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Background: QuADRANT was a study funded by the European Commission to evaluate clinical audit uptake and implementation across Europe, with an emphasis on clinical audit as mandated within the BSSD (Basic Safety Standards Directive). AIMS: QuADRANT objectives—obtain an overview of European clinical audit activity; identify good practices and resources, barriers and challenges; provide guidance and recommendations going forwards; identify the potential for European Union action on quality and safety in the three core project specialties, radiology, radiotherapy and nuclear medicine. Findings and recommendations: QuADRANT identified that developments in national clinical audit infrastructure are required. National professional societies can be pivotal in improving clinical audit implementation, but resource allocation and national prioritisation of clinical audit are needed in many countries. Lack of staff time and expertise are also barriers. Enablers to enhance clinical audit participation are not widely employed. Development of hospital accreditation programmes can facilitate clinical audit uptake. An active and formalised role for patients in clinical audit practice and policy development is recommended. There is persisting variation in European awareness of BSSD clinical audit requirements. Work is needed to improve dissemination of information on the legislative requirements relating to clinical audit in the BSSD and in relation to inspection processes to ensure these include clinical audit and that they encompass all clinics and specialties involved in medical applications using ionising radiation. Conclusion: QuADRANT provides an important step towards enhancing clinical audit uptake and implementation across Europe and improving patient safety and outcomes. Key points: QuADRANT was a multiprofessional study, on behalf of the European Commission, examining clinical audit across three core specialties—radiology, radiotherapy and nuclear medicine—with an emphasis on radiation protection. QuADRANT aimed to provide an overview of the status of European clinical audit uptake and implementation and to identify barriers and good practices. QuADRANT recommendations include increased prioritisation and resourcing of clinical audit, use of enablers, motivation of staff and developing the role of the national professional societies in clinical audit uptake and promotion. [ABSTRACT FROM AUTHOR]

Clinical audit is an important quality improvement activity and has significant benefits for patients in terms of enhanced care, safety, experience and outcomes. Clinical audit in support of radiation protection is mandated within the European Council Basic Safety Standards Directive (BSSD), 2013/59/Euratom. The European Society of Radiology (ESR) has recognised clinical audit as an area of particular importance in the delivery of safe and effective health care. The ESR, alongside other European organisations and professional bodies, has developed a range of clinical audit-related initiatives to support European radiology departments in developing a clinical audit infrastructure and fulfilling their legal obligations. However, work by the European Commission, the ESR and other agencies has demonstrated a persisting variability in clinical audit uptake and implementation across Europe and a lack of awareness of the BSSD clinical audit requirements. In recognition of these findings, the European Commission supported the QuADRANT project, led by the ESR and in partnership with ESTRO (European Association of Radiotherapy and Oncology) and EANM (European Association of Nuclear Medicine). QuADRANT was a 30-month project which completed in Summer 2022, aiming to provide an overview of the status of European clinical audit and identifying barriers and challenges to clinical audit uptake and implementation. This paper summarises the current position of European radiological clinical audit and considers the barriers and challenges that exist. Reference is made to the QuADRANT project, and a range of potential solutions are suggested to enhance radiological clinical audit across Europe. Key Points: Clinical audit is an important component of effective clinical governance and improves patient experience, safety and outcomes. The European Council Basic Safety Standards Directive (BSSD), 2013/59/Euratom, mandates clinical audit in support of radiation protection. There is persisting variability in clinical audit activity and BSSD awareness across Europe. QuADRANT was a project on behalf of the European Commission overviewing current European clinical audit status. This paper overviews ESR clinical audit initiatives including the ESR-led QuADRANT project. [ABSTRACT FROM AUTHOR]

