Exploring Analysis Approaches for Using the Dopamine Transporter Striatal Binding Ratio in Early- to Mid-Stage Parkinson's Disease Modification Trials.

BACKGROUND: The dopamine transporter striatal binding ratio (DAT SBR) has been used as an outcome measure in Parkinson's disease (PD) trials of potential disease-modifying therapies; however, both patient characteristics and analysis approach potentially complicate its interpretation. OBJECTIVE: The aim was to explore how well DAT SBR reflects PD motor severity across different striatal subregions and the relationship to disease duration, and side of onset. METHODS: DAT SBR for the anterior and posterior putamen and caudate in both hemispheres was obtained using validated automated quantitative software on baseline scans of 132 patients recruited for the Exenatide PD2 and PD3 trials. Associations between mean and lateralized SBR subregions (posterior and anterior putamen and caudate) and summed and lateralized motor characteristics were explored using regression analysis. Analyses were repeated considering disease duration and limiting analysis to the less-affected hemisphere. RESULTS: Lateralized bradykinesia was most consistently associated with the loss of DAT uptake in the contralateral anterior putamen. There was much higher variance in the posterior putamen, and in all regions in those with longer duration disease, although bradykinesia remained robustly associated with anterior putaminal DAT uptake even in longer-duration patients. Restricting analyses to the less-affected side did not usefully reduce the variance compared to the overall cohort. CONCLUSION: These data suggest that DAT SBR could be a useful biomarker in disease-modifying trials, but a focus on anterior striatal subregions and incorporating disease duration into analyses may improve its utility.

From SPECT/CT towards absolute quantification? - the case of unilateral condylar hyperplasia of the mandible.

BACKGROUND: Unilateral condylar hyperplasia (UCH) of the mandible is a rare condition characterized by asymmetric growth of the mandibular condyles. Bone scintigraphy with SPECT(/CT) is commonly used to diagnose UCH and guide treatment. Still, varying results have been reported using the traditional threshold of 55%:45% in relative tracer uptake. While absolute quantification of uptake on SPECT/CT could improve results, optimal correction and reconstruction settings are currently unknown. METHODS: Three anthropomorphic phantoms representing UCH were developed from patient CT volumes and produced using 3D printing technology. Fillable spherical inserts of different sizes (Ø: 8-15 mm) were placed in the condylar positions representing symmetrical and asymmetrical distributions. Recovery coefficients were determined for SPECT/CT using various reconstruction corrections, including attenuation and scatter correction (ACSC), resolution modeling (RM), and partial volume correction (PVC) using phantom measurements. Uptake ratios between condyles and condyle to clivus were evaluated. Finally, the impact of these correction techniques on absolute activity and diagnostic accuracy was assessed in a retrospective patient cohort for the diagnostic threshold of 55%:45%. RESULTS: The activity was only partially recovered in all spherical inserts (range: 22.5-64.9%). However, RM improved relative recovery by 20.2-62.3% compared to ACSC. In the symmetric phantoms, the 95% confidence interval (CI) of condyle ratios included the diagnostic threshold (57.6%:42.4%) for UCH when using ACSC potentially leading to false positives, but not for ACSCRM datasets. Partial volume corrections coefficients from the NEMA IQ phantom was positionally dependent, with improvements seen performing PVC using coefficients derived from anthropomorphic phantoms. Retrospective application in a patient cohort showed only a weak linear correlation (R²: 0.25-0.67) and large limits of agreement (9.6-12.5%) between different reconstructions. Up to 44% of patients were reclassified using the 55%:45% threshold. Using clinical outcome data, ACSCRM had highest sensitivity (91%; 95% CI 59-100%) and specificity (66%; 95% CI 47-81%), significantly improving specificity (P = 0.038). CONCLUSIONS: Anthropomorphic phantoms were shown to be essential in determining optimal settings for acquisition, reconstruction, and analysis. SPECT/CT reconstructions with attenuation and scatter correction and resolution modeling are recommended and could improve specificity when using the 55%:45% threshold to assess condylar growth.

Fungi and bacteria occupy distinct spatial niches within carious dentin.

