Joint EANM/SNMMI guideline on radiomics in nuclear medicine : Jointly supported by the EANM Physics Committee and the SNMMI Physics, Instrumentation and Data Sciences Council.

PURPOSE: The purpose of this guideline is to provide comprehensive information on best practices for robust radiomics analyses for both hand-crafted and deep learning-based approaches. METHODS: In a cooperative effort between the EANM and SNMMI, we agreed upon current best practices and recommendations for relevant aspects of radiomics analyses, including study design, quality assurance, data collection, impact of acquisition and reconstruction, detection and segmentation, feature standardization and implementation, as well as appropriate modelling schemes, model evaluation, and interpretation. We also offer an outlook for future perspectives. CONCLUSION: Radiomics is a very quickly evolving field of research. The present guideline focused on established findings as well as recommendations based on the state of the art. Though this guideline recognizes both hand-crafted and deep learning-based radiomics approaches, it primarily focuses on the former as this field is more mature. This guideline will be updated once more studies and results have contributed to improved consensus regarding the application of deep learning methods for radiomics. Although methodological recommendations in the present document are valid for most medical image modalities, we focus here on nuclear medicine, and specific recommendations when necessary are made for PET/CT, PET/MR, and quantitative SPECT.

Potential no man's land for the 4th year dental graduate.

The Royal College of Surgeons of England stipulates that to hold a substantive specialty or associate specialist (SAS) grade post a person must be a minimum of 4 years post-graduation and have at least 2 years' experience in their chosen speciality. We have noticed an increasing number of excellent applications for specialty doctor adverts posted by our trust without the necessary 4 years of post-graduate experience. Many of these applicants who do not comply with the RCS stipulations may be forced to take a job outside of their chosen career path. The reasons for this may be multifactorial, but it could have a worrying impact on their own future career and hospital service provision. We looked at the number of SAS grade adverts placed on NHS jobs in the year 2019 and the type of job advertised. We also considered the possible reasons for a rise in the number of applicants for SAS roles in oral surgery and oral and maxillofacial surgery, and what changes, if any, could be made to support this group of clinicians.

A systematic review of the outcomes of using voice hearing simulation in the education of health care professionals and those in training.

OBJECTIVES: To identify and synthesise data from studies that have evaluated the outcomes of voice hearing simulation as an educational intervention with health care professionals and those in training. DESIGN: The research employed a systematic review that was informed by Centre for Reviews and Dissemination DATA SOURCES: The databases Web of Science, Medline, Embase, PsycINFO, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials Register and CINAHL were systematically searched to January 2020. REVIEW METHODS: Identified studies were screened by title (n = 509), abstract (n = 246) and full text (n = 56) using the following inclusion criteria: studies employing either qualitative and/or quantitative research methods, which have evaluated voice hearing simulation as a principal educational intervention with health care professionals during training or post-qualification. RESULTS: Twenty six studies were included in the review. Eleven studies adopted mixed methods, five adopted quantitative methods and ten used qualitative methods. Although most of the studies were of low to medium quality the findings were encouraging and suggest that voice hearing simulation may be a useful educational intervention. Positive outcomes of simulation included improvements in empathy, attitudes, knowledge, understanding about voice hearing experiences and increased confidence in practice. The majority of participants that took part in voice hearing simulation thought that it was a powerful learning experience that should be offered to other health care professionals and those in training. CONCLUSIONS: Voice hearing simulation is a valuable educational intervention that should be routinely used by academics when teaching health professionals and those in training about the experiences of people who hear voices. However, to confirm its true effects and optimum mode of delivery further better quality research is needed.

Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction.