The recently implemented European Council Basic Safety Standards Directive (BSSD), 2013/59/Euratom lays down core radiation protection standards for European radiology departments, including a mandatory requirement for supporting processes of clinical audit. A repeat survey on behalf of the European Society of Radiology (ESR) was undertaken in February 2021, involving the ESR EuroSafe Imaging Star department network, to re-assess compliance with selected key BSSD requirements following an initial survey in 2018 where variable compliance was demonstrated. 61% (78/128) of eligible departments participated and overall the survey results revealed a mixed picture in terms of implementation of BSSD requirements when compared to the 2018 survey with both improvement and deterioration observed. This pattern was seen also in relation to supporting processes of regulatory audit and re-audit. Higher levels of "skipping" of responses were also observed in 2021. These findings were unexpected in light of the interventions in relation to audit (clinical and regulatory) and radiation protection undertaken by the ESR and other organisations in recent years, but can reasonably be explained by the onset of the COVID-19 pandemic, with consequent significant disruption of radiology services. The 2021 survey results do serve to highlight again the need for co-ordinated intervention involving relevant European bodies, organisations and governmental agencies to address the important issues raised by this survey. The European Commission clinical audit and radiation protection initiatives, QuADRANT, led by the ESR, and SAMIRA will act as important drivers for improvement in patient safety, experience and outcomes across Europe. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate organisational reporting infrastructure and patient-related reporting data in the diagnosis of vertebral fragility fractures (VFFs) as demonstrated on computed tomography (CT).Methods: Organisational and patient-specific questionnaires were developed by consensus between The Royal College of Radiologists, the Royal College of Physicians, and the Royal Osteoporosis Society. The patient-specific component of the audit involved analysis of CT reporting data acquired from 50 consecutive non-traumatic studies including the thoracolumbar spine. Ethical approval for this type of study is not required in the UK. All UK radiology departments with an audit lead (auditor) registered with The Royal College of Radiologists (RCR) were invited to participate in this retrospective audit.Results: In total, 127 out of 202 departments (63%) supplied data to the study, with inclusion of 6357 patients. Overall, 1362/6357 patients (21.4%) had a fracture present on auditor review of the CT imaging. There was a lack of compliance with all audit standards: 79% of reports commented on the vertebrae (target 100%), fracture severity was mentioned in 26.2% (target 100%), the recommended terminology 'vertebral fracture' was used in 60.1% (target 100%), and appropriate onward referral was recommended in 2.6% (target 100%).Conclusions: The findings from this study should be used to provide impetus to improve the diagnosis and care for patients with osteoporotic VFFs. Solutions are multifactorial, but radiologist and local osteoporosis/fracture liaison service engagement is fundamental, combined with necessary development of electronic report notification systems and expansion of supporting fracture services.Key Points: • Early detection and diagnosis of vertebral fragility fractures (VFFs) significantly reduce patient morbidity and mortality. This study describes the results of a retrospective UK-wide audit evaluating current radiology reporting practice in the opportunistic diagnosis of VFFs as demonstrated on computed tomography (CT) studies including the spine. • Key audit standards included comment made on bone integrity in primary report (target 100%), comment made on severity of fractures (90%), report used recommended terminology 'fracture' (100%), and report made appropriate recommendations for referral/further assessment (100%). The audit results demonstrated a lack of compliance with all audit standards; lack of compliance was most marked in the use of recommended terminology (achieved 60.3%), in relation to comment on fracture severity (achieved 26.2%) and for recommendation for referral/further assessment (achieved 2.6%). • Solutions are challenging and multifactorial but the opportunity exists for all radiologists to examine their practice and directly improve patient care. [ABSTRACT FROM AUTHOR]

Clinical audit "according to national procedures" is a legal requirement as defined within the recently implemented European Council Basic Safety Standards Directive (BSSD), 2013/59/Euratom. A survey was undertaken in 2019 to assess the current status of clinical audit in European radiology departments and for feedback on the recently published "ESR Guide to Clinical Audit in Radiology" and the "ESR Clinical Audit Tool (Esperanto)". The survey was distributed within the European Society of Radiology (ESR) EuroSafe Imaging Star network and also to European national radiological societies which are institutional members of the ESR. A total of 47/116 (41%) EuroSafe Imaging Star departments responded, and responses were received from 43 radiology departments from 16/48 national radiological societies. Survey findings demonstrated a low awareness of recent key ESR audit-related publications (Esperanto), a lack of clinical audit infrastructure for BSSD compliance and by inference a poorly developed local/national communication and audit infrastructure in many cases. Key stakeholders, including the ESR and the European national radiological societies, will need to continue to work with other bodies to further promote, integrate and to encourage resourcing of clinical audit at all levels, facilitating BSSD compliance and improving patient care. [ABSTRACT FROM AUTHOR]

The recently implemented European Council Basic Safety and Standards Directive (BSSD), 2013/59/Euratom lays down core radiation protection standards for European radiology departments, with a mandatory requirement for supporting clinical audit processes. A survey on behalf of the European Society of Radiology (ESR) was undertaken in November 2018 involving the ESR EuroSafe Imaging Star department network to assess compliance with selected key BSSD requirements, with emphasis also on clinical audit/re-audit. 64% of invited departments participated and the survey results revealed a lack of compliance with BSSD requirements even when allowing for work in progress within departments. Justification processes showed the lowest rates of compliance overall, with varying results relating to dose limits, patient information and significant accidental exposure notification. Questions around implementation of diagnostic reference levels (DRLs) revealed generally far higher compliance with requirements. The survey findings confirm a lack of compliance with key BSSD radiation protection indicators and also a lack of supporting clinical audit structures. These findings are likely to be representative of the wider radiological community in Europe. There is a need for a co-ordinated response, involving relevant European agencies, national bodies and societies and also individual radiology departments to address these issues. ESR publications on clinical audit (Esperanto) and the 2018 EuroSafe Imaging Call for Action will be important components of this response. [ABSTRACT FROM AUTHOR]