The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of dentin in advanced caries especially merits additional research. We evaluated the fungal and bacterial community composition and spatial distribution within carious dentin. Amplicon 16S rRNA gene sequencing together with quantitative PCR was used to profile bacterial and fungal species in caries-free children (n = 43) and 4 stages of caries progression from children with severe early childhood caries (n = 32). Additionally, healthy (n = 10) and carious (n = 10) primary teeth were decalcified, sectioned, and stained with Grocott's methenamine silver, periodic acid Schiff (PAS) and calcofluor white (CW) for fungi. Immunolocalization was also performed using antibodies against fungal ß-D-glucan, gram-positive bacterial lipoteichoic acid, gram-negative endotoxin, Streptococcus mutans, and Candida albicans. We also performed field emission scanning electron microscopy (FESEM) to visualize fungi and bacteria within carious dentinal tubules. Bacterial communities observed included a high abundance of S. mutans and the Veillonella parvula group, as expected. There was a higher ratio of fungi to bacteria in dentin-involved lesions compared to less severe lesions with frequent preponderance of C. albicans, C. dubliniensis, and in one case C. tropicalis. Grocott's silver, PAS, CW and immunohistochemistry (IHC) demonstrated the presence of fungi within carious dentinal tubules. Multiplex IHC revealed that fungi, gram-negative, and gram-positive bacteria primarily occupied separate dentinal tubules, with rare instances of colocalization. Similar findings were observed with multiplex immunofluorescence using anti-S. mutans and anti-C. albicans antibodies. Electron microscopy showed monomorphic bacterial and fungal biofilms within distinct dentin tubules. We demonstrate a previously unrecognized phenomenon in which fungi and bacteria occupy distinct spatial niches within carious dentin and seldom co-colonize. The potential significance of this phenomenon in caries progression warrants further exploration.

Neuropathologic Validation and Diagnostic Accuracy of Presynaptic Dopaminergic Imaging in the Diagnosis of Parkinsonism.

BACKGROUND AND OBJECTIVES: Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism. METHODS: Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism. RESULTS: All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%). DISCUSSION: DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

The Impact of Anti-Amyloid Immunotherapies on Stroke Care.

Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer's disease. While these therapies have demonstrated efficacy in clearing amyloid-ß and slowing cognitive decline, they have also been associated with amyloid-related imaging abnormalities (ARIA) which include both edema (ARIA-E) and hemorrhage (ARIA-H). Given that ARIA have been associated with significant morbidity in cases of antithrombotic or thrombolytic therapy, an understanding of mechanisms of and risk factors for ARIA is of critical importance for stroke care. We discuss the latest data regarding mechanisms of ARIA, including the role of underlying cerebral amyloid angiopathy, and implications for ischemic stroke prevention and management.

Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with ß-amyloid status in cognitively normal adults at age 70.

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3.

BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Injectable Devices for Delivery of Liquid or Solid Protein Formulations.

Sustained delivery of protein therapeutics remains a largely unsolved problem across anatomic locations. Miniaturized devices that can provide sustained delivery of protein formulations have the potential to address this challenge via minimally invasive administration. In particular, methodologies that can optimize protein formulation independent of device manufacture have the greatest potential to provide a platform suitable for wide applications. The techniques developed here demonstrate the fabrication of tubular devices for sustained release of protein therapeutics. Utilizing a dip-casting process, fine-scale tubes can be reliably produced with wall thickness down to 30 µm. Techniques were developed that enabled effective loading of either solid or liquid formulations, while maintaining a cylindrical form-factor compatible with placement in a 22-gauge needle. Further, highly compacted protein pellets that approach the expected density of the raw materials were produced with a diameter (∼300 µm) suitable for miniaturized devices. Release from a solid-loaded device was capable of sustaining release of a model protein in excess of 400 days. Given significant interest in ocular applications, intravitreal injection was demonstrated in a rabbit model with these devices. In addition, to simulate repeated injections in ocular applications, serial intravitreal injection of two devices in a rabbit model demonstrated acceptable ocular safety without significant intraocular inflammation from clinical exam and histology.

