Psychosurgery: A History from Prefrontal Lobotomy to Deep Brain Stimulation

Neurosurgical treatment for psychiatric disorders features a long and controversial history. This article explores a ‘spectrum of psychosurgery,’ describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day, mainstream scientific deep brain stimulation (DBS). We focus on the rise, fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy, which evoked stern criticism from both public and professionals, through to the development of modern day DBS - performed for patients suffering from severe, treatment resistant symptoms of obsessive-compulsive disorder (OCD), epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities, whilst simultaneously challenging any public/professional preconceptions of psychosurgery, which may indirectly be obstructing patient care.Additionally, we carried out a qualitative survey displayed in WordCloud Format, capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust, on ‘psychosurgery,’ ‘prefrontal lobotomy’ and ‘DBS’, which may well reflect wider public opinion.In summary, the article provides a brief, yet comprehensive overview of the controversial history of psychosurgery, present-day practice, and future trends of neurosurgery for psychiatric disorders

Senescence in dahlia flowers is regulated by a complex interplay between flower age and floret position

Mechanisms regulating flower senescence are not fully understood in any species and are particularly complex in composite flowers. Dahlia (Dahlia pinnata Cav.) florets develop sequentially, hence each composite flower head includes florets of different developmental stages as the whole flower head ages. Moreover, the wide range of available cultivars enables assessment of intraspecific variation. Transcriptomes were compared amongst inner (younger) and outer (older) florets of two flower head ages to assess the effect of floret vs. flower head ageing. More gene expression, including ethylene and cytokinin pathway expression changed between inner and outer florets of older flower heads than between inner florets of younger and older flower heads. Additionally, based on Arabidopsis network analysis, different patterns of co-expressed ethylene response genes were elicited. This suggests that changes occur in young inner florets as the whole flower head ages that are different to ageing florets within a flower head. In some species floral senescence is orchestrated by the plant growth regulator ethylene. However, there is both inter and intra-species variation in its importance. There is a lack of conclusive data regarding ethylene sensitivity in dahlia. Speed of senescence progression, effects of ethylene signalling perturbation, and patterns of ethylene biosynthesis gene expression differed across three dahlia cultivars (‘Sylvia’, ‘Karma Prospero’ and ‘Onesta’) suggesting differences in the role of ethylene in their floral senescence, while effects of exogenous cytokinin were less cultivar-specific

SDSS-IV MaNGA: the spatial distribution of star formation and its dependence on mass, structure, and environment

We study the spatially resolved star formation of 1494 galaxies in the SDSS-IV MaNGA Survey. Star formation rates (SFRs) are calculated using a two-step process, using H α in star-forming regions and Dn4000 in regions identified as active galactic nucleus/low-ionization (nuclear) emission region [AGN/LI(N)ER] or lineless. The roles of secular and environmental quenching processes are investigated by studying the dependence of the radial profiles of specific star formation rate on stellar mass, galaxy structure, and environment. We report on the existence of ‘centrally suppressed’ galaxies, which have suppressed Specific Star Formation Rate (SSFR) in their cores compared to their discs. The profiles of centrally suppressed and unsuppressed galaxies are distributed in a bimodal way. Galaxies with high stellar mass and core velocity dispersion are found to be much more likely to be centrally suppressed than low-mass galaxies, and we show that this is related to morphology and the presence of AGN/LI(N)ER like emission. Centrally suppressed galaxies also display lower star formation at all radii compared to unsuppressed galaxies. The profiles of central and satellite galaxies are also compared, and we find that satellite galaxies experience lower specific star formation rates at all radii than central galaxies. This uniform suppression could be a signal of the stripping of hot halo gas in the process known as strangulation. We find that satellites are not more likely to be suppressed in their cores than centrals, indicating that the core suppression is an entirely internal process. We find no correlation between the local environment density and the profiles of star formation rate surface density

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd

Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades

From Wiley via Jisc Publications RouterHistory: received 2021-03-17, rev-recd 2021-04-12, pub-electronic 2021-05-19Article version: VoRPublication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/ L013762/1, BB/M027791/1, BB/M02903411, BB/ M028836/1Funder: H2020 European Research Council; Grant(s): 788231-ProgrES-ERC-2017-ADGAbstract: A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out multistep cascades in a controlled and selective way. As biocatalytic cascades get more complex, reactions become unattainable under typical batch conditions. Here a number of continuous flow systems were used to overcome batch incompatibility, thus allowing for successful biocatalytic cascades. As proof‐of‐principle, reactive carbonyl intermediates were generated in situ using alcohol oxidases, then passed directly to a series of packed‐bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade via an oxidase/transaminase/imine reductase sequence, introducing different amine reagents at each step without cross‐reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product 4O‐methylnorbelladine