Deficiency in Sphingosine-1-phosphate lyase (S1P lyase) is associated with a multi-systemic disorder incorporating primary adrenal insufficiency (PAI), steroid resistant nephrotic syndrome and neurological dysfunction. Accumulation of sphingolipid intermediates, as seen with loss of function mutations in SGPL1, has been implicated in mitochondrial dysregulation, including alterations in mitochondrial membrane potentials and initiation of mitochondrial apoptosis. For the first time, we investigate the impact of S1P lyase deficiency on mitochondrial morphology and function using patient-derived human dermal fibroblasts and CRISPR engineered SGPL1-knockout HeLa cells. Reduced cortisol output in response to progesterone stimulation was observed in two patient dermal fibroblast cell lines. Mass spectrometric analysis of patient dermal fibroblasts revealed significantly elevated levels of sphingosine-1-phosphate, sphingosine, ceramide species and sphingomyelin when compared to control. Total mitochondrial volume was reduced in both S1P lyase deficient patient and HeLa cell lines. Mitochondrial dynamics and parameters of oxidative phosphorylation were altered when compared to matched controls, though differentially across the cell lines. Mitochondrial dysfunction may represent a major event in the pathogenesis of this disease, associated with severity of phenotype.

Estrus synchronization and expression of estrus behaviors during periovulatory period in doublesynch treated buffalypso (Bubalus bubalis) in Trinidad

Objectives: Experiment was conducted to investigate (a) the effect of the doublesynch protocol on pregnancy rate in buffalypso (b) the effectiveness of the doublesynch protocol for estrous synchronization and (c) to observe and record signs of estrous in buffalypso. Design and Methodology: In this study, eleven buffalypsoes (n=11) were administered Prostaglandin (PGF2α)on day 0, Gonadotropin-releasing hormone (GnRH) on day 2, a second PGF2α injection on day 9, and a second GnRH injection on day 11. Timed artificial insemination (TAI) was performed 16 and 24 hours after the second GnRH injection. Eleven buffalypso females (n=11) were bred after spontaneous estrus was detected (control group). Oestrous behaviour and intensity were recorded in all the experimental animals, transrectal palpation and ultrasound was performed 60 days postinsemination to determine conception rate. Results: All buffalypsoes treated with the doublesynch protocol elicited signs of swollen vulva and frequent urination which are classical signs of behavioural estrus. The pregnancy rates were 54.5% using TAI in all the treated buffalypsoes and 45.5% for the control group buffalypsoes. The conception rate between doublesynch treatment and Aripo farm herd were also compared and it was found that doublesynch treated buffalypsoes had higher conception rate (54.5%) compared to the overall Aripo farm herd (24.0%) by artificial insemination. Conclusion: The doublesynch protocol effectively synchronized the estrus in buffalypsoes. The study also demonstrated that this protocol followed by TAI enhanced the pregnancy rate with classical signs of estrus in the buffalypsoes.

A novel approach for quantitative harmonization in PET.

Positron emission tomography (PET) imaging allows for measurement of activity concentrations of a given radiotracer in vivo. The quantitative capabilities of PET imaging are particularly important in the context of monitoring response to treatment, where quantitative changes in tracer uptake could be used as a biomarker of treatment response. Reconstruction algorithms and settings have a significant impact on PET quantification. In this work we introduce a novel harmonization methodology requiring only a simple cylindrical phantom and show that it can match the performance of more complex harmonization approaches based on phantoms with spherical inserts. Resolution and noise measurements from cylindrical phantoms are used to simulate the spherical inserts from NEMA image quality phantoms. An optimization algorithm was used to find the optimal smoothing filters for the simulated NEMA phantom images to identify those that best harmonized the PET scanners. Our methodology was tested on seven different PET models from two manufacturers installed at five institutions. Our methodology is able to predict contrast recovery coefficients (CRCs) from NEMA phantoms with errors within ±5.2% for CRCmax and ±3.7% for CRCmean (limits of agreement = 95%). After applying the proposed harmonization protocol, all the CRC values were within the tolerances from EANM. Quantitative harmonization in compliance with the EARL FDG-PET/CT accreditation program is achieved in a simpler way, without the need of NEMA phantoms. This may lead to simplified scanner harmonization workflows more accessible to smaller institutions.

Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging.

The short shelf-life of water-soluble quantum dots (QDs) due to colloidal instability represents a major drawback to their exploitation. This work examines the colloidal stability of PbS nanoparticles capped with dihydrolipoic acid-polyethylene glycol (DHLA-PEG) ligands terminated with functional groups such as -NH2, -COOH, OMe and -N3. and their application for in vivo imaging. We prove a mechanism of colloidal instability and develop a strategy to produce for the first time stable PEG-capped PbS quantum dots with high quantum yield and optical emission in the first and the second near-infrared (NIR) windows of low absorption of biological tissues. The NIR imaging of in vivo biodistribution is demonstrated at wavelengths >1000 nm, with benefits of reduced tissue absorption and light scattering. The stability, biocompatibility and potential for further QD functionalization open up realistic prospects for non-invasive bioimaging applications.

Cannabis use and symptom severity in individuals at ultra high risk for psychosis: a meta-analysis.

OBJECTIVE: We aimed to assess whether individuals at ultra high risk (UHR) for psychosis have higher rates of cannabis use and cannabis use disorders (CUDs) than non-UHR individuals and determine whether UHR cannabis users have more severe psychotic experiences than non-users. METHOD: We conducted a meta-analysis of studies reporting cannabis use in the UHR group and/or positive or negative symptoms among UHR cannabis users and non-users. Logit event rates were calculated for cannabis use, in addition to odds ratios to assess the difference between UHR and controls. Severity of clinical symptoms in UHR cannabis users and non-users was compared using Hedges' g. RESULTS: Thirty unique studies were included (UHR n = 4205, controls n = 667) containing data from cross-sectional and longitudinal studies, and randomised control trials. UHR individuals have high rates of current (26.7%) and lifetime (52.8%) cannabis use, and CUDs (12.8%). Lifetime use and CUDs were significantly higher than controls (lifetime OR: 2.09; CUD OR: 5.49). UHR cannabis users had higher rates of unusual thought content and suspiciousness than non-users. CONCLUSION: Ultra high risk individuals have high rates of cannabis use and CUDs, and cannabis users had more severe positive symptoms. Targeting substance use during the UHR phase may have significant benefits to an individual's long-term outcome.

Substance use in youth at risk for psychosis.

BACKGROUND: People with schizophrenia have high rates of substance use which contributes to co-morbidity and premature mortality. Some evidence suggests people at-risk for psychosis have high rates of substance use. We aimed to assess substance use in a help-seeking cohort, comparing those at-risk and not at-risk for psychosis, and to establish any relationship with clinical symptoms. METHOD: Participants were help-seeking youth presenting to mental health services in Sydney and Melbourne. 279 (34.8%) were at-risk for psychosis, and 452 (56.4%) did not meet criteria for a psychotic disorder or risk for psychosis. The excluded individuals were made up of 59 (7.4%) young people who met criteria for a psychotic disorder and 11 (1.4%) who were unable to be evaluated. We assessed the association of substance use involvement with risk status and clinical symptoms using multivariate regression. RESULTS: Individuals at-risk for psychosis had significantly higher tobacco, alcohol and cannabis use than those not at-risk. Multivariate analysis revealed at-risk status was significantly associated with higher alcohol involvement scores when adjusting for age and gender, but no association was found for cannabis or tobacco. At-risk status was no longer associated with alcohol involvement when cannabis or tobacco use was added into the analysis. CONCLUSION: Tobacco smoking, alcohol consumption and cannabis use are common in help-seeking youth, particularly those at-risk for psychosis. It is important to consider co-occurring use of different substances in adolescents. Early substance misuse in this phase of illness could be targeted to improve physical and mental health in young people.

Mindfulness interventions for psychosis: a systematic review of the literature.