The importance of clinical audit in radiological practice is increasingly recognised and undertaking clinical audit "in accordance with national procedures" is mandatory for radiology departments within the European Union following implementation of the Basic Safety Standard Directive (BSSD), 2013/59/Euratom in 2018. This survey, sent to all National Radiological Societies in Europe in 2018, evaluated the current status of clinical audit at national level and supporting infrastructure, and explored the potential for wider co-operation and collaboration in developing and evaluating clinical audit processes. Responses were received from 36/47 (76.6%) National Societies. Broadly responses indicated an increasing awareness of the importance of clinical audit, but highlighted deficiencies in necessary infrastructure and resources required for enhancement and development of existing clinical audit systems. National Societies are well placed, in the context of appropriate and prioritised resource allocation, to collaborate with other European bodies, in particular the European Society of Radiology (ESR), to help lead on these important changes, with the potential to provide external direction. [ABSTRACT FROM AUTHOR]

The importance of clinical audit in radiological practice is increasingly recognised and undertaking clinical audit "in accordance with national procedures" is mandatory for radiology departments within the European Union following implementation of the Basic Safety Standard Directive (BSSD), 2013/59/Euratom in 2018. This survey, sent to all National Radiological Societies in Europe in 2018, evaluated the current status of clinical audit at national level and supporting infrastructure, and explored the potential for wider co-operation and collaboration in developing and evaluating clinical audit processes. Responses were received from 36/47 (76.6%) National Societies. Broadly responses indicated an increasing awareness of the importance of clinical audit, but highlighted deficiencies in necessary infrastructure and resources required for enhancement and development of existing clinical audit systems. National Societies are well placed, in the context of appropriate and prioritised resource allocation, to collaborate with other European bodies, in particular the European Society of Radiology (ESR), to help lead on these important changes, with the potential to provide external direction. [ABSTRACT FROM AUTHOR]

The recently implemented European Council Basic Safety and Standards Directive (BSSD), 2013/59/Euratom lays down core radiation protection standards for European radiology departments, with a mandatory requirement for supporting clinical audit processes. A survey on behalf of the European Society of Radiology (ESR) was undertaken in November 2018 involving the ESR EuroSafe Imaging Star department network to assess compliance with selected key BSSD requirements, with emphasis also on clinical audit/re-audit. 64% of invited departments participated and the survey results revealed a lack of compliance with BSSD requirements even when allowing for work in progress within departments. Justification processes showed the lowest rates of compliance overall, with varying results relating to dose limits, patient information and significant accidental exposure notification. Questions around implementation of diagnostic reference levels (DRLs) revealed generally far higher compliance with requirements. The survey findings confirm a lack of compliance with key BSSD radiation protection indicators and also a lack of supporting clinical audit structures. These findings are likely to be representative of the wider radiological community in Europe. There is a need for a co-ordinated response, involving relevant European agencies, national bodies and societies and also individual radiology departments to address these issues. ESR publications on clinical audit (Esperanto) and the 2018 EuroSafe Imaging Call for Action will be important components of this response. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies ( DLB) and Parkinson's disease dementia ( PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease ( AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus ( BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits. [ABSTRACT FROM AUTHOR]

Thus, the European Commission presented the tender for the QuADRANT project in 2019 [[2]], entitled "Constant improvement in quality and safety of radiology, radiotherapy and nuclear medicine through clinical audit", being summarised with the acronym QuADRANT (Quality Improvement Through Clinical Audit in Diagnostic Radiology, Radiotherapy and Nuclear Medicine (Including Therapies)). The QuADRANT study: current status and recommendations for improving uptake and implementation of clinical audit of medical radiological procedures in Europe - the nuclear medicine perspective 28969766 15 Dondi M, Torres L, Marengo M, Massardo T, Mishani E, Van Zyl Ellmann A. Comprehensive auditing in nuclear medicine through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine Program. 23561453 14 Dondi M, Torres L, Marengo M, Massardo T, Mishani E, Van Zyl Ellmann A. Comprehensive auditing in nuclear medicine through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine (QUANUM) Program. [Extracted from the article]

The essay presents the second entry in a roundtable discussion series, originally presented at the Mormon History Association's annual conference in 2013. This entry suggests that the academic discipline of comparative religion in regard to Asian religions in both history and theology could be useful to Mormon scholars in their research. Additional topics addressed include the concept of translation and defense against criticism of comparative studies in general.

