CAMeL-View TestRig

CAMeL-View is a software application, which is used for the model based design of mechatronic systems (multi-body simulation, block diagrams, pneumatic systems, hydraulic systems, general simulation, linear analysis and Hardware-in-the-Loop). CAMeL-View enables object-oriented model creation of mechatronic systems through the use of graphic blocks. The basic elements of multi-body system dynamics, control technology, hydraulics and hardware connectivity support the modeling process. The user’s proprietary C-Code can also be integrated into the models, which allows CAMeL-View TestRig to be implemented in all phases of the model based design process ( modeling, physical testing and prototyping), and lends itself especially well to mechatronic system design. The model’s structure is described and displayed with the help of directional connectors. Physical connections (such as mechanical or hydraulic linkages) as well as input and output connections (signal flow) are also available. The input of equations is done via mathematical expressions, e.g. the input of constitutive differential equations in vector and matrix form. Based on the model’s structure, the descriptive equations are converted into non-linear state space representations and converted into executable C-Code. CAMeL-View supports the simulation process with a configurable “experiment environment” (for simulator and instrumentation components) which allows the user to apply simulation models to supported targets (MPC5200, TriCore, X86, etc.) without the need for additional software tools for Hardware-in-the-Loop applications. In addition, the generation of so-called S-Functions for use in Simulink and the generation of ANSI C-Code for use in stand-alone simulators is also supported. A particularly noteworthy feature in CAMeL-View TestRig is the way in which the descriptive equations for multi-body system models are created. All multi-body simulation formalisms used for code generation create their equations in the form of typical explicit differential equations (ODE). This is especially important in Hardware-in-the-Loop applications where the calculation of simulation results within a specific, defined time frame must be assured. Only then is it possible to implement complex multi-body simulation models for Hardware-in-the-Loop applications under stringent real-time conditions. These constraints cannot be met when using DAE-based methods. Additional Toolboxes are available for linear analysis (Eigenvalues, pole-zero analysis, frequency response, etc.) of VRML-based animation. Development of CAMeL-View began in 1991 in the Paderborn Mechatronic Laboratory of Professor Dr. Ing. J. Lückel. The software was based on predecessors that had been developed there since 1986. The name stands for Computer Aided Mechatronic Laboratory – Virtual Engineering Workbench and describes the basic intent of one of the specific demands placed on development engineers in the computer lab.

CrocBITE

CrocBITE (currently CrocAttack) was an online database of wild crocodilian attacks reported on humans in the world. The non-profit online research tool helped to scientifically analyze crocodilian behavior via complex models. Users were encouraged to feed information in a crowdsourcing manner. This website excludes captive crocodilian attacks, as well as non-fatal bites on professional handlers, rangers, staff, or researchers, and crocodilian attacks on pets and livestock, because its primary goal is to analyze natural human-crocodilian conflict in the wild for conservation and management purposes, and that these incidents do are not considered indicative of natural species behavior or typical human-wildlife conflict, as well as not providing enough useful data and helping researchers understand wild population behavior or typical human-wildlife conflict dynamics and helps create safety strategies for people living or working near wild crocodilians, rather than tracking workplace accidents in zoos or farms. While fatal incidents involving handlers are sometimes included on the website, typical captive incidents (such as handlers being bitten by them in zoos) are excluded because they are considered manageable professional risks rather than general public safety threats. == About == The online database was established in 2013 (2013) by Dr Adam Britton, a researcher at Charles Darwin University, his student Brandon Sideleau and Erin Britton. It was a compilation of government records, individual reports, registered contributors and historical data. Dr Simon Pooley, Junior Research fellow, Imperial College London joined hands to further the studies. The collaboration culminated when Dr Pooley met Dr Britton at the IUCN Crocodile Specialist Group, in Louisiana in 2014. The program received funds from Economic and Social Research Council, United Kingdom to the tune of A$30,000 and unspecified resourced plus amount from Big Gecko Crocodilian Research, Crocodillian.com and Charles Darwin University. The research yielded pertinent observations that provide inside into crocodile attacks. It was observed that most attacks on humans occur from bites of Saltwater crocodile as against the popular understanding of Nile crocodiles taking the top spot. This is not, however, believed to be the actual case, as most attacks by the Nile crocodile are believed to go unreported or only reported on a local level. The broad category of Nile crocodile attacks were segmented into West African crocodile and Crocodylus niloticus (the Nile Crocodile) species to get a clear understanding of their respective attack zones. The objective was that the information would be used by communities and conservation managers to help inform and educate people about how to keep safe. The information was vital for Australia and Africa where such attacks are more likely than in other parts of the world. This was the only database of its kind with such comprehensive collection of information made available online. The database is no longer online, and its founder Adam Britton is in custody having pleaded guilty to charges of bestiality on September 25, 2023. It has been rebranded and renamed CrocAttack, and serves as a updated database focusing on human-crocodilian conflict and records over 8,500 incidents from the past decades.

