A Model of R&D Valuation and the Design of Research Incentives

We develop a real options model of R&D valuation, which takes into account the uncertainty in the quality of the research output, the time and cost to completion, and the market demand for the R&D output. The model is then applied to study the problem of pharmaceutical under-investment in R&D for vaccines to treat diseases affecting the developing regions of the world. To address this issue, world organizations and private foundations are willing to sponsor vaccine R&D, but there is no consensus on how to administer the sponsorship effectively. Different research incentive contracts are examined using our valuation model. Their effectiveness is measured in the following four dimensions: cost to the sponsor, the probability of development success, the consumer surplus generated and the expected cost per person successfully vaccinated. We find that, in general, purchase commitment plans (pull subsidies) are more effective than cost subsidy plans (push subsidies), while extending patent protection is completely ineffective. Specifically, we find that a hybrid subsidy constructed from a purchase commitment combined with a sponsor co-payment feature produces the best results in all four dimensions of the effectiveness measure.

Preoperative and postoperative features of macular holes on en face imaging and optical coherence tomography angiography

AbstractPurposeTo characterize and quantify the pre- and postoperative foveal structural and functional patterns in full-thickness macular holes.MethodsSubjects presenting with a full-thickness macular hole that had pre- and postoperative imaging were included. En face optical coherence tomography (OCT) and OCT angiography (OCTA) was performed. Foveal avascular zone (FAZ) area, macular hole size, number and size of perifoveal cysts were measured.ResultsFive eyes from 5 patients were included in the study. The hole was closed in all eyes after the initial surgery. OCTA showed enlargement of the FAZ and delineation of the holes within the FAZ. Mean preoperative FAZ area was 0.41 ± 0.104 mm2. Visual acuity was improved and mean FAZ area was reduced to 0.27 ± 0.098 mm2 postoperatively (P < 0.05) with resolution of the macular hole and adjacent cystic areas. En face images of the middle retina showed a range of preoperative cystic patterns surrounding the hole. Smaller holes showed fewer but larger cystic areas and larger holes had more numerous but smaller cystic areas.Conclusions and ImportanceQuantitative evaluation of vascular and cystic changes following macular hole repair demonstrates the potential for recovery due to neuronal and vascular plasticity. Perifoveal microstructural patterns and their quantitative characteristics may serve as useful anatomic biomarkers for assessment of macular holes

Smart Object Reminders with RFID and Mobile Technologies

[[abstract]]In this paper, we present a reminder system that sends a reminder list to the user's mobile device based on the history data collected from the same user and the events in the user's calendar on that day. The system provides an individualized service. The list is to remind the user with objects he/she might have forgotten at home. The objects that the user brings along with are detected by passive RFID technology. Objects are classified into three different levels based on their frequencies in the history data. Rules of the three levels are then followed to decide if a certain object should be in the reminder list or not. A feedback mechanism is also designed to lower the possibility of unnecessary reminding.[[incitationindex]]SCI[[booktype]]電子

The evolution of Taiwan’s National Health Insurance drug reimbursement scheme

Background: The rapid growth of health care expenditures, especially pharmaceutical spending, is a challenge for many countries. To control increasing pharmaceutical expenditures and to enhance rational use of drugs, Taiwan’s National Health Insurance drug reimbursement system has evolved over time since its introduction in 1995. This study reviewed Taiwan’s drug reimbursement scheme: its development and evolution in the last two decades, and implications and impacts of recent policies for drug pricing. We also provide recommendations for possible improvement. Methods: We conducted a review of Taiwan’s National Health Insurance drug reimbursement scheme. We focused on three major components of the scheme: (i) the scope of drug coverage; (ii) pricing system for pharmaceuticals under the scheme; and (iii) adjustment of drug reimbursement prices. We reviewed the literature and public policy documents. Results: The National Health Insurance delisted 176 and another 240 behind-the-counter products (e.g., antacids, vitamins) between 2005 and 2006 to reduce pharmaceutical expenditures. For the pricing of pharmaceuticals, policy evolution can be divided into four phases since 1995; the present system emphasizes stakeholder engagement, health technology assessment, domestic R&D, and improving quality of products. To close the gap between drug reimbursement prices and procurement prices, eight rounds of drug price surveys and adjustments have been implemented since 2000. Conclusions: Taiwan’s National Health Insurance drug reimbursement scheme has evolved substantially over time to provide more equitable and affordable access to prescription medicines. However, more work is still needed as irrational difference in reimbursement and procurement prices persists and the total expenditure of the drug reimbursement scheme continues to increase at unsustainable rates