Dementia with Lewy bodies and Parkinson's disease dementia are different clinical phenotypes of Lewy body dementias differentiated by the temporal relationship between parkinsonism and dementia onset. At present, it is unclear whether the glutamatergic system is affected in these disorders. In this study, we measured α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA subunits in the postmortem neocortex of a cohort of prospectively studied Lewy body dementia cases, as well as age-matched controls by immunoblotting. We found losses of GluA2/3/4 immunoreactivities in Lewy body dementias which correlated with higher pre-death Hoehn and Yahr scores and with longer Parkinson's disease duration before dementia onset, but not with dementia severity, cortical Lewy body burden, or amyloid plaque and neurofibrillary tangle burden. Our study suggests that GluA2/3/4 losses may be a neurochemical marker of motor disability in Lewy body dementias. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have pointed to clusterin (apolipoprotein J) as being linked to the occurrence of Alzheimer's disease ( AD); studies have identified the protein as a possible biomarker. The association between clusterin and senile plaques in AD brain is well known, and clusterin levels in AD brain are 40% higher than that in control subjects. The present study investigates, immunohistochemically, the association between clusterin and Aβ peptides in AD and control cortex. A unique and specific association between clusterin and Aβ40 was observed in plaques in the cerebral cortex from AD subjects in that only plaques that contained Aβ40 showed clusterin immunoreactivity, while the many plaques with Aβ42 alone lacked clusterin labeling. Cerebrovascular Aβ in AD brain generally lacked Aβ42 but was positively labeled by both the Aβ40 and the clusterin antibodies. In control subjects, however, Aβ40 was absent from plaques, although very occasional plaques were found to be labeled by both the Aβ42 and the clusterin antibodies. Overall, in AD, but not aged control brain, clusterin was associated specifically with the Aβ40 form of Aβ in the brain. The lack of clusterin in association with Aβ42 may be a significant feature in neuronal loss and neurodegeneration in the disease state. [ABSTRACT FROM AUTHOR]

Ultrasound is the first-line imaging investigation in the evaluation of parotid gland lesions; however, ultrasound alone cannot differentiate between benign and malignant lesions. An imaging technique with this capability would be of great value, as fine needle aspiration cytology (FNAC) is not always accurate and partial/total parotidectomy is associated with facial nerve palsy and Frey's syndrome. Sonoelastography is a novel imaging technique that has been employed in the research setting in the evaluation of tissues including breast, thyroid, prostate and the salivary glands. More recently it has been used as a diagnostic adjunct in the sonographic evaluation of major salivary gland lesions. This review article outlines the current role of sonoelastography in the diagnostic imaging of parotid lesions, with particular reference to the findings of two research papers published in European Radiology. These papers employ slightly different techniques: the first utilises shear wave elastography whilst the second uses real-time sonoelastography. Sonoelastography may have potential as a diagnostic imaging adjunct to conventional ultrasound. However, it seems likely that FNAC/core biopsy will continue to be necessary. Further studies to evaluate the reproducibility of sonoelastographic results across a range of operators and systems are also needed. Key Points • Ultrasound is the initial and often definitive investigation for parotid lesions • Ultrasound-based strain elastography has been attempted but offered little additional information • New shear wave elastographic techniques did not confer much advantage either • However, analysis of elastographic patterns seems to provide advantages over ultrasound alone [ABSTRACT FROM AUTHOR]

Abstract: The etiology of Alzheimer''s disease (AD) is complex with oxidative stress being a possible contributory factor to pathogenesis and disease progression. TASTPM transgenic mice expressing familial AD-associated amyloid precursor protein (APPswe) and presenilin transgenes (PS1M146V) show increased brain amyloid beta (Aβ) levels and Aβ plaques from 3 months. We tested if enhancing oxidative stress through diet would accelerate Aβ-related pathology. TASTPM were fed a pro-oxidant diet for 3 months resulting in increased brain levels of protein carbonyls, increased Nrf2, and elevated concentrations of glutathione (GSH). The diet increased both amyloid precursor protein (APP) and Aβ in the cortex of TASTPM but did not alter Aβ plaque load, presenilin 1, or β-secretase (BACE1) expression. TASTPM cortical neurons were cultured under similar pro-oxidant conditions resulting in increased levels of APP and Aβ likely as a result of enhanced β/γ secretase processing of APP. Thus, pro-oxidant conditions increase APP levels and enhance BACE1-mediated APP processing and in doing so might contribute to pathogenesis in AD. [Copyright &y& Elsevier]

