Investigation of the corneal frequency response to modulated sound excitation

Purpose : To investigate the possibility of determining the eye's intraocular pressure (IOP), biomechanical parameters (BM), and geometrical distortion through its frequency response to acoustic excitation as measured by phase-sensitive swept source optical coherence tomography (PhS-ssOCT). Methods : Experimental (E): Freshly enucleated porcine eyes (<45h) were mounted in front of a PhS-ssOCT at 15mmHg IOP. A loudspeaker was placed 10mm to the corneal apex, and a frequency sweep (0-1000Hz) was applied at sound pressure levels of 0.88Pa. Resonance amplitude and frequency were measured for different corneal treatments: 1) de-epithelized, 2) applied photosensitizer Riboflavin (RF), 3) cross-linked (CXL, Dresden protocol), and different measurement set-ups: a) at/around apex, b) IOP 15 - 30 mmHg, c) eye mounted on artificial orbital fat, mimicked by silicone. Simulations (S): Nonlinear hyperelastic FE models of porcine eyes were built and subjected to a modulated pressure, equal to (E). The frequency response was determined by monitoring the apex displacement over time then using fast Fourier transformation (FFT) analysis to determine the frequency peaks. Resonance frequency and amplitudes were determined across corneal meridians for homogeneous BM and for corneas with local BM variations. For both (E) and (S), resonance frequencies were defined at the positions of peak amplitudes. Results : (S) and (E) results were in good correspondence and both showed resonance frequencies of 370Hz. An increase of 15 mmHg in IOP resulted in a decrease of the resonance amplitude of up to 1.24±0.61μm (E) and a frequency shift of up to 22.7± 9.3Hz (E). BM changes produced by CXL led to a decrease in amplitude of 2.19±0.78μm, without significant frequency shifts (E). (S) supported these trends, but showed up to 13Hz higher frequency shifts with IOP increase. Additionally, (S) showed that localized BM changes could be detected by examining asymmetries of the resonance amplitude across opposite corneal meridians. Presence of artificial orbital fat resulted in a damping of the resonance amplitude of >50% for (E) and (S). Conclusions : Sound-coupled OCT measurements made it possible to detect corneal resonance frequencies. IOP and BM could be decoupled, due to differential dependencies of amplitude and resonance frequency on IOP and BM

Tailored lighting intervention (TLI) for improving sleep-wake cycles in older adults living with dementia

Introduction: Sleep disturbance is a hallmark of Alzheimer’s disease and related dementias, and caregiver stress caused by patients’ nighttime wandering, injuries, and agitation are frequently at the root of decisions to move them to assisted living facilities, where typically dim institutional lighting can further exacerbate their sleep problems. This study explored the effects of a circadian-effective lighting intervention on actigraphic sleep measures and subjective assessments of sleep disturbance, depression, and sleep-disturbed behaviors.Methods: Fourteen older adult (≥60 years) participants (11 females, mean age = 84.1 [SD 8.9]), all diagnosed with moderate to severe dementia and sleep disturbance, were recruited from 3 assisted living and memory care facilities. Following a crossover, placebo-controlled design, 3 different lighting modes were used to deliver high levels of circadian stimulus to the participants’ eyes for two 8-week intervention periods in a counter balanced order with a 4-week washout between the study’s 2 conditions (dim light control vs. active intervention). Actigraphy and questionnaire data were collected over 7-day assessment periods that preceded (baseline weeks 1 and 9) and concluded (post-intervention week 9 and 22) the intervention periods. Actigraphic outcomes included sleep duration, sleep time, sleep efficiency, sleep start time, and sleep end time. Subjective assessments included the Cornell Scale for Depression in Dementia (CSDD), Pittsburgh Sleep Quality Index (PSQI), and Sleep Disorders Inventory (SDI) instruments.Results: Under the active condition, sleep duration significantly (p = 0.018) increased and sleep start time significantly (p = 0.012) advanced after the intervention compared to baseline. Also under the active condition, PSQI (p = 0.012), CSDD (p = 0.007), Sleep Disorders Inventory frequency (p = 0.015), and SDI severity (p = 0.015) scores were significantly lower after the intervention compared to baseline.Discussion: This study demonstrates that a circadian-effective lighting intervention delivering bright days and dark nights improves measures of sleep and mood in dementia patients living in controlled environments

Brainstorm-Duneuro: An Integrated and User-Friendly Finite Element Method for Modeling Electromagnetic Brain Activity

