Overall Probability Of Success Research Articles

Long-Term Efficacy of Selective Laser Trabeculoplasty in Primary Angle-Closure Disease After Laser Peripheral Iridotomy

ABSTRACT Purpose To evaluate the long-term efficacy of selective laser trabeculoplasty (SLT) in eyes with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) following a laser peripheral iridotomy (LPI). Method In this prospective cross-sectional study, 45 eyes of 34 patients with PAC/PACG diagnosis, uncontrolled intraocular pressure (IOP), and visible pigmented trabecular-meshwork (TM) at least 180° on gonioscopy following a LPI were recruited. Following a detailed baseline ophthalmic evaluation, all eligible eyes underwent SLT, and the patients were examined on day1, at 1 week, 1-, 3-, and 6-months, and 1-, 2-, 3-, 4-, and 5-year subsequently. The main outcomes measured were IOP, number of IOP-lowering agents, and complications. Results The mean age of the cohort was 57.80 ± 6.44 years, the male–female ratio was 8:26, and 17 eyes were PACG, and 28 were PAC. The baseline IOP was 23.81 ± 1.78 mm Hg, and was significantly declined at all follow-ups (p < .0001). The cumulative probability of overall success was 91% and 84% at 2-, and 5-year, respectively. At 5-year SLT provided drug-freedom in 80% of PAC and 23% of PACG eyes. Six eyes had IOP spike at 1-week and two patients underwent repeat SLT after 1-year. No other complications, such as pain/discomfort, inflammation, an increase in peripheral anterior synechiae and cystoid-macular-edema, were noted. Conclusions SLT appears a safe and cost-effective procedure in PAC/mild- moderate PACG eyes with uncontrolled IOP after laser iridotomy. The long-term effectiveness of SLT as adjuvant treatment was good, but need large sized randomized studies for more validation.

The influence of pair duration on reproductive success in the monogamous ‘Alalā (Hawaiian crow, Corvus hawaiiensis)

Conservation breeding program practitioners select potential mates in an attempt to maximize pair compatibility and maintain genetic diversity. Therefore, pair duration, or the number of breeding seasons that individuals retain the same mate, is practitioner-determined in these settings. There is a critical need to evaluate whether pair duration influences reproductive success in ex situ assurance populations, particularly for socially monogamous species. The ‘Alalā (Hawaiian crow, Corvus hawaiiensis) is a monogamous forest bird that is currently extinct in the wild. Today, ‘Alalā exist only in human care for intensive conservation breeding. We analyzed breeding program data from 2018-2021 to determine the effects of ‘Alalā pair duration and age on reproduction (nest building, egg laying, hatching, and fledging). We found that pair duration does not influence reproductive outcomes, and thus practitioners can be more proactive when re-pairing birds. Female and male age, on the other hand, influenced the probability of nest building, clutch production, and overall reproductive success. Nest building and clutch production probabilities were high (near 1) and stable as females aged from 2 to ~ 12 years old, declining sharply thereafter. In males, overall reproductive success (from building robust nests to rearing at least one nestling to fledge) increased with age from 2 to ~ 9 years old, peaked and reached an asymptote with males ≳ 9 to ~ 13 years old, and decreased in males ≳ 13 years old. Thus, integrating age into the pair selection process will increase the likelihood of achieving conservation goals. To our knowledge, we are the first to utilize empirical pair duration results to provide specific management recommendations for mate selection in an avian conservation breeding program. Our findings have critical utility for guiding ‘Alalā pairing decisions, and more broadly underscore the importance of evaluating mate retention and selection protocols in other conservation breeding programs.

Needing everything (or just one thing) to go right: Myopic preferences for consolidating or spreading risks.