Abstract: Aim: To review the initial experience of blending a variety of online educational techniques with traditional face to face or contact-based teaching methods to deliver final year undergraduate radiology content at a UK Medical School. Materials and methods: The Brighton and Sussex Medical School opened in 2003 and offers a 5-year undergraduate programme, with the final 5 spent in several regional centres. Year 5 involves several core clinical specialities with onsite radiology teaching provided at regional centres in the form of small-group tutorials, imaging seminars and also a one-day course. An online educational module was introduced in 2007 to facilitate equitable delivery of the year 5 curriculum between the regional centres and to support students on placement. This module had a strong radiological emphasis, with a combination of imaging integrated into clinical cases to reflect everyday practice and also dedicated radiology cases. For the second cohort of year 5 students in 2008 two additional online media-rich initiatives were introduced, to complement the online module, comprising imaging tutorials and an online case discussion room. Results: In the first year for the 2007/2008 cohort, 490 cases were written, edited and delivered via the Medical School managed learning environment as part of the online module. 253 cases contained a form of image media, of which 195 cases had a radiological component with a total of 325 radiology images. Important aspects of radiology practice (e.g. consent, patient safety, contrast toxicity, ionising radiation) were also covered. There were 274,000 student hits on cases the first year, with students completing a mean of 169 cases each. High levels of student satisfaction were recorded in relation to the online module and also additional online radiology teaching initiatives. Conclusion: Online educational techniques can be effectively blended with other forms of teaching to allow successful undergraduate delivery of radiology. Efficient IT links and good image quality are essential ingredients for successful student/clinician engagement. [Copyright &y& Elsevier]

Abstract: Elevated Aβ and its deposition as senile plaques are pathogenic features of Alzheimer''s disease. Aβ has been shown to be toxic to neurons and to inhibit long-term potentiation yet, the intracellular signalling pathways underlying these actions are unknown. We report for the first time that acute exposure of primary mouse neurons to 400nM Aβ1–42 increased Akt phosphorylation in an α7 nicotinic receptor and NMDA receptor dependant manner. However, prolonged incubation resulted in Akt phosphorylation returning to baseline consistent with the action of a physiological regulator. Analysis of an APP transgenic mouse (TAS10) revealed a significant deficit in hippocampal Akt phosphorylation at 13 months. This time point corresponds to the emergence of plaque formation and memory impairments in these mice. The present study suggests that Aβ1–42 regulates Akt phosphorylation in a complex manner. Acutely, Aβ1–42 stimulates Akt phosphorylation however, chronic exposure to Aβ in TAS10 mice resulted in a downregulation of Akt phosphorylation consistent with abnormalities in excitatory neurotransmission in these mice and with recent reports of Aβ1–42 driven internalisation of NMDA receptors. [Copyright &y& Elsevier]

The article presents an essay concerning a case study on failed prophecy. It was revealed that religious group often spiritualize a failed prophecy and/or reaffirm the faith's basic beliefs and commitments in the wake of failed prediction. In addition, other stewards felt that the community had relied too much on divine intervention.

Several transgenic mouse models of Alzheimer''s disease (AD) have been developed that exhibit β-amyloid (Aβ) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswe×PS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Aβ neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Aβ antibodies demonstrated that cerebral Aβ deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Aβ deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Aβ deposition. The cerebral Aβ load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Aβ plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Aβ deposition, which first occurs 3 months earlier. [Copyright &y& Elsevier]

Introduction: Magnetic resonance cholangiopancreatography (MRCP) has been demonstrated as a reliable, non-invasive means of biliary tract imaging among patients with suspected choledocholithiasis. The aim of this study was to establish the impact of intravenous glucagon administration (IVGA) upon visualisation of the common bile duct (CBD) and ampulla of Vater during MRCP. Materials and methods: Forty-two consecutive, non-diabetic subjects with a working diagnosis of symptomatic choledocholithiasis were scanned, pre- and post-IVGA using the half-Fourier, single shot, turbo-spin-echo (HASTE) sequence. Maximum intensity projections (optimised for the extra-hepatic biliary tree and ampulla of Vater) were reviewed blindly by three consultant radiologists. The CBD images were graded (0–3) according to the length of duct seen. The ampullary images were graded according to whether to it was visualised clearly (1), or not (0). Results: Following IVGA the CBD was visualised at grade 3 (75–100% of length seen) in 14 additional patients compared with images prior to IVGA. Furthermore, ampullary visualisation was considered diagnostic in 18 additional patients post-IVGA. No glucagon-associated adverse effects were observed. Conclusion: These results demonstrate that IVGA improved visualisation of the CBD and ampulla of Vater during magnetic resonance cholangiopanctreatography. This may reduce the requirement for repeat investigation or recourse to invasive diagnostic procedures (e.g. endoscopic retrograde cholangiopancreatography (ERCP)). [Copyright &y& Elsevier]

Mutations in the Presenilin 1 gene are the cause of the majority of autosomal dominant familial forms of Alzheimer''s disease. Presenilin 1 (PS1) is produced as a holoprotein but is then rapidly processed to amino- (N-PS1) and carboxy-terminal (C-PS1) fragments that are incorporated into stable high molecular mass complexes. The mechanisms that control PS1 cleavage and stability are not properly understood but sequences within C-PS1 have been shown to regulate both of these properties. Here we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates PS1 on threonine354 within C-PS1 both in vitro and in vivo. Threonine354 phosphorylation functions to selectively stabilize C-PS1. Our results demonstrate that cdk5/p35 is a regulator of PS1 metabolism. [Copyright &y& Elsevier]

Examines the role played by beta-amyloid in the pathology of Alzheimer's disease. Processes involved in the production of beta-amyloid; Approaches used to identify the enzyme Asp2; Prospects for therapeutic beta-secretase inhibitors.