WHAT IS KNOWN ON THE SUBJECT?: Psychosis and the more specific diagnosis of schizophrenia constitute a major psychiatric disorder which impacts heavily on the self-esteem, functioning and quality of life of those affected. A number of mindfulness therapies have been developed in recent years, showing promising results when used with people with the disorder. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This review of the literature included only randomized controlled trials (RCTs), rather than other typically less robust methods of research (e.g. case studies, noncontrolled studies). WHAT ARE THE IMPLICATIONS FOR PRACTICE?: We concluded that mindfulness therapies can be safely used with people with psychosis and that they provide a number of therapeutic benefits compared with routine care and, in some cases, other interventions. Larger, methodologically improved trials are now recommended to evaluate the benefits of mindfulness therapies further. ABSTRACT: Introduction A growing number of mindfulness interventions are being used with individuals with psychosis. These therapies employ elements of acceptance and compassion in addition to mindfulness. A number of randomized controlled trials (RCTs) of these interventions have emerged in recent years, but no review of these latest trials exists. Question 'For individuals with psychosis, are mindfulness interventions more effective than treatment as usual or an alternative intervention, in improving patient-related outcomes as demonstrated in RCTs?' Method We undertook a systematic review of randomized controlled studies of mindfulness interventions for psychosis and schizophrenia (MIps). Studies were identified by searching the databases Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and Allied and Complementary Medicine. Findings The review identified 11 RCTs investigating eight mindfulness interventions. Significant improvements were reported on a number of measures, although gains were mostly smaller in trials employing well-designed controls and where assessors were blind to treatment allocation. There was considerable heterogeneity amongst trials in the diversity of treatments reviewed and the range of outcomes assessed. Implications for Practice The findings suggest MIps are feasible for individuals with psychosis and provide a number of significant benefits over routine care and, in some cases, other interventions.

Developing a self-healing supramolecular nucleoside hydrogel.

Low molecular weight gelator hydrogels provide a viable alternative to traditional polymer based drug delivery platforms, owing to their tunable stability and in most cases inherent biocompatibility. Here we report the first self-healing nucleoside hydrogel using N4-octanoyl-2'-deoxycytidine (0.5% w/v) for drug delivery. The hydrogel's cross-linked nanofibrillar structure, was characterised using oscillatory rheology and confirmed using SEM and TEM imaging. The potential of this gel for drug delivery was explored in vitro using fluorescently labelled tracers. Cell viability assays were conducted using pancreatic cell lines which tolerated the gels well; whilst no adverse effects on the viability or proliferation of cells were observed for fibroblast cell lines.

Exploring why people with SMI smoke and why they may want to quit: baseline data from the SCIMITAR RCT.

ACCESSIBLE SUMMARY: People with severe mental ill health are up to three times more likely to smoke than other members of the general population. Life expectancy in this client group is reduced by up to 30 years, and smoking is the single most important cause of premature death. The aim of this study was to explore why people with severe mental ill health smoked and why they might want to stop smoking or cut down on the amount of cigarettes that they smoked. The study found that people with severe mental ill health are motivated to cut down or stop smoking, and this is mainly due to concerns about their own health. The reasons people gave for smoking were to relieve stress, to help relax and for something to do when they are bored. Health professionals should offer evidence supported smoking cessation therapy to people with severe mental ill health. In addition to standard National Health Service smoking cessation treatments such as pharmacotherapy and behavioural support. Practitioners should help people with serious mental ill health to identify meaningful activities to relieve boredom and challenge any incorrect beliefs they hold that smoking helps relaxation and relieves stress. ABSTRACT: Smoking is the single most preventable cause of premature mortality for people with serious mental ill health (SMI). Yet little is known about the reasons why service users smoke or what their motivations for quitting might be. The aim of this paper is to explore smoking behaviours, reasons for smoking and motivations for cutting down/stopping smoking in individuals with SMI who expressed an interest in cutting down or stopping smoking. Prior to randomization, the smoking behaviours and motivations for wanting to cut down or stop smoking of participants in a randomized trial were systematically assessed. Participant's primary reasons for continuing to smoke were that they believed it helped them to cope with stress, to relax and relieve boredom. Participant's main motivations for wanting to cut down or stop smoking were related to concerns for their own health. Previous attempts to stop smoking had often been made alone without access to evidence supported smoking cessation therapy. Future recommendations include helping people with SMI to increase their activity levels to relieve boredom and inspire confidence in their ability to stop smoking and challenging beliefs that smoking aids relaxation and relieves stress.