Succeeding at a task often depends on the success or failure of component events. Such multicomponent risks can take one of two general forms. Disjunctive risks require the success of just one such component; conjunctive risks, all of them. Seven studies converge to show people prefer to consolidate disjunctive risks into fewer components and to spread conjunctive risks across more components, independent of the objective or subjective implications for the probability of overall success. These tendencies were reflected in preferences for how to approach potential investors, decisions about how much to invest in different business opportunities, and gamble valuations. Such preferences were specific to multicomponent risks as compared to single-component risks whose overall prospects for success were yoked to participants' own perceptions of a matched multicomponent risk. Participants confronted multicomponent risks myopically, swayed by whether positive or disappointing news would likely be delivered at a single point in time instead of by the overall prospects for success. Supporting this account, these preferences for consolidating or spreading risks were reduced when the components' outcomes would be revealed at once. Anticipated confidence while proceeding through the risk (even controlling for perceived probabilities of success) explained these preferences. After all, these preferred risk structures actually do allow people to traverse a multicomponent risk with more confidence that the next piece of news they receive will be positive (or not negative), though such myopic perspectives neglect just how many components will offer a chance for success (disjunctive risks) or the potential for failure (conjunctive risks). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Analysis of Physicians’ Probability Estimates of a Medical Outcome Based on a Sequence of Events

The probability of a conjunction of 2 independent events is the product of the probabilities of the 2 components and therefore cannot exceed the probability of either component; violation of this basic law is called the conjunction fallacy. A common medical decision-making scenario involves estimating the probability of a final outcome resulting from a sequence of independent events; however, little is known about physicians' ability to accurately estimate the overall probability of success in these situations. To ascertain whether physicians are able to correctly estimate the overall probability of a medical outcome resulting from 2 independent events. This survey study consisted of 3 separate substudies, in which 215 physicians were asked via internet-based survey to estimate the probability of success of each of 2 components of a diagnostic or prognostic sequence as well as the overall probability of success of the 2-step sequence. Substudy 1 was performed from April 2 to 4, 2021, substudy 2 from November 2 to 11, 2021, and substudy 3 from May 13 to 19, 2021. All physicians were board certified or board eligible in the primary specialty germane to the substudy (ie, obstetrics and gynecology for substudies 1 and 3 and pulmonology for substudy 2), were recruited from a commercial survey service, and volunteered to participate in the study. Case scenarios presented in an online survey. Respondents were asked to provide their demographic information in addition to 3 probability estimates. The first substudy included a scenario describing a brow presentation discovered during labor; the 2 conjuncts were the probabilities that the brow presentation would resolve and that the delivery would be vaginal. The second substudy involved a diagnostic evaluation of an incidentally discovered pulmonary nodule; the 2 conjuncts were the probabilities that the patient had a malignant condition and that a technically successful transthoracic needle biopsy would reveal a malignant condition. The third substudy included a modification of the first substudy in an attempt to debias the conjunction fallacy prevalent in the first substudy. Respondents' own probability estimates of the individual events were used to calculate the mathematically correct conjunctive probability. Among 215 respondents, the mean (SD) age was 54.0 (9.5) years; 142 respondents (66.0%) were male. Data on race and ethnicity were not collected. A total of 168 physicians (78.1%) estimated the probability of the 2-step sequence to be greater than the probability of at least 1 of the 2 component events. Compared with the product of their 2 estimated components, respondents overestimated the combined probability by 12.8% (95% CI, 9.6%-16.1%; P < .001) in substudy 1, 19.8% (95% CI, 16.6%-23.0%; P < .001) in substudy 2, and 18.0% (95% CI, 13.4%-22.5%; P < .001) in substudy 3, results that were mathematically incoherent (ie, formally illogical and mathematically incorrect). In this survey study of 215 physicians, respondents consistently overestimated the combined probability of 2 events compared with the probability calculated from their own estimates of the individual events. This biased estimation, consistent with the conjunction fallacy, may have substantial implications for diagnostic and prognostic decision-making.

