The definitions of three-dimensional landmarks on the human face: an interdisciplinary view.

The analysis of shape is a key part of anatomical research and in the large majority of cases landmarks provide a standard starting point. However, while the technology of image capture has developed rapidly and in particular three-dimensional imaging is widely available, the definitions of anatomical landmarks remain rooted in their two-dimensional origins. In the important case of the human face, standard definitions often require careful orientation of the subject. This paper considers the definitions of facial landmarks from an interdisciplinary perspective, including biological and clinical motivations, issues associated with imaging and subsequent analysis, and the mathematical definition of surface shape using differential geometry. This last perspective provides a route to definitions of landmarks based on surface curvature, often making use of ridge and valley curves, which is genuinely three-dimensional and is independent of orientation. Specific definitions based on curvature are proposed. These are evaluated, along with traditional definitions, in a study that uses a hierarchical (random effects) model to estimate the error variation that is present at several different levels within the image capture process. The estimates of variation at these different levels are of interest in their own right but, in addition, evidence is provided that variation is reduced at the observer level when the new landmark definitions are used.

Loss of normal facial asymmetry in schizophrenia and bipolar disorder: Implications for development of brain asymmetry in psychotic illness.

Development of the craniofacies occurs in embryological intimacy with development of the brain and both show normal left-right asymmetries. While facial dysmorphology occurs to excess in psychotic illness, facial asymmetry has yet to be investigated as a putative index of brain asymmetry. Ninety-three subjects (49 controls, 22 schizophrenia, 22 bipolar disorder) received 3D laser surface imaging of the face. On geometric morphometric analysis with (x, y, z) visualisations of statistical models for facial asymmetries, in controls the upper face and periorbital region, which share embryological intimacy with the forebrain, showed marked asymmetries. Their geometry included: along the x-axis, rightward asymmetry in its dorsal-medial aspects and leftward asymmetry in its ventral-lateral aspects; along the z-axis, anterior protrusion in its right ventral-lateral aspect. In both schizophrenia and bipolar disorder these normal facial asymmetries were diminished, with residual retention of asymmetries in bipolar disorder. This geometry of normal facial asymmetries shows commonalities with that of normal frontal lobe asymmetries. These findings indicate a trans-diagnostic process that involves loss of facial asymmetries in both schizophrenia and bipolar disorder. Embryologically, they implicate loss of face-brain asymmetries across gestational weeks 7-14 in processes that involve genes previously associated with risk for schizophrenia.

The underestimated fraction: diversity, challenges and novel insights into unicellular cyanobionts of lichens.

Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.

Unsupervised mitochondria segmentation using recursive spectral clustering and adaptive similarity models.

The unsupervised segmentation method proposed in the current study follows the evolutional ability of human vision to extrapolate significant structures in an image. In this work we adopt the perceptual grouping strategy by selecting the spectral clustering framework, which is known to capture perceptual organization features, as well as by developing similarity models according to Gestaltic laws of visual segregation. Our proposed framework applies but is not limited to the detection of cells and organelles in microscopic images and attempts to provide an effective alternative to presently dominating manual segmentation and tissue classification practice. The main theoretical contribution of our work resides in the formulation of robust similarity models which automatically adapt to the statistical structure of the biological domain and return optimal performance in pixel classification tasks under the wide variety of distributional assumptions.

Convective tissue movements play a major role in avian endocardial morphogenesis.

Endocardial cells play a critical role in cardiac development and function, forming the innermost layer of the early (tubular) heart, separated from the myocardium by extracellular matrix (ECM). However, knowledge is limited regarding the interactions of cardiac progenitors and surrounding ECM during dramatic tissue rearrangements and concomitant cellular repositioning events that underlie endocardial morphogenesis. By analyzing the movements of immunolabeled ECM components (fibronectin, fibrillin-2) and TIE1 positive endocardial progenitors in time-lapse recordings of quail embryonic development, we demonstrate that the transformation of the primary heart field within the anterior lateral plate mesoderm (LPM) into a tubular heart involves the precise co-movement of primordial endocardial cells with the surrounding ECM. Thus, the ECM of the tubular heart contains filaments that were associated with the anterior LPM at earlier developmental stages. Moreover, endocardial cells exhibit surprisingly little directed active motility, that is, sustained directed movements relative to the surrounding ECM microenvironment. These findings point to the importance of large-scale tissue movements that convect cells to the appropriate positions during cardiac organogenesis.

Impact of the demand for 'proxy assent' on recruitment to a randomised controlled trial of vaccination testing in care homes.