Extremal Ensemble Learning

Extremal Ensemble Learning (EEL) is a machine learning algorithmic paradigm for graph partitioning. EEL creates an ensemble of partitions and then uses information contained in the ensemble to find new and improved partitions. The ensemble evolves and learns how to form improved partitions through extremal updating procedure. The final solution is found by achieving consensus among its member partitions about what the optimal partition is. == Reduced-Network Extremal Ensemble Learning (RenEEL) == A particular implementation of the EEL paradigm is the Reduced-Network Extremal Ensemble Learning (RenEEL) scheme for partitioning a graph. RenEEL uses consensus across many partitions in an ensemble to create a reduced network that can be efficiently analyzed to find more accurate partitions. These better quality partitions are subsequently used to update the ensemble. An algorithm that utilizes the RenEEL scheme is currently the best algorithm for finding the graph partition with maximum modularity, which is an NP-hard problem.

Witness set

In combinatorics and computational learning theory, a witness set is a set of elements that distinguishes a given Boolean function from a given class of other Boolean functions. Let C {\displaystyle C} be a concept class over a domain X {\displaystyle X} (that is, a family of Boolean functions over X {\displaystyle X} ) and c {\displaystyle c} be a concept in X {\displaystyle X} (a single Boolean function). A subset S {\displaystyle S} of X {\displaystyle X} is a witness set for c {\displaystyle c} in X {\displaystyle X} if S {\displaystyle S} distinguishes c {\displaystyle c} from all the other functions in C {\displaystyle C} , in the sense that no other function in C {\displaystyle C} has the same values on S {\displaystyle S} . For a concept class with | C | {\displaystyle |C|} concepts, there exists a concept that has a witness of size at most log 2 ⁡ | C | {\displaystyle \log _{2}|C|} ; this bound is tight when C {\displaystyle C} consists of all Boolean functions over X {\displaystyle X} . By a result of Bondy (1972) there exists a single witness set of size at most | C | − 1 {\displaystyle |C|-1} that is valid for all concepts in C {\displaystyle C} ; this bound is tight when C {\displaystyle C} consists of the indicator functions of the empty set and some singleton sets. One way to construct this set is to interpret the concepts as bitstrings, and the domain elements as positions in these bitstrings. Then the set of positions at which a trie of the bitstrings branches forms the desired witness set. This construction is central to the operation of the fusion tree data structure. The minimum size of a witness set for c {\displaystyle c} is called the witness size or specification number and is denoted by w C ( c ) {\displaystyle w_{C}(c)} . The value max { w C ( c ) : c ∈ C } {\displaystyle \max\{w_{C}(c):c\in C\}} is called the teaching dimension of C {\displaystyle C} . It represents the number of examples of a concept that need to be presented by a teacher to a learner, in the worst case, to enable the learner to determine which concept is being presented. Witness sets have also been called teaching sets, keys, specifying sets, or discriminants. The "witness set" terminology is from Kushilevitz et al. (1996), who trace the concept of witness sets to work by Cover (1965).