CORRELATION BETWEEN DIGNITY, EMPATHY AND EMPLOYEE PRODUCTIVITY AMONG WORKERS IN PRIVATE HOSPITALS IN RIVERS STATE.

Background and aim: Workplace humanization, when effectively managed can be instrumental in steering an organization towards efficient, and effective work processes. It is on this backdrop that this study aimed at determining the inter-relationship between employee productivity, dignity and empathy. Materials and methods: This was a cross-sectional study that identified the relationship between the study variables. It was conducted among 233 randomly selected employees of private hospitals in Port Harcourt, Rivers State, Nigeria. A self-administered structured questionnaire was used to assess the study variables. Data analysis was conducted using the Statistical Package for Social Sciences (SPSS) software and the relationship between variables tested using the Spearman correlation test. Statistical significance was set at 0.05. Results: The indicators of employee dignity, empathy and productivity were found to have high mean values which were above the threshold of 2.0. A strong positive significant correlation was found to exist between dignity and task accomplishment (r2: 0.796, p-value: <0.001) as well as empathy and task accomplishment (r2: 0.843, p-value: <0.001). Also, a moderate positive statistically significant correlation was found to exist between dignity and service quality (r2=0.373, p-value: <0.001) as well as between employee empathy and service quality (r2= 0.402, p-value: <0.001). Conclusion and Recommendations: The dignity of an employee alongside empathy as measures of work humanization are significant correlates of employee productivity which can be exploited for organizational growth. It is recommended that organizations through institutionalized policies can successfully manage their workplace for optimal productivity via improved employee dignity and empathy as a means of increasing job satisfaction and reduce brain drain.

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer's Disease.

BACKGROUND: Single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis. OBJECTIVE: In this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer's disease (AD). METHODS: We analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD. RESULTS: Regional perfusion reduction in the precuneus and medial temporal regions predicted Aß42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85. CONCLUSIONS: Study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds.

We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular health. Participants born in the same week in March 1946 (British 1946 birth cohort) underwent PET-MRI around age 70. Mean standardized normal-appearing white matter integrity metrics (fractional anisotropy, mean diffusivity, neurite density index and orientation dispersion index) were derived from diffusion MRI. Linear regression was used to test associations between normal-appearing white matter metrics and (i) concurrent measures, including whole brain volume, white matter hyperintensity volume, PET amyloid and cognition; (ii) the influence of demographic and genetic predictors, including sex, childhood cognition, education, socio-economic position and genetic risk for Alzheimer's disease (APOE-ɛ4); (iii) systolic and diastolic blood pressure and cardiovascular health (Framingham Heart Study Cardiovascular Risk Score) across adulthood. Sex interactions were tested. Statistical significance included false discovery rate correction (5%). Three hundred and sixty-two participants met inclusion criteria (mean age 70, 49% female). Higher white matter hyperintensity volume was associated with lower fractional anisotropy [b = -0.09 (95% confidence interval: -0.11, -0.06), P < 0.01], neurite density index [b = -0.17 (-0.22, -0.12), P < 0.01] and higher mean diffusivity [b = 0.14 (-0.10, -0.17), P < 0.01]; amyloid (in men) was associated with lower fractional anisotropy [b = -0.04 (-0.08, -0.01), P = 0.03)] and higher mean diffusivity [b = 0.06 (0.01, 0.11), P = 0.02]. Framingham Heart Study Cardiovascular Risk Score in later-life (age 69) was associated with normal-appearing white matter {lower fractional anisotropy [b = -0.06 (-0.09, -0.02) P < 0.01], neurite density index [b = -0.10 (-0.17, -0.03), P < 0.01] and higher mean diffusivity [b = 0.09 (0.04, 0.14), P < 0.01]}. Significant sex interactions (P < 0.05) emerged for midlife cardiovascular health (age 53) and normal-appearing white matter at 70: marginal effect plots demonstrated, in women only, normal-appearing white matter was associated with higher midlife Framingham Heart Study Cardiovascular Risk Score (lower fractional anisotropy and neurite density index), midlife systolic (lower fractional anisotropy, neurite density index and higher mean diffusivity) and diastolic (lower fractional anisotropy and neurite density index) blood pressure and greater blood pressure change between 43 and 53 years (lower fractional anisotropy and neurite density index), independently of white matter hyperintensity volume. In summary, poorer normal-appearing white matter microstructural integrity in ∼70-year-olds was associated with measures of cerebral small vessel disease, amyloid (in males) and later-life cardiovascular health, demonstrating how normal-appearing white matter can provide additional information to overt white matter disease. Our findings further show that greater 'midlife' cardiovascular risk and higher blood pressure were associated with poorer normal-appearing white matter microstructural integrity in females only, suggesting that women's brains may be more susceptible to the effects of midlife blood pressure and cardiovascular health.

