healthy subjects were comparison groups.
In all, 245 risk patients were included. At baseline, they reported lower QoL than non-risk patients and healthy controls. Basic symptoms associated negatively with QoL, and there were differences between the study centres. During the follow-up, QoL raised less in risk patients than in non-risk patients. Baseline QoL did not predict transition to psychosis. However, its development was poorer in patients with than in those without transition to psychosis.
Those of the psychiatric patients who are at risk of psychosis have lower QoL than other psychiatric patients or healthy controls. QoL does not predict transition to psychosis, but its changes correlates with changes in clinical state. The results indicate that there is a need for comprehensive intervention with the patients at risk of psychosis.
Both schizophrenia and ultra high risk (UHR) patients show reduced neurocognitive performance compared to matched healthy control subjects. In the current study we compared neurocognitive performance at baseline and follow up between UHR patients who made the transition to psychosis and patients who did not.
Patients were eligible for the study when they met criteria for one or more of the following groups: Attenuated symptoms or brief limited intermitted psychotic symptoms or a first degree family member with a psychotic disorder and reduced functioning or basic symptoms. We assessed 216 UHR patients (166 males, mean age: 22,6 SD 5,2) with a neuropsychological test battery composed of the National adult reading test (premorbid IQ), California verbal memory test (verbal memory), spatial working memory test, verbal fluency first letter and categories (executive functioning), finger tapping test (motor speed) and continuous performance test (sustained attention). Data were collected in 7 participating centres of EPOS. Follow up was at 9 months.
37 UHR patients made the transition to psychosis (25 males, mean age 21,5 SD 4,8). The only test that showed a significant difference between the transition and non transition group at baseline was verbal fluency categories (t= 2.79, p = 0.006).
Patients who later make the transition to psychosis perform significantly worse on verbal fluency categories than patients who do not make the transition to psychosis. Verbal fluency may contribute to an improved prediction of psychosis in UHR patients. Follow up results will also be presented.
The European Prediction of Psychosis Study (EPOS) involved a large (n=245) sample of young individuals at high-risk of developing psychosis. Participants appraisals of criticism and emotional over-involvement were described employing the Level of Expressed Emotion (LEE) measure. This presentation explores results and implications over an 18 month follow-up period.
Across six European centres, n=245 patients aged 16 – 35 years and ascertained to be at high-risk of developing psychosis were assessed over a period of eighteen months. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Appraisals of familial expressed emotion from participants towards key family members were examined for relationships to risk of transition to psychosis, psychotic symptomatology and demographical data.
Individuals at high-risk of psychosis were included and compared on the five sub-scales of LEE. Levels of Criticism, Irritability, Intrusiveness and Lack of emotional support were examined with significant correlations found between patient-perceived intrusive over-involvement and depression as well as between sub-scales of LEE and positive symptoms of psychosis. Transition to psychosis was not predicted by LEE in participants.
Perceived LEE of significant others by individuals at high-risk of developing psychosis may have a role in the maintenance of both affective and positive psychotic symptoms prior to the onset of full psychosis. Further explorations of the impact of EE appraisal on developing psychotic symptoms may inform potential targets for therapeutic intervention in both at-risk individuals and family members.
One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.
245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.
In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.
Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
Emergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.
Two critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.
The novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.
Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations.
HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response. Prehosp Disaster Med. 2018;33(6):668–672.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
Hamiltonian extended magnetohydrodynamics (XMHD) is restricted to respect helical symmetry by reducing the Poisson bracket for the three-dimensional dynamics to a helically symmetric one, as an extension of the previous study for translationally symmetric XMHD (Kaltsas et al., Phys. Plasmas, vol. 24, 2017, 092504). Four families of Casimir invariants are obtained directly from the symmetric Poisson bracket and they are used to construct Energy–Casimir variational principles for deriving generalized XMHD equilibrium equations with arbitrary macroscopic flows. The system is then cast into the form of Grad–Shafranov–Bernoulli equilibrium equations. The axisymmetric and the translationally symmetric formulations can be retrieved as geometric reductions of the helically symmetric one. As special cases, the derivation of the corresponding equilibrium equations for incompressible plasmas is discussed and the helically symmetric equilibrium equations for the Hall MHD system are obtained upon neglecting electron inertia. An example of an incompressible double-Beltrami equilibrium is presented in connection with a magnetic configuration having non-planar helical magnetic axis.