Differential evolution

Differential evolution (DE) is an evolutionary algorithm to optimize a problem by iteratively trying to improve a candidate solution with regard to a given measure of quality. Such methods are commonly known as metaheuristics as they make few or no assumptions about the optimized problem and can search very large spaces of candidate solutions. However, metaheuristics such as DE do not guarantee an optimal solution is ever found. DE is used for multidimensional real-valued functions but does not use the gradient of the problem being optimized, which means DE does not require the optimization problem to be differentiable, as is required by classic optimization methods such as gradient descent and quasi-newton methods. DE can therefore also be used on optimization problems that are not even continuous, are noisy, change over time, etc. DE optimizes a problem by maintaining a population of candidate solutions and creating new candidate solutions by combining existing ones according to its simple formulae, and then keeping whichever candidate solution has the best score or fitness on the optimization problem at hand. In this way, the optimization problem is treated as a black box that merely provides a measure of quality given a candidate solution and the gradient is therefore not needed. == History == Storn and Price introduced Differential Evolution in 1995. Books have been published on theoretical and practical aspects of using DE in parallel computing, multiobjective optimization, constrained optimization, and the books also contain surveys of application areas. Surveys on the multi-faceted research aspects of DE can be found in journal articles. == Algorithm == A basic variant of the DE algorithm works by having a population of candidate solutions (called agents). These agents are moved around in the search-space by using simple mathematical formulae to combine the positions of existing agents from the population. If the new position of an agent is an improvement then it is accepted and forms part of the population, otherwise the new position is simply discarded. The process is repeated and by doing so it is hoped, but not guaranteed, that a satisfactory solution will eventually be discovered. Formally, let f : R n → R {\displaystyle f:\mathbb {R} ^{n}\to \mathbb {R} } be the fitness function which must be minimized (note that maximization can be performed by considering the function h := − f {\displaystyle h:=-f} instead). The function takes a candidate solution as argument in the form of a vector of real numbers. It produces a real number as output which indicates the fitness of the given candidate solution. The gradient of f {\displaystyle f} is not known. The goal is to find a solution m {\displaystyle \mathbf {m} } for which f ( m ) ≤ f ( p ) {\displaystyle f(\mathbf {m} )\leq f(\mathbf {p} )} for all p {\displaystyle \mathbf {p} } in the search-space, which means that m {\displaystyle \mathbf {m} } is the global minimum. Let x ∈ R n {\displaystyle \mathbf {x} \in \mathbb {R} ^{n}} designate a candidate solution (agent) in the population. The basic DE algorithm can then be described as follows: Choose the parameters NP ≥ 4 {\displaystyle {\text{NP}}\geq 4} , CR ∈ [ 0 , 1 ] {\displaystyle {\text{CR}}\in [0,1]} , and F ∈ [ 0 , 2 ] {\displaystyle F\in [0,2]} . NP : NP {\displaystyle {\text{NP}}} is the population size, i.e. the number of candidate agents or "parents". CR : The parameter CR ∈ [ 0 , 1 ] {\displaystyle {\text{CR}}\in [0,1]} is called the crossover probability. F : The parameter F ∈ [ 0 , 2 ] {\displaystyle F\in [0,2]} is called the differential weight. Typical settings are N P = 10 n {\displaystyle NP=10n} , C R = 0.9 {\displaystyle CR=0.9} and F = 0.8 {\displaystyle F=0.8} . Optimization performance may be greatly impacted by these choices; see below. Initialize all agents x {\displaystyle \mathbf {x} } with random positions in the search-space. Until a termination criterion is met (e.g. number of iterations performed, or adequate fitness reached), repeat the following: For each agent x {\displaystyle \mathbf {x} } in the population do: Pick three agents a , b {\displaystyle \mathbf {a} ,\mathbf {b} } , and c {\displaystyle \mathbf {c} } from the population at random, they must be distinct from each other as well as from agent x {\displaystyle \mathbf {x} } . ( a {\displaystyle \mathbf {a} } is called the "base" vector.) Pick a random index R ∈ { 1 , … , n } {\displaystyle R\in \{1,\ldots ,n\}} where n {\displaystyle n} is the dimensionality of the problem being optimized. Compute the agent's potentially new position y = [ y 1 , … , y n ] {\displaystyle \mathbf {y} =[y_{1},\ldots ,y_{n}]} as follows: For each i ∈ { 1 , … , n } {\displaystyle i\in \{1,\ldots ,n\}} , pick a uniformly distributed random number r i ∼ U ( 0 , 1 ) {\displaystyle r_{i}\sim U(0,1)} If r i < C R {\displaystyle r_{i}