Priority Weights for Predicting the Success of Hotel Sustainable Business Models

This study proposes the use of consistent fuzzy preference relations to evaluate the structure of hotel sustainable business model (HSBM) dimensions and the corresponding hierarchy of evaluation indicators, and predict the overall probability of success. As fuzzy preference relations require, a group of hotel professionals in Taiwan was asked to process pairwise comparisons using linguistic variables to determine the weights of dimensions and indicators. According to the results, finances were found to be the most important dimension, followed by human capital. The number of local cultural events in the hotel was identified as the most important indicator. The predictive values revealed the possibility for successful HSBM implementation, shedding light on the vision of sustainability for the hotel industry. The results of the present study contribute to the literature on sustainability by determining the importance and weights of dimensions and indicators for hotel business models, providing an example of the use of this strategic tool in generating and modifying sustainable business models for the hotel industry.

Field Methods for Translocating Female Greater Sage‐Grouse (Centrocercus urophasianus) with their Broods

ABSTRACTGreater sage‐grouse (Centrocercus urophasianus) have experienced considerable range contraction and reduced abundance in response to habitat loss and degradation. Translocation is a conservation action that is often used to reintroduce extirpated populations or augment existing small populations. Translocations have had limited success in restoring viable populations of sage‐grouse; a lack of success is attributed to long‐distance post‐release movements away from release sites, reduced survival, and lack of reproductive success of translocated individuals. Translocating female sage‐grouse with their chicks (brood translocation) is a technique aimed at promoting breeding area fidelity and reproduction and may be beneficial to population restoration efforts. Furthermore, the ability to capture, relocate, and release individuals while minimizing translocation‐induced loss increases the overall probability of restoration success. Accordingly, we developed a protocol to translocate female sage‐grouse and their broods simultaneously, using a delayed‐release system that included a custom release box and acclimation pen. We tested our protocol across 2 separate restoration projects in North Dakota and California during 2017–2019 with a total of 38 translocated females and 196 chicks. We successfully released 174/196 chicks (88.8%) from 32/38 (84.2%) broods. Our protocol builds on existing translocation methods used to translocate sage‐grouse and will likely prove to be a critical technique in restoring sage‐grouse populations. © 2021 The Wildlife Society.

Developing Novel Anticancer Drugs for Targeted Populations: An Update.

Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process, the rate of opportunity to get new, safe and efficacious drugs for the targeted population, including pediatric patients with cancer, becomes sluggish. This paper discusses the development of novel anticancer drugs focusing on the identification and selection of targeted anticancer drug development for the targeted population. Information presented in this review was obtained from different databases, including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which take 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10- 17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. Therefore, to continue with the progress of developing novel anticancer drugs for the targeted population, identification and selection of target to specific disease type is important. Considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we study the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

Rock Mass Classification by Multivariate Statistical Techniques and Artificial Intelligence

This study aims to improve the quality and accuracy of RMR classification system for rock masses in open pit mines. A database of open pit mines comprising basic parameters for obtaining the RMR was used. Techniques applied in this research were multivariate statistics and artificial intelligence. In relation to multivariate statistics, factor analysis was capable of identifying underlying factors not observable in the original variables, using the variables of these factors in the classification system, instead of all RMR variables. The proposed classifier was obtained by training neural networks. The results of the factor analysis allowed the identification of three common factors. Factor 1 represents the strength and weathering of the rock mass. Factor 3 represents the fracturing degree of the rock mass. Finally Factor 2 represents water flow conditions. Thirty artificial neural networks were trained with randomly selected training samples. The trained networks proved to be effective and stable. Regarding the validation of the networks, the values obtained for the overall probability of success and apparent error rate showed normal distributions and a low dispersion rate, with average rates of 0.87 and 0.13, respectively. Regarding specific errors, error values were recorded only between contiguous RMR classes. The major contribution of the study is to present a new methodology for achieving rock mass classifications based on mathematical and statistical fundamentals, aiming at optimising the selection of variables and consequent reduction of subjectivity in the parameters and classification methods.

