Age-dependence of the average and equivalent refractive indices of the crystalline lens

Lens average and equivalent refractive indices are required for purposes such as lens thickness estimation and optical modeling. We modeled the refractive index gradient as a power function of the normalized distance from lens center. Average index along the lens axis was estimated by integration. Equivalent index was estimated by raytracing through a model eye to establish ocular refraction, and then backward raytracing to determine the constant refractive index yielding the same refraction. Assuming center and edge indices remained constant with age, at 1.415 and 1.37 respectively, average axial refractive index increased (1.408 to 1.411) and equivalent index decreased (1.425 to 1.420) with age increase from 20 to 70 years. These values agree well with experimental estimates based on different techniques, although the latter show considerable scatter. The simple model of index gradient gives reasonable estimates of average and equivalent lens indices, although refinements in modeling and measurements are required.

Thermal conductivity of Si nanowires with faulted stacking layers

Faulted stacking layers are ubiquitously observed during the crystal growth of semiconducting nanowires (NWs). In this paper, we employ the reverse non-equilibrium molecular dynamics simulation to elucidate the effect of various faulted stacking layers on the thermal conductivity (TC) of silicon (Si) NWs. We find that the stacking faults can greatly reduce the TC of the Si NW. Among the different stacking faults that are parallel to the NW's axis, the 9R polytype structure, the intrinsic and extrinsic stacking faults (iSFs and eSFs) exert more pronounced effects in the reduction of TC than the twin boundary (TB). However, for the perpendicularly aligned faulted stacking layers, the eSFs and 9R polytype structures are observed to induce a larger reduction to the TC of the NW than the TB and iSFs. For all considered NWs, the TC does not show a strong relation with the increasing number of faulted stacking layers. Our studies suggest the possibility of tuning the thermal properties of Si NWs by altering the crystal structure via the different faulted stacking layers.

Somatostatin, its receptors and analogs, in lung cancer

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer. Copyright © 2001 S. Karger AG, Basel.

The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

Modelling of ellipsoidal nanowires : control and application

The properties of ellipsoidal nanowires are yet to be examined. They have likely applications in sensing, solar cells, microelectronics and cloaking devices. Little is known of the qualities that ellipse nanowires exhibit as we vary the aspect ratio with different dielectric materials and how varying these attributes affects plasmon coupling and propagation. It is known that the distance a plasmon can travel is further if it is supported by a thicker circular nanowire, while thinner nanowires are expected to be able to increase QD coupling. Ellipsoidal nanowires may be a good compromise due to their ability to have both thin and thick dimensions. Furthermore it has been shown that the plasmon resonances along the main axis of an ellipsoidal particle is governed by the relative aspect ratio of the ellipsoid, which may lead to further control of the plasmon. Research was done by the use of COMSOL Multiphysics by looking at the fundamental plasmon mode supported by an ellipsoidal nanowire and then studying this mode for various geometrical parameters, materials and illumination wavelength. Accordingly it was found that ellipsoidal nanowires exhibit a minimum for the wavenumber and a maximum for the propagation distance at roughly the same dimensions - Highlighting that there is an aspect ratio for which there is poor coupling but low loss. Here we investigate these and related attributes.

