Optimizing Population Variability to Maximize Benefit.
Ontology highlight
ABSTRACT:
SUBMITTER: Izu LT
PROVIDER: S-EPMC4674128 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Optimizing Population Variability to Maximize Benefit.
Izu Leighton T LT Bányász Tamás T Chen-Izu Ye Y
PloS one 20151209 12
Variability is inherent in any population, regardless whether the population comprises humans, plants, biological cells, or manufactured parts. Is the variability beneficial, detrimental, or inconsequential? This question is of fundamental importance in manufacturing, agriculture, and bioengineering. This question has no simple categorical answer because research shows that variability in a population can have both beneficial and detrimental effects. Here we ask whether there is a certain level ...[more]
Similar Datasets
Project description:BackgroundInfluenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency.ObjectiveWe present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA.MethodsCO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines.ResultsResults indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize.ConclusionSignificant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget.
| S-EPMC7347519 | biostudies-literature
Project description:For HIV-infected children, formulation development, pharmacokinetic (PK) data, and evaluation of early toxicity are critical for licensing new antiretroviral drugs; direct evidence of efficacy in children may not be needed if acceptable safety and PK parameters are demonstrated in children. However, it is important to address questions where adult trial data cannot be extrapolated to children. In this fast-moving area, interventions need to be tailored to resource-limited settings where most HIV-infected children live and take account of decreasing numbers of younger HIV-infected children after successful prevention of mother-to-child HIV transmission. Innovative randomized controlled trial (RCT) designs enable several questions relevant to children's treatment and care to be answered within the same study. We reflect on key considerations, and, with examples, discuss the relative merits of different RCT designs for addressing multiple scientific questions including parallel multi-arm RCTs, factorial RCTs, and cross-over RCTs. We discuss inclusion of several populations (eg, untreated and pretreated children; children and adults) in "basket" trials; incorporation of secondary randomizations after enrollment and use of nested substudies (particularly PK and formulation acceptability) within large RCTs. We review the literature on trial designs across other disease areas in pediatrics and rare diseases and discuss their relevance for addressing questions relevant to HIV-infected children; we provide an example of a Bayesian trial design in prevention of mother-to-child HIV transmission and consider this approach for future pediatric trials. Finally, we discuss the relevance of these approaches to other areas, in particular, childhood tuberculosis and hepatitis.
| S-EPMC6071856 | biostudies-other
Project description:Several single-center studies and one large multicenter clinical trial demonstrated that directional deep brain stimulation (DBS) could optimize the volume of tissue activated (VTA) based on the individual placement of the lead in relation to the target. The ability to generate axially asymmetric fields of stimulation translates into a broader therapeutic window (TW) compared to conventional DBS. However, changing the shape and surface of stimulating electrodes (directional segmented vs. conventional ring-shaped) also demands a revision of the programming strategies employed for DBS programming. Model-based approaches have been used to predict the shape of the VTA, which can be visualized on standardized neuroimaging atlases or individual magnetic resonance imaging. While potentially useful for optimizing clinical care, these systems remain limited by factors such as patient-specific anatomical variability, postsurgical lead migrations, and inability to account for individual contact impedances and orientation of the systems of fibers surrounding the electrode. Alternative programming tools based on the functional assessment of stimulation-induced clinical benefits and side effects allow one to collect and analyze data from each electrode of the DBS system and provide an action plan of ranked alternatives for therapeutic settings based on the selection of optimal directional contacts. Overall, an increasing amount of data supports the use of directional DBS. It is conceivable that the use of directionality may reduce the need for complex programming paradigms such as bipolar configurations, frequency or pulse width modulation, or interleaving. At a minimum, stimulation through directional electrodes can be considered as another tool to improve the benefit/side effect ratio. At a maximum, directionality may become the preferred way to program because of its larger TW and lower energy consumption.
| S-EPMC7229063 | biostudies-literature
Project description:Tsetse flies are cyclical vectors of trypanosomes, the causative agents of sleeping sickness or Human African Trypanosomosis and nagana or African Animal Trypanosomosis in Sub-Saharan Africa. The Insectarium de Bobo-Dioulasso (IBD) was created and equipped in the frame of Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) with the main goal to provide sterile males for the different eradication programs in West Africa which is already the case with the ongoing eradication program in Senegal. The aim of this study was to identify the best feeding regime in mass-rearing colonies of Glossina palpalis gambiensis to optimize the yield of sterile males. We investigated the mortality and fecundity for various feeding regimes and day alternation (3×: Monday-Wednesday-Friday, 4×: Monday-Wednesday-Friday-Saturday, 4×: Monday-Wednesday-Thursday-Friday and 6×: all days except Sunday) on adult tsetse flies in routine rearing over 60 days after emergence. The day alternation in the 4 blood meals per week (feeding regimes 2 and 3) had no effect on tsetse fly mortality and fecundity. The best feeding regime was the regime of 4 blood meals per week which resulted in higher significant fecundity (PPIF = 2.5; P = 0.003) combined with lower mortality of females (P = 0.0003) than the 3 blood meals per week (PPIF = 2.0) and in similar fecundity (PPIF = 2.6; P = 0.70) and mortality (P = 0.51) than the 6 blood meals per week. This feeding regime was extended to the whole colonies, resulting in an improved yield of sterile males for the ongoing eradication program in Senegal and would be more cost-effective for the implementation of the next-coming sterile insect technique (SIT) programs in West Africa.
