A unified framework for constructing, tuning and assessing photometric redshift density estimates in a selection bias setting.

Photometric redshift estimation is an indispensable tool of precision cosmology. One problem that plagues the use of this tool in the era of large-scale sky surveys is that the bright galaxies that are selected for spectroscopic observation do not have properties that match those of (far more numerous) dimmer galaxies; thus, ill-designed empirical methods that produce accurate and precise redshift estimates for the former generally will not produce good estimates for the latter. In this paper, we provide a principled framework for generating conditional density estimates (i.e. photometric redshift PDFs) that takes into account selection bias and the covariate shift that this bias induces. We base our approach on the assumption that the probability that astronomers label a galaxy (i.e. determine its spectroscopic redshift) depends only on its measured (photometric and perhaps other) properties [Formula: see text] and not on its true redshift. With this assumption, we can explicitly write down risk functions that allow us to both tune and compare methods for estimating importance weights (i.e. the ratio of densities of unlabelled and labelled galaxies for different values of [Formula: see text]) and conditional densities. We also provide a method for combining multiple conditional density estimates for the same galaxy into a single estimate with better properties. We apply our risk functions to an analysis of ≈106 galaxies, mostly observed by Sloan Digital Sky Survey, and demonstrate through multiple diagnostic tests that our method achieves good conditional density estimates for the unlabelled galaxies.

Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebro spinal venous insufficiency.

The truncular venous malformation (VM) represents an embryologically defective vein where developmental arrest has occurred during the vascular trunk formation period in the 'later stage' of the embryonic development. A relatively simple truncular VM lesion such as a venous web at the hepatic venous outlet causes portal hypertension giving a profound damage/impact to the liver. A similar condition involving the head and neck venous system may cause chronic cerebro-spinal venous insufficiency (CCSVI) and may be involved in the development or exacerbation of multiple sclerosis.

A summative, Objective, Structured, Clinical Examination in ENT used to assess postgraduate doctors after one year of ENT training, as part of the Diploma of Otorhinolaryngology, Head and Neck Surgery.

CONTEXT: 'High stakes' postgraduate medical examinations should conform to current educational standards. In the UK and Ireland, national assessments in surgery are devised and managed through the examination structure of the Royal Colleges of Surgeons. Their efforts are not reported in the medical education literature. In the current paper, we aim to clarify this process. OBJECTIVES: To replace the clinical section of the Diploma of Otorhinolaryngology with an Objective, Structured, Clinical Examination, and to set the level of the assessment at one year of postgraduate training in the specialty. METHODS: After 'blueprinting' against the whole curriculum, an Objective, Structured, Clinical Examination comprising 25 stations was divided into six clinical stations and 19 other stations exploring written case histories, instruments, test results, written communication skills and interpretation skills. The pass mark was set using a modified borderline method and other methods, and statistical analysis of the results was performed. RESULTS: The results of nine examinations between May 2004 and May 2008 are presented. The pass mark varied between 68 and 82 per cent. Internal consistency was good, with a Cronbach's alpha value of 0.99 for all examinations and split-half statistics varying from 0.96 to 0.99. Different standard settings gave similar pass marks. CONCLUSIONS: We have developed a summative, Objective, Structured, Clinical Examination for doctors training in otorhinolaryngology, reported herein. The objectives and standards of setting a high quality assessment were met.

BSACI guidelines for the management of rhinosinusitis and nasal polyposis.

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.

Dental otalgia.

BACKGROUND: Secondary or referred otalgia can represent a diagnostic challenge to the otolaryngologist. Collectively, dental disorders are the most common causes of secondary otalgia presenting to the ENT clinic, and may account for up to 50 per cent of referred otalgia. Temporomandibular joint dysfunction syndrome represents the most common dental cause of referred otalgia. Decay and pulpal inflammation of posterior teeth can also frequently present as otalgia. The common embryological developmental origin of both oral and dental structures and the ear is responsible for their overlapping sensory nerve supplies, and this explains referred otalgia secondary to dental and temporomandibular joint disorders. These disorders can be easily overlooked, resulting in unnecessary and costly investigations. AIMS: This review aims to give a succinct overview of common dental causes of otalgia, and to provide ENT clinicians with guidelines for performing a rapid and simple dental and temporomandibular joint examination, which will reliably diagnose or exclude dental otalgia.

Total serum IgE and IgE antibodies specific to house dust mite found in two aged-matched cohorts of children with and without otitis media with effusion.

