Identification of a Command Neuron Directing the Expression of Feeding Behavior in \u3cem\u3eDrosophila melanogaster\u3c/em\u3e: A Dissertation

Feeding is one of the most important behaviors for an animal’s survival. At a gross level, it is known that the nervous system plays a major role in the expression of this complex behavior, yet a detailed understanding of the neural circuits directing feeding behavior remains unknown. Here we identify a command neuron in Drosophila melanogaster whose artificial activation, using dTrpA1, a heat-activated cation channel, induces the appearance of complete feeding behavior. We use behavioral, genetic, cellular and optical imaging techniques to show that the induced behavior is composed of multiple motor programs and can function to uptake exogenous, even noxious, material. Furthermore, we resolve the neuron’s location to the subesophageal ganglion, characterize its pre and post-synaptic sites, and determine its responsiveness to sucrose stimulation. Interestingly, the neuron’s dendritic field is proximal to sweet sensing axon terminals and its baseline activity corresponds to the fly’s satiation state, suggesting a potential point of integration between sensory, motor and motivational systems. The identification of a command neuron for feeding in a genetically tractable organism provides a useful model to develop a deeper understanding of the neural control of this ubiquitous and evolutionarily ancient behavior

Antipsychotic medication side effects knowledge amongst registered mental health nurses in England: A national survey

© 2020 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd What is known on the subject?: Research findings indicate the percentage of knowledge-related errors in medicines management is high, accounting for approximately 75% of all errors, with insufficient knowledge levels one of the most significant contributors of medication errors. Patients should be able to trust nurses to engage therapeutically and actively listen to their needs and concerns, responding using skills that are helpful, providing information that is clear, accurate, meaningful and free from jargon. However, without knowledge of pharmacology, it is impossible for nurses to be able to provide adequate advice. What the paper adds to the existing knowledge?: This study has examined an area that had not yet been systematically examined previously, which draws together previous research findings on mental health nurses' knowledge of adverse events, including side effects and medication errors, related to antipsychotic medication within NHS inpatient settings. What are the implications for practice?: A recent study has found that almost three-quarters (73%) of patients taking antipsychotic medication reported side effects to some degree. This high number of people experiencing antipsychotic medication side effects is likely to compromise care, especially in situations where nurses have inadequate knowledge of side effects and are unable to provide effective advice to patients. The findings from this study allow the mental health nursing profession an opportunity to reflect on the best means to increase knowledge and increase patient safety awareness and benefits for mental health service users. Abstract: Introduction Antipsychotic medications play a significant role in the treatment and recovery of people with several psychiatric disorders. However, research findings indicate mental health nurses are insufficiently knowledgeable about antipsychotic medication side effects. Aim To assess practising mental health nurses' knowledge of antipsychotic medication side effects using a Multiple-Choice Questionnaire (MCQ) across National Health Service (NHS) Trusts in England. Hypothesis Knowledge of antipsychotic medication side effects amongst registered mental health nurses is related to their academic qualification, clinical banding and length of experience. Method A national survey of registered mental health nurses was carried out using an online questionnaire which was disseminated by Research and Development departments. Results A total of 504 questionnaires were returned, 245 of which had full data and further analysed. The mean score for the sample was 14.4 and only 21 participants attained a mark of >80%. Implications for Practice Two out of three of our hypotheses (that length of experience and clinical banding are directly related to knowledge of antipsychotic medication side effects) were supported. Our study found many nurses have a suboptimal working knowledge of antipsychotic medication side effects which has the potential to compromise care. Strategies need to be put in place to enhance pharmacology knowledge

A Large-Scale Behavioral Screen to Identify Neurons Controlling Motor Programs in the Drosophila Brain

Drosophila is increasingly used for understanding the neural basis of behavior through genetically targeted manipulation of specific neurons. The primary approach in this regard has relied on the suppression of neuronal activity. Here, we report the results of a novel approach to find and characterize neural circuits by expressing neuronal activators to stimulate subsets of neurons to induce behavior. Classical electrophysiological studies demonstrated that stimulation of command neurons could activate neural circuits to trigger fixed action patterns. Our method was designed to find such command neurons for diverse behaviors by screening flies in which random subsets of brain cells were activated. We took advantage of the large collection of Gal4 lines from the NP project and crossed 835 Gal4 strains with relatively limited Gal4 expression in the brain to flies carrying a UAS transgene encoding TRPM8, a cold-sensitive ion channel. Low temperatures opened the TRPM8 channel in Gal4-expressing cells, leading to their excitation, and in many cases induced overt behavioral changes in adult flies. Paralysis was reproducibly observed in the progeny of crosses with 84 lines, whereas more specific behaviors were induced with 24 other lines. Stimulation performed using the heat-activated channel, TrpA1, resulted in clearer and more robust behaviors, including flight, feeding, and egg-laying. Through follow-up studies starting from this screen, we expect to find key components of the neural circuits underlying specific behaviors, thus providing a new avenue for their functional analysis.National Institute of Mental Health (U.S.) (Grant MH85958)Worcester Foundation for Biomedical ResearchJapan Society for the Promotion of Science (grant-in-aid)National Institute of Mental Health (U.S.) (Intramural Research Program

Antipsychotic medication side effects knowledge amongst registered mental health nurses in England: A National Survey