Longitudinal trends in use and costs of targeted therapies for common cancers in Taiwan: a retrospective observational study

Objectives: Some targeted therapies have improved survival and overall quality of cancer care generally, but these increasingly expensive medicines have led to increases in pharmaceutical expenditure. This study examined trends in use and expenditures of antineoplastic agents in Taiwan, and estimated market shares by prescription volume and costs of targeted therapies over time. We also determined which cancer types accounted for the highest use of targeted therapies. Design: This is a retrospective observational study focusing on the utilisation of targeted therapies for treatment of cancer. Setting: The monthly claims data for antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009–2012). Main outcome measures We calculated market shares by prescription volume and costs for each class of antineoplastic agent by cancer type. Using a time series design with Autoregressive Integrated Moving Average (ARIMA) models, we estimated trends in use and costs of targeted therapies. Results: Among all antineoplastic agents, use of targeted therapies grew from 6.24% in 2009 to 12.29% in 2012, but their costs rose from 26.16% to 41.57% in that time. Monoclonal antibodies and protein kinase inhibitors contributed the most (respectively, 23.84% and 16.12% of costs for antineoplastic agents in 2012). During 2009–2012, lung (44.64% of use; 28.26% of costs), female breast (16.49% of use; 27.18% of costs) and colorectal (12.11% of use; 13.16% of costs) cancers accounted for the highest use of targeted therapies. Conclusions: In Taiwan, targeted therapies are increasingly used for different cancers, representing a substantial economic burden. It is important to establish mechanisms to monitor their use and outcomes

Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury.

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging. METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment. CONCLUSIONS: Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI

Spontaneous Follicular Exclusion of SHP1-deficient B Cells Is Conditional on the Presence of Competitor Wild-type B Cells

Engagement of antigen receptors on mature B lymphocytes is known to block cell entry into lymphoid follicles and promote accumulation in T cell zones, yet the molecular basis for this change in cell distribution is not understood. Previous studies have shown that follicular exclusion requires a threshold level of antigen receptor engagement combined with occupancy of follicles by B cells without equivalent receptor engagement. The possibility has been raised that follicular composition affects B cell positioning by altering the amount of available antigen and the degree of receptor occupancy. Here we show that follicular composition affects migration of mature B cells under conditions that are independent of antigen receptor occupancy. B cells deficient in the negative regulatory protein tyrosine phosphatase, SHP1, which have elevated intracellular signaling by the B cell receptor, are shown to accumulate in the T zone in the absence of their specific antigen. Follicular exclusion of SHP1–deficient B cells was found to be conditional on the presence of excess B cells that lack elevated intracellular signaling, and was not due to a failure of SHP-1–deficient cells to mature and express the follicle-homing chemokine receptor Burkitt's lymphoma receptor 1. These findings strongly suggest that signals that are negatively regulated by SHP1 promote B cell localization in T cell zones by reducing competitiveness for follicular entry, and provide further evidence that follicular composition influences the positioning of antigen-engaged B cells

An Inflationary Scenario in Intersecting Brane Models

We propose a new scenario for D-term inflation which appears quite straightforwardly in the open string sector of intersecting brane models. We take the inflaton to be a chiral field in a bifundamental representation of the hidden sector and we argue that a sufficiently flat potential can be brane engineered. This type of model generically predicts a near gaussian red spectrum with negligible tensor modes. We note that this model can very naturally generate a baryon asymmetry at the end of inflation via the recently proposed hidden sector baryogenesis mechanism. We also discuss the possibility that Majorana masses for the neutrinos can be simultaneously generated by the tachyon condensation which ends inflation. Our proposed scenario is viable for both high and low scale supersymmetry breaking.Comment: 30 pages, 2 figures; v2 references and comments adde

Orientifolds, RG Flows, and Closed String Tachyons

We discuss the fate of certain tachyonic closed string theories from two perspectives. In both cases our approach involves studying directly configurations with finite negative tree-level cosmological constant. Closed string analogues of orientifolds, which carry negative tension, are argued to represent the minima of the tachyon potential in some cases. In other cases, we make use of the fact, noted in the early string theory literature, that strings can propagate on spaces of subcritical dimension at the expense of introducing a tree-level cosmological constant. The form of the tachyon vertex operator in these cases makes it clear that a subcritical-dimension theory results from tachyon condensation. Using results of Kutasov, we argue that in some Scherk-Schwarz models, for finely-tuned tachyon condensates, a minimal model CFT times a subcritical dimension theory results. In some instances, these two sets of ideas may be related by duality.Comment: 15 pages, 2 figures, uses harvmac; v2: references adde