Legal frameworks are in place to protect those who lack the capacity to consent to research, such as the Mental Capacity Act in the UK. Assent is sought instead from a proxy, usually a relative. However, the same legislation may, perversely, affect the welfare of those who lack capacity and of others by hindering the process of recruitment into otherwise potentially beneficial research. In addition, the onus of responsibility is moved from those who know most about the study (ie, the scientific community) to those who know less (the proxies). In this paper, we describe the characteristics of a sample at different stages of the recruitment process of an influenza vaccine-based randomised control trial in elderly care home residents (the FEVER study). 62% (602/968) of potential subjects lacked capacity but only 29% (80/277) of those actually randomised. Older age, being female and living in an Elderly Mentally Ill care home were the only variables associated with lacking capacity. Considering this was a study based in a care home setting where the prevalence of dementia approximates 80%, the trial, like many others, was thus significantly biased. We believe that difficulties seeking proxy assent contributed significantly to this problem. Further thought should be given to how assent to enter research for those who lack capacity should be provided, and we suggest avenues for further discussion such as independent risk/benefit expert panels.

Management of a patient with locally advanced prostate cancer with degarelix: a case report.

Gonadotropin releasing hormone (GnRH) antagonists, such as degarelix, are emerging as an androgen deprivation therapy primary agents in a treatment of advanced prostate cancer. The role of GnRH antagonists in management of lower urinary tract symptoms associated with prostate cancer has not been clearly established. In this report, we describe the case of a patient with locally advanced prostate cancer who presented with symptoms of urinary retention and renal failure. The use of degarelix in this patient led to a rapid reduction in the prostate-specific antigen level; however, obstructive symptoms persisted despite the use of degarelix and radiation treatment.

Delirium scales: A review of current evidence.

OBJECTIVES: Delirium is a common neuropsychiatric condition with many adverse outcomes in elderly populations including death. Despite this, it is often misdiagnosed and mistreated. A number of scales can be used to detect delirium. We review scales that have been used in delirium studies and report their psychometric properties. METHOD: An extensive MEDLINE database search and subsequent examination of reference lists was conducted to identify the various delirium scales that have been designed, primarily for use in the elderly. RESULTS: Twenty-four scales were identified. Delirium instruments differed according to the classification system they were based on, length of time to administer, the rater and whether they were screening scales or measured symptom severity. The psychometric properties of each scale is reported. CONCLUSION: A large number of scales exist, but not all are properly evaluated in terms of psychometric properties, and there is not unanimity about which scale is the best. However, a small number of scales may be considered already to be robust and useable: the CAM, the DRS, the MDAS and the NEECHAM.

Refining the resolution of craniofacial dysmorphology in bipolar disorder as an index of brain dysmorphogenesis.

As understanding of the genetics of bipolar disorder increases, controversy endures regarding whether the origins of this illness include early maldevelopment. Clarification would be facilitated by a 'hard' biological index of fetal developmental abnormality, among which craniofacial dysmorphology bears the closest embryological relationship to brain dysmorphogenesis. Therefore, 3D laser surface imaging was used to capture the facial surface of 21 patients with bipolar disorder and 45 control subjects; 21 patients with schizophrenia were also studied. Surface images were subjected to geometric morphometric analysis in non-affine space for more incisive resolution of subtle, localised dysmorphologies that might distinguish patients from controls. Complex and more biologically informative, non-linear changes distinguished bipolar patients from control subjects. On a background of minor dysmorphology of the upper face, maxilla, midface and periorbital regions, bipolar disorder was characterised primarily by the following dysmorphologies: (a) retrusion and shortening of the premaxilla, nose, philtrum, lips and mouth (the frontonasal prominences), with (b) some protrusion and widening of the mandible-chin. The topography of facial dysmorphology in bipolar disorder indicates disruption to early development in the frontonasal process and, on embryological grounds, cerebral dysmorphogenesis in the forebrain, most likely between the 10th and 15th week of fetal life.

The role of AA sponsors: a pilot study.