Introduction Antipsychotic medications play a significant role in the treatment and recovery of people with several psychiatric disorders. However, research findings indicate mental health nurses are insufficiently knowledgeable about antipsychotic medication side effects. Aim To assess practising mental health nurses’ knowledge of antipsychotic medication side effects using a Multiple‐Choice Questionnaire (MCQ) across National Health Service (NHS) Trusts in England. Hypothesis Knowledge of antipsychotic medication side effects amongst registered mental health nurses is related to their academic qualification, clinical banding and length of experience. Method A national survey of registered mental health nurses was carried out using an online questionnaire which was disseminated by Research and Development departments. Results 504 questionnaires were returned, 245 of which had full data and further analysed. The mean score for the sample was 14.4 and only 21 participants attained a mark of >80%. Implications for Practice Two out of three of our hypotheses (that length of experience and clinical banding are directly related to knowledge of antipsychotic medication side effects) were supported. Our study found many nurses have a suboptimal working knowledge of antipsychotic medication side effects which has the potential to compromise care. Strategies need to be put in place to enhance pharmacology knowledge

Energy and time resolution for a LYSO matrix prototype of the Mu2e experiment

We have measured the performances of a LYSO crystal matrix prototype tested with electron and photon beams in the energy range 60$-$450 MeV. This study has been carried out to determine the achievable energy and time resolutions for the calorimeter of the Mu2e experiment.Comment: 2 pages, 3 figures, 13th Pisa Meeting on Advanced Detector

Quantitative analysis of high-resolution, contrast-enhanced, cone-beam CT for the detection of intracranial in-stent hyperplasia

BACKGROUND: Intracranial in-stent hyperplasia is a stroke-associated complication that requires routine surveillance. OBJECTIVE: To compare the results of in vivo experiments to determine the accuracy and precision of in-stent hyperplasia measurements obtained with modified C-arm contrast-enhanced, cone-beam CT (CE-CBCT) imaging with those obtained by \u27gold standard\u27 histomorphometry. Additionally, to carry out clinical analyses comparing this CE-CBCT protocol with digital subtraction angiography (DSA). METHODS: A non-binned CE-CBCT protocol (VasoCT) was used that acquires x-ray images with a small field-of-view and applies a full-scale reconstruction algorithm providing high-resolution three-dimensional (3D) imaging with 100 microm isotropic voxels. In an vivo porcine model, VasoCT cross-sectional area measurements were compared with gold standard vessel histology. VasoCT and DSA were used to calculate in-stent stenosis in 23 imaging studies. RESULTS: Porcine VasoCT cross-sectional stent, lumen, and in-stent hyperplasia areas strongly correlated with histological measurements (r(2)=0.97, 0.93, 0.90; slope=1.14, 1.07, and 0.76, respectively; p\u3c0.0001). Clinical VasoCT percentage stenosis correlated well with DSA percentage stenosis (r(2)=0.84; slope=0.76), and the two techniques were free of consistent bias (Bland-Altman, bias=3.29%; 95% CI -14.75% to 21.33%). An illustrative clinical case demonstrated the advantages of VasoCT, including 3D capability and non-invasive IV contrast administration, for detection of in-stent hyperplasia. CONCLUSIONS: C-arm VasoCT is a high-resolution 3D capable imaging technique that has been validated in an animal model for measurement of in-stent tissue growth. Successful clinical implementation of the protocol was performed in a small case series. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Evaluation of Load-To-Strength Ratios in Metastatic Vertebrae and Comparison With Age- and Sex-Matched Healthy Individuals.

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines' predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal-Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically

IODP workshop: developing scientific drilling proposals for the Argentina Passive Volcanic Continental Margin (APVCM) – basin evolution, deep biosphere, hydrates, sediment dynamics and ocean evolution

The Argentine margin contains important sedimentological, paleontological and chemical records of regional and local tectonic evolution, sea level, climate evolution and ocean circulation since the opening of the South Atlantic in the Late Jurassic–Early Cretaceous as well as the present-day results of post-depositional chemical and biological alteration. Despite its important location, which underlies the exchange of southern- and northern-sourced water masses, the Argentine margin has not been investigated in detail using scientific drilling techniques, perhaps because the margin has the reputation of being erosional. However, a number of papers published since 2009 have reported new high-resolution and/or multichannel seismic surveys, often combined with multi-beam bathymetric data, which show the common occurrence of layered sediments and prominent sediment drifts on the Argentine and adjacent Uruguayan margins. There has also been significant progress in studying the climatic records in surficial and near-surface sediments recovered in sediment cores from the Argentine margin. Encouraged by these recent results, our 3.5-day IODP (International Ocean Discovery Program) workshop in Buenos Aires (8–11 September 2015) focused on opportunities for scientific drilling on the Atlantic margin of Argentina, which lies beneath a key portion of the global ocean conveyor belt of thermohaline circulation. Significant opportunities exist to study the tectonic evolution, paleoceanography and stratigraphy, sedimentology, and biosphere and geochemistry of this margin.Facultad de Ciencias Naturales y Muse

Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage – a Randomized Placebo-Controlled Trial to assess Safety, Tolerability and Feasibility

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos \u3e5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusions: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences

Characterization of a prototype for the electromagnetic calorimeter of the Mu2e experiment

The Mu2e experiment at Fermilab searches the neutrinoless conversion of the muon into electron in the field of an Aluminum nucleus. The observation of this process would be a proof of the Charged Lepton Flavor Violation (CLFV). In case of no observation, the upper limit will be set to Rμe < 6×10−17 @ 90% CL, improving by a factor of 4 the previous best determination. The Mu2e detector apparatus consists of a straw tubes tracker that will measure the electrons momentum, and an electromagnetic calorimeter that provides a tracking-independent measurement of the electron energy, time and position. In this paper, we describe the baseline project of the EMC and present results in terms of performances and R&D