Replies to a commentary made by Allan Hood concerning an article about the tradition of Latin inscriptions. Chronological and geographical distribution of the style; Relation of microcosm and macrocosm; Numerological techniques of the authors of the 13th century book 'Arts of Poetry'; Examples of compositions.

The article describes the case of a 24-day-old male infant diagnosed with fibromatosis colli. Topics discussed include a unilateral neck mass caused by swelling of the sternocleidomastoid, physiotherapy prescribed for the patient, and complete resolution of the mass and full movement regained after four months. Also mentioned are rates of fibromatosis colli incidence, recommendations of ultrasound evaluation of the neck, and the treatment of extreme cases with surgery or physiotherapy.

Examines a case of ectopic salivary gland pleomorphic adenoma of the parapharyngeal adenoma. Clinical presentation; Diagnostic findings; Clinical management; Treatment outcomes.

To reaudit the use of safety checklists in radiology departments in NHS departments throughout the UK. This audit was performed on behalf of The Royal College of Radiologists Audit Committee in 2016 and was sent to radiology audit leads at every NHS department in the UK to determine the use of safety checks in various modalities and subspecialties. Free-form text boxes gathered data on problems with checklist implementation. 109/177 (62%) trusts responded. 48% of respondents used safety checklists for all radiological procedures in all modalities. 50% used checklists for some procedures. 2% did not use a checklist. Checklist use had increased since the previous audit (98% 2016, compared to 94% in 2012) but implementation for different procedures remains variable. For example, in ultrasound-guided fine needle and breast stereotactic procedures (49%), use has not increased since 2012. Reasons for not using checklists include a perception that intervention suite checklists were not appropriate for minor procedures and the limited flexibility of radiology information systems. The limitations of checklists are discussed. Our reaudit shows that in spite of increased implementation, use of safety checks is variable. Local ownership and radiology information system flexibility are needed to support the culture of safety processes in radiology departments. [ABSTRACT FROM AUTHOR]

The article presents a case of a 76-year-old female who was presented due to acute onset left sided hemiparesis and facial assymmetry and was eventually diagnosed with acute ischaemic stroke through computed tomography.

Key Points: • Importance of appropriate preoperative diagnosis of parotid tumours. • The reasons why FNAC and USCB are the preferred diagnostic method. • USCB as the diagnostic biopsy tool of choice in many institutions. [ABSTRACT FROM AUTHOR]

An abstract of the study "Real-time, Online Teaching to Enhance Undergraduate Learning," by David C. Howlett, James P. Connelly and Tim Vincent is presented.

• QuADRANT was a multiprofessional research project, conducted on behalf of the European Commission, examining clinical audit across the three core specialties – radiology, radiotherapy and nuclear medicine – with an emphasis on radiation protection. • QuADRANT aimed to provide an overview of the status of European clinical audit uptake and implementation and to identify good practice and barriers to implementation. • For Radiotherapy there is a long tradition of dosimetry audit and comprehensive IAEA QUATRO audits, however comprehensive clinical audit has not been widely implemented in individual European Countries. • QuADRANT recommendations include increased prioritisation and resourcing of clinical audit, use of enablers, education and training of staff, motivation of staff and call for role development of the national professional societies in clinical audit uptake and promotion. QuADRANT was a research project funded by the European Commission to evaluate clinical audit uptake and implementation across Europe, with an emphasis on clinical audit as mandated within the BSSD (Basic Safety Standards Directive). Focusing on the QuADRANT objectives – to obtain an overview of European clinical audit activity; identify good practices, resources, barriers and challenges; provide guidance and recommendations going forwards; identify the potential for European Union action on quality and safety focusing on the field of radiotherapy. A pan-European survey, expert interviews and a literature review conducted within the framework of the QuADRANT project indicated that developments in national clinical audit infrastructure are required. While in radiotherapy, there is a strong tradition and high level of experience of dosimetry audits and well-established practice through the IAEA's QUATRO audits, few countries have a well-established comprehensive clinical audit programme or international/national initiatives on tumour specific clinical audits. Even if sparse, the experience from countries with established system of quality audits can be used as role-models for national professional societies to promote clinical audit implementation. However, resource allocation and national prioritisation of clinical audit are needed in many countries. National and international societies should take the initiative to promote and facilitate training and resources (guidelines, experts, courses) for clinical audits. Enablers used to enhance clinical audit participation are not widely employed. Development of hospital accreditation programmes can facilitate clinical audit uptake. An active and formalised role for patients in clinical audit practice and policy development is recommended. Because there is a persisting variation in European awareness of BSSD clinical audit requirements, work is needed to improve dissemination of information on the legislative requirements relating to clinical audit in the BSSD and in relation to inspection processes. The aim is to ensure these include clinical audit and that they encompass all clinics and specialties involved in medical applications using ionising radiation. QuADRANT provided an overarching view of clinical audit practice in Europe, with all its related aspects. Unfortunately, it showed that the awareness of the BSSD requirements for clinical audit are highly variable. Therefore, there is an urgent need to dedicate efforts towards ensuring that regulatory inspections also incorporate an assessment of clinical audit program(s), affecting all aspects of clinical work and specialties involved in patient exposure to ionising radiation. [ABSTRACT FROM AUTHOR]