Cloud Native Computing Foundation

The Cloud Native Computing Foundation (CNCF) is a subsidiary of the Linux Foundation founded in 2015 to support cloud-native computing. == History == It was announced alongside Kubernetes 1.0, an open source container cluster manager, which was contributed to the Linux Foundation by Google as a seed technology. Founding members include Google, CoreOS, Mesosphere, Red Hat, Twitter, Huawei, Intel, RX-M, Cisco, IBM, Docker, Univa, and VMware. Today, CNCF is supported by over 450 members. In August 2018 Google announced that it was handing over operational control of Kubernetes to the community. == Projects == Argo is a collection of tools for getting work done with Kubernetes. Among its main features are Workflows and Events. It was accepted to CNCF on March 26, 2020 at the Incubating maturity level and then moved to the Graduated maturity level on December 6, 2022. cert-manager provisions and manages TLS certificates in Kubernetes. It was accepted to CNCF on November 10, 2020, moved to the Incubating maturity level on September 19, 2022, and then moved to the Graduated maturity level on September 29, 2024. Cilium provides networking, security, and observability for Kubernetes deployments using eBPF technology. It joined the CNCF at incubation level in October 2021 and the CNCF announced its graduation in October 2023. containerd is an industry-standard core container runtime. It is currently available as a daemon for Linux and Windows, which can manage the complete container lifecycle of its host system. In 2015, Docker donated the OCI Specification to The Linux Foundation with a reference implementation called runc. Since February 28, 2019 it is an official CNCF project. Its general availability and intention to donate the project to CNCF was announced by Docker in 2017. CoreDNS is a DNS server that chains plugins. Its graduation was announced in 2019. Dapr, the distributed application runtime, provides APIs for building secure and reliable microservices and agentic AI systems. Dapr was donated to the CNCF in November 2021 and joined at incubation level. The CNCF announced its graduation in November 2024. Envoy: Originally built at Lyft to move their architecture away from a monolith, Envoy is a high-performance open source edge and service proxy that makes the network transparent to applications. Lyft contributed Envoy to Cloud Native Computing Foundation in September 2017. etcd is a distributed key value store, providing a method of storing data across a cluster of machines. It became a CNCF incubating project in 2018 at KubeCon+CloudNativeCon North America in Seattle that year. Falco is an open source and cloud native runtime security initiative. It is the "de facto Kubernetes threat detection engine". It became an incubating project in January 2020 and graduated in February 2024. Flux is an open source project for powering GitOps in Kubernetes clusters. It provides the GitOps Toolkit, a set of Kubernetes APIs that allow you to define how configuration source code is securely pulled into your cluster and deployed by popular Kubernetes manifests rendering engines like Kustomize and Helm. The most recommended source mechanism is the OCIRepository API, which provides enhanced security and benefits from container image tooling out there. Flux has also notification integrations with popular services like Prometheus Alertmanager, PagerDuty, Slack and so on. Flux has graduated in CNCF in 2022. Harbor is an "open source trusted cloud native registry project that stores, signs, and scans content." It became an incubating project in September 2019 and graduated in June 2020. Helm is a package manager that helps developers "easily manage and deploy applications onto the Kubernetes cluster." It joined the incubating level in June 2018 and graduated in April 2020. Istio is a service mesh technology. It was accepted by CNCF in September 2022 and graduated on July 12, 2023. Jaeger, Created by Uber Engineering, Jaeger is an open source distributed tracing system inspired by Google Dapper paper and OpenZipkin community. It can be used for tracing microservice-based architectures, including distributed context propagation, distributed transaction monitoring, root cause analysis, service dependency analysis, and performance/latency optimization. The Cloud Native Computing Foundation Technical Oversight Committee voted to accept Jaeger as the 12th hosted project in September 2017 and became a graduated project in 