Brain PET and SPECT imaging and quantification: a survey of the current status in the UK.

OBJECTIVES: With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. METHODS: A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. RESULTS: Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitative Brain analysis is used in 86% of sites performing DaTscans, 40% for Perfusion SPECT, 63% for FDG PET and 42% for Amyloid PET. Commercial tools are used more frequently than in-house software. CONCLUSION: The survey showed variations across the UK, with high availability of DaTscan imaging and quantification and lower availability of other SPECT and PET scans. The main drivers for quantification were improved reporting confidence and diagnostic accuracy, while the main barriers were a perception of a need for an appropriate database of healthy controls and a lack of training, time, and software availability.

A UK consensus statement on thromboprophylaxis for autologous breast reconstruction.

Microsurgical breast reconstruction accounts for 22% of breast reconstructions in the UK. Despite thromboprophylaxis, venous thromboembolism (VTE) occurs in up to 4% of cases. Using a Delphi process, this study established a UK consensus on VTE prophylaxis strategy, for patients undergoing autologous breast reconstruction using free-tissue transfer. It captured geographically divergent views, producing a guide that reflected the peer opinion and current evidence base. METHODS: Consensus was ascertained using a structured Delphi process. A specialist from each of the UK's 12 regions was invited to the expert panel. Commitment to three to four rounds of questions was sought at enrollment. Surveys were distributed electronically. An initial qualitative free-text survey was distributed to identify likely lines of consensus and dissensus. Each panelist was provided with full-text versions of key papers on the topic. Initial free-text responses were analyzed to develop a set of structured quantitative statements, which were refined via a second survey as a consensus was approached. RESULTS: The panel comprised 18 specialists: plastic surgeons and thrombosis experts from across the UK. Each specialist completed three rounds of surveys. Together, these plastic surgeons reported having performed more than 570 microsurgical breast reconstructions in the UK in 2019. A consensus was reached on 27 statements, detailing the assessment and delivery of VTE prophylaxis. CONCLUSION: To our knowledge, this is the first study to collate current practice, expert opinion from across the UK, and a literature review. The output was a practical guide for VTE prophylaxis for microsurgical breast reconstruction in any UK microsurgical breast reconstruction unit.

Operationalizing the centiloid scale for [18F]florbetapir PET studies on PET/MRI.

INTRODUCTION: The Centiloid scale aims to harmonize amyloid beta (Aß) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI). METHODS: We transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian-mixture-modelling-derived cutpoints for Aß PET positivity were converted. RESULTS: The Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM-based Centiloids. Linear adjustment produced a WM-based cutpoint of 18.1. DISCUSSION: Transformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed. HIGHLIGHTS: Centiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results.Centiloid values can be influenced by differences in acquisition.We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort.Whole cerebellum referenced values could be reliably transformed to Centiloids.White matter referenced values may be less generalizable between datasets.

A diagrammatic summary of updated NICE melanoma guidance: A simple way to mitigate human factors in MDTs and clinics.