Problems of particle dynamics involving unsteady Stokes flows in confined geometries are typically harder to solve than their steady counterparts. Approximation techniques are often the only resort. Felderhof (see e.g. J. Phys. Chem. B, vol. 109 (45), 2005, pp. 21406–21412; J. Fluid Mech., vol. 637, 2009, pp. 285–303) has developed a point-particle approximation framework to solve such problems, especially in the context of Brownian motion. Despite excellent agreement with past experiments, this framework produces unsteady drag coefficients that depend on particle density. This is inconsistent, since the problem can be formulated mathematically without any reference to the particle’s density. We address this inconsistency in our work. Upon implementing our modifications, the framework passes consistency checks that it previously failed. Further, it is not obvious that such an approximation should work for short-time-scale motion. We investigate its validity by deriving it from a general formalism based on integral equations through a series of systematic approximations. We also compare results from the point-particle framework against a calculation performed using the method of reflections, for the specific case of a sphere near a full-slip plane boundary. We find from our analysis that the reasons for the success of the point-particle approximation are subtle and have to do with the nature of the unsteady Oseen tensor. Finally, we provide numerical predictions for Brownian motion near a full-slip and a no-slip plane wall based on the point-particle approximation as used by Felderhof, our modified point-particle approximation and the method of reflections. We show that our modifications to Felderhof’s framework would become significant for systems of metallic nanoparticles in liquids.
The Vlasov–Maxwell equations possess a Hamiltonian structure expressed in terms of a Hamiltonian functional and a functional bracket. In the present paper, the transformation (‘lift’) of the Vlasov–Maxwell bracket induced by the dynamical reduction of single-particle dynamics is investigated when the reduction is carried out by Lie-transform perturbation methods. The ultimate goal of this work is to provide an explicit pathway to the Hamiltonian formulations for the guiding-centre and gyrokinetic Vlasov–Maxwell equations, which have found important applications in our understanding of turbulent magnetized plasmas. Here, it is shown that the general form of the reduced Vlasov–Maxwell equations possesses a Hamiltonian structure defined in terms of a reduced Hamiltonian functional and a reduced bracket that automatically satisfies the standard bracket properties.
Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.
This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.
SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.
Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.
Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow’s milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45–2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42–0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51–0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.
Mathematical models are important tools to estimate nutritional requirements and animal growth. Very few calf models generated from other countries with different feeding programs, environment and production systems have been evaluated. The objective of this paper is to evaluate two calf models: (i) the National Research Council (NRC) in 2001 and (ii) the updates published by Van Amburgh and Drackley in 2005 and inputted into Agricultural Modeling and Training Systems (AMTS, version 3.5.8). Data from 16 previous studies involving 51 diets for dairy calves under tropical conditions (n=485 calves, initial BW 37.5±4.35 kg and weaning weight of 62.0±10.16 kg) were used. The calves were fed with whole milk, milk replacer or fermented colostrum, plus starter (20.9±1.78% of CP). The accuracy of the average daily gain (ADG) prediction was evaluated by mean bias, mean square prediction error (MSPE), concordance correlation coefficient, bias correction factor (Cb), and regression between the observed and predicted values. The ADG observed from birth to weaning was 0.452±0.121 kg/day. Calves fed with whole milk had greater ADG compared with calves fed milk replacer (0.477 v. 0.379 kg/day) during the milk-feeding period. When all data were pooled (n=51 diets), predictions had a mean bias of −0.019 and 0.068 kg/day for energy-allowable gain using NRC and AMTS models, respectively. The regression equation between observed and predicted values obtained from energy of diets showed an intercept different from zero (P<0.0001) and slope that differed from unity (P<0.0001). In a second evaluation, when calves were fed only milk replacer, the energy-allowable gain from AMTS showed the lowest mean bias (0.008 kg/day) and 82.1% of the MSPE value originated from random errors. The lowest MSPE, the higher Cb value and no significant slope bias (P>0.05) indicate that the AMTS growth model resulted in accurate predictions for calves fed with milk replacer. However, within these latter two approaches, the goodness of fit (R2) was low, representing low precision. The weight gain estimated by the energy available from the diet was overestimated by 19 g/day when calculated by the NRC and underestimated by 68 g/day when calculated by AMTS. The reasons for this discrepancy need to be understood, for only then new models could be developed and parameterized to estimate animal performance in tropical conditions more accurately and precisely.