2019. In 2020 it became an approved and fully integrated part of the CNCF ecosystem. Kubernetes is an open source framework for automating deployment and managing applications in a containerized and clustered environment. "It aims to provide better ways of managing related, distributed components across the varied infrastructure." It was originally designed by Google and donated to The Linux Foundation to form the Cloud Native Computing Foundation with Kubernetes as the seed technology. The "large and diverse" community supporting the project has made its staying power more robust than other, older technologies of the same ilk. In January 2020, the CNCF annual report showed significant growth in interest, training, event attendance and investment related to Kubernetes. Linkerd is CNCF's fifth member project, and the project that coined the term "service mesh". Linkerd adds observability, security, and reliability features to applications by adding them to the platform rather than the application layer, and features a "micro-proxy" to maximize speed and security of its data plane. Linkerd graduated from CNCF in July 2021. Open Policy Agent (OPA) is "an open source general-purpose policy engine and language for cloud infrastructure." It became a CNCF incubating project in April 2019. OPA graduated from CNCF in February 2021. Prometheus is a cloud monitoring tool sponsored by SoundCloud in early iterations. In August 2018, the tool was designated a graduated project by the Cloud Native Computing Foundation. It is now a Cloud Native Computing Foundation member project. Rook is CNCF's first cloud native storage project. It became an incubation level project in 2018 and graduated in October 2020. SPIFFE is an open standard and framework for workload identity, much the same way that OAuth is an open standard and framework for human identity. It is built from the ground up to accommodate modern computing environments, which operate with systems scale and velocity (as opposed to human scale and velocity), while still maintaining interoperability with existing technologies like OAuth and X.509 Public key infrastructure. Unlike other identity standards, SPIFFE supports multiple credential types for a single identity, ensuring that the highly varied needs of production environments are consistently met without compromise. SPIFFE joined the CNCF as a sandbox project in 2018, was accepted to incubation in 2020, and graduated in 2022. SPIRE is an open source identity provider for workloads based on the SPIFFE framework. It is highly pluggable, and fills the attestation and issuance needs required by any workload identity solution. The plugin interfaces it exposes allows users to write integrations with in-house systems, build internal self-service portals, and more. It is a very powerful building block for issuing short-lived identity credentials to dynamic cloud workloads. SPIRE became a CNCF Graduated project in 2022. The Update Framework (TUF) helps developers to secure new or existing software update systems, which are often found to be vulnerable to many known attacks. TUF addresses this widespread problem by providing a comprehensive, flexible security framework that developers can integrate with any software update system. TUF was CNCF's first security-focused project and the ninth project overall to graduate from the foundation's hosting program. TiKV provides a distributed key–value database. Vitess is a database clustering system for horizontal scaling of MySQL, first created for internal use by YouTube. It became a CNCF project in 2018 and graduated in November 2019. Contour is a management server for Envoy that can direct the management of Kubernetes' traffic. Contour also provides routing features that are more advanced than Kubernetes' out-of-the-box Ingress specification. VMWare contributed the project to CNCF in July 2020. Cortex offers horizontally scalable, multi-tenant, long-term storage for Prometheus and works alongside Amazon DynamoDB, Google Bigtable, Cassandra, S3, GCS, and Microsoft Azure. It was introduced into the ecosystem incubator alongside Thanos in August 2020. CRI-O is an Open Container Initiative (OCI) based "implementation of Kubernetes Container Runtime Interface". CRI-O allows Kubernetes to be container runtime-agnostic. It became an incubating project in 2019. gRPC is a "modern open source high performance RPC framework that can run in any environment." The project was formed in 2015 when Google decided to open sou