Association between adjuvant posterior repair and success of native tissue apical suspension

Posterior repairs and perineorrhaphies are often performed in prolapse surgery to reduce the size of the genital hiatus. The benefit of an adjuvant posterior repair at the time of sacrospinous ligament fixation or uterosacral ligament suspension is unknown. We aimed to determine whether an adjuvant posterior repair at transvaginal apical suspension is associated with improved surgical success. This secondary analysis of Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial compared 24-month outcomes in 190 participants who had a posterior repair (posterior repair group) and 184 who did not (no posterior repair group) at the time of sacrospinous ligament fixation or uterosacral ligament suspension. Concomitant posterior repair was performed at the surgeon's discretion. Primary composite outcome of "surgical success" was defined as no prolapse beyond the hymen, point C ≤-2/3 total vaginal length, no bothersome bulge symptoms, and no retreatment at 24 months. The individual components were secondary outcomes. Propensity score methods were used to build models that balanced posterior repair group and the no posterior repair group for ethnographic factors and preoperative Pelvic Organ Prolapse Quantification values. Adjusted odds ratios were calculated to predict surgical success based on the performance of a posterior repair. Groups were also compared with unadjusted χ2 analyses. An unadjusted probability curve was created for surgical success as predicted by preoperative genital hiatus. Women in the posterior repair group were less likely to be Hispanic or Latina, and were more likely to have had a prior hysterectomy and to be on estrogen therapy. The groups did not differ with respect to preoperative Pelvic Organ Prolapse Quantification stage; however, subjects in the posterior repair group had significantly greater preoperative posterior wall prolapse. There were no group differences in surgical success using propensity score methods (66.7% posterior repair vs 62.0% no posterior repair; adjusted odds ratio, 1.07; 95% confidence interval, 0.56-2.07; P= 0.83) or unadjusted test (66.2% posterior repair vs 61.7% no posterior repair; P= 0.47). Individual outcome measures of prolapse recurrence (bothersome bulge symptoms, prolapse beyond the hymen, or retreatment for prolapse) also did not differ by group. Similarly, there were no differences between groups in anatomic outcomes of any individual compartment (anterior, apical, or posterior) at 24 months. There was high variation in performance of posterior repair by surgeon (interquartile range, 15-79%). The unadjusted probability of overall success at 24 months, regardless of posterior repair, decreased with increasing genital hiatus, such that a genital hiatus of 4.5 cm was associated with 65.8% success (95% confidence interval, 60.1-71.1%). Concomitant posterior repair at sacrospinous ligament fixation or uterosacral ligament suspension was not associated with surgical success after adjusting for baseline covariates using propensity scores or unadjusted comparison. Posterior repair may not compensate for the pathophysiology that leads to enlarged preoperative genital hiatus, which remains prognostic of prolapse recurrence.

Correction Activities by France’s Supreme Courts and Control over their Dockets

L’objectif de cet article est d’observer la façon dont les Cours Suprêmes utilisent leur pouvoir de choisir les cas qui leur sont soumis pour corriger les décisions des cours d’appel selon leur propre interoprétation du droit. En France, deux Cours Suprêmes existent, le Conseil d’État pour les affaires administratives et la Cour de Cassation pour les affaires civiles. ces deux cours ont fait l’objet, à des dates différentes, d’une réforme qui modifia leur pouvoir discrétionnaire de choix des cas à revoir. En conséquence, si les Cours prennent des décisions différentes pour des cas similaires, cela peut s’expliquer par des attitudes correctrices différentes ou par des stratégies de sélection des cas différentes ou encore par une combinaison des deux. Il est donc nécessaire de dinstinguer l’impact de ces différentes stratégies pour comprendre les comportements des Cours et être en mesure de les comparer. Pour ce faire, nous menons une étude économétrique visant à comparer les attitudes correctrices des deux Cours et à déterminer si ces attitudes sont influencées par la possibilité de sélectionner les cas à revoir. A partir d’une base de données originale comprenant l’ensemble des cas environnementaux jugés par les deux Cours entre 1956 et 2010, nous menons une analyse contrefactuelle pour comparer les décisions des deux Cours avant et après les réformes les autorisant à sélectionner les cas à revoir. Nous observons que les deux Cours ont une attitude correctrice similaire tant qu’elles sont soumises à la même règle de sélection des cas. Par ailleurs, nous observons que les Cours utilisent leur pouvoir de sélection des cas pour favoriser les plaignants de telle sorte que leur comportement modifie la probabilité de victoire des plaignants et défendeurs depuis le procès en première instance jusqu’à l’appel devant la Cour Suprême. Classification JEL : K32, K41

