119 research outputs found
Measuring the viscous flow behaviour of molten metals under shear
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The flow behaviour of liquid metals (Sn, Pb and Sn-Pb eutectic) under different shearing conditions is investigated. Experiments were performed with two designs of concentric cylinder viscometers: rotating the inner cylinder (Searle) and rotating the outer cylinder (Couette). The latter technique is uncommon and the equipment was optimised with standard oils. The flow behaviour for the metals differs in the two systems. The curves of “apparent” viscosity versus shear rate may be divided into two regimes: I. At lower shear rates (<200 s-1): a reduction of “apparent” viscosity with shear was observed with both viscometers. It is suggested that the high density and high surface tension of the metals and eccentricity between the cylinders at low shear rates, leads to instabilities. Results at low shear rates were therefore discarded and further detailed analysis would be required for a fuller understanding of this behaviour. II. At higher shear rates: a steady, shear-independent behaviour of “apparent” viscosity with shear rate is observed in the Couette system (upto 600 s-1) whereas in the Searle system the “apparent” viscosity increases with shear rate (upto 2600 s-1). From hydrodynamic theory about Newtonian fluids, it is suggested that in the Searle type viscometer, the fluid is unstable and Taylor vortices are expected at low shear rates (~80 s-1). This gives rise to an increase in the “apparent” viscosity with shear rate. Whereas, in the Couette type, the flow is more stable, resulting in a steady “apparent” viscosity. This interpretation is consistent with liquid metals behaving as Newtonian fluids, but further research is required to confirm this. The author suggests further experiments, with the prime one being the investigation of the fluid with counter and co-rotation of the cylinders in order to observe more complex flows. The results are expected to have implications in the modelling of flow for liquid metal processes, especially the initiation of Taylor vortices under the unstable flow conditions produced by rotating the inner cylinder
Comparative efficacy and acceptability of pharmacological treatments for insomnia in adults: a systematic review and network meta-analysis
No full textThis is the protocol for a review and there is no abstract. The objectives are as follows: 1) To compare individual pharmacological treatments for insomnia in adults in terms of: efficacy, measured as self-rated quality of sleep or satisfaction with sleep; and acceptability of treatment. 2) To generate a clinically-useful hierarchy of available pharmacological treatments for insomnia in adults, according to their efficacy and acceptability
Serotonin receptor mechanisms in anti-depressant action
No full textBibliography: leaves 221-270.Serotonin neurones have been implicated in the pathophysiology and treatment of clinical depression to a greater degree than any other neurotransmitter. Additionally, serotonin pathways may playa role in the pathophysiology and treatment of eating disorders, anxiety states and schizophrenia. Molecular biological studies have confirmed pharmacological evidence suggesting the existence of multiple serotonin receptor subtypes and the genes for these receptors, as well as that of the serotonin transporter, have common polymorphic variants. To investigate the effect of repeated treatment with selective serotonin fe-uptake inhibitors (SSRI's) on the function of central 5-HT2C receptors. To assess the effect of polymorphic variation in the 5-HT2c receptor and serotonin transporter on functional responses to selective pharmacological challenge. To determine whether polymorphic variation in the 5-HT receptor and serotonin transporter influence the clinical response of patients with major depression to treatment with serotonergic antidepressants. To assess the effect of repeated treatment with selective serotonin re-uptake inhibitors (SSRI's) on the function of central 5-HT2c receptors I used the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP) as a 5-HT2c probe in a neuroendocrine challenge paradigm. I used the same approach to assess whether polymorphic variation in the 5-HT2c receptor (serine vs cysteine substitution) was associated with differences in functional response to 5-HT2C receptor challenge. I then studied whether polymorphic variation in the serotonin transporter promotor region (long versus short form) was associated with differing functional responses to acute challenge with clomipramine, a tricyclic antidepressant with a high affinity for the serotonin transporter. Finally, I studied whether either of these polymorphic variants influenced the clinical response of patients with major depression to treatment with SSRI's and clomipramine. SSRI treatment significantly lowered the sensitivity of 5-HT2c receptors as predicted from animal experimental studies. However polymorphic variation in the 5-HTzc receptor did not significantly influence functional responses to m-CPP challenge. In contrast polymorphic variation in the serotonin transporter was associated with differing neuroendocrine responses to acute clomipramine challenge with greater prolactin release being seen in subjects with the long polymorphic variant. Neither the 5-HTzc nor the transporter polymorphisms correlated with clinical response to SSRI and clomipramine treatment in patients with major depression. The ability of SSRI's to produce a functional down-regulation of 5-HTzc receptors may be relevant to certain of their therapeutic effects. Polymorphic variation in the 5-HT2c receptor (serine vs cysteine) seems unlikely to explain functional differences in responses to 5-HTzc receptor challenge or antidepressant responses to SSRI treatment. In contrast variation in the serotonin transporter promotor is associated with differing functional responses to acute serotonin re-uptake blockade. However, this did not correlate with clinical response to longer-term SSRI treatment
Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
No full textBACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre
Influence of ultrasonic melt treatment on the formation of primary intermetallics and related grain refinement in aluminum alloys
No full textThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited - The article can also be accessed from the link below - Copyright @ 2011 SpringerUltrasonic melt treatment (UST) is known to induce grain refining in aluminum alloys. Previous studies have clearly shown that in Al-Zr-Ti alloys, the primary Al(3)Zr intermetallics were dramatically refined by cavitation-assisted fragmentation, and a good refinement effect was achieved. In this article, Al-Ti, Al-Ti-Zr alloys, and some commercial aluminum alloys are used to analyze the effect of UST on primary intermetallics and grain refinement. The addition of a small amount of Al-3Ti-B master alloy is also studied in order to compare with the addition of Ti and Zr in commercial aluminum alloys. Experimental results show that the ultrasonic grain refining effect is not only related to the size of particles which are refined and/or dispersed by UST, but also related to an undercooling available for activation of these particles in the solidification process. Athermal heterogeneous nucleation theory is considered to explain the effect of size and distribution of substrate particles on the grain structure with different undercoolings. The distribution of primary particle sizes results in the distribution of required undercoolings. Grain refining occurs when the undercooling is large enough to activate the refined primary intermetallics or dispersed inoculants.This study is supported by the Materials Innovation Institute and China Scholarship Counci
Street slang and schizophrenia
No full textWe report the case of a 26 year old streetwise young postman who presented with a six month history of reduced occupational and social function, low mood, and lack of motivation. He complained of feeling less sociable and less interested in his friends and of being clumsy and finding it harder to think. He was otherwise fit and healthy, with no physical abnormalities, neurological signs, or objective cognitive impairments. There was no history of a recent stressor that might have precipitated his symptoms. He was referred to a specialist service for patients in the prodromal phase of psychotic illness for further assessment after he had seen his general practitioner and the local community mental health team. The differential diagnosis at this stage was depression, the prodrome of schizophrenia, or no formal clinical disorder.
His premorbid occupational and social function had been good. There was no history of abnormal . social, language, and motor development and he left school with two A levels. After three years of service at the post office he had been promoted to a supervisory role. He had a good relationship with his family and had six or so good friends. There has been a number of previous heterosexual relationships, although none in the past year. Aside from smoking cannabis on two occasions when he was 19, there was no history of illicit substance use.
Detailed and repeated assessment of his mental state found a normal affect, no delusions, hallucinations, or catatonia, and no cognitive dysfunction. His speech, however, was peppered with what seemed (to his middle class and older psychiatrist) to be an unusual use of words, although he said they were street slang (table).Go It was thus unclear whether he was displaying subtle signs of formal thought disorder (manifest as disorganised speech, including the use of unusual words or phrases, and neologisms) or using a "street" argot. This was a crucial diagnostic distinction as thought disorder is a feature of psychotic illnesses and can indicate a diagnosis of schizophrenia.
We sought to verify his explanations using an online dictionary of slang (urbandictionary.com). To our surprise, many of the words he used were listed and the definitions accorded with those he gave (see table). We further investigated whether his speech showed evidence of thought disorder by examining recordings of his speech as he described a series of ambiguous pictures from the thematic apperception test, a procedure that elicits thought disordered speech. His speech was transcribed and rated with the thought and language index, a standardised scale for assessing thought disorder. Slang used in a linguistically appropriate way is not scored as abnormal on this scale. His score was 5.25, primarily reflecting a mild loosening of associations. For example, he described a picture of a boat on a lake thus: "There’s a boat and a tree. There seems to be a reflection. There are no beds, and I wonder why there are no beds. There’s a breeze going through the branches of the tree."
His score was outside the normal range (mean for normal controls 0.88, SD 1.15) and indicates subtle thought disorder, equivalent to that evident in remitted patients with schizophrenia (mean in remitted patients 3.89, SD 2.56) but lower than that in patients with formal thought disorder (mean 27.4, SD 8.3).
Over the following year his social and occupational functioning deteriorated further, and he developed frank formal thought disorder as well as grandiose and persecutory delusions to the extent that he met DSM-IV criteria for schizophrenia. His speech was assessed as before, and the thought and language index score had increased to 11.75. This mainly reflected abnormalities on items comprising "positive" thought disorder, particularly the use of neologisms such as "chronocolising" and non-sequiturs.