Targeted maximum likelihood estimation

Targeted Maximum Likelihood Estimation (TMLE) (also more accurately referred to as Targeted Minimum Loss-Based Estimation) is a general statistical estimation framework for causal inference and semiparametric models. TMLE combines ideas from maximum likelihood estimation, semiparametric efficiency theory, and machine learning. It was introduced by Mark J. van der Laan and colleagues in the mid-2000s as a method that yields asymptotically efficient plug-in estimators while allowing the use of flexible, data-adaptive algorithms such as ensemble machine learning for nuisance parameter estimation. TMLE is used in epidemiology, biostatistics, and the social sciences to estimate causal effects in observational and experimental studies. Applications of TMLE include Longitudinal TMLE (LTMLE) for time-varying treatments and confounders. Variations in how the targeting step in TMLE is carried out have resulted in various versions of TMLE such as Collaborative TMLE (CTMLE) and Adaptive TMLE for improved finite-sample performance and automated variable selection. == History == The TMLE framework was first described by van der Laan and Rubin (2006) as a general approach for the construction of efficient plug-in estimators of smooth features of the data density. It was demonstrated in the context of causal inference and missing data problems. It was developed to address limitations of traditional doubly robust methods, such as Augmented Inverse Probability Weighting (AIPW), by respecting the plug-in principle in the sense that it respects that the target parameter is a function of the data density that is an element of the statistical model. TMLE estimates the data density or relevant parts of it with machine learning and targets these machine learning fits before it is plugged in the target parameter mapping. In this manner, a TMLE always respects global knowledge and satisfies known bounds such as that the target parameter is a probability . Since its introduction, TMLE has been developed in a series of theoretical and applied papers, culminating in book-length treatments of the method and its applications to survival analysis, adaptive designs, and longitudinal data. == Methodology == At its core, TMLE is a two-step estimation procedure: Initial estimation: Machine learning methods (such as the Super Learner ensemble) are used to obtain flexible estimates of nuisance parameters, such as outcome regressions and propensity scores. Targeting step: The initial estimate is updated by solving a score equation (the efficient influence function) so that the final estimator is consistent, asymptotically normal, and efficient under mild regularity conditions. The targeted machine learning fit is then mapped into the corresponding estimator of the target parameter by simply plugging it in the target parameter mapping. This approach balances the bias–variance trade-off by combining data-adaptive estimation with semiparametric efficiency theory. TMLE is doubly robust, meaning it remains consistent if either the outcome model or the treatment model is consistently estimated. === Formula === Here we explain the TMLE of the average treatment effect of a binary treatment on an outcome adjusting for baseline covariates. Consider i.i.d. observations O i = ( W i , A i , Y i ) {\displaystyle O_{i}=(W_{i},A_{i},Y_{i})} from a distribution P 0 {\displaystyle P_{0}} , where W {\displaystyle W} are baseline covariates, A {\displaystyle A} is a binary treatment, and Y {\displaystyle Y} is an outcome. Let Q ¯ ( a , w ) = E [ Y ∣ A = a , W = w ] {\displaystyle {\bar {Q}}(a,w)=\mathbb {E} [Y\mid A=a,W=w]} represent the outcome model and g ( a ∣ w ) = P ( A = a ∣ W = w ) {\displaystyle g(a\mid w)=P(A=a\mid W=w)} represent the propensity score. The average treatment effect (ATE) is given by ψ 0 = E { Q ¯ ( 1 , W ) − Q ¯ ( 0 , W ) } . {\displaystyle \psi _{0}=\mathbb {E} \{{\bar {Q}}(1,W)-{\bar {Q}}(0,W)\}.} A basic TMLE for the ATE proceeds as follows: Step 1: Estimate initial models. Obtain estimates Q ¯ ^ ( a , w ) {\displaystyle {\hat {\bar {Q}}}(a,w)} and g ^ ( a ∣ w ) {\displaystyle {\hat {g}}(a\mid w)} , often using flexible methods such as Super Learner. Step 2: Compute the clever covariate. Define: H ( A , W ) = A g ^ ( 1 ∣ W ) − 1 − A g ^ ( 0 ∣ W ) . {\displaystyle H(A,W)={\frac {A}{{\hat {g}}(1\mid W)}}-{\frac {1-A}{{\hat {g}}(0\mid W)}}.