Kleptoparasitic strategies of Mallards towards conspecifics and Eurasian Coots

We describe interspecific and intraspecific kleptoparasitic behaviour in Mallards Anas platyrhynchos, attempting to steal Zebra Mussels Dreissena polymorpha from other Mallards and Eurasian Coots Fulica atra. Both Coots and Mallards were most often attacked by Mallards perpetrating kleptoparasitic attacks when they handled large or intermediate-sized prey items. The probability of attack was nearly halved when the foraging birds had small versus large prey items in their bills. The overall probability of success of a kleptoparasitic attack was lowest when the attacked birds had small prey items, but higher if they had intermediate or large prey items. Kleptoparasitic attacks carried out on Coots were more often successful than those on Mallards. The results suggest that the optimal foraging theory, where animals tend to maximize net benefits, may be applicable to kleptoparasitic behaviour.

Estimating Clinical Trial Success Rates and Related Parameters in Oncology

We extend earlier large-scale studies of clinical trial statistics by focusing on the performance of oncology trials. Using 108,248 data points between January 1, 2005, and September 31, 2018, compiled from the Citeline database, we investigate the duration of clinical trials and compute the probabilities of success of 24,448 oncology drug development programs by disease group. While the overall phase 1 to approval rate for all oncology-related drug development programs is 3.3%, individual disease groups have approval rates ranging from 0% to 10.1%. Similar patterns can be seen for oncology orphan drug development programs, where the overall probability of success ranges from 0% to 8.3%, with an overall average of 1.9%. We find overwhelming evidence that using biomarkers for patient selection is effective in almost all disease groups within oncology, raising the overall probability of success by an average of 13.3%.

System reliability analysis of piezoelectric vibration energy harvesting considering multiple safety events under physical uncertainty

The most important duty of a piezoelectric vibration energy harvesting (PVEH) device is to reliably generate electric power as an output for sustainable operation of wireless sensor nodes, without experiencing mechanical failure. However, physical uncertainty, such as inherent variability in material properties and manufacturing tolerances, makes it difficult to guarantee satisfactory performance of the required functions of a PVEH device. Reliability analysis has been widely recognized as of great importance to evaluate system performance, while accounting for physical uncertainty. There have been a few prior attempts to delve into reliability analysis for the design of PVEH devices; these prior efforts were limited to calculating the probability of component success. However, PVEH devices need system reliability analysis that examines multiple performance functions, with the aim of calculating the probability of overall system success. The objective of this study is thus to present a systematic methodology for system reliability analysis of multiple safety events of a PVEH device under physical uncertainty. In this research, after deriving the electroelastically-coupled analytical model, the limit state functions of a PVEH device are derived under multiple safety events including: (1) resistance against fatigue failure; and (2) fulfillment of the target output electrical performances. Finally, system reliability analysis is performed by using the complementary intersection method. This study can provide insightful guidelines for designing a PVEH device under physical uncertainty.

Experimentally quantifying the effect of nest-site depth on the predation risk and breeding success of Blue Tits

