'The last channel': vision at the temporal margin of the field.

The human visual field, on the temporal side, extends to at least 90° from the line of sight. Using a two-alternative forced-choice procedure in which observers are asked to report the direction of motion of a Gabor patch, and taking precautions to exclude unconscious eye movements in the direction of the stimulus, we show that the limiting eccentricity of image-forming vision can be established with precision. There are large, but reliable, individual differences in the limiting eccentricity. The limiting eccentricity exhibits a dependence on log contrast; but it is not reduced when the modulation visible to the rods is attenuated, a result compatible with the histological evidence that the outermost part of the retina exhibits a high density of cones. Our working hypothesis is that only one type of neural channel is present in the far periphery of the retina, a channel that responds to temporally modulated stimuli of low spatial frequency and that is directionally selective.

Metastasising Pleomorphic Salivary Adenoma: A Rare Case Report of a Massive Untreated Minor Salivary Gland Pleomorphic Adenoma with Concurrent Ipsilateral Cervical Node Metastases.

Salivary gland tumours constitute approximately 1-5% of all human neoplasms. Pleomorphic adenoma (PA) is the commonest benign neoplasm affecting the parotid gland most often (> 75%), followed by the submandibular gland (13%), then the palate (9%). Metastasising pleomorphic adenoma (MPA) is extremely rare. The effects can be severe and a reported 40% of MPA patients die with disease. This case represents the first known case in English literature of an untreated minor salivary gland PSA of the palate metastasising to an ipsilateral cervical node. We report a 61 year old female who presented with a large tumour occupying the palatal vault, and cervical neck mass. The oral tumour was believed to have been growing over four decades. The patient died eight months following surgical resection. Of known cases, male: female ratio is 35:51 and the mean age at diagnosis is 49.2. Most commonly, MPA is detected in bone 33.3% (n = 29), lung 31% (n = 27) and cervical lymph nodes 20.7% (n = 18). Thorough reporting is deemed essential to further understand the biological differences of non metastasising and metastasising PAs, treatment outcomes, prognosis and survival rates.

Engineering an NADPH/NADP+ Redox Biosensor in Yeast.

Genetically encoded biosensors have emerged as powerful tools for timely and precise in vivo evaluation of cellular metabolism. In particular, biosensors that can couple intercellular cues with downstream signaling responses are currently attracting major attention within health science and biotechnology. Still, there is a need for bioprospecting and engineering of more biosensors to enable real-time monitoring of specific cellular states and controlling downstream actuation. In this study, we report the engineering and application of a transcription factor-based NADPH/NADP+ redox biosensor in the budding yeast Saccharomyces cerevisiae. Using the biosensor, we are able to monitor the cause of oxidative stress by chemical induction, and changes in NADPH/NADP+ ratios caused by genetic manipulations. Because of the regulatory potential of the biosensor, we also show that the biosensor can actuate upon NADPH deficiency by activation of NADPH regeneration. Finally, we couple the biosensor with an expression of dosage-sensitive genes (DSGs) and thereby create a novel tunable sensor-selector useful for synthetic selection of cells with higher NADPH/NADP+ ratios from mixed cell populations. We show that the combination of exploitation and rational engineering of native signaling components is applicable for diagnosis, regulation, and selection of cellular redox states.

Medium- and long-term results of high tibial osteotomy using Garches external fixator and gait analysis for dynamic correction in varus osteoarthritis of the knee.

In arthritis of the varus knee, a high tibial osteotomy (HTO) redistributes load from the diseased medial compartment to the unaffected lateral compartment. We report the outcome of 36 patients (33 men and three women) with 42 varus, arthritic knees who underwent HTO and dynamic correction using a Garches external fixator until they felt that normal alignment had been restored. The mean age of the patients was 54.11 years (34 to 68). Normal alignment was achieved at a mean 5.5 weeks (3 to 10) post-operatively. Radiographs, gait analysis and visual analogue scores for pain were measured pre- and post-operatively, at one year and at medium-term follow-up (mean six years; 2 to 10). Failure was defined as conversion to knee arthroplasty. Pre-operative gait analysis divided the 42 knees into two equal groups with high (17 patients) or low (19 patients) adductor moments. After correction, a statistically significant (p < 0.001, t-test,) change in adductor moment was achieved and maintained in both groups, with a rate of failure of three knees (7.1%), and 89% (95% confidence interval (CI) 84.9 to 94.7) survivorship at medium-term follow-up. At final follow-up, after a mean of 15.9 years (12 to 20), there was a survivorship of 59% (95% CI 59.6 to 68.9) irrespective of adductor moment group, with a mean time to conversion to knee arthroplasty of 9.5 years (3 to 18; 95% confidence interval ± 2.5). HTO remains a useful option in the medium-term for the treatment of medial compartment osteoarthritis of the knee but does not last in the long-term. Cite this article: Bone Joint J 2016;98-B:601-7.