Everolimus method comparison between Waters MassTrak™ Immunosuppressants XE (IUO) kit and an in-house laboratory developed LC-MS/MS method in renal transplant patients.

UNLABELLED: Everolimus is an immunosuppressant drug that was approved for prophylactic use in the United States to prevent organ rejection in adult kidney and liver transplant recipients. Therapeutic drug management (TDM) is required to optimize the dose for efficacy and to minimize toxicity. Prior to the development of immunoassay reagents for everolimus, laboratory developed chromatographic methods were routinely used to support TDM for everolimus testing. However, the use of high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS)for everolimus TDM is not widely utilized in hospitals or transplant centers due to either a lack of mass spectrometry instrumentation or resources for assay development. An everolimus reagent kit and method was developed by Waters Corporation for use on the Waters ACQUITY TQD mass spectrometer system. PURPOSE: The purpose for this study was to evaluate the investigational use only (IUO) Waters MassTrak Immunosuppressants XE (IUO) kit on a Waters ACQUITY(®) ultra performance liquid chromatography (UPLC) coupled to an ACQUITY(®) TQD mass spectrometer and to compare this test system to a laboratory developed mass spectrometry assay for everolimus. METHOD: We evaluated precision and performed a patient comparison study on 56 renal transplant patients that received everolimus against a validated in house HPLC-MS/MS method. RESULTS: 5-day precision was performed on two patient pooled samples and analyzed in triplicate. Total imprecision for the low patient pool (3.77 ng/mL) and high patient pool (10.87 ng/mL) was <15 %CV. Deming regression analysis was performed for the patient comparison and the linear regression equation was y=0.973x+0.03, Sy/x 0.55, and the correlation coefficient was 0.9815. CONCLUSION: The Waters MassTrak Immunosuppressants XE (IUO) kit and method had good correlation between the concentration range of 3-15 ng/mL to the established in-house HPLC-MS/MS method.

Music therapy for service users with dementia: a critical review of the literature.

Dementia is an organic mental health problem that has been estimated to affect over 23 million people worldwide. With increasing life expectancy in most countries, it has been estimated that the prevalence of dementia will continue to significantly increase in the next two decades. Dementia leads to cognitive impairments most notably short-term memory loss and impairments in functioning and quality of life (QOL). National policy in the UK advocates the importance of early diagnosis, treatment and social inclusion in maintaining a good QOL. First-line treatment options often involve drug therapies aimed at slowing down the progression of the illness and antipsychotic medication to address challenging behaviours. To date, research into non-pharmacological interventions has been limited. In this manuscript, we review the literature that has reported evaluations of the effects of music therapy, a non-pharmacological intervention. The results of six studies reviewed suggest that music therapy may have potential benefits in reducing anxiety, depression and agitated behaviour displayed by elderly people with dementia as well as improving cognitive functioning and QOL. Furthermore, music therapy is a safe and low-cost intervention that could potentially be offered by mental health nurses and other carers working in residential settings.

Gelation properties of self-assembling N-acyl modified cytidine derivatives.

In this study we report the synthesis of new cytidine derived gelators possessing acyl chains of different lengths. These low molecular weight gelators were shown to form self-supporting gels at 0.5% (w/v) in binary systems of aqueous miscible polar organic solvent and water. The representative gels were studied using rheology and their fibrillar structure confirmed by TEM imaging and FTIR. We further demonstrated the use of these gels as potential drug delivery platforms by monitoring release characteristics of both high and low molecular weight fluorescently labelled tracers.