| S-EPMC7808581 | biostudies-literature
Project description:The choice of the best sampling strategy to capture mean values of functional traits for a species/population, while maintaining information about traits' variability and minimizing the sampling size and effort, is an open issue in functional trait ecology. Intraspecific variability (ITV) of functional traits strongly influences sampling size and effort. However, while adequate information is available about intraspecific variability between individuals (ITVBI) and among populations (ITVPOP), relatively few studies have analyzed intraspecific variability within individuals (ITVWI). Here, we provide an analysis of ITVWI of two foliar traits, namely specific leaf area (SLA) and osmotic potential (?), in a population of Quercus ilex L. We assessed the baseline ITVWI level of variation between the two traits and provided the minimum and optimal sampling size in order to take into account ITVWI, comparing sampling optimization outputs with those previously proposed in the literature. Different factors accounted for different amount of variance of the two traits. SLA variance was mostly spread within individuals (43.4% of the total variance), while ? variance was mainly spread between individuals (43.2%). Strategies that did not account for all the canopy strata produced mean values not representative of the sampled population. The minimum size to adequately capture the studied functional traits corresponded to 5 leaves taken randomly from 5 individuals, while the most accurate and feasible sampling size was 4 leaves taken randomly from 10 individuals. We demonstrate that the spatial structure of the canopy could significantly affect traits variability. Moreover, different strategies for different traits could be implemented during sampling surveys. We partially confirm sampling sizes previously proposed in the recent literature and encourage future analysis involving different traits.
| S-EPMC5743657 | biostudies-literature
Project description:A greater understanding of anti-tumor immunity has resulted in rapid development of immunotherapy for a wide variety of cancers. Antibodies targeting the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1), or its ligand (PD-L1) have demonstrated clinical activity and are approved for treatment of melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, head and neck cancers, esophageal cancer, hepatocellular carcinoma, and Hodgkin lymphoma, among others. Treatment is generally well tolerated with relatively few adverse events compared with standard treatments such as chemotherapy. However, immune activation can potentially affect any organ system and a small fraction of patients are at risk for developing severe immune-related adverse events. Immune checkpoint inhibitors (ICIs) and other immunotherapeutic modalities such as cancer vaccines are in nascent stages of development for treatment of thymic epithelial tumors (TETs). Since the thymus plays a key role in the development of immune tolerance, thymic tumors have a unique biology which can influence the risk-benefit balance of immunotherapy. Indeed, early results from clinical trials have demonstrated clinical activity, albeit at a cost of a higher incidence of immune-related adverse events, which seem to particularly affect skeletal and cardiac muscle and the neuromuscular junction. In this paper we describe the effects of thymic physiology on the immune system and review the results of clinical trials that have evaluated immunotherapy for treatment of relapsed thymoma and thymic carcinoma. We review ongoing efforts to mitigate the risk of immune-related complications in patients with TETs receiving immunotherapy and offer our thoughts for making immunotherapy a feasible alternative for treatment of thymic tumors.
| S-EPMC6788636 | biostudies-literature
Project description:The human plasma proteome is clinically highly significant and has been studied extensively because it is thought that its molecular makeup provides a window into the health state of an individual. However, neither the quantitative variability of the plasma proteome nor the origins of the variation are known. To determine the relative contributions of heritability, environmental and longitudinal factors to plasma proteome variability we systematically decomposed the biological variance of 1904 peptides defining 342 unique plasma protein profiles from 232 plasma samples that were collected with 2-7 year intervals from monozygotic (MZ) and dizygotic (DZ) twins. The data were collected via SWATH mass spectrometry (SWATH-MS), an emerging technology characterized by high degree of reproducibility and quantitative accuracy. The data indicate abundance variability is an important feature for different proteins among population, that the abundances of about 20% of plasma protein are considerably heritable, and that the degrees of genetic control and aging effects vary across specific biological processes. Moreover, we identified 13 cis- SNPs significantly influencing the abundance level of specific plasma proteins. These results substantially extend the understanding of the impact of heritability on the human proteomic dynamics and therefore have implications for the effective design of plasma-based biomarker studies.