The Camitz transfer and its modifications: a review.

UNLABELLED: The Camitz procedure involves transfer of the insertion of the palmaris longus tendon with a strip of the palmar aponeurosis to the insertion of abductor pollicis brevis in order to improve thumb opposition, and is usually done when severe carpal tunnel syndrome results in complete wasting of the thenar muscles. We carried out a systematic review of the published reports of this procedure. Analysis of available outcome data showed improvement in overall hand function in 86-100% of patients undergoing the original Camitz procedure. Several modifications of the original Camitz transfer have been described, with most focusing on the incorporation and placement of pulleys. All studies are limited by their small sample sizes. Overall, there is a lack of studies comparing the Camitz transfer with other opponensplasty techniques and comparing the various modifications of the original procedure. LEVEL OF EVIDENCE: IV.

Are medical eponyms really dying out? A study of their usage in the historical biomedical literature.

Eponyms are a prominent feature of medical language. Many feel they have had their time and serve only to complicate medical education and conversation. Others argue that eponyms can make unmemorable concepts memorable, can concisely label complex concepts, and promote a valuable interest in medical history. It is frequently assumed that medical eponyms are marching towards extinction. However, this hypothesis has not been adequately tested. The fate of 8,636 eponyms from contemporary and historical registers is presented here. The annual usage of each eponym in PubMed indexed articles since 1900 is analysed with metrics of eponym prevalence, coinage and extinction. The fate of eponyms named for those implicated in Nazi war crimes is also measured. The analysis shows that more publications used an eponym in their title in 2014 than ever before. However, the proportion using an eponym title has fallen from a peak of 3% in 1991 to 2% today, while annual extinction of eponyms overtook coinage in the 1980s. This suggests that, while not in dramatic decline, they are perhaps losing market share to more scientific descriptions. There is no ambiguity in the fate of eponyms related to Nazi war crimes which have almost entirely fallen out of use in the last decade.

Postoperative complications after major head and neck surgery with free flap repair--prevalence, patterns, and determinants: a prospective cohort study.

This study aims to give a better understanding of the prevalence, patterns, and determinants of postoperative complications, to evaluate the Clavien-Dindo classification of surgical complications, and to set out a protocol to improve postoperative recovery. Over a period of 27 months we studied 192 patients who had had major head and neck operations with free flaps. Data on complications were gathered prospectively along with patients' details, comorbidities, factors indicative of the magnitude of the surgical insult, and variations in perioperative care. Complications were classified according to the Clavien-Dindo system. Outcomes analysed comprised any complication, major complications (Clavien-Dindo III and above), wound complications, and pulmonary complications. A total of 64% of patients had complications, and in around one third they were serious; wound and pulmonary complications were the most common. Factors significantly associated with complications reflected an interaction between coexisting conditions of the patient at operation and the magnitude of the surgery. Perioperative interventions to ensure preoperative optimisation of patients, and to lessen the systemic inflammatory response that results from operation offer the best prospect of reducing the burden of surgical complications. A protocol to improve recovery after operation would be appropriate. The Clavien-Dindo classification of surgical complications is useful in this group.

Reducing the need for general anaesthesia in children: use of LAT gel in treating facial lacerations.

Facial lacerations in children are common emergencies that often require debridement and closure under general anaesthesia because of poor cooperation by the patient. General anaesthesia in children is not without risk so any technique that avoids its use is beneficial. LAT gel (lidocaine, adrenaline, and tetracaine) is a topical anaesthetic, which is ideal for suturing facial lacerations in children. In our experience its use has resulted in the effective treatment of these injuries, and has reduced distress and discomfort, and the need for hospital admission and general anaesthesia.