Science Programs for a 2 m-class Telescope at Dome C, Antarctica: PILOT, the Pathfinder for an International Large Optical Telescope

The cold, dry and stable air above the summits of the Antarctic plateau provides the best ground-based observing conditions from optical to sub-mm wavelengths to be found on the Earth. PILOT is a proposed 2 m telescope, to be built at Dome C in Antarctica, able to exploit these conditions for conducting astronomy at optical and infrared wavelengths. While PILOT is intended as a pathfinder towards the construction of future grand-design facilities, it will also be able to undertake a range of fundamental science investigations in its own right. This paper provides the performance specifications for PILOT, including its instrumentation. It then describes the kinds of science projects that it could best conduct. These range from planetary science to the search for other solar systems, from star formation within the Galaxy to the star formation history of the Universe, and from gravitational lensing caused by exo-planets to that produced by the cosmic web of dark matter. PILOT would be particularly powerful for wide-field imaging at infrared wavelengths, achieving near-diffraction limited performance with simple tip-tilt wavefront correction. PILOT would also be capable of near-diffraction limited performance in the optical wavebands, as well be able to open new wavebands for regular ground based observation; in the mid-IR from 17 to 40 microns and in the sub-mm at 200 microns.Comment: 74 pages, 14 figures, PASA, in pres

Storage of halved strawberry fruits affects aroma, phytochemical content and gene expression, and is affected by pre-harvest factors

Introduction: Strawberry fruit are highly valued for their aroma which develops during ripening. However, they have a short shelf-life. Low temperature storage is routinely used to extend shelf-life for transport and storage in the supply chain, however cold storage can also affect fruit aroma. Some fruit continue to ripen during chilled storage; however, strawberries are a non-climacteric fruit and hence ripening postharvest is limited. Although most strawberry fruit is sold whole, halved fruit is also used in ready to eat fresh fruit salads which are of increasing consumer demand and pose additional challenges to fresh fruit storage. Methods: To better understand the effects of cold storage, volatilomic and transcriptomic analyses were applied to halved Fragaria x ananassa cv. Elsanta fruit stored at 4 or 8°C for up to 12 days over two growing seasons. Results and discussion: The volatile organic compound (VOC) profile differed between 4 or 8°C on most days of storage. Major differences were detected between the two different years of harvest indicating that aroma change at harvest and during storage is highly dependent on environmental factors during growth. The major component of the aroma profile in both years was esters. Over 3000 genes changed in expression over 5 days of storage at 8°C in transcriptome analysis. Overall, phenylpropanoid metabolism, which may also affect VOCs, and starch metabolism were the most significantly affected pathways. Genes involved in autophagy were also differentially expressed. Expression of genes from 43 different transcription factor (TF) families changed in expression: mostly they were down-regulated but NAC and WRKY family genes were mainly up-regulated. Given the high ester representation amongst VOCs, the down-regulation of an alcohol acyl transferase (AAT) during storage is significant. A total of 113 differentially expressed genes were co-regulated with the AAT gene, including seven TFs. These may be potential AAT regulators

Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity

Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent

Identifying Unique Neighborhood Characteristics to Guide Health Planning for Stroke and Heart Attack: Fuzzy Cluster and Discriminant Analyses Approaches

Socioeconomic, demographic, and geographic factors are known determinants of stroke and myocardial infarction (MI) risk. Clustering of these factors in neighborhoods needs to be taken into consideration during planning, prioritization and implementation of health programs intended to reduce disparities. Given the complex and multidimensional nature of these factors, multivariate methods are needed to identify neighborhood clusters of these determinants so as to better understand the unique neighborhood profiles. This information is critical for evidence-based health planning and service provision. Therefore, this study used a robust multivariate approach to classify neighborhoods and identify their socio-demographic characteristics so as to provide information for evidence-based neighborhood health planning for stroke and MI.The study was performed in East Tennessee Appalachia, an area with one of the highest stroke and MI risks in USA. Robust principal component analysis was performed on neighborhood (census tract) socioeconomic and demographic characteristics, obtained from the US Census, to reduce the dimensionality and influence of outliers in the data. Fuzzy cluster analysis was used to classify neighborhoods into Peer Neighborhoods (PNs) based on their socioeconomic and demographic characteristics. Nearest neighbor discriminant analysis and decision trees were used to validate PNs and determine the characteristics important for discrimination. Stroke and MI mortality risks were compared across PNs. Four distinct PNs were identified and their unique characteristics and potential health needs described. The highest risk of stroke and MI mortality tended to occur in less affluent PNs located in urban areas, while the suburban most affluent PNs had the lowest risk.Implementation of this multivariate strategy provides health planners useful information to better understand and effectively plan for the unique neighborhood health needs and is important in guiding resource allocation, service provision, and policy decisions to address neighborhood health disparities and improve population health