A recent editorial claimed that the 2014 National Institute for Health and Care Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent 2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased towards psychosocial treatments and against drug treatments. In this paper we underline that the NICE and SIGN guidelines recommend similar interventions, but that the NICE guideline has more rigorous methodology. Our analysis suggests that the authors of the editorial appear to have succumbed to bias themselves.
We conducted a program of research to derive and test the reliability of a clinical prediction rule to identify high-risk older adults using paramedics’ observations.
We developed the Paramedics assessing Elders at Risk of Independence Loss (PERIL) checklist of 43 yes or no questions, including the Identifying Seniors at Risk (ISAR) tool items. We trained 1,185 paramedics from three Ontario services to use this checklist, and assessed inter-observer reliability in a convenience sample. The primary outcome, return to the ED, hospitalization, or death within one month was assessed using provincial databases. We derived a prediction rule using multivariable logistic regression.
We enrolled 1,065 subjects, of which 764 (71.7%) had complete data. Inter-observer reliability was good or excellent for 40/43 questions. We derived a four-item rule: 1) “Problems in the home contributing to adverse outcomes?” (OR 1.43); 2) “Called 911 in the last 30 days?” (OR 1.72); 3) male (OR 1.38) and 4) lacks social support (OR 1.4). The PERIL rule performed better than a proxy measure of clinical judgment (AUC 0.62 vs. 0.56, p=0.02) and adherence was better for PERIL than for ISAR.
The four-item PERIL rule has good inter-observer reliability and adherence, and had advantages compared to a proxy measure of clinical judgment. The ISAR is an acceptable alternative, but adherence may be lower. If future research validates the PERIL rule, it could be used by emergency physicians and paramedic services to target preventative interventions for seniors identified as high-risk.
Offenders with an intellectual disability pose a major challenge to Intellectual Disability Service providers in the Republic of Ireland. This is especially so as no national Forensic Intellectual Disability Service currently exists.
The Forensic Intellectual Disability Working Group of the Irish College of Psychiatrists was established in order to take steps to address this issue by establishing the level of need for a Forensic Intellectual Disability Service in Ireland and developing a college position paper.
No previous study has been carried out to measure offending behaviour amongst persons with an intellectual disability attending mental health services in Ireland.
A postal survey was undertaken targeting the lead clinicians of all Intellectual Disability Psychiatry, General Adult Psychiatry and Forensic Psychiatry Services in the Republic of Ireland. This survey requested anonymous data regarding service users with an intellectual disability and offending behaviour in this population.
Data relating to 431 service users was returned. Those reported to engage in offending behaviour were predominantly young males. Assault was the most common offence type. A significant number of serious offences such as unlawful killing, sexual assault and arson were reported.
There is an urgent need for the development of a Forensic Intellectual Disability Service in the Republic of Ireland. The current efforts of the National Forensic Mental Health Service to establish such a service by the creation of a post of Consultant Forensic Psychiatrist (special interest in intellectual disability) are to be welcomed.