The effect of photopigment optical density on the color vision of the anomalous trichromat.

We present a theoretical model to estimate the influence of photopigment optical density (OD) on the color vision of anomalous trichromats. Photopigment spectral sensitivities are generated using the Lamb (1995) template, which we correct for OD and pre-receptoral filters. Sixteen hyperspectral images (Foster, Nascimento, & Amano, 2004; Nascimento, Ferreira, & Foster, 2002) are analyzed, and the signals produced in the post-receptoral channels calculated. In the case of anomalous trichromats whose two longer-wavelength cones have peak sensitivities that lie close together in the spectrum, color vision can be substantially enhanced if the cones differ in optical density by a realistic amount.

Systematic variations in immune response-related gene transcript abundance suggest new questions about environmental influences on lacrimal gland immunoregulation.

PURPOSE: Retrospective analyses were undertaken to assess the hypothesis that environmental variables influenced immunophysiological status of lacrimal glands from untreated female rabbits that had been housed out-of-doors until they were acquired for use as controls for experimental studies. MATERIALS AND METHODS: Rabbits were euthanized within 5 days of arrival at University Vivaria. Glands were divided for histology and RNA extraction. Transcript abundances were determined with real time RT-PCR. Sections were stained for CD18 and rabbit thymic lymphocyte antigen. Environmental variables assessed were mean daily high temperature, low humidity, high temperature/low humidity ratio, and days with above average temperature/humidity ratio ("adverse days") during the prior 30 days. RESULTS: Spearman's analyses revealed numerous significant correlations. Numbers of T cells and abundances of mRNAs for CD8; CCL2, and CCL4; IL-1α and IL-1ß; the T(H)1 cytokine, IL-2; and the T(H)2- and B cell cytokines, IL-4, IL-6, IL-10, APRIL, and BAFF, all increased with adverse days, while IFN-γ mRNA abundance decreased. Glands from the group exposed to the most adverse days remained free of immunopathological lesions. Glands from the group exposed to the highest temperatures fell above the regression curves for IL-4, APRIL, and BAFF calculated for the other groups and had significantly higher abundances of mRNAs for prolactin, IL-18, CCL21, CCL28, CXCL8, and CXCL13. One of six glands from this group contained small immune cell aggregates; the others appeared normal. The only gland that presented with frank histopathology was from a group that had experienced benign conditions. CONCLUSIONS: Increasing adverse days correlated with increasing abundances of transcripts, including mRNAs for IL-2, IL-10, and CD8, outside the T(H)1/T(H)2 paradigm. The findings raise intriguing questions as to whether and how such changes might be associated with homeostatic phenomena.

Autoimmune dacryoadenitis and keratoconjunctivitis induced in rabbits by subcutaneous injection of autologous lymphocytes activated ex vivo against lacrimal antigens.

Autologous peripheral blood lymphocytes (PBL), activated in a mixed cell reaction when co-cultured with purified rabbit lacrimal epithelial cells, are known to induce a Sjögren's-like autoimmune dacryoadenitis and keratoconjunctivitis when injected directly back into the donor animal's inferior lacrimal gland (LG). This study shows that autoreactive lymphocytes injected subcutaneously in a site away from the LG is capable of inducing an autoimmune disease in a rabbit. Induced disease (ID) develops more slowly, taking 4weeks as compared to 2weeks in the direct injection model. Initially, both clinical symptoms and histopathology are less pronounced than in the direct injection ID model, but later the immunocytochemistry shows the same CD4+/CD8+ ratio of 4:1 for both injection methods. The finding that lymphocytes activated against lacrimal antigens can travel or home from the injection site back to the inferior and superior LG, as well as the conjunctiva, suggests that these anatomical sites may have common epitopes that induce pathogenic CD4+ T cells that produce a Sjögren's-like syndrome.

Measuring multi-dimensional, time-dependent mechanical properties of a human tibial fracture using an automated system.