Human brain activity generates scalp potentials (electroencephalography - EEG), intracranial potentials (iEEG), and external magnetic fields (magnetoencephalography - MEG). These electrophysiology (e-phys) signals can often be measured simultaneously for research and clinical applications. The forward problem involves modeling these signals at their sensors for a given equivalent current dipole configuration within the brain. While earlier researchers modeled the head as a simple set of isotropic spheres, today\u27s magnetic resonance imaging (MRI) data allow for a detailed anatomic description of brain structures and anisotropic characterization of tissue conductivities. We present a complete pipeline, integrated into the Brainstorm software, that allows users to automatically generate an individual and accurate head model based on the subject\u27s MRI and calculate the electromagnetic forward solution using the finite element method (FEM). The head model generation is performed by integrating the latest tools for MRI segmentation and FEM mesh generation. The final head model comprises the five main compartments: white-matter, gray-matter, CSF, skull, and scalp. The anisotropic brain conductivity model is based on the effective medium approach (EMA), which estimates anisotropic conductivity tensors from diffusion-weighted imaging (DWI) data. The FEM electromagnetic forward solution is obtained through the DUNEuro library, integrated into Brainstorm, and accessible with either a user-friendly graphical interface or scripting. With tutorials and example data sets available in an open-source format on the Brainstorm website, this integrated pipeline provides access to advanced FEM tools for electromagnetic modeling to a broader neuroscience community

Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Abstract Aim This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m 2 24-h intravenous (i.v.) infusion every 3weeks (q3wk) ( Arm A ), or doxorubicin 75mg/m 2 i.v. q3wk, or doxorubicin 60mg/m 2 i.v. plus ifosfamide (range, 6–9g/m 2 ) i.v. q3wk ( Arm B ). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p =0.9573; hazard ratio=0.86, p =0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma

Developing Symptom Lists for People with Cancer Treated with Targeted Therapies

Background: Targeted Therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical managementObjective: the aim of this study is to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. Patients and Methods: symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2 positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with health care professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. Results: a total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set.Conclusions: symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.<br/

Entry and Exit Strategies in Migration Dynamics

This work is devoted to study the role of combined entry and exit strategies in the migration process. We develop a real option model in which the community of immigrants in the host country is described as a club and the immigrants benefits is a U-shaped function, depending on the dimension of the district. There exist two threshold levels: the first one triggers the migration choice, while the second triggers the return to the country of origin. The theoretical results show that the phenomenon of hysteresis is amplified by the existence of a community both in the entry case and in the exit case. Furthermore, the community can reduce the minimum wage level required to trigger both exit and entry: this fact could explain why in some cases we observe migration inflows with a low wage differential and also with underunemployment. We show also some possible further extensions of the model: in one case we introduce a possible way to select the entrants skills and in another case we show some theoretical implementations to include possible policy shocks in the migrants choice

Energy Demand and Temperature: A Dynamic Panel Analysis

This paper is a first attempt to investigate the effect of climate on the demand for different energy vectors from different final users. The ultimate motivation for this is to arrive to a consistent evaluation of the impact of climate change on key consumption goods and primary factors such as energy vectors. This paper addresses these issues by means of a dynamic panel analysis of the demand for coal, gas, electricity, oil and oil products by residential, commercial and industrial users in OECD and (a few) non-OECD countries. It turns out that temperature has a very different influence on the demand of energy vectors as consumption goods and on their demand as primary factors. In general, residential demand responds negatively to temperature increases, while industrial demand is insensitive to temperature increases. As to the service sector, only electricity demand displays a mildly significant negative elasticity to temperature changes

The Nontradable Share Reform in the Chinese Stock Market

Nontradable shares (NTS) are an unparalleled feature of the ownership structure of Chinese listed companies and represented a major hurdle to domestic financial market development. After some failed attempts, in 2005 the Chinese authorities have launched a structural reform program aiming at eliminating NTS. In this paper, we evaluate the stock price effects of the actual implementation of this reform in 368 firms. The NTS reform generated a statistically significant 8 percent positive abnormal return over the event window, adjusting prices for the compensation requested by tradable shareholders. Results are consistent with the expectation of improved economic fundamentals such as better corporate governance and enhanced liquidity

Participatory Approach in Decision Making Processes for Water Resources Management in the Mediterranean Basin

This paper deals with the comparative analysis of different policy options for water resources management in three south-eastern Mediterranean countries. The applied methodology follows a participatory approach throughout its implementation and is supported by the use of three different software packages dealing with water allocation budget, water quality simulation, and Multi Criteria Analysis, respectively. The paper briefly describes the general objectives of the SMART project and then presents the three local case studies, the valuation objectives and the applied methodology - developed as a general replicable framework suitable for implementation in other decision-making processes. All the steps needed for a correct implementation are therefore described. Following the conceptualisation of the problem, the choice of the appropriate indicators as well as the calculation of their weighting and value functions are detailed. The paper concludes with the results of the Multi Criteria and the related Sensitivity Analyses performed, showing how the different policy responses under consideration can be assessed and furthermore compared through case studies thanks to their relative performances. The adopted methodology was found to be an effective operational approach for bridging scientific modelling and policy making by integrating the model outputs in a conceptual framework that can be understood and utilised by non experts, thus showing concrete potential for participatory decision making