} Step 3: Estimate the fluctuation parameter. Fit a logistic regression of Y {\displaystyle Y} on H ( A , W ) {\displaystyle H(A,W)} with logit ⁡ ( Q ¯ ^ ( A , W ) ) {\displaystyle \operatorname {logit} ({\hat {\bar {Q}}}(A,W))} as offset. This yields ε ^ {\displaystyle {\hat {\varepsilon }}} , the MLE that solves the score equation: 1 n ∑ i = 1 n H ( A i , W i ) { Y i − Q ¯ ^ ε ( A i , W i ) } = 0. {\displaystyle {\frac {1}{n}}\sum _{i=1}^{n}H(A_{i},W_{i}){\big \{}Y_{i}-{\hat {\bar {Q}}}^{\varepsilon }(A_{i},W_{i}){\big \}}=0.} Step 4: Update the initial estimate. Apply the "blip" to obtain the targeted estimate: Q ¯ ^ ∗ ( A , W ) = expit ⁡ ( logit ⁡ ( Q ¯ ^ ( A , W ) ) + ε ^ H ( A , W ) ) . {\displaystyle {\hat {\bar {Q}}}^{}(A,W)=\operatorname {expit} {\Big (}\operatorname {logit} {\big (}{\hat {\bar {Q}}}(A,W){\big )}+{\hat {\varepsilon }}\,H(A,W){\Big )}.} Step 5: Compute the TMLE. The ATE estimate is: ψ ^ TMLE = 1 n ∑ i = 1 n [ Q ¯ ^ ∗ ( 1 , W i ) − Q ¯ ^ ∗ ( 0 , W i ) ] . {\displaystyle {\hat {\psi }}_{\text{TMLE}}={\frac {1}{n}}\sum _{i=1}^{n}{\big [}{\hat {\bar {Q}}}^{}(1,W_{i})-{\hat {\bar {Q}}}^{}(0,W_{i}){\big ]}.} Inference. The efficient influence function (EIF) for the ATE is: D ∗ ( O ) = H ( A , W ) { Y − Q ¯ ∗ ( A , W ) } + Q ¯ ∗ ( 1 , W ) − Q ¯ ∗ ( 0 , W ) − ψ . {\displaystyle D^{}(O)=H(A,W)\{Y-{\bar {Q}}^{}(A,W)\}+{\bar {Q}}^{}(1,W)-{\bar {Q}}^{}(0,W)-\psi .} The variance is estimated by σ ^ 2 = n − 1 ∑ i = 1 n ( D ∗ ( O i ) ) 2 {\displaystyle {\hat {\sigma }}^{2}=n^{-1}\sum _{i=1}^{n}{\big (}D^{}(O_{i}){\big )}^{2}} , yielding Wald-type confidence intervals ψ ^ TMLE ± z 1 − α / 2 σ ^ / n {\displaystyle {\hat {\psi }}_{\text{TMLE}}\pm z_{1-\alpha /2}\,{\hat {\sigma }}/{\sqrt {n}}} . Remark. For continuous outcomes, a linear fluctuation Q ¯ ^ ∗ = Q ¯ ^ + ε ^ H {\displaystyle {\hat {\bar {Q}}}^{}={\hat {\bar {Q}}}+{\hat {\varepsilon }}\,H} may be used instead. For bounded continuous outcomes, the logistic fluctuation (after rescaling Y {\displaystyle Y} to [ 0 , 1 ] {\displaystyle [0,1]} ) is often preferred for improved finite-sample performance. == Applications == TMLE has been applied in: Epidemiology: Estimating causal effects of exposures and interventions in observational cohort studies. Clinical trials and real-world evidence: The Targeted Learning roadmap provides a structured framework for generating and validating real-world evidence (RWE), bridging randomized trials and observational data using TMLE and related estimation techniques. This approach enables transparency, sensitivity analysis, and stronger causal inference for regulatory and clinical trial contexts. High-dimensional settings: Integration with ensemble methods for causal effect estimation. TMLE has been successfully applied in pharmacoepidemiology where a large number of covariates are automatically selected to adjust for confounding. In a study of post–myocardial infarction statin use and 1-year mortality, TMLE demonstrated robust performance relative to inverse probability weighting in scenarios with hundreds of potential confounders. == Derivatives and extensions == Longitudinal TMLE (LTMLE): A methodological extension of TMLE for longitudinal data with time-varying treatments, confounders, and censoring. It allows the estimation of dynamic treatment regimes and intervention-specific causal effects over time. This framework was originally introduced by van der Laan & Gruber (2012). Collaborative TMLE (CTMLE): Enhances finite-sample performance and variable selection by collaboratively fitting the treatment mechanism in conjunction with the target parameter. == Software == Several R packages implement TMLE and related methods: tmle: Functions for binary, categorical, and continuous outcomes. ltmle: Implementation for longitudinal data with time-varying treatments and outcomes. ctmle: Algorithms for collaborative TMLE and adaptive variable selection. SuperLearner: A theoretically grounded, cross-validated ensemble learning method that combines predictions from multiple algorithms to minimize predictive risk. Widely used in TMLE for estimating nuisance parameters. The original implementation is available as the R package SuperLearner. Recent machine learning platforms like H2O AutoML implement similar ensemble strategies, combining diverse learners in parallel and leveraging stacking and blending techniques, effectively functioning as a large-scale Super Learner.