This paper presents an element of a long-term research project determining a clinically quantifiable end point for fracture healing in humans. An automated loading and measurement device is presented. It has been developed as a research tool for the assessment of the mechanical properties of a healing human tibial fracture. The device has been specifically designed for use with patients treated with external fixation. The characteristics of the device have been presented together with an assessment of errors. A typical sample of results has been presented to demonstrate the significance of the device; subsequent papers will examine the whole data set in greater depth. The results presented here confirm the non-linear behaviour of callus and reinforce the requirement to measure the load rate when measuring the fracture stiffness. A new material property for the assessment of fracture healing, namely gamma, is examined and preliminary results are shown. Polar plots of stiffness demonstrate that, when measuring fracture stiffness, not only should the load rate be considered, but also the orientation of measurement. The results from this work support the view that the fracture stiffness should be measured in at least two planes. Currently a fracture can be considered healed when the fracture stiffness exceeds 15 N m/deg; this paper questions whether this value is now valid and suggests that it should be re-examined.

Fracture healing assessment comparing stiffness measurements using radiographs.

Based on published reports, we presumed radiographs would be unreliable as a sole measure of fracture healing. To confirm this presumption we correlated radiographic fracture healing assessments with fracture stiffness measurements. We showed 100 plain radiographs of fractures with corresponding fracture stiffness measurements to 92 observers. The radiographs were shown twice to assess intraobserver variation. Observers were divided into three groups and asked to determine whether each fracture had healed (union corresponded to a fracture stiffness greater than 15 nm/degrees). Group 1 based fracture healing on the general appearance of healing. Groups 2 and 3 assessed fracture healing based on the number of cortices bridged by callus. In Group 2, the fracture was considered healed if two or more cortices were bridged on both radiographic views and in Group 3 if three or more cortices were bridged by callus. All groups performed poorly. There was no difference in terms of correct prediction of healing between methods, although there was a trend toward more reliability with cortical callus bridging assessment. We found substantial intraobserver variability, which improved using cortical bridging methods. Observers were less reliable at predicting healing when there was a metaphyseal extension to a diaphyseal fracture.

The effects of atorvastatin in experimental autoimmune uveitis.

AIM: To investigate the effect of atorvastatin (Lipitor), a commonly used drug for dyslipidaemia in experimental autoimmune uveitis (EAU). METHODS: 48 B10-RIII mice were immunised with human interphotoreceptor retinoid binding protein (IRBP) peptide p161-180. They were divided into three groups of 16 each and treated orally once daily for 14 days; group one received phosphate buffered saline (control group), group two received 1 mg/kg of atorvastatin (low dose group), and group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and right eyes were harvested. RNA was extracted from lymph nodes for RNase protection assay (RPA) to determine proinflammatory (IL-1 alpha and IL-1 beta), Th1 (TNF-alpha, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from spleens for western blot to detect the expression of phosphorylated signal transducer and activator of transcription (STAT) 4 and STAT6. The severity of inflammation in enucleated eyes was graded by a masked observer. Paired t test was performed for the mean difference in histological scoring between treated groups and the immunised control group. RESULTS: Surprisingly, atorvastatin did not modulate the immune response. The proinflammatory cytokines, IL-1 alpha and IL-1 beta, and Th1 cytokines, TNF-alpha and IL-2, were upregulated equally in control and atorvastatin treated groups. IL-12 and Th2 cytokines were not upregulated in all three groups. Western blot analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the control and atorvastatin treated groups. Mean differences in histological scoring between treated groups and the immunised control group were not statistically significant. CONCLUSIONS: Atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription. Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.

Modelling the Rayleigh match.

We use the photopigment template of Baylor et al. (1987) to define the set of Rayleigh matches that would be satisfied by a photopigment having a given wavelength of peak sensitivity (lambda(max)) and a given optical density (OD). For an observer with two photopigments in the region of the Rayleigh primaries, the observer's unique match is defined by the intersection of the sets of matches that satisfy the individual pigments. The use of a template allows us to illustrate the general behavior of Rayleigh matches as the absorption spectra of the underlying spectra are altered. In a plot of the Y setting against the red-green ratio (R), both an increase in lambda(max) and an increase in optical density lead to an anticlockwise rotation of the locus of the matches satisfied by a given pigment. Since both these factors affect the match, it is not possible to reverse the analysis and define uniquely the photopigments corresponding to a specific Rayleigh match. However, a way to constrain the set of candidate photopigments would be to determine the trajectory of the change of match as the effective optical density is altered (by, say, bleaching or field size).