National Institute for Health and Care Excellence (NICE) has published an updated guideline on melanoma assessment and management in July 2022, which has included recommendation on BRAF analysis of primary melanoma tissue samples, staging with sentinel lymph node biopsy, guidance on patient follow-up as well as surveillance imaging requirement based on patients' melanoma stages. However, very often, assimilating this considerable amount of information in an efficient and accurate way can be challenging, especially in the setting of a busy multidisciplinary team (MDT) meeting. Human factors are well recognised as a key principle to mitigate against mistakes and human errors and thereby aiming to optimise patient care. To date, there is very limited literature available on the subject of the role of human factors in the context of MDT meetings. In recent years, the numbers and complexity of patients in cancer MDT meetings have grown significantly. Long MDT meetings could lead to distraction, loss of attention span, miscommunication, missed information, and hence increasing the risk of clinical error. We present a diagrammatic summary of the most recent NICE guidance for melanoma follow-up that is currently being used locally in our department. This aims to offer clarity and ease of use to help health care professionals to check patients' treatment pathways. It can also be included in patients' medical record for annotation or reference in future follow-up clinics, which is a simple measure to mitigate the risks of human factors, as well as ensuring consistency in continuity of patient care.

Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease.

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition.

Altered localization of nucleoporin 98 in primary tauopathies.

Nucleoporin 98 is a nuclear pore complex component that is mislocalized in Alzheimer's disease and the alteration in nucleoporin 98 has been attributed to tau. In order to determine if nucleoporin 98 mislocalization is a general feature of tauopathies, we assessed the localization of nucleoporin 98 in neurons in primary tauopathies, including frontotemporal lobar degeneration-tau, corticobasal degeneration and progressive supranuclear palsy. Immunofluorescence staining was performed on frontal cortex and occipital cortex tissue from cases of primary tauopathies and controls without neurodegenerative disease using antibodies to identify nucleoporin 98, phospho-tau (Ser202, Thr205) monoclonal antibody and neuronal marker microtubule-associated protein 2. The stained tissue was imaged by fluorescence microscopy and the number of neurons with mislocalized nucleoporin 98 and phospho-tau (Ser202, Thr205) monoclonal antibody staining was quantified. In frontal cortex tissue, all primary tauopathies examined demonstrated significantly increased numbers of neurons with abnormal localization of nucleoporin 98 along the nuclear envelope compared with control tissue. Additionally, frontotemporal lobar degeneration-tau and corticobasal degeneration in the frontal cortex demonstrated significantly increased numbers of neurons with a cytoplasmic mislocalization of nucleoporin 98 compared with control tissue. The number of neurons with mislocalized nucleoporin 98 was significantly correlated with the number of neurons with phospho-tau (Ser202, Thr205) monoclonal antibody-positive tau staining. In the occipital cortex, which is relatively spared from pathological tau accumulations in these primary tauopathies, the localization of nucleoporin 98 was not significantly altered. This study demonstrates that nucleoporin 98 mislocalization is a feature of primary tauopathies and is associated with pathological tau accumulation. In the context of prior research demonstrating nucleoporin 98 mislocalization in Alzheimer's disease and an interaction between tau and nucleoporin 98, these results further support the hypothesis that pathological tau may contribute to nucleoporin 98 mislocalization. Given the critical role of the nuclear pore complex in nucleocytoplasmic transport, the identification of nucleoporin 98 mislocalization in primary tauopathies highlights a potential pathophysiological disruption in these disorders.

EANM guidelines for PET-CT and PET-MR routine quality control.

We present guidelines by the European Association of Nuclear Medicine (EANM) for routine quality control (QC) of PET-CT and PET-MR systems. These guidelines are partially based on the current EANM guidelines for routine quality control of Nuclear Medicine instrumentation but focus more on the inherent multimodal aspect of the current, state-of-the-art PET-CT and PET-MR scanners. We briefly discuss the regulatory context put forward by the International Electrotechnical Commission (IEC) and European Commission (EC) and consider relevant guidelines and recommendations by other societies and professional organizations. As such, a comprehensive overview of recommended quality control procedures is provided to ensure the optimal operational status of a PET system, integrated with either a CT or MR system. In doing so, we also discuss the rationale of the different tests, advice on the frequency of each test and present the relevant MR and CT tests for an integrated system. In addition, we recommend a scheme of preventive actions to avoid QC tests from drifting out of the predefined range of acceptable performance values such that an optimal performance of the PET system is maintained for routine clinical use.