A Patient-Specific Anisotropic Diffusion Model for Brain Tumour Spread.

Gliomas are primary brain tumours arising from the glial cells of the nervous system. The diffuse nature of spread, coupled with proximity to critical brain structures, makes treatment a challenge. Pathological analysis confirms that the extent of glioma spread exceeds the extent of the grossly visible mass, seen on conventional magnetic resonance imaging (MRI) scans. Gliomas show faster spread along white matter tracts than in grey matter, leading to irregular patterns of spread. We propose a mathematical model based on Diffusion Tensor Imaging, a new MRI imaging technique that offers a methodology to delineate the major white matter tracts in the brain. We apply the anisotropic diffusion model of Painter and Hillen (J Thoer Biol 323:25-39, 2013) to data from 10 patients with gliomas. Moreover, we compare the anisotropic model to the state-of-the-art Proliferation-Infiltration (PI) model of Swanson et al. (Cell Prolif 33:317-329, 2000). We find that the anisotropic model offers a slight improvement over the standard PI model. For tumours with low anisotropy, the predictions of the two models are virtually identical, but for patients whose tumours show higher anisotropy, the results differ. We also suggest using the data from the contralateral hemisphere to further improve the model fit. Finally, we discuss the potential use of this model in clinical treatment planning.

The diagnostic utility of 99mTc-HMPAO SPECT imaging: a retrospective case series from a tertiary referral early-onset cognitive disorders clinic.

BACKGROUND/AIMS: Patients with early-onset dementia (EOD) often present atypically, making an accurate diagnosis difficult. Single-photon emission-computed tomography (SPECT) provides an indirect measure of cerebral metabolic activity and can help to differentiate between dementia subtypes. This study aims to investigate the clinical utility of SPECT imaging in the diagnosis of early-onset Alzheimer's disease. METHODS: All patients attending a tertiary referral clinic specialising in EOD between April 2012 and October 2013 were included in the study. Statistical analysis of SPECT patterns with clinical diagnoses, Addenbrooke's Cognitive Examination version 3 scores, and magnetic resonance imaging (MRI) atrophy was undertaken. RESULTS: The results demonstrated a highly significant association between SPECT hypoperfusion patterns and clinical diagnoses. SPECT changes were demonstrated more frequently than MRI atrophy. CONCLUSIONS: The results suggest that SPECT imaging may be a useful adjunct to clinical evaluation and a more sensitive biomarker than standard structural imaging.

Psychiatric diagnosis and quality of life: the additional burden of psychiatric comorbidity.

OBJECTIVES: To compare quality of life (QoL) in mental health outpatients to non-clinical norms, and examine the associations between QoL and principal diagnosis, number of comorbid Axis I diagnoses, and type of comorbidity. METHODS: Consecutively referred and assessed patients (n = 2024) formed the study sample pool. Of these, 1486 individuals who had completed a QoL instrument at intake and had a principal diagnosis amenable to comparison by group analysis were included in the study. Principal diagnoses were unipolar mood disorder (n = 687), eating disorder (n = 226), bipolar disorder (n = 165), social anxiety disorder (n = 165), generalized anxiety disorder (n = 125), and panic disorder (n = 118). QoL for psychiatric groups was compared to non-clinical norms using a valid and reliable measure. RESULTS: QoL was significantly impaired in all psychiatric groups compared to nonclinical norms. There was a significant interaction between principal diagnosis and number of comorbid Axis I disorders, controlling for age, sex, marital status, employment, and years of school. The addition of one comorbidity significantly attenuated QoL in social anxiety disorder, panic disorder, and bipolar disorder. For all other conditions, a significant loss in QoL occurred with two or more comorbidities. Axis I depressive and anxiety comorbidity significantly attenuated QoL across all diagnostic groups. CONCLUSIONS: QoL is significantly impaired in psychiatric outpatients and diagnostic groups vary in the extent to which they experience additional QoL burden with increasing comorbidities.

Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer.