Reliability of radiographs in defining union of internally fixed fractures.

We assessed whether radiographs can predict union of internally fixed fractures, and therefore be used as end-points in studies of fracture healing. Forty-seven radiographic series of forearm, femoral and tibial fractures treated by internal fixation over a 3-year period were reviewed. All forearm fractures were treated with dynamic compression plates (DCP), and all tibial and femoral fractures with intra-medullary nails. Callus formation and fracture line filling with time were measured on each radiograph. The ability of five orthopaedic surgeons to chronologically rank the blinded radiographs and to agree on the point of union was assessed. Correlation between callus formation, fracture line filling and union was noted. The ability of surgeons to correctly rank the radiographs and to agree on the point of union was in the order of 70%. Callus formation and union progression was significant in femoral fractures (P<0.05). Fracture line filling and union progression showed significance in the forearm (P<0.01) and femoral groups (P<0.05). Taking serial radiographs to assess healing would have led to only one early intervention. Radiographs do not define union in internally fixed fractures with sufficient accuracy to enable their use as end-points of fracture healing. Studies quoting radiographic end-points should be interpreted with care.

The current management of tibial fractures: are clinical guidelines effective?

BACKGROUND: The production of clinical guidelines is increasing and will continue to do so with the introduction of clinical governance. In 1997, the British Orthopaedic Association (BOA) and the British Association of Plastic Surgeons (BAPS) published joint guidelines on the management of open tibial fractures. It is not known whether these guidelines reached their target audience, or indeed influenced clinical practice. METHODS: We determined the effectiveness of these guidelines by sending a postal questionnaire survey to 172 orthopaedic surgeons. RESULTS: Only 57% of consultants were aware of the guidelines, 70% of registrars and 25% of staff grades. Less than 29% of orthopaedic consultants would choose to consult the plastic surgical team pre-operatively in the management of an open tibial fracture and only 43% would seek plastic surgical involvement at all. The primary aim of increasing multidisciplinary communication has not been achieved. CONCLUSIONS: The awareness of, and adherence to, these guidelines is sub-optimal. This clearly has implications for both the future management of open tibial fractures and the further production of guidelines.

The difficult paediatric airway: a new method of intubation using the laryngeal mask airway, Cook airway exchange catheter and tracheal intubation fibrescope.

We describe a new technique of intubation for use in difficult paediatric airway cases utilizing the laryngeal mask airway, a Cook Airway Exchange Catheter and a paediatric intubation fibrescope. This method has a number of potential advantages over previously described methods.

Mechanical properties of callus in human tibial fractures: a preliminary investigation.

OBJECTIVE: Investigate the mechanical properties of callus in tibial fractures treated with external fixation. In particular any time-dependent or non-linear characteristics. DESIGN: A clinical-based investigative study. BACKGROUND: A fracture bending stiffness in the sagittal plane of 15 N m/deg. has been stated as a satisfactory endpoint of clinical healing. However using this criterion in 76 previous tibial fractures, four continued to a malunion. METHODS: Fracture properties were measured in clinic. The fixator was removed for the tests and a specially designed system was used to measure displacement and load. Fracture stiffness was measured in different planes and at various loading rates. Passive stressing of the leg was performed whilst fracture displacement was recorded. A constant load was applied for a longer period to assess creep properties. RESULTS: Fracture stiffness was found to vary between different planes of measurement and on load rate. The visco-elastic characteristics of the callus changed with time. In early measurements, the callus absorbed a large proportion of energy when a load was applied. Later tests showed a progressive change with the callus absorbing less energy. This demonstrates that the properties of the callus changed with time, with the viscous element diminishing and the elastic element increasing. This sometimes occurred with no change in the measured fracture stiffness. CONCLUSIONS: Further investigation is needed, focusing on the visco-elastic properties of callus, to develop a more reliable method of determining clinical union. RELEVANCE: Improved understanding of the mechanical properties of callus could result in improved methods of measuring fracture healing.