Predation is a key factor in the nesting preferences of birds. Studies indicate that cavity-breeding birds prefer deeper nest sites, possibly because they are more safe from predation. We studied the Blue Tit (Cyanistes caeruleus), a cavity-breeding passerine, to test (1) whether nest-site depth affects breeding success and (2) whether potential effects of nest-site depth on breeding success are related to predation risk. We performed 2 experiments to separate effects of nest-box depth from potential effects of the quality of the breeding pair. In the first (free-choice) experiment, Blue Tits competed for scarce deep nest boxes that were provided well before nest-box choice, enabling an association between nest-box quality and bird quality. In the second (forced-choice) experiment, we randomly altered nest-box depth after Blue Tits had chosen a nest box, thus disconnecting the association between nest-box quality and bird quality. We found no evidence that the occurrence of signs of predation was related to nest-box depth. However, we did find clear positive effects of nest-box depth (1) on clutch size and hatching success throughout the study area and (2) on fledging success, the number of fledglings, and the overall probability of nest success, specifically in parts of the study area with high predation. We found no indication of independent effects of parental quality on breeding success. Parents also seemed to perceive the shallower boxes as more risky; in shallower boxes, nest thickness was decreased, irrespective of the local predation pressure during the free-choice experiment. Parents nesting in shallow boxes may have had lower breeding success because of (1) increased actual (but undetected) predation and (2) reduced reproductive investment by parents, based on the latter's experience with predation or an evolutionary response to past predation risk.

Evaluation of Rock Slope Stability Conditions Through Discriminant Analysis

A methodology to predict the stability status of mine rock slopes is proposed. Two techniques of multivariate statistics are used: principal component analysis and discriminant analysis. Firstly, principal component analysis was applied in order to change the original qualitative variables into quantitative ones, as well as to reduce data dimensionality. Then, a boosting procedure was used to optimize the resulting function by the application of discriminant analysis in the principal components. In this research two analyses were performed. In the first analysis two conditions of slope stability were considered: stable and unstable. In the second analysis three conditions of slope stability were considered: stable, overall failure and failure in set of benches. A comprehensive geotechnical database consisting of 18 variables measured in 84 pit-walls all over the world was used to validate the methodology. The discriminant function was validated by two different procedures, internal and external validations. Internal validation presented an overall probability of success of 94.73% in the first analysis and 68.42% in the second analysis. In the second analysis the main source of errors was due to failure in set of benches. In external validation, the discriminant function was able to classify all slopes correctly, in analysis with two conditions of slope stability. In the external validation in the analysis with three conditions of slope stability, the discriminant function was able to classify six slopes correctly of a total of nine slopes. The proposed methodology provides a powerful tool for rock slope hazard assessment in open-pit mines.

Cogeneration of electricity and liquid fuels using a high temperature gas-cooled reactor as the heat source

A thermal-hydraulic model of high temperature gas-cooled reactor used for cogeneration of electricity and liquid transportation fuels was developed using Aspen HYSYS. The model transfers heat through: (1) a steam generator to a supercritical Rankine cycle producing electricity, and (2) an intermediate heat exchanger to a biomass gasifier and Fischer-Tropsch process producing gasoline, jet fuel, diesel, liquefied petroleum gas and/or naphtha. The individual systems and components in the cogeneration model are mature technologies and commercially available, because minimizing the need for additional innovation increases the overall probability of success for a new and unique hybrid system. Technical evaluations of cogeneration on the island of Oahu in the State of Hawaii, using eucalyptus and sugarcane as the biomass feedstock, indicated that high thermal efficiency was achievable and that the concept is technically viable. Economic evaluations of cogeneration, based on construction and finance costs and current electricity and liquid fuel prices, indicated that the cogeneration plant is economically viable. Additional analyses quantified the potential number of jobs created and the reduction in carbon emissions. Further analyses indicated that cogeneration would significantly enhance Hawaii’s energy security.

Badapple: promiscuity patterns from noisy evidence.

