Three dedicated approaches to the calculation of the risk-adjusted net present value (rNPV) in drug discovery projects under different assumptions are suggested. The probability of finding a candidate drug suitable for clinical development and the time to the initiation of the clinical development is assumed to be flexible in contrast to the previously used models. The rNPV of the post-discovery cash flows is calculated as the probability weighted average of the rNPV at each potential time of initiation of clinical development. Practical considerations how to set probability rates, in particular during the initiation and termination of a project is discussed.
The cylindrical Bessel differential equation and the spherical Bessel differential equation in the interval [Formula: see text] with Neumann boundary conditions are considered. The eigenfunctions are linear combinations of the Bessel function [Formula: see text] or linear combinations of the spherical Bessel functions [Formula: see text]. The orthogonality relations with analytical expressions for the normalization constant are given. Explicit expressions for the Lommel integrals in terms of Lommel functions are derived. The cross product zeros [Formula: see text] and [Formula: see text] are considered in the complex plane for real as well as complex values of the index [Formula: see text] and approximations for the exceptional zero [Formula: see text] are obtained. A numerical scheme based on the discretization of the two-dimensional and three-dimensional Laplace operator with Neumann boundary conditions is presented. Explicit representations of the radial part of the Laplace operator in form of a tridiagonal matrix allow the simple computation of the cross product zeros.
Assessing the probability of very low or high water levels is an important issue in the management of hydroelectric dams. In the case of the Akosombo dam, very low and high water levels result in load shedding of electrical power and flooding in communities downstream respectively. In this paper, we use extreme value theory to estimate the probability and return period of very low water levels that can result in load shedding or a complete shutdown of the dam’s operations. In addition, we assess the probability and return period of high water levels near the height of the dam and beyond. This provides a framework for a possible extension of the dam to sustain the generation of electrical power and reduce the frequency of spillage that causes flooding in communities downstream. The results show that an extension of the dam can reduce the probability and prolong the return period of a flood. In addition, we found a negligible probability of a complete shutdown of the dam due to inadequate water level.
This study investigated effects of far-infrared sauna (FIRS) bathing on recovery from strength training and endurance training sessions, but also possible differences between FIRS and traditional (TRAD) Finnish sauna bathing.
Japan has four seasons and many chances of low atmospheric pressure or approaches of typhoon, therefore it has been empirically known that the fluctuation of weather induces migraine in people. Generally, its mechanism has been interpreted as follows: physical loading, attributed by atmospheric pressure to human bodies, compresses or dilates human blood vessels, which leads to abnormality in blood flow and induces migraine. We report our examination of the stage in which migraine tends to be induced focusing on the variation of atmospheric pressure.
Changes or introductions of technology or equipment can affect how a sport is played or influence its performances. This article conducted a systematic review of peer-reviewed literature to identify any case studies of controversial events surrounding the implementation or use of sports technology. 56 articles were identified that highlighted 31 different case studies found over a three decade time period. Thematic analysis revealed six distinctive themes when reviewing the articles. Whilst the sport of golf had the highest number of case studies, it was found that a significant level of attention had been recorded in the cases of Oscar Pistorius use of prosthetic legs in athletics and the use of full length swimsuits in swimming. The trend surrounding the number of articles was shown to be initially intermittent but saw a peak period from 2008 to 2010. However, the frequency of such articles since this peak has been more consistent. It is proposed that long periods of time without intervention or resolution by a governing body often increases the peer-reviewed attention paid to such cases in examples such as those identified in this systematic review.
Gluten-free diet has shown promising effects in preventing type 1 diabetes (T1D) in animals as well as beneficial effects on the immune system. Gluten-free diet at diabetes onset may alter the natural course and outcome of autoimmune diseases such as T1D.
Climate change has resulted in increased vulnerability of smallholder farmers in marginal areas of Zimbabwe where there is limited capacity to adapt to changing climate. One approach that has been used to adapt to changing climate is in-field water harvesting for improved crop yields in the semi- arid regions of Zimbabwe. This review analyses the history of soil and water conservation in Zimbabwe, efforts of improving water harvesting in the post independence era, farmer driven innovations, water harvesting technologies from other regions, and future directions of water harvesting in semi arid marginal areas. From this review it was observed that the blanket recommendations that were made on the early conservation method were not suitable for marginal areas as they resulted in increased losses of the much needed water. In the late 1960 and 70s', soil and water conservation efforts was a victim of the political environment and this resulted in poor uptake. Most of the water harvesting innovations which were promoted in the 1990s' and some farmer driven innovations improved crop yields in marginal areas but were poorly taken up by farmers because they are labour intensive as the structures should be made annually. To address the challenges of labour shortages, the use of permanent in-field water harvesting technologies are an option. There is also need to identify ways for promoting water harvesting techniques that have been proven to work and to explore farmer-led knowledge sharing platforms for scaling up proven technologies.
Recent developments in genetics and molecular biology have classified breast cancer into subtypes based on tumor markers of estrogen (ER), progesterone (PR) and human epidermal growth Factor-2 receptors (Her-2), with the basal-like (ER-, PR-, Her2-) subtype commonly referred to as “triple negative” breast cancer (TNBC) being the most aggressive. Prior studies have provided evidence that higher socio-economic status (SES) is associated with increased breast cancer risk, likely due to hormone related risk factors such as parity and hormonal contraceptive use. However, it is unclear if the relationship between SES and overall breast cancer incidence exists within each subtype, and if this association varies by race/ethnicity. Analysis was based on data obtained from the SEER database linked to 2008-2012 American Community Survey data, and restricted to women diagnosed with breast cancer in 2010. The NCI SES census tract SES index based on measures of income, poverty, unemployment, occupational class, education and house value, was examined and categorized into quintiles. Age-adjusted incidence rate ratios were calculated comparing the lowest to the highest SES groups by subtype, separately for each race/ethnic group. We identified 47,586 women with breast cancer diagnosed in 2010. The majority was diagnosed with Her2-/HR+ tumors (73 %), while 12 % had triple negative tumors (TNBC). There was a significant trend of higher incidence with increasing SES for Her2-/HR+ (IRR Highest vs. Lowest SES: 1.32, 95 % CI 1.27-1.39; p value trend: 0.01) and Her2+/HR+ tumors (IRR Highest vs. Lowest SES: 1.46, 95 % CI 1.27-1.68; p value trend: 0.01) among White cases. There was no association between SES and incidence of HR- subtypes (Her2+/HR- or TNBC). Similar associations were observed among Black, Hispanic and Asian or Pacific Islander cases. The positive association between SES and breast cancer incidence is primarily driven by hormone receptor positive tumors. To the extent that neighborhood SES is a proxy for individual SES, future studies are still needed to identify etiologic risk factors for other breast cancer subtypes.
The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.