AIMS: The aim of this study was to explore the roles of Alcoholics Anonymous (AA) sponsors and to describe the characteristics of a sample of sponsors. METHODS: Twenty-eight AA sponsors, recruited using a purposive sampling method, were administered an unstructured qualitative interview and standardized questionnaires. The measurements included: a content analysis of sponsors' responses; Severity of Alcohol Dependence Questionnaire-Community version (SADQ-C) and Alcoholics Anonymous Affiliation Scale (AAAS). RESULTS: Sample characteristics were as follows: the median length of AA attendance was 9.5 years (range 5-28); the median length of sobriety was 11 years (range 4.5-28); the median number of sponsees per sponsor was 1 but there was a wide range (0-17, interquartile range 3.75); and the sponsors were highly affiliated to AA (median AAAS score 8.75, range 5.5-8.75, maximum possible score 9). Past alcohol dependence scores were surprisingly low: 5 (18%) sponsors had mild, 14 (50%) moderate and 9 (32%) severe dependence according to the SADQ-C (median 26.5, range 11-56). Sponsorship roles were as follows: 16 roles were identified through the initial content analysis. These were distilled into three super-ordinate roles through a thematic analysis: (1) encouraging sponsees to work the programme of AA (doing the 12 steps and engaging in AA activity); (2) support (regular contact, emotional support and practical support); and (3) carrying the message of AA (sharing sponsor's personal experience of recovery with sponsees). CONCLUSIONS: The roles identified broadly corresponded with the AA literature delineating the duties of a sponsor. This non-random sample of sponsors was highly engaged in AA activity but only had a past history of moderate alcohol dependence.

Using standardized patients' marks in scoring postgraduate psychiatry OSCEs.

OBJECTIVE: Standardized patients (SPs) do not contribute scores in postgraduate psychiatry objective structured clinical examinations (OSCEs) in the United Kingdom. However, this may change in the near future. The primary aim of this study was to measure the degree of agreement between scores given by examiners and those given by SPs in an OSCE. METHODS: The authors measured the degree of agreement in two consecutive postgraduate OSCEs for psychiatric residents on a London training scheme. RESULTS: Fifty-five candidates participated in the two OSCEs. There was a moderate degree of agreement between examiner and SP scores for communication and for the overall mark. However, there was a stronger relationship between the examiner score for communication and the candidates' overall mark. CONCLUSION: Examiners and SPs scored candidates differently. Therefore, the decision to include SP scores in the marking scheme for postgraduate OSCEs would be a significant development.

Segmentation of the left ventricle of the heart in 3-D+t MRI data using an optimized nonrigid temporal model.

Modern medical imaging modalities provide large amounts of information in both the spatial and temporal domains and the incorporation of this information in a coherent algorithmic framework is a significant challenge. In this paper, we present a novel and intuitive approach to combine 3-D spatial and temporal (3-D + time) magnetic resonance imaging (MRI) data in an integrated segmentation algorithm to extract the myocardium of the left ventricle. A novel level-set segmentation process is developed that simultaneously delineates and tracks the boundaries of the left ventricle muscle. By encoding prior knowledge about cardiac temporal evolution in a parametric framework, an expectation-maximization algorithm optimally tracks the myocardial deformation over the cardiac cycle. The expectation step deforms the level-set function while the maximization step updates the prior temporal model parameters to perform the segmentation in a nonrigid sense.

A fully automatic CAD-CTC system based on curvature analysis for standard and low-dose CT data.

Computed tomography colonography (CTC) is a rapidly evolving noninvasive medical investigation that is viewed by radiologists as a potential screening technique for the detection of colorectal polyps. Due to the technical advances in CT system design, the volume of data required to be processed by radiologists has increased significantly, and as a consequence the manual analysis of this information has become an increasingly time consuming process whose results can be affected by inter- and intrauser variability. The aim of this paper is to detail the implementation of a fully integrated CAD-CTC system that is able to robustly identify the clinically significant polyps in the CT data. The CAD-CTC system described in this paper is a multistage implementation whose main system components are: 1) automatic colon segmentation; 2) candidate surface extraction; 3) feature extraction; and 4) classification. Our CAD-CTC system performs at 100% sensitivity for polyps larger than 10 mm, 92% sensitivity for polyps in the range 5 to 10 mm, and 57.14% sensitivity for polyps smaller than 5 mm with an average of 3.38 false positives per dataset. The developed system has been evaluated on synthetic and real patient CT data acquired with standard and low-dose radiation levels.

CTex--an adaptive unsupervised segmentation algorithm based on color-texture coherence.

This paper presents the development of an unsupervised image segmentation framework (referred to as CTex) that is based on the adaptive inclusion of color and texture in the process of data partition. An important contribution of this work consists of a new formulation for the extraction of color features that evaluates the input image in a multispace color representation. To achieve this, we have used the opponent characteristics of the RGB and YIQ color spaces where the key component was the inclusion of the Self Organizing Map (SOM) network in the computation of the dominant colors and estimation of the optimal number of clusters in the image. The texture features are computed using a multichannel texture decomposition scheme based on Gabor filtering. The major contribution of this work resides in the adaptive integration of the color and texture features in a compound mathematical descriptor with the aim of identifying the homogenous regions in the image. This integration is performed by a novel adaptive clustering algorithm that enforces the spatial continuity during the data assignment process. A comprehensive qualitative and quantitative performance evaluation has been carried out and the experimental results indicate that the proposed technique is accurate in capturing the color and texture characteristics when applied to complex natural images.