Developing a healthy living intervention for people with early psychosis using the Medical Research Council's guidelines on complex interventions: phase 1 of the HELPER - InterACT programme.

BACKGROUND: Young people with early psychosis often gain a significant amount of weight after the initiation of anti-psychotic treatment. Despite the current policy guidance to develop and evaluate 'healthy living' interventions for people with psychosis there remains a paucity of research. Our aim was to develop an acceptable, feasible, culturally sensitive and potentially effective 'healthy living' intervention, specifically for young people with early psychosis. METHODS: Using the Medical Research Council guidelines for developing and evaluating complex interventions we conducted a number of studies to devise a 'healthy living' intervention. We used a 'top down' (published evidence), bottom up (stakeholder perspectives) approach, which included updating a systematic review, identifying a theoretical basis for the intervention, exploring the perspectives of service users and health professionals, and identifying key cultural issues. The results of these studies were synthesised to determine the content and delivery of the intervention. RESULTS: The intervention developed comprised eight individual sessions to be delivered by a support time recovery worker over a 12 month period with emphasis on individualised action plans to facilitate participatory exercise and changes in diet. To optimise engagement, choice and self management a booklet and website were developed to provide participants with educational advice, healthy eating recipes and other materials. CONCLUSION: Using the Medical Research Council guidelines we have developed a potentially effective, feasible and acceptable 'healthy living' intervention for people with psychosis using early intervention services in the UK.

Demonstration of a high-field short-period superconducting helical undulator suitable for future TeV-scale linear collider positron sources.

The first demonstration of a full-scale working undulator module suitable for future TeV-scale positron-electron linear collider positron sources is presented. Generating sufficient positrons is an important challenge for these colliders, and using polarized e(+) would enhance the machine's capabilities. In an undulator-based source polarized positrons are generated in a metallic target via pair production initiated by circularly polarized photons produced in a helical undulator. We show how the undulator design is developed by considering impedance effects on the electron beam, modeling and constructing short prototypes before the successful fabrication, and testing of a final module.

Acalypha wilkesiana extracts induce apoptosis by causing single strand and double strand DNA breaks.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and inflammation. AIM OF THE STUDY: There is an increasing interest among researchers in searching for new anticancer drugs from natural resources, particularly plants. This study aimed to investigate the anticancer properties of Acalypha wilkesiana extracts and the characteristics of DNA damage against brain and lung cancer cells. MATERIALS AND METHODS: The antiproliferative activity of Acalypha wilkesiana extracts (ethyl acetate, hexane, and ethanol) was examined on human glioma (U87MG), human lung carcinoma (A549), and human lung fibroblast (MRC5) cells. RESULTS: Cell viability MTT assay revealed that ethyl acetate extract of the plant possessed significant antiproliferative effects against both U87MG (GI(50)=28.03 ± 6.44 µg/ml) and A549 (GI(50)=89.63 ± 2.12 µg/ml) cells (p value<0.0001). The hexane extract was found to exhibit crucial antiproliferative effects on U87MG (GI(50)=166.30 ± 30.50 µg/ml) (p value<0.0001) but not on A549 cells. Neither plant extract possessed noticeable antiproliferative effects on the non-cancerous MRC5 cells (GI(50)>300 µg/ml). The ethanol extract showed no antiproliferative effects on any cell line examined. Haematoxylin & Eosin (H & E) staining and single cell gel electrophoresis (SCGE) comet assay confirmed that plant extract-treated cells underwent apoptosis and not necrosis. SCGE comet assays confirmed that plant extracts caused both single strand (SSB) and double strand (DSB) DNA breaks that led to the execution of apoptosis. CONCLUSION: The extracts (especially ethyl acetate and hexane) of Acalypha wilkesiana possess valuable cytotoxic effects that trigger apoptosis in U87MG and A549 cancer cells through induction of DNA SSBs and DSBs.