dataesr/scientific-paragraphs-categorization huggingface dataset:
ACKNOWLEDGEMENTS The authors would like to thank everyone who took the time to respond to the survey. We would also like to thank Dravet Syndrome European Federation-affiliated patient-advocacy group members for piloting the English survey, and translating and proofreading the survey and campaign materials. The authors would also like to thank  Dingeman Wolfert  and  Najida Begum  for their help with data analysis. This study was sponsored by  Zogenix International Ltd. LL received consultancy fees and is on advisory boards of  Zogenix ,  UCB ,  Novartis ,  Shire ,  LivaNova ,  GW Pharma , and  Takeda. EG and AB are employed by  Wickenstones Ltd  and received support from  Zogenix International Ltd  to complete this study. IB and AM have no conflicts of interest.
In part B, a modified 3 + 3 safety lead-in design was used to enroll patients to once-weekly dosing with LY2787106 without oral iron supplementation before opening enrollment into two separate cohorts that received the study drug with and without oral iron, respectively. All patients entered follow-up once study drug treatment was discontinued. This study was conducted in accordance with the International Conference on Harmonisation Guidelines for Good Clinical Practice and the Declaration of Helsinki after approval by each site's institutional review board. All patients gave written informed consent before undergoing any study-specific procedures. This study was registered at www. clinicaltrials. gov as #NCT01340976.
Statistical analyses The total sample size for this study was determined by the incidence of DLTs (at least 3 evaluable patients per dose cohort and up to 6 patients per dose group in part A prior to establishing the MTD). In part B, the plan was to treat approximately 32 patients so that each of cohorts B1 and B2 would have at least 12 evaluable patients, assuming an approximately 25% early dropout rate. Assuming an improvement in mean hemoglobin of 0. 75 g/dL from baseline to the end of cycle 4 and a standard deviation in hemoglobin change of 1. 5 g/dL, a sample size of 12 patients in each cohort in part B was determined to have 80% power to detect a statistically significant increase in hemoglobin with a 1-sided type I error rate of 0. 20. Safety analyses were based on data from all patients who had received at least one dose of LY2787106 (safety population).
Pharmacokinetic parameters were computed by standard noncompartmental analysis methods. Data were also analyzed using nonlinear mixed-effect modeling (as implemented in NONMEM). Data from all patients were pooled for analysis to determine compartmental PK parameters and between-and within-patient variability. The primary parameters analyzed were C max and AUC of LY2787106. Other parameters analyzed were t 1/2 , V d , and CL. The primary parameters (C max and AUC) were evaluated statistically to delineate the effects of dose proportionality using methods described previously  [9]. Least-square estimates of geometric means and corresponding 90% CIs were determined for each dose, together with the dosenormalized ratio of geometric means and CIs. The absolute percent change from baseline for all PD and immunogenicity endpoints was summarized for each cohort and each sample day or time combination, and the maximum change over the entire study was determined.
While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education, parental smoking, pets, parental asthma, doctor-diagnosed allergic rhinitis, doctor-diagnosed eczema and wheeze severity.
Methods We analysed cross-sectional differences in childhood asthma and wheeze by child age and wheeze with asthma at age 4 years in datasets from European cohorts with harmonised variables on asthma and wheeze. Data were requested from 13 MeDALL cohort studies  [6]. Table  1  provides an overview of the 10 included cohorts, representing eight countries and a total sample of 26 663 children. More information about the cohorts can be found in the ENRIECO database (www. enrieco. dk).
The energies of such parts (Scheme 1) were calculated without timization at the MP2(full)/6-311++G(2d,2p) level and used to calculate the strengths of hydrogen nds according the Equation (1) given in Scheme 1. EHB = EM1 + EM2 -EM3 -EMH (1) Scheme 1. General principles of molecular tailoring approach (MTA) fragmentation. All candidate structures were first optimized by the B3LYP density function  [41, 42]  of the 3LYP/6-311++G(d,p) basis set  [21]  using the Gaussian 09  [43]  program package, as described reviously  [25, 30] , due to the fact that this method provided credible results in the past  [44]  when ealing with H-bonded systems. In the next step the structures were checked by the vibrational alysis at this level and were found to represent the true energy minima. The calculated νOH and C=O frequencies were identified with the GaussView 5.