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC. Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v <35g/L) and overall survival (OS) was examined. Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23-2.7) (p =0.003) and HR2.55 (95%CI 1.78-3.65) (p < 0.001), respectively. Pre-treatment albumin <35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20-41.72, p = 0.003) and RR3.60 (95%CI 1.74-6.57, p < 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86-4.46) (p < 0.001) and HR2.67 (95%CI 1.74-4.08) (p < 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin <35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61-3.82) (p < 0.001) and HR2.87 (95%CI 1.91-4.31) (p < 0.001) respectively). Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.

Feasibility of streamline upwind Petrov-Galerkin angular stabilization of the linear Boltzmann transport equation with magnetic fields.

To accurately model dose in a magnetic field, the Lorentz force must be included in the traditional linear Boltzmann transport equation (LBTE). Both angular and spatial stabilization are required to deterministically solve this equation. In this work, a streamline upwind Petrov-Galerkin (SUPG) method is applied to achieve angular stabilization of the LBTE with magnetic fields. The spectral radius of the angular SUPG method is evaluated using a Fourier analysis method to characterize the convergence properties. Simulations are then performed on homogeneous phantoms and two heterogeneous slab geometry phantoms containing water, bone, lung/air and water for 0.5 T parallel and 1.5 T perpendicular magnetic field configurations. Fourier analysis determined that the spectral radius of the SUPG scheme is unaffected by magnetic field strength and the SUPG free parameter, indicating that the Gauss-Seidel source iteration method is unconditionally stable and the convergence rate is not degraded with increasing magnetic field strength. 100% of simulation points passed a 3D gamma analysis at a 2%/2 mm (3%/3 mm) gamma criterion for both magnetic field configurations in the homogeneous phantom study, with the exception of the 1.5 T perpendicular magnetic field in the pure lung phantom where a 77.4% (87.0%) pass rate was achieved. Simulations in the lung slab geometry phantom resulted in 100% of points passing a 2%/2 mm gamma analysis in a 0.5 T parallel magnetic field, and 97.7% (98.8%) of points passing a 2%/2 mm (3%/3 mm) gamma criterion in a 1.5 T perpendicular magnetic field. For the air slab geometry phantom, 72.1% (79.2%) of points passed a 2%/2 mm gamma criterion in a 0.5 T parallel magnetic field and 90.3% (92.8%) passed the same gamma criterion in a 1.5 T perpendicular magnetic field. While the novel SUPG angular stabilization method shows feasibility in some cases, it was found that the accuracy of this method was degraded for very low density media such as air.

Quality of life in depression: an important outcome measure in an outpatient cognitive-behavioural therapy group programme?

Studies have shown that psychiatric patients have significantly impaired quality of life (QOL) in comparison to community samples who are not suffering a mental illness. Despite an increase in research in the mental health field, there still remains little consensus as to the merit of using such questionnaires within a mental health population. There is a concern that QOL is redundant with affective state and symptomatology. We investigated the usefulness of the Quality of Life Enjoyment and Satisfaction Questionnaire-short form (QLESQ-SF) in a depressed outpatient sample receiving time-limited, standardized group cognitive-behavioural therapy. QLESQ-SF ratings were examined at admission and 10-week endpoint in an intention-to-treat (N = 212) and completers (N = 164) sample. QLESQ-SF ratings and symptom ratings (Beck Depression Inventory-II; Beck Anxiety Inventory) improved significantly over time. Hierarchical regression analyses revealed that, although affective state and change in symptomatology were significantly correlated with QOL and change in QOL, a large proportion of variance was unexplained. These results are inconsistent with the theory of measurement redundancy. QOL appears to be a useful measure that provides additional treatment outcome information distinct from affective state and symptomatology.

Patient perceptions of their decision to undergo palliative chemotherapy in the Edinburgh Cancer Centre.

BACKGROUND: The decision to undergo chemotherapy for incurable cancer demands informed discussions about the risks and benefits of proposed treatments. Research has shown that many patients have a poor grasp of these factors. METHODS: An evaluation of the patient experience of palliative chemotherapy decision-making was undertaken. Patients with lung or gynaecological cancers were surveyed about their decision, what they understood about its risks and benefits, and how supported they felt. RESULTS: A total of 29 people with lung cancer (n = 21) or gynaecological cancer (n = 8) completed questionnaires. The majority felt sure about their decision, though many were less sure of the risks and benefits of treatment. Unprompted comments revealed significant nuance, including that the decision to undergo chemotherapy may not necessarily have felt like a choice. CONCLUSIONS: Our positive findings may reflect participant selection bias, or could represent genuine comfort in decision-making in Scottish oncology clinics. Further research is needed.