An anatomy quiz particularly on the axial contrast enhanced computed tomogram of the upper thorax is presented.

Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined. Furthermore, the main proteolytic-like (chymotrypsin- and PGPH-) activities have also been analyzed. The middle frontal (Brodmann, BA9), inferior parietal (BA40), and anterior cingulate (BA24) gyrus' cortex were selected as regions of interest from Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and control (n = 24) brains. Clinical and pathological data available included the MMSE score. DLB, PDD, and AD were characterized by significant reductions of RPT6 (one-way ANOVA, p < 0.001; Bonferroni post hoc test) in prefrontal cortex and parietal cortex compared with controls. Strong associations were observed between RPT6 levels in prefrontal, parietal cortex, and anterior cingulate gyrus and cognitive impairment (p = 0.001, p = 0.001, and p = 0.008, respectively). These findings highlight the involvement of the UPS in Lewy body dementia and indicate that targeting the UPS may have the potential to slow down or reduce the progression of cognitive impairment in DLB and PDD. [ABSTRACT FROM AUTHOR]

Aim The unfolded protein response ( UPR) is a pro-survival defence mechanism induced during periods of endoplasmic reticulum stress, and it has recently emerged as an attractive therapeutic target across a number of neurodegenerative conditions, but has not yet been studied in synuclein disorders. Methods The level of a key mediator of the UPR pathway, glucose-regulated protein 78 ( GRP78), also known as binding immunoglobulin protein ( BiP), was measured in post mortem brain tissue of patients with dementia with Lewy bodies ( DLB) and Parkinson's disease dementia ( PDD) in comparison with Alzheimer's disease ( AD) and age-matched controls using Western blot. The UPR activation was further confirmed by immunohistochemical detection of GRP78/ BiP and phosphorylated protein kinase RNA-like endoplasmic reticulum ( ER) kinase ( p-PERK). Results GRP78/ BiP was increased to a greater extent in DLB and PDD patients compared with AD and control subjects in cingulate gyrus and parietal cortex. However, there were no changes in the prefrontal and temporal cortices. There was a significant positive correlation between GRP78/ BiP level and α-synuclein pathology in the cingulate gyrus, while AD-type pathology showed an inverse correlation relationship in the parietal cortex. Conclusion Overall, these results give emphasis to the role of UPR in Lewy body dementias, and suggest that Lewy body degeneration, in combination with AD-type pathologies, is associated with increased UPR activation to a greater extent than AD alone, possibly as a consequence of the increasing load of ER proteins. This work also highlights a novel opportunity to explore the UPR as a therapeutic target in synuclein diseases. [ABSTRACT FROM AUTHOR]

Background: Biopurification has been used to disclose an evolutionarily conserved inhibitory reproductive hormone involved in tissue mass determination. A (rat) bioassay-guided physicochemical fractionation using ovine materials yielded via Edman degradation a 14-residue amino acid (aa) sequence. As a 14mer synthetic peptide (EPL001) this displayed antiproliferative and reproduction-modulating activity, while representing only a part of the native polypeptide. Even more unexpectedly, a scrambled-sequence control peptide (EPL030) did likewise. Methods: Reproduction has been investigated in the nematode Steinernema siamkayai, using a fermentation system supplemented with different concentrations of exogenous hexapeptides. Peptide structure-activity relationships have also been studied using prostate cancer and other mammalian cells in vitro, with peptides in solution or immobilized, and via the use of mammalian assays in vivo and through molecular modelling. Results: Reproduction increased (x3) in the entomopathogenic nematode Steinernema siamkayai after exposure to one synthetic peptide (IEPVFT), while fecundity was reduced (x0.5) after exposure to another (KLKMNG), both effects being dose-dependent. These hexamers are opposite ends of the synthetic peptide KLKMNGKNIEPVFT (EPL030). Bioactivity is unexpected as EPL030 is a control compound, based on a scrambled sequence of the test peptide MKPLTGKVKEFNNI (EPL001). EPL030 and EPL001 are both bioinformatically obscure, having no convincing matches to aa sequences in the protein databases. EPL001 has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Peptides up to a 20mer have also been shown to inhibit the proliferation of human cancer and other mammalian cells in vitro, with reproductive upregulation demonstrated previously in fish and frogs, as well as nematodes. EPL001 encodes the sheep neuroendocrine prohormone secretogranin II (sSgII), as deduced on the basis of immunoprecipitation using an anti-EPL001 antibody, with bespoke bioinformatics. Six sSgII residues are key to EPL001's bioactivity: MKPLTGKVKEFNNI. A stereospecific bimodular tri-residue signature is described involving simultaneous accessibility for binding of the side chains of two specific trios of amino acids, MKP & VFN. An evolutionarily conserved receptor is conceptualised having dimeric binding sites, each with ligand-matching bimodular stereocentres. The bioactivity of the 14mer control peptide EPL030 and its hexapeptide progeny is due to the fortuitous assembly of subsets of the novel hormonal motif, MKPVFN, a default reproductive and tissue-building OFF signal. [ABSTRACT FROM AUTHOR]