0. 9 package, without correction for the ro-point energies. At the same level, the absolute proton shielding for each structure and TMS etramethylsilane standard) were obtained using the gauge-including atomic orbital (GIAO) ethod  [45]. The SCF GIAO magnetic isotropic shielding tensors of H-bonded hydrogen atoms were sed to calculate the chemical shifts (δH). Afterwards, the electron correlation was included via the øller-Plesset treatment of the second order (MP2), in which each structure was finally optimized ith MP2(FC)/6-311++G(2d,2p) and its energy was specified with MP2(full)/6-311++G(2d,2p) lculations. The topological properties of the electron density at the bond critical points (BCPs) were aracterized using the Bader Atoms In Molecules methodology (AIM) with the AIM2000  [46]  and IMAll  [47]  program packages for every fully-optimized geometry.
The AIM analyses of the avefunction have been conducted on true MP2 wavefunctions (using "natural orbitals" of the MP2 rst-order total density matrix). Similarly to a previous report  [25, 30] , the electron density ρBCP at the ,-1) bond critical point, its Laplacian ∇ 2 ρBCP (for the BCP between the hydrogen atom of the OH onor group, and the oxygen atom of the O=C acceptor group), potential energy density VBCP, and Scheme 1. General principles of molecular tailoring approach (MTA) fragmentation. All candidate structures were first optimized by the B3LYP density function  [41, 42]  of the B3LYP/6-311++G(d,p) basis set  [21]  using the Gaussian 09  [43]  program package, as described previously  [25, 30] , due to the fact that this method provided credible results in the past  [44]  when dealing with H-bonded systems.
The topological properties of the electron density at the bond critical points (BCPs) were characterized using the Bader Atoms In Molecules methodology (AIM) with the AIM2000  [46]  and AIMAll  [47]  program packages for every fully-optimized geometry. The AIM analyses of the wavefunction have been conducted on true MP2 wavefunctions (using "natural orbitals" of the MP2 first-order total density matrix). Similarly to a previous report  [25, 30] , the electron density ρ BCP at the (3,-1) bond critical point, its Laplacian ∇ 2 ρ BCP (for the BCP between the hydrogen atom of the OH donor group, and the oxygen atom of the O=C acceptor group), potential energy density V BCP , and the electron density ρ RCP (at the ring critical point in the centre of the newly-formed six-membered ring, which includes the hydrogen bonded atoms, further named as the "HB-ring") were selected to describe the nature of the hydrogen bonding.
Acknowledgments: This study was supported by  Poznan University of Technology   03/32/DSPB/0700. The authors also acknowledge  Poznanskie Centrum Superkomputerowo-Sieciowe, Poznan, Poland , for computational time. The author would like to express gratitude to  Marek Lozynski  from  Poznan University of Technology  for insightful discussion during the preparation of the manuscript.
Of course, the sequences of service names occurring in all runs of the system are the same in both specifications. The main results of the paper establish under what circumstances the linear-time or branching-time service views are regular (with effective specifications). We consider the tuple artifact model used in  [17, 11] , and several natural restrictions derived from the GSM design methodology, some of which have been considered in the context of verification  [11]. We also consider the impact of database dependencies on regularity of the views. We show that linear-time service views of tuple artifacts are ω-regular, but branching-time views are not regular. We then consider artifacts obeying a natural restriction previously used in the context of verification, called feedback freedom  [11].
We show that branching-time views of feedback-free artifacts are still not regular, but become so under a slightly stronger restriction called global feedback freedom. This restriction is naturally obeyed by specifications resulting from the GSM hierarchical design methodology. It turns out that there is a tight connection between the result on view regularity and the verification of artifact systems. Properties to be verified are specified using extensions of the classical temporal logics LTL, CTL and CTL*, in which propositions are interpreted as existential FO formulas on the tuple artifact and the underlying database. This yields the logics LTL-FO, CTL-FO and CTL*-FO  [17, 11, 20]. It can be shown that regularity of the linear or branching-time service views for a class of artifact systems, with effectively constructible specifications, implies decidability of LTL-FO, resp.
CTL*-FO properties for that class. The converse is false: decidability of LTL-FO or CTL*-FO properties may hold even though the corresponding service views may not be regular. Thus, regularity is a stronger result than decidability of verification. Indeed, our results imply that CTL*-FO properties are decidable for globally feedback-free artifact systems. On the other hand, we show that CTL-FO properties are undecidable for feedback-free artifact systems (also implying non-regularity of their branching-time views). The proof techniques developed here have additional side-effects beneficial to verification. In our previous approaches to automatic verification of business artifacts  [17, 11] , given an artifact specification A and an LTL-FO property ϕ, the verifier either certifies satisfaction of the property or produces a counter-example run on some database D(A, ϕ) depending on both A and ϕ.