Stress, lies and red tape: the views, success rates and stress levels of the MTAS cohort.

OBJECTIVE: To track the success rates in obtaining a specialist training (ST) post of a cohort of medical training application system (MTAS) applicants, as well as canvassing their views of the process and measuring symptoms of psychological distress during application and after job allocation. DESIGN: A follow-up cross-sectional survey. Setting Two large south London psychiatry training schemes. Participants 101 MTAS applicants. MAIN OUTCOME MEASURES: Success in obtaining an ST post, respondents' views about MTAS and General Health Questionnaire-12 (GHQ-12) scores. RESULTS: 48 Of the original sample responded to the follow-up survey. Data were available about post-MTAS job status for a further 41 trainees. 64% of candidates obtained an ST post. Of those, however, 12% were only offered a fixed-term post. Most unsuccessful candidates were doing locum (34%) or non-training grade (21%) jobs. UK/European Economic Area (EEA) doctors were more successful than non-EEA applicants in obtaining an ST post (odds ratio 5.5, 95% confidence interval 2.1-14.3), as were women candidates compared to men (3.7, 0.5-9.3). The respondents' views about MTAS were globally negative (even if they were successful in obtaining an ST post). The median GHQ-12 score for respondents was 7 out of a potential total score of 12. 79% of the sample scored above the threshold (GHQ-12 > or =4) for psychological distress and 21% experienced significant distress (GHQ-12 > or =8). CONCLUSIONS: MTAS was a flawed system. A considerable proportion (36%) of candidates who had been on a Senior House Officer training scheme were left without a training post after MTAS. The system seems to favour UK/EEA applicants. Applicants suffered significant psychological distress during and after the MTAS process.

Development of a synthetic phantom for the selection of optimal scanning parameters in CAD-CT colonography.

The aim of this paper is to present the development of a synthetic phantom that can be used for the selection of optimal scanning parameters in computed tomography (CT) colonography. In this paper we attempt to evaluate the influence of the main scanning parameters including slice thickness, reconstruction interval, field of view, table speed and radiation dose on the overall performance of a computer aided detection (CAD)-CTC system. From these parameters the radiation dose received a special attention, as the major problem associated with CTC is the patient exposure to significant levels of ionising radiation. To examine the influence of the scanning parameters we performed 51 CT scans where the spread of scanning parameters was divided into seven different protocols. A large number of experimental tests were performed and the results analysed. The results show that automatic polyp detection is feasible even in cases when the CAD-CTC system was applied to low dose CT data acquired with the following protocol: 13 mAs/rotation with collimation of 1.5 mm x 16 mm, slice thickness of 3.0mm, reconstruction interval of 1.5 mm, table speed of 30 mm per rotation. The CT phantom data acquired using this protocol was analysed by an automated CAD-CTC system and the experimental results indicate that our system identified all clinically significant polyps (i.e. larger than 5 mm).

The use of 3D surface fitting for robust polyp detection and classification in CT colonography.

In this paper we describe the development of a computationally efficient computer-aided detection (CAD) algorithm based on the evaluation of the surface morphology that is employed for the detection of colonic polyps in computed tomography (CT) colonography. Initial polyp candidate voxels were detected using the surface normal intersection values. These candidate voxels were clustered using the normal direction, convexity test, region growing and Gaussian distribution. The local colonic surface was classified as polyp or fold using a feature normalized nearest neighborhood classifier. The main merit of this paper is the methodology applied to select the robust features derived from the colon surface that have a high discriminative power for polyp/fold classification. The devised polyp detection scheme entails a low computational overhead (typically takes 2.20min per dataset) and shows 100% sensitivity for phantom polyps greater than 5mm. It also shows 100% sensitivity for real polyps larger than 10mm and 91.67% sensitivity for polyps between 5 to 10mm with an average of 4.5 false positives per dataset. The experimental data indicates that the proposed CAD polyp detection scheme outperforms other techniques that identify the polyps using features that sample the colon surface curvature especially when applied to low-dose datasets.

Fast colon centreline calculation using optimised 3D topological thinning.

Topological thinning can be used to accurately identify the central path through a computer model of the colon generated using computed tomography colonography. The central path can subsequently be used to simplify the task of navigation within the colon model. Unfortunately standard topological thinning is an extremely inefficient process. We present an optimised version of topological thinning that significantly improves the performance of centreline calculation without compromising the accuracy of the result. This is achieved by using lookup tables to reduce the computational burden associated with the thinning process.