Moments of von Mises and Fisher distributions and applications.

The von Mises and Fisher distributions are spherical analogues to the Normal distribution on the unit circle and unit sphere, respectively. The computation of their moments, and in particular the second moment, usually involves solving tedious trigonometric integrals. Here we present a new method to compute the moments of spherical distributions, based on the divergence theorem. This method allows a clear derivation of the second moments and can be easily generalized to higher dimensions. In particular we note that, to our knowledge, the variance-covariance matrix of the three dimensional Fisher distribution has not previously been explicitly computed. While the emphasis of this paper lies in calculating the moments of spherical distributions, their usefulness is motivated by their relationship to population statistics in animal/cell movement models and demonstrated in applications to the modelling of sea turtle navigation, wolf movement and brain tumour growth.

Group metacognitive therapy for repetitive negative thinking in primary and non-primary generalized anxiety disorder: an effectiveness trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a common and highly comorbid anxiety disorder characterized by repetitive negative thinking (RNT). Treatment trials tend to exclude individuals with non-primary GAD, despite this being a common presentation in real world clinics. RNT is also associated with multiple emotional disorders, suggesting that it should be targeted regardless of the primary disorder. This study evaluated the acceptability and effectiveness of brief group metacognitive therapy (MCT) for primary or non-primary GAD within a community clinic. METHODS: Patients referred to a specialist community clinic attended six, two-hour weekly sessions plus a one-month follow-up (N=52). Measures of metacognitive beliefs, RNT, symptoms, positive and negative affect, and quality of life were completed at the first, last, and follow-up sessions. RESULTS: Attrition was low and large intent-to-treat effects were observed on most outcomes, particularly for negative metacognitive beliefs and RNT. Treatment gains increased further to follow-up. Benchmarking comparisons demonstrated that outcomes compared favorably to longer disorder-specific protocols for primary GAD. LIMITATIONS: No control group or independent assessment of protocol adherence. CONCLUSIONS: Brief metacognitive therapy is an acceptable and powerful treatment for patients with primary or non-primary GAD.

Assessment of arrays of in-stream tidal turbines in the Bay of Fundy.

Theories of in-stream turbines are adapted to analyse the potential electricity generation and impact of turbine arrays deployed in Minas Passage, Bay of Fundy. Linear momentum actuator disc theory (LMADT) is combined with a theory that calculates the flux through the passage to determine both the turbine power and the impact of rows of turbine fences. For realistically small blockage ratios, the theory predicts that extracting 2000-2500 MW of turbine power will result in a reduction in the flow of less than 5 per cent. The theory also suggests that there is little reason to tune the turbines if the blockage ratio remains small. A turbine array model is derived that extends LMADT by using the velocity field from a numerical simulation of the flow through Minas Passage and modelling the turbine wakes. The model calculates the resulting speed of the flow through and around a turbine array, allowing for the sequential positioning of turbines in regions of strongest flow. The model estimates that over 2000 MW of power is possible with only a 2.5 per cent reduction in the flow. If turbines are restricted to depths less than 50 m, the potential power generation is reduced substantially, down to 300 MW. For large turbine arrays, the blockage ratios remain small and the turbines can produce maximum power with a drag coefficient equal to the Betz-limit value.

Imaging and sizing of diamond nanoparticles.

Typical disturbances of biological environment such as background scatter and refractive index variations have little effect on the size-dependent scattering property of highly refractive nanocrystals, which are potentially attractive optical labels. We report on what is to our knowledge the first investigation of these scattering optical labels, and their sizing, in particular, by imaging at subvideo frame rates and analyzing samples of diamond nanocrystals deposited on a glass substrate in air and in a matrix of weakly scattering polymer. The brightness of a diffraction-limited spot appears to serve as a reliable measure of the particle size in the Rayleigh scattering limit.