In contrast, the techniques of the present paper allow to show that, for specifications and properties without constants, there exists a single database D(A), depending only on A, which serves as a universal counter-example for all LTL-FO properties violated by A. Pre-computing such a database may allow more efficient generation of counter-examples for specific LTL-FO properties. Decidability results on verification of branching-time properties of infinite-state artifact systems are scarce and require significant restrictions. In  [22, 13] , decidability results are shown for properties expressed in an FO extension of µ-calculus, under restrictions on the artifact system orthogonal to ours. In  [2] , the artifact model is extended to a multi-agent setting, and decidability results are shown for properties expressed in an FO extension of CTL that can also refer to each agent's knowledge using a Kripke-style semantics.
Background After some basic definitions, we present the tuple artifact model, the languages LTL-FO and CTL ( * ) -FO, and review previous results on verification of LTL-FO properties. We assume an infinite data domain dom. A relational schema is a finite set of relation symbols with associated arities. An database instance over a relational schema DB is a mapping I associating to each R ∈ DB a finite relation over dom with the same arity as R (denoted arity(R)). We assume familiarity with first-order logic (FO) over relational schemas (e. g. , see  [1, 26] ). FO formulas may use equality and constants from dom.
Artifact systems. In the tuple artifact model, an artifact consists of a finite set of variables whose values evolve during the workflow execution. Transitions are specified declaratively, using pre-and-post conditions that may query an underlying database. Definition 2. An artifact schema is a a tuple A = x, DB where x is a finite sequence x 1 ,. , x k of artifact variables and DB is a relational schema. For each x, we also define a set of variables x = {x | x ∈ x} where each x is a distinct new variable. In a transition, a primed variable represents the value of the variable in the new artifact. Definition 3. An instance of an artifact schema A = x, DB is a tuple A = ν, D where ν is a valuation of x into dom and D is a finite instance of DB. Definition 4. A service over an artifact schema A is a pair σ = π, ψ where: π(x), called pre-condition, is a quantifier-free 2  FO formula over DB with variables x; ψ(x, x ), called post-condition, is a quantifier-free FO formula over DB with variables x, x.
Definition 5. An artifact system is a triple Γ = A, Σ, Π , where A is an artifact schema, Σ is a non-empty set of services over A, and Π is a pre-condition restricting the value of the initial artifact variables (as above, a quantifier-free FO formula over DB, with variables x). Definition 6. Let σ = π, ψ be a service over an artifact schema A = x, DB , and let D be an instance over DB. Let ν, ν be valuations of x. We say that ν is a possible successor of ν w. r. t. σ and D (denoted ν σ -→ ν when D is understood) iff: D |= π(ν), and D |= ψ(ν, ν ). Note that ψ(x, x ) need not bind x to the database, so ν may contain values not in D. Definition 7. Let Γ = A, Σ, Π be an artifact system, where A = x, DB. A run of Γ on database instance D over DB is an infinite sequence ρ = {(ρ i , σ i )} i≥0 , where for each i ≥ 0, ρ i is a valuation of x, σ i ∈ Σ, ρ i σi -→ ρ i+1 , and D |= Π(ρ 0 ).
The assumption that runs are infinite is not a restriction, since finite runs can be artificially extended to infinite runs by adding a self-looping transition. The linear-time semantics of an artifact system Γ is provided by the set of all runs. Specifically, we denote by Runs D (Γ) the set of all runs of Γ on database instance D, and by Runs(Γ) the union of Runs D (Γ) for all databases D. The more informative branching-time semantics is provided by its tree of runs, additionally capturing all choices of transitions available at each point in the run. More precisely, TRuns D (Γ) is a labeled tree whose nodes are all finite prefixes of runs of Γ on D, such that the children of a prefix are all prefixes extending it by one transition. Each node ρ is labeled by the value of the last artifact tuple in ρ, and each edge from ρ to ρ.