2015-01-05 | PXD001064 | Pride
Project description:Identifying the determinants of cumulative cultural evolution is a key issue in the interdisciplinary field of cultural evolution. A widely held view is that large and well-connected social networks facilitate cumulative cultural evolution because they promote the spread of useful cultural traits and prevent the loss of cultural knowledge through factors such as drift. This view stems from models that focus on the transmission of cultural information, without considering how new cultural traits actually arise. In this paper, we review the literature from various fields that suggest that, under some circumstances, increased connectedness can decrease cultural diversity and reduce innovation rates. Incorporating this idea into an agent-based model, we explore the effect of population fragmentation on cumulative culture and show that, for a given population size, there exists an intermediate level of population fragmentation that maximizes the rate of cumulative cultural evolution. This result is explained by the fact that fully connected, non-fragmented populations are able to maintain complex cultural traits but produce insufficient variation and so lack the cultural diversity required to produce highly complex cultural traits. Conversely, highly fragmented populations produce a variety of cultural traits but cannot maintain complex ones. In populations with intermediate levels of fragmentation, cultural loss and cultural diversity are balanced in a way that maximizes cultural complexity. Our results suggest that population structure needs to be taken into account when investigating the relationship between demography and cumulative culture.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.
| S-EPMC5812974 | biostudies-literature
Project description:Traditional clinical trial designs strive to definitively establish the superiority of an experimental treatment, which results in risk-adverse criteria and large sample sizes. Increasingly, common cancers are recognized as consisting of small subsets with specific aberrations for targeted therapy, making large trials infeasible.To compare the performance of different trial design strategies over a long-term research horizon.We simulated a series of two-treatment superiority trials over 15 years using different design parameters. Trial parameters examined included the number of positive trials to establish superiority (one-trial vs. two-trial rule), ? level (2.5%-50%), and the number of trials in the 15-year period, K (thus, trial sample size). The design parameters were evaluated for different disease scenarios, accrual rates, and distributions of treatment effect. Metrics used included the overall survival gain at a 15-year horizon measured by the hazard ratio (HR), year 15 versus year 0. We also computed the expected total survival benefit and the risk of selecting as new standard of care at year 15 a treatment inferior to the initial control treatment, P(detrimental effect).Expected survival benefits over the 15-year horizon were maximized when more (smaller) trials were conducted than recommended under traditional criteria, using the criterion of one positive trial (vs. two), and relaxing the ? value from 2.5% to 20%. Reducing the sample size and relaxing the ? value also increased the likelihood of selecting an inferior treatment at the end. The impact of ? and K on the survival benefit depended on the specific disease scenario and accrual rate: greater gains for relaxing ? in diseases with good outcome and/or low accrual rates and greater gains for increasing K for diseases with poor outcomes. Trials with smaller sample size did not perform well when using stringent (standard) level of evidence. For each disease scenario and accrual rate studied, the optimal design, defined as the design that the maximized expected total survival benefit while constraining P(detrimental effect) < 2.5%, specified ? = 20% or 10%, and a sample size considerably smaller than that recommended by the traditional designs. The results were consistent under different assumed distributions for treatment effect.The simulations assumed no toxicity issues and did not consider interim analyses.It is worthwhile to consider a design paradigm that seeks to maximize the expected survival benefit across a series of trials, over a longer research horizon. In today's environment of constrained, biomarker-selected populations, our results indicate that smaller sample sizes and larger ? values lead to greater long-term survival gains compared to traditional large trials designed to meet stringent criteria with a low efficacy bar.
| S-EPMC3904223 | biostudies-literature
Project description:Multiple-scale mobility is ubiquitous in nature and has become instrumental for understanding and modeling animal foraging behavior. However, the impact of individual movements on the long-term stability of populations remains largely unexplored. We analyze deterministic and stochastic Lotka-Volterra systems, where mobile predators consume scarce resources (prey) confined in patches. In fragile systems (that is, those unfavorable to species coexistence), the predator species has a maximized abundance and is resilient to degraded prey conditions when individual mobility is multiple scaled. Within the Lévy flight model, highly superdiffusive foragers rarely encounter prey patches and go extinct, whereas normally diffusing foragers tend to proliferate within patches, causing extinctions by overexploitation. Lévy flights of intermediate index allow a sustainable balance between patch exploitation and regeneration over wide ranges of demographic rates. Our analytical and simulated results can explain field observations and suggest that scale-free random movements are an important mechanism by which entire populations adapt to scarcity in fragmented ecosystems.
| S-EPMC5899458 | biostudies-other