OBJECTIVES: To determine whether otitis media with effusion (OME) is associated with elevated serum immunoglobulin E (IgE) and IgE specific for house dust mite. DESIGN: Forty-seven children who had evidence of bilateral OME, both otoscopically and on tympanometry, on two separate occasions, 3 months apart were admitted for ventilation tubes. Forty-eight children admitted for minor eye surgery who had otoscopically normal ears and no history of middle ear problems were used as controls. Bloods samples were taken under anaesthesia. Total IgE and IgE radioallergosorbent test (RAST) to house dust mite was measured by the Pharmacia Unicap 100 system. The results from the two groups were compared. SETTING: Birmingham Children's Hospital. PARTICIPANTS: Children between the ages of 3 and 10. Children with Down's syndrome, cleft lip and palate, ciliary abnormalities, known immunodeficiencies and cardiac abnormalities were excluded. MAIN OUTCOME MEASURES: Total IgE and RAST to house dust mite. A RAST of >0.35 was taken to be positive. RESULTS: There was no statistical difference between the control and study groups for the total IgE. Six children from both study and control groups had a raised house dust mite RAST. There was no difference in the levels between either group. CONCLUSIONS: Our findings indicate that there is no direct relationship between OME and biochemical evidence of allergy, specifically to house dust mite.

Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE. METHODS: In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined. RESULTS: Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low-density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE; 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors. CONCLUSION: Impaired endothelial function as shown by decreased SAE, and an adverse profile of novel proatherogenic and prothrombotic vascular disease risk factors were prevalent in clinically quiescent SLE. These findings show the vulnerability of patients with SLE for atherosclerosis, and emphasize that assessments based on traditional risk factors alone may be inadequate.

Geometric diffusions as a tool for harmonic analysis and structure definition of data: multiscale methods.

In the companion article, a framework for structural multiscale geometric organization of subsets of R(n) and of graphs was introduced. Here, diffusion semigroups are used to generate multiscale analyses in order to organize and represent complex structures. We emphasize the multiscale nature of these problems and build scaling functions of Markov matrices (describing local transitions) that lead to macroscopic descriptions at different scales. The process of iterating or diffusing the Markov matrix is seen as a generalization of some aspects of the Newtonian paradigm, in which local infinitesimal transitions of a system lead to global macroscopic descriptions by integration. This article deals with the construction of fast-order N algorithms for data representation and for homogenization of heterogeneous structures.

Geometric diffusions as a tool for harmonic analysis and structure definition of data: diffusion maps.

We provide a framework for structural multiscale geometric organization of graphs and subsets of R(n). We use diffusion semigroups to generate multiscale geometries in order to organize and represent complex structures. We show that appropriately selected eigenfunctions or scaling functions of Markov matrices, which describe local transitions, lead to macroscopic descriptions at different scales. The process of iterating or diffusing the Markov matrix is seen as a generalization of some aspects of the Newtonian paradigm, in which local infinitesimal transitions of a system lead to global macroscopic descriptions by integration. We provide a unified view of ideas from data analysis, machine learning, and numerical analysis.

Parapharyngeal abscess: diagnosis, complications and management in adults.

Parapharyngeal abscess may cause life-threatening complications. Peritonsillar abscess and tonsillitis may result in parapharyngeal abscess. Since the introduction of antibiotics, the incidence of parapharyngeal abscess secondary to tonsillitis and peritonsillar abscess has decreased dramatically. We present five cases of parapharyngeal abscess resulting from tonsillitis and peritonsillar infection extending to the parapharyngeal space in adult patients. Two were complicated by mediastinitis despite early treatment by wide spectrum antibiotics. We believe that early diagnosis and aggressive antibiotic treatment with early surgical drainage in cases associated with pus collection are the key points in preventing serious and fatal complications. We emphasize the diagnostic role of computerized tomography (CT) scan and the importance of early and proper drainage of these abscesses.

Wegener's granulomatosis and subglottic stenosis: management of the airway.

Wegener's granulomatosis is a multisystemic disease characterized by foci of necrotizing vasculitis and granuloma formation. Subglottic stenosis may occur either as a presenting feature or a late-stage manifestation of the disease, but will occur in approximately 10-20 per cent of cases. We present a series of seven cases of Wegener's granulomatosis with subglottic stenosis and discuss our management of this condition. Where there is active disease, tracheostomy is the first-line surgical treatment of respiratory obstruction, as an adjunct to full medical therapy. More aggressive or elaborate surgical treatments should be reserved for non-active cases in which patients have not required medical treatment for one year.

Nasal polyps.

Nasal polyps are as common as adult onset asthma and unilateral polyps require histological examination. Medical therapy with corticosteroids should be tried before surgery. The anatomy should be demonstrated with computed tomography before endoscopic surgery.

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged-matched cohorts of children with and without otitis media with effusion.

The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA2 is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG2 acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non-parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti-PCP and the IgG2 anti-PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG2 anti-PCP against IgA total anti-PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age-related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.

Allergen immunotherapy in ENT: historical perspective.

The origins of immunology and allergy are founded upon the early 19th century microbiological studies of Jenner and Pasteur. It was discovered that the immune system could cause harm. The subspecialty of allergy began with the coining of the term by Von Pirquet in 1906 to describe disorders resulting from hyper-reaction to normally innocuous environmental agents. Understanding the scientific basis of the immune system and allergy allowed Noon and Freeman, and later Cooke, to develop allergen immunotherapy. Initially the technique was crude, but with the subsequent key discovery of IgE, more accurate methods of diagnosis (such as the radioallergosorbent test (RAST)) and treatment ensued. The efficacy of specific immunotherapy has been demonstrated by many double-blind trials culminating in the WHO position paper. DNA recombinant technology has provided detailed molecular understanding of allergic disorders, which has resulted in several novel methods of immunotherapy that are potentially safer and more effective. Use of recombinant allergens, T-cell peptides, DNA vaccination with CpG motifs or plasmid vectors and anti-IgE strategies with monoclonal antibodies are showing promise.