Pupil shape as viewed along the horizontal visual field

Purpose: Changes in pupil size and shape are relevant for peripheral imagery by affecting aberrations and how much light enters and/or exits the eye. The purpose of this study is to model the pattern of pupil shape across the complete horizontal visual field and to show how the pattern is influenced by refractive error. Methods: Right eyes of thirty participants were dilated with 1% cyclopentolate and images were captured using a modified COAS-HD aberrometer alignment camera along the horizontal visual field to ±90°. A two lens relay system enabled fixation at targets mounted on the wall 3m from the eye. Participants placed their heads on a rotatable chin rest and eye rotations were kept to less than 30°. Best-fit elliptical dimensions of pupils were determined. Ratios of minimum to maximum axis diameters were plotted against visual field angle. Results: Participants’ data were well fitted by cosine functions, with maxima at (–)1° to (–)9° in the temporal visual field and widths 9% to 15% greater than predicted by the cosine of the field angle . Mean functions were 0.99cos[( + 5.3)/1.121], R2 0.99 for the whole group and 0.99cos[( + 6.2)/1.126], R2 0.99 for the 13 emmetropes. The function peak became less temporal, and the width became smaller, with increase in myopia. Conclusion: Off-axis pupil shape changes are well described by a cosine function which is both decentered by a few degrees and flatter by about 12% than the cosine of the viewing angle, with minor influences of refraction.

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

IL-23R is epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn's disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease.

Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus

The bed nucleus of the stria terminalis (BNST) is believed to be a critical relay between the central nucleus of the amygdala (CE) and the paraventricular nucleus of the hypothalamus in the control of hypothalamic–pituitary– adrenal (HPA) responses elicited by conditioned fear stimuli. If correct, lesions of CE or BNST should block expression of HPA responses elicited by either a specific conditioned fear cue or a conditioned context. To test this, rats were subjected to cued (tone) or contextual classical fear conditioning. Two days later, electrolytic or sham lesions were placed in CE or BNST. After 5 days, the rats were tested for both behavioral (freezing) and neuroendocrine (corticosterone) responses to tone or contextual cues. CE lesions attenuated conditioned freezing and corticosterone responses to both tone and con- text. In contrast, BNST lesions attenuated these responses to contextual but not tone stimuli. These results suggest CE is indeed an essential output of the amygdala for the expres- sion of conditioned fear responses, including HPA re- sponses, regardless of the nature of the conditioned stimu- lus. However, because lesions of BNST only affected behav- ioral and endocrine responses to contextual stimuli, the results do not support the notion that BNST is critical for HPA responses elicited by conditioned fear stimuli in general. Instead, the BNST may be essential specifically for contex- tual conditioned fear responses, including both behavioral and HPA responses, by virtue of its connections with the hippocampus, a structure essential to contextual condition- ing. The results are also not consistent with the hypothesis that BNST is only involved in unconditioned aspects of fear and anxiety.

Predicting the likelihood of QA failure using treatment plan accuracy metrics

This study used automated data processing techniques to calculate a set of novel treatment plan accuracy metrics, and investigate their usefulness as predictors of quality assurance (QA) success and failure. 151 beams from 23 prostate and cranial IMRT treatment plans were used in this study. These plans had been evaluated before treatment using measurements with a diode array system. The TADA software suite was adapted to allow automatic batch calculation of several proposed plan accuracy metrics, including mean field area, small-aperture, off-axis and closed-leaf factors. All of these results were compared the gamma pass rates from the QA measurements and correlations were investigated. The mean field area factor provided a threshold field size (5 cm2, equivalent to a 2.2 x 2.2 cm2 square field), below which all beams failed the QA tests. The small aperture score provided a useful predictor of plan failure, when averaged over all beams, despite being weakly correlated with gamma pass rates for individual beams. By contrast, the closed leaf and off-axis factors provided information about the geometric arrangement of the beam segments but were not useful for distinguishing between plans that passed and failed QA. This study has provided some simple tests for plan accuracy, which may help minimise time spent on QA assessments of treatments that are unlikely to pass.

Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii

Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt’s bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4–8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt’s bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt’s bat.

A biomechanical analysis of anterior instrumentation used in the surgical correction of adolescent idiopathic scoliosis

Scoliosis is a deformity of the spine which affects children and adolescents, and remains a challenge to treat. This study measured the forces used during surgery to correct scoliosis and studied changes to spinal mechanics from the implantation of metal rods used to hold the spine straight. The results of this study will help surgeons and engineers understand how to straighten the spine more efficiently to provide patients with better outcomes.