Ultrasound-guided wire localization of impalpable lesions is a well-recognized technique in the management of breast pathology, but its use in the head and neck is not well described. Performed under local anesthesia, high-resolution ultrasound provides real-time imaging for accurate placement of the wire resulting in fewer complications. Wire localization can focus the surgical approach, which reduces operating time and minimizes trauma to surrounding tissues. In this technical note, we describe two cases of pre-operative ultrasound-guided wire localization to facilitate the surgical excision of impalpable neck lesions. [ABSTRACT FROM AUTHOR]

MAPK-activated protein kinase 2 (MAPKAP K2 or MK2) is one of several kinases directly regulated by p38 MAPK. A role for p38 MAPK in the pathology of Alzheimer disease (AD) has previously been suggested. Here, we provide evidence to suggest that MK2 also plays a role in neuroinflammatory and neurodegenerative pathology of relevance to AD. MK2 activation and expression were increased in lipopolysaccharide (LPS) + interferon γ-stimulated microglial cells, implicating a role for MK2 in eliciting a pro-inflammatory response. Microglia cultured ex vivo from MK2-deficient (MK2-/-) mice demonstrated significant inhibition in release of tumor necrosis factor α, KC (mouse chemokine with highest sequence identity to human GROs and interleukin-8), and macrophage inflammatory protein 1α on stimulation with LPS + interferon γ or amyloid-β peptide (1-42) compared with MK2+/+ wild-type microglia. Consistent with an inhibition in pro-inflammatory mediator release, cortical neurons co-cultured with LPS + interferon γ-stimulated or amyloid-β peptide (1-42)-stimulated MK2-/- microglia were protected from microglial-mediated neuronal cell toxicity. In a transgenic mouse model of AD in which amyloid precursor protein and presenilin-1 harboring familial AD mutations are over-expressed in specific regions of the brain, elevated activation and expression of MK2 correlated with β-amyloid deposition, microglial activation, and up-regulation of tumor necrosis factor α, macrophage inflammatory protein 1α, and KC gene expression in the same brain regions. Our data propose a role for MK2 in AD brain pathology, for which neuroinflammation involving cytokines and chemokines and overt neuronal loss have been documented. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of parotid neoplasia is a key to determine the most appropriate patient management choice, including the need for surgery. This review provides an update of the literature on current practice and outcomes of parotid tissue sampling techniques, with an emphasis on ultrasound-guided core biopsy (USCB) and comparison with fine needle aspiration cytology (FNAC). A literature review of EMBASE, Medline, PubMed and Google Scholar was conducted. USCB has higher sensitivity, specificity and lower non-diagnostic rates than optimized FNAC. It also has a significantly higher sensitivity for the detection of malignancy. Significant complications post-USCB are uncommon, with only one reported case of tumour seeding and no cases of permanent facial nerve dysfunction. The technique is less operator-dependent than FNAC, with less reported variation in results between institutions. USCB can be considered as the optimum tool of choice for the diagnosis of parotid neoplasia. This would particularly be the case in centres utilizing FNAC with high non-diagnostic rates or reduced diagnostic accuracy when compared to USCB published data, or in centres establishing a new service. An update of the role and outcomes of USCB in the diagnosis of parotid gland pathologies. Research shows that USCB preforms better than FNAC, in terms of sensitivity and specificity, particularly in the case of malignant neoplasia. Complications following USCB were found to be higher than that of FNAC; however, no long-term major complications following either method have been reported in the literature. [ABSTRACT FROM AUTHOR]

The authors comment on the masterclass on multiple myeloma. They note recent changes to guidelines by the National Institute for Care and Health Excellence for the diagnosis of myeloma that recommends whole body magnetic resonance imaging (MRI) as first line imaging for suspected myeloma patients which has higher sensitivity for the detection of bone morrow infiltration. They add that wider uptake of MRI in this case can translate into improved patient outcomes through earlier diagnosis.