BackgroundBioassay data analysis continues to be an essential, routine, yet challenging task in modern drug discovery and chemical biology research. The challenge is to infer reliable knowledge from big and noisy data. Some aspects of this problem are general with solutions informed by existing and emerging data science best practices. Some aspects are domain specific, and rely on expertise in bioassay methodology and chemical biology. Testing compounds for biological activity requires complex and innovative methodology, producing results varying widely in accuracy, precision, and information content. Hit selection criteria involve optimizing such that the overall probability of success in a project is maximized, and resource-wasteful “false trails” are avoided. This “fail-early” approach is embraced both in pharmaceutical and academic drug discovery, since follow-up capacity is resource-limited. Thus, early identification of likely promiscuous compounds has practical value.ResultsHere we describe an algorithm for identifying likely promiscuous compounds via associated scaffolds which combines general and domain-specific features to assist and accelerate drug discovery informatics, called Badapple: bioassay-data associative promiscuity pattern learning engine. Results are described from an analysis using data from MLP assays via the BioAssay Research Database (BARD) http://bard.nih.gov. Specific examples are analyzed in the context of medicinal chemistry, to illustrate associations with mechanisms of promiscuity. Badapple has been developed at UNM, released and deployed for public use two ways: (1) BARD plugin, integrated into the public BARD REST API and BARD web client; and (2) public web app hosted at UNM.ConclusionsBadapple is a method for rapidly identifying likely promiscuous compounds via associated scaffolds. Badapple generates a score associated with a pragmatic, empirical definition of promiscuity, with the overall goal to identify “false trails” and streamline workflows. Unlike methods reliant on expert curation of chemical substructure patterns, Badapple is fully evidence-driven, automated, self-improving via integration of additional data, and focused on scaffolds. Badapple is robust with respect to noise and errors, and skeptical of scanty evidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-016-0137-3) contains supplementary material, which is available to authorized users.

Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease

IntroductionRecent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. MethodsWe designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. ResultsThe study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. DiscussionBayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

Observer effects strongly influence estimates of daily nest survival probability but do not substantially increase rates of nest failure in Greater Sage-Grouse

ABSTRACT Researchers have long recognized that the process of observing nests may influence nest success by increasing depredation risk or causing females to abandon nests. The effects of observer-related nest abandonment may also reduce estimates of daily nest survival when time to nest fate is reduced and the average nest exposure period within the sample becomes shorter. We used an 8-yr record of observer visitations of nesting female Greater Sage-Grouse (Centrocercus urophasianus) in central Nevada, USA, to assess whether observers influenced either the probability of daily nest survival or the overall probability of nest success. Because nest success is influenced by factors other than visitation, we also accounted for the overall quality of a nest (i.e. probability of success in the absence of observer effects) based on potential confounding factors. Nest visitation (no flushing) had no effect on daily nest survival, regardless of nest quality or female age. Flushing a female from a nest substantial...

Cost-Effectiveness of Linezolid versus Vancomycin among Patients with Methicillin-Resistant Staphylococcus aureus Confirmed Nosocomial Pneumonia in China

ObjectiveTo estimate the cost-effectiveness of intravenous linezolid as a first-line agent against intravenous vancomycin in treating methicillin-resistant Staphylococcus aureus–confirmed nosocomial pneumonia in four Chinese cities. MethodsA decision-analytic model of 4-week time horizon was used to conduct cost-effectiveness analyses from the payer’s perspective. Clinical outcomes and resource use data were derived from a head-to-head trial, supplemented with local cost estimates based on hospital data via an expert panel. A series of scenario analyses were conducted to evaluate the impact of uncertainty around model inputs. All results were reported in 2012 Chinese Renminbi. ResultsThe predicted probability of overall treatment success was 0.629 and 0.602 for linezolid and vancomycin, respectively. Total inpatient costs varied across the four cities, ranging from ¥58,835 to ¥86,894 for linezolid and ¥58,390 to ¥87,033 for vancomycin, respectively. Linezolid was demonstrated to be a dominant treatment strategy in Guangzhou. In Beijing, Nanjing, and Xi’an, incremental cost-effectiveness ratios in terms of additional successfully treated patient were ¥1,861, ¥163, and ¥16,509, respectively. Dominance by linezolid was observed in some scenario analyses with parameters such as treatment duration, inclusion of cost of managing adverse events, and drug acquisition costs being the main drivers of cost-effectiveness results. ConclusionsDespite linezolid’s higher drug acquisition cost, its superior clinical efficacy renders it a likely cost-effective alternative for the treatment of methicillin-resistant Staphylococcus aureus–confirmed nosocomial pneumonia as compared with branded vancomycin from the payer perspectives of Beijing, Guangzhou, Nanjing, and Xi’an.