To our knowledge this is the first case report to describe difficulties in distinguishing "street" argots from formal thought disorder. It is perhaps not surprising that slang can complicate the assessment of disorganised speech as psychotic illnesses usually develop in young adults, whereas the assessing clinician is often from an older generation (and different sociocultural background) less familiar with contemporary urban slang. Online resources offer a means of distinguishing street argot from neologisms or a peculiar use of words, and linguistic rating scales may be a useful adjunct to clinical assessment when thought disorder is subtle. Differentiating thought disorder from slang can be especially difficult in the context of "prodromal" signs of psychosis, when speech abnormalities, if present, are usually subtle. Nevertheless, accurate speech assessment is important as subtle thought disorder can, as in this case, predate the subsequent onset of schizophrenia, and early detection and treatment of psychosis might be associated with a better long term clinical outcome
Presynaptic dopaminergic function in schizophrenia: a Positron Emission Tomographic [18F]Fluorodopa study
No full textContext: The dopamine overactivity hypothesis of schizophrenia remains one of the most influential theories of the pathophysiology of the illness. Radiotracer brain imaging studies are now directly testing aspects of the overactivity hypothesis.
Objective: To assess presynaptic dopaminergic function in a large cohort of patients with schizophrenia by means of [18F]fluorodopa uptake and a high-sensitivity 3-dimensional positron emission tomograph. We predicted elevations in striatal [18F]fluorodopa uptake and reductions in prefrontal cortical [18F]fluorodopa uptake in patients with schizophrenia.
Design: Case-control study.
Setting Research institute investigation recruiting hospital outpatients.
Patients Sixteen male medicated hospital outpatients with a DSM-IV diagnosis of schizophrenia (mean age, 38 years) and 12 age-matched male volunteers free of psychiatric and neurologic illness.
Intervention [18F]fluorodopa positron emission tomographic scanning.
Main Outcome Measure [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses.
Results Statistical parametric mapping (P<.05 corrected) and region-of-interest analyses (P<.01) showed increased [18F]fluorodopa uptake, confined primarily to the ventral striatum in patients with schizophrenia. No reductions in prefrontal cortical [18F]fluorodopa uptake Ki were seen in the statistical parametric mapping and region-of-interest analyses, although dorsal anterior cingulate [18F]fluorodopa Ki correlated with performance on the Stroop Color-Word Test in both groups.
Conclusions As in studies in unmedicated patients, presynaptic striatal dopamine dysfunction is present in medicated schizophrenic patients, adding further in vivo support for dopamine overactivity in the illness
Feudi ecclesiastici e pontifici nel Milanese in età spagnola
No full textL’Autore affronta il problema della identificazione dei feudi pontifici nello Stato di Milano partendo dalla loro incerta genesi altomedievale, per chiarire le ragioni di una rivendicazione la cui legittimità in età moderna appare ambigua. Ne aiuta la comprensione la lettura fatta dal senatore milanese Carlo Maria Maggi in occasione della ricognizione del 1678 richiesta da Madrid. Di qui la riflessione sulle ragioni che ne hanno determinato la rivendicazione per una loro sopravvivenza all’interno dei giochi politici tra Madrid, il Papato e i ve-scovi, nonché nell’ambito conflittuale fra giurisdizioni e poteri locali.The Author examines the problem of pontifical fiefs identification in the Mil-anese starting from their uncertain origin in the early Middle Ages, with the aim of explaining the reasons of this unclear legitimacy claim in the early modern period. The Author focuses on Senator Carlo Maria Maggi’s report re-quested by Madrid in 1678, that helps to understand why these fiefs were claimed in the context of the political contest between Spain, the Papacy and the bishops
Parents’ attitude to education of children in Children's and Youth Sports School
No full textPurpose: to determine the attitudes of parents of young athletes to the educational process in youth. Objectives: to identify the expectations of the respondents in relation to the objectives, factors, key actors of the educational process. Material: parents (n = 22) pupils youth (Zaporozhye). Results : the main objectives of the educational process, parents believe their children purchasing habits for a healthy lifestyle. Just acquisition of skills necessary for socialization. Important goals are the recovery teaching loads and providing meaningful leisure activities for children. Found that the majority of parents are not supported targets educational process to achieve a higher athletic performance. As a result of the factors influencing the educational process called parents of the young athlete communication with the coach and team. Just overcoming their child difficulties encountered in training and competitions. Revealed that parents do not consider the planned educational activities effective factor in the educational process. Conclusions: from the educational process in the Youth parents expect improved health and assist in the socialization of children. Achieving these goals is associated with effective educational work of coaches, sports team influence, through their own efforts of the young athlete
- …
