Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease

BACKGROUND: Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients. METHODS: Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master (TradeMark). Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls. RESULTS: Ten minutes after fluorescein installition, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 ± 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 ± 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 ± 52.83 ng/ml) compared with that of controls (mean = 40.64 ± 7.96 ng/ml), averaging a three-fold increase. CONCLUSION: Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease

Rapid cryogenic characterisation of 1024 integrated silicon quantum dots

Quantum computers are nearing the thousand qubit mark, with the current focus on scaling to improve computational performance. As quantum processors grow in complexity, new challenges arise such as the management of device variability and the interface with supporting electronics. Spin qubits in silicon quantum dots are poised to address these challenges with their proven control fidelities and potential for compatibility with large-scale integration. Here, we demonstrate the integration of 1024 silicon quantum dots with on-chip digital and analogue electronics, all operating below 1 K. A high-frequency analogue multiplexer provides fast access to all devices with minimal electrical connections, enabling characteristic data across the quantum dot array to be acquired in just 5 minutes. We achieve this by leveraging radio-frequency reflectometry with state-of-the-art signal integrity, reaching a minimum integration time of 160 ps. Key quantum dot parameters are extracted by fast automated machine learning routines to assess quantum dot yield and understand the impact of device design. We find correlations between quantum dot parameters and room temperature transistor behaviour that may be used as a proxy for in-line process monitoring. Our results show how rapid large-scale studies of silicon quantum devices can be performed at lower temperatures and measurement rates orders of magnitude faster than current probing techniques, and form a platform for the future on-chip addressing of large scale qubit arrays.Comment: Main text: 14 pages, 8 figures, 1 table Supplementary: 8 pages, 6 figure

Clinical implication of HLA class I expression in breast cancer

<p>Abstract</p> <p>Background</p> <p>Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified.</p> <p>Methods</p> <p>A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed.</p> <p>Results</p> <p>The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval.</p> <p>Conclusion</p> <p>The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.</p

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

We are grateful to Breast Cancer Campaign for funding our collection of male breast carcinomas and for supporting DLH and SP. SAS was funded by the Wolfson Foundation and a Wellcome Trust Vacation Scholarship. HHT was funded by Cancer Research UK. We convey special thanks to members of the Leeds Breast Team for input and support at various stages of this project.Peer reviewedPublisher PD

Mathematical modeling of gallic acid release from chitosan films with grape seed extract and carvacrol

Controlled release of antimicrobial and antioxidant compounds from packaging films is of utmost importance for extending the shelf-life of perishable foods. This study focused on the mathematical modeling of gallic acid release into an aqueous medium from three chitosan films, formulated with grape seed extract (GSE) and carvacrol. We quantified the release by HPLC technique during 30days at three temperatures (5, 25 and 45°C). The diffusion coefficients, varying with temperature according to an Arrhenius-type relationship, and the respective activation energies for Film-1 and Film-2 were, respectively [Formula: see text] m2s-1 and [Formula: see text] m2s-1, Ea1=58kJmol-1 and Ea2=60kJmol-1 as obtained from the Fickian fit. The low concentrations of gallic acid released by Film-3 could not be detected by HPLC, therefore the respective diffusion coefficient was not estimated. This study will help with the development and optimization of active packaging (AP) films aiming at improved food preservation and shelf-life extension.Javiera F. Rubilar gratefully acknowledges her Ph.D. grant from ErasmusMundus 2008-1022/001 Frame ECW/17, EACEA(European Union), financial support of the Fondecyt-Postdoctoral #3140349 project from CONICYT, and also “Dirección de Investigación e Innovación Escuela de Ingeniería” at Pontificia Universidad Católica de Chile. Rui M. S. Cruz acknowledges grant SFRH/BPD/70036/2010 from Fundac¸ ão para a Ciência e Tecnologia, Portugalinfo:eu-repo/semantics/publishedVersio

High heat flux capabilities of the Magnum-PSI linear plasma device

Magnum-PSI is an advanced linear plasma device uniquely capable of producing plasma conditions similar to those expected in the divertor of ITER both steady-state and transients. The machine is designed both for fundamental studies of plasma-surface interactions under high heat and particle fluxes, and as a high-heat flux facility for the tests of plasma-facing components under realistic plasma conditions. To study the effects of transient heat loads on a plasma-facing surface, a novel pulsed plasma source system as well as a high power laser is available. In this article, we will describe the capabilities of Magnum-PSI for high-heat flux tests of plasma-facing material

Хирургическое лечение «раннего» рака молочной железы: что изменилось? (опыт международного сотрудничества)

The study included patients with noninvasive cancer and stage T1a-b-cN0M0 invasive breast cancer who were treated between 1985 to 2009 in Russia (at the N.N. Blokhin Russian Cancer Research Center and at the Clinic of the Russian Medical Academy of Postgraduate Training, 1036 patients), and in the Netherlands (LUMC, 560 patients, National Cancer Register, 22196 patients). The comparative analysis of surgery types between countries was carried out. The frequency of organ-preserving surgeries for early breast cancer in Russian and in the Netherlands was identical (53.7 % and 52.5 %). The percentage of organ-preserving surgeries over the past 20 years in Russia was not significantly changed, whereas the decrease in the rate of organ-preserving treatment from 56.2 % to 41.2 % was observed in the Netherlands.This is most likely due to an increase in the number of patients in postmenopause (&gt;60 years) from 53.1 % to 63.8 %. The main type of organ-preserving treatment in Russia is radical resection of the breast. In the Netherlands, lumpectomy with sentinel lymph node biopsy or axillary lymphodissection is the most common form of breast-conserving surgery today.В исследование включены пациентки с неинвазивным раком и раком молочной железы c T1a-b-cN0M0 стадией, получившие лечение с 1985 по 2009 г. в России (РОНЦ им. Н.Н. Блохина РАМН и Клиника РМАПО – 1036 больных) и в Нидерландах (LUMC – 560 пациенток, Национальный Канцрегистр – 22196 больных). Проведен сравнительный анализ типов выполненных операций по странам, а также во временных подгруппах. Частота органосохраняющего лечения при «раннем» раке молочной железы вРоссии и Нидерландах идентична – 53,7 % и 52,5 %. Доля органосохраняющих операций в течение 20 лет в России существенно не изменилась, тогда как в Нидерландах отмечено уменьшение доли органосохраняющего лечения с 56,2 % до 41,2 %, что, вероятнее всего, объясняется увеличением числа пациенток, находящихся в постменопаузе (&gt;60 лет) с 53,1 % до 63,8 %. Основным вариантом органосохраняющего лечения в России является радикальная резекция молочной железы, в Нидерландах – лампэктомия с БСЛУ или аксиллярной лимфодиссекцией, причем БСЛУ и в настоящее время не является «рутинной» операцией во всей стране

The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis

Background:Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer.Methods:A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours.Results:In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43-0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62-0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84-1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34-0.68), but was used in relatively few studies. Sample size and follow-up time seemed to influence study outcomes.Conclusion:Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis. In this context, ratios between TIL subsets may be more informative.British Journal of Cancer advance online publication, 31 May 2011; doi:10.1038/bjc.2011.189 www.bjcancer.com