Infection, allergy and the hygiene hypothesis: historical perspective.

The 'hygiene hypothesis' was popularized in the late 1980s to explain the high prevalence of atopic disorders in the developed countries. It links atopic disorders and the lack of early life infections. An association between the two is not novel and dates back to the beginnings of allergy, immunology and microbiology. Allergy and infection have always been closely related and the study of one has often provided new insights into the pathobiology of the other. Early research into bacterial infections led to the discovery of the human immune system and the concept of allergy. An important relationship exists between parasite infections and the development of atopic disorders. This review traces the long and intimate historical relationship between infection and allergy.

Th2 dominance in nasal mucosa in patients with Wegener's granulomatosis.

Wegener's granulomatosis initially affects upper respiratory tract organs including the nasal mucosa in more than 90% of patients. The inflammation is typically granulomatous with associated vasculitis. T lymphocytes are usually a prominent component of the leucocyte infiltrate. Previous studies using peripheral blood T cells have implicated IFN-gamma rich Th1-type responses. This study addressed the cytokine milieu in nasal mucosa from 10 patients with active Wegener's granulomatosis using immunohistochemistry. Increased levels of CD3+ T cells and eosinophils were present compared with normal and disease controls. There was increased expression of IL-4, down-regulation of IL-2 and no detectable IFN-gamma. There was increased expression of the chemokine receptor CCR3 by infiltrating cells, consistent with an IL-4 dominant, Th2-biased response. In contrast, renal biopsy tissue from 10 patients with active Wegener's granulomatosis showed expression of IL-2 and IL-4. The Th2-type environment within nasal mucosa, often the initial site of disease activity in Wegener's, is consistent with a local allergic response in these patients.

Clinical and histopathological correlation of nasal polyps: are there any surprises?

Nasal polypectomy is a common operation. There is debate about whether all nasal polyps removed at operation should be sent for histopathological examination. To investigate this, a prospective study was performed to check the correlation of clinical and histopathological examination. Three hundred and forty-four nasal polypectomy specimens during the period from September 1997 to September 1999 were sent for histopathological diagnosis, with the clinical diagnosis documented on the pathology form. The clinical diagnosis was then correlated with the histological diagnosis. Three hundred and twenty-eight specimens were diagnosed as inflammatory polyps and 16 as tumours, of which seven were malignant. There was a good correlation between the clinical and histological findings in 340 cases. There was disagreement between the forms and reports in four cases. When the notes were consulted, three cases had forms that were incorrectly filled in. There was only one unsuspected case of inverted papilloma in a polyp specimen, which looked like a benign inflammatory polyp. This study indicates there is a 99.7% correlation between clinical and histopathological diagnosis.

Statistics of lateral geniculate nucleus (LGN) activity determine the segregation of ON/OFF subfields for simple cells in visual cortex.

The receptive fields for simple cells in visual cortex show a strong preference for edges of a particular orientation and display adjacent excitatory and inhibitory subfields. These subfields are projections from ON-center and OFF-center lateral geniculate nucleus cells, respectively. Here we present a single-cell model using ON and OFF channels, a natural scene environment, and synaptic modification according to the Bienenstock, Cooper, and Munro (BCM) theory. Our results indicate that lateral geniculate nucleus cells must act predominantly in the linear region around the level of spontaneous activity, to lead to the observed segregation of ON/OFF subfields.

Assessment of mucociliary transport in patients with chronic mucoid rhinitis.

Chronic rhinitis is the manifestation of a heterogeneous group of disease entities and often proves difficult to manage successfully. We present the investigations of the mucociliary system in 40 patients with mucoid rhinorrhoea as their principal symptom of whom 20 had pan respiratory disease. The saccharin clearance time (SCT) was measured and classified as normal if it was below 20 min. Objective measurement of clearance was made using 99mTechnetium-labelled human serum albumin (99mTc-HSA). We have standardized our method using a micrometer syringe driver to produce a droplet of consistent size (droplet size, 0.01 ml, SD 0.0002 ml) that reduces the dose of radiation. The movement of the droplet was measured over 20 min (RLT). The mean, maximum rate and percentage moved were calculated. Patients were divided into those who had chest disease (20) and those without and a chi 2-test was performed for the mean RLT time between the two groups. There was a strong correlation between mean and maximum rates (r = 0.91). One patient has a normal SCT and normal RLT. Patients with chest disease had a significantly lower mean RLT (P > 0.01). Assuming that RLT is the standard investigation, six patients were normal but had an abnormal SCT, this is a false positive error of 15%. The false negative error was 4/40 (10%). The association between sinus and chest disease with abnormal mucociliary clearance is stressed.