A simple method for EPID-based in vivo dosimetry for radiotherapy treatments of head-and-neck cancers

This study used a homogeneous water-equivalent model of an electronic portal imaging device (EPID), contoured as a structure in a radiotherapy treatment plan, to produce reference dose images for comparison with in vivo EPID dosimetry images. Head and neck treatments were chosen as the focus of this study, due to the heterogeneous anatomies involved and the consequent difficulty of rapidly obtaining reliable reference dose images by other means. A phantom approximating the size and heterogeneity of a typical neck, with a maximum radiological thickness of 8.5 cm, was constructed for use in this study. This phantom was CT scanned and a simple treatment including five square test fields and one off-axis IMRT field was planned. In order to allow the treatment planning system to calculate dose in a model EPID positioned a distance downstream from the phantom to achieve a source-to-detector distance (SDD) of 150 cm, the CT images were padded with air and the phantom’s “body” contour was extended to encompass the EPID contour. Comparison of dose images obtained from treatment planning calculations and experimental irradiations showed good agreement, with more than 90% of points in all fields passing a gamma evaluation, at γ (3%, 3mm )Similar agreement was achieved when the phantom was over-written with air in the treatment plan and removed from the experimental beam, suggesting that water EPID model at 150 cm SDD is capable of providing accurate reference images for comparison with clinical IMRT treatment images, for patient anatomies with radiological thicknesses ranging from 0 up to approximately 9 cm. This methodology therefore has the potential to be used for in vivo dosimetry during treatments to tissues in the neck as well as the oral and nasal cavities, in the head-and-neck region.

Metabolic dysfunction and laminitis

Objective: This review focuses on laminitis that develops as a result of metabolic dysfunction and aims to provide a concise assessment of the current state of knowledge on this form of the disease. Outline: The most prevalent form of laminitis is associated with metabolic or endocrinopathic diseases, such as Equine Metabolic Syndrome and pituitary pars intermedia dysfunction, and the feeding of high-energy diets, particularly those rich in non-structural carbohydrates. Insulin dysregulation is the key hormonal imbalance implicated in causing this form of laminitis and hyperinsulinaemia is an important risk factor for the disease. Hyperinsulinaemia can occur in association with insulin resistance, obesity, regionalised adiposity, dysregulated cortisol metabolism and may also be related to other factors, such as breed and genetic predisposition. Recognition of hyperinsulinaemia is best achieved by using a dynamic oral glucose test that can be performed relatively easily under field conditions. Insulin produces a unique pathological lesion in the lamellae and the features of this lesion have informed investigations on the pathogenesis of the disease. Research into the mechanism of disease is continuing so that more targeted therapies than are currently available can be developed. However, dietary restriction and exercise remain effective management strategies for metabolic disease. Conclusions: Although the pathogenic mechanism/s of metabolic and endocrinopathic forms of laminitis remain the subject of intense research, ample data on risk factors for the disease are available. Efforts focussed on preventing the disease should aim to identify metabolic disease and reduce obesity and insulin resistance in at-risk individuals.

Poly[μ-aqua-bis(μ5-2,4-dichlorobenzoato)dipotassium

In the title compound, [K2(C7H3Cl2O2)2(H2O)]n, the potassium salt of 2,4-dichlorobenzoic acid, the repeating unit in the polymeric structure consists of two identical irregular KO6Cl complex units related by twofold rotational symmetry, linked by a bridging water molecule lying on the twofold axis. The coordination polyhedron about each K+ comprises a carboxyl O-atom and a Cl-atom donor from a bidentate chelate ligand interaction, four O-atom donors from a doubly bridging bidentate carboxyl (O,O')-chelate interaction and the water molecule. A two-dimensional layered coordination polymer structure lying parallel to (100) is generated through a series of conjoined cyclic bridges between K centres and is stabilized by water O-H...O(carboxyl) hydrogen-bonding interactions.