(ν, σ) is labeled by σ. The global tree of runs TRuns * (Γ) is the tree obtained by placing all trees TRuns D (Γ) (for every database D) under a common root, connected by edges with a special label init. The tree of runs allows to define properties in branching-time temporal logic, such as "any client has the option of canceling a purchase at any time". Note that such a property is not captured by the linear runs in Runs(Γ). Temporal properties of artifact systems. Temporal properties are specified using extensions of LTL (linear-time temporal logic) and CTL ( * ) (branching-time temporal logics). We begin with LTL. Recall that LTL is propositional logic augmented with temporal operators G (always), F (eventually), X (next) and U (until) (e. g. , see  [32] ). Informally, Gp says that p holds at all times in the run, Fp says that p will eventually hold, Xp says that p holds at the next configuration, and pUq says that q will hold at some point in the future and p holds up to that point.
For example, G(p → Fq) says that whenever p holds, q must hold sometime in the future. The extension of LTL used in  [11] , called 3  LTL-FO, is obtained from LTL by replacing propositions with quantifier-free FO statements about particular artifact records in the run. The statements use the artifact variables and the database. In addition, they may use global variables, shared by different statements and allowing to refer to values in different records. The global variables are universally quantified over the entire property. We illustrate LTL-FO with a simple example. Example 8. The following specifies a desirable business rule for an e-commerce workflow with artifact variables including amount_paid, amount_refunded, status, amount_owed (with obvious meaning). (ϕ) ∀xG((amount_paid = x ∧ amount_paid = amount_owed) → F(status = "shipped" ∨ amount_refunded = x)) Property ϕ states that if a correct payment is submitted then at some time in the future either the product is shipped or the customer is refunded the correct amount.
Specifically, as shown in  [17, 11] , verification becomes undecidable as soon as the database is equipped with at least one key dependency, or if the specification of the artifact system uses simple arithmetic constraints allowing to increment and decrement by one the value of some atributes. Hence, a restriction is needed to achieve decidability for these extensions. We discuss this next. To gain some intuition, consider the undecidability of verification for artifact systems with increments and decrements. The proof of undecidability is based on the ability of such systems to simulate counter machines, for which the problem of state reachability is known to be undecidable  [30]. To simulate counter machines, an artifact system uses an attribute for each counter. A service performs an increment (or decrement) operations by "feeding back" the incremented (or decremented) value into the next occurrence of the corresponding attribute.
Indeed, there is evidence that the feedback freedom condition is permissive enough to capture a wide class of applications of practical interest. This is confirmed by numerous examples of real-life business processes modeled as artifact systems, encountered in IBM's practice  [11]. Feedback freedom turns out to ensure decidability of verification in the presence of arithmetic constraints, and also under a large class of data dependencies including key and foreign key constraints on the database. Theorem 10. [11]  It is decidable, given an artifact system Γ using arithmetic (linear inequalities over Q) and whose database satisfies a set of key and foreign key constraints, and an LTL-FO property ϕ such that (Γ, ϕ) is feedback free, whether every run of A on a valid database satisfies ϕ. Unfortunately, the complexity is non-elementary with respect to the number of artifact variables.
We make this more precise. Let ≈ be the transitive closure of ∪ i≥0 i. Clearly, ≈ is an equivalence relation on ∪ i≥0 xi ∪ C. It is easily seen that i is the restriction of ≈ to xi ∪ xi+1 ∪ C. Let [x i ] i and [x i ] ≈ denote the equivalence class of x i in i , resp. ≈. Definition 12. Let {(x i , H i , i , σ i )} i≥0 be a symbolic run of Γ. An enactment of is a triple (D, ρ, θ) where D is a database over DB, ρ = {(ρ i , σ i )} i≥0 is a run of Γ over D, and θ is a mapping from (∪ i≥0 xi ) to dom such that, for each i ≥ 0: θ(x i ) = ρ i (x) for every x ∈ x, if y, z ∈ xi ∪ xi+1 and (y, z) ∈ i then θ(y) = θ(z) the function θ defined by θ([y] i ) = ρ(y) for y ∈ xi ∪ xi+1 is an isomorphism from H i / i to D|(ρ i ∪ ρ i+1 ). Lemma 13. For every database D over DB and run ρ of Γ over D there exists a symbolic run of Γ and a mapping h from (∪ i≥0 xi ) to dom such that (D, ρ, h) is an enactment of.
Proof. The run can be easily constructed by induction from ρ. Consider the converse of Lemma 13: does every symbolic run have an enactment on some database? This is much less obvious. It is easy to construct, for each symbolic run = {(x i , H i , i , σ i )} i≥0 , a triple (D , ρ, h) satisfying the definition of enactment except for the finiteness of D. This can be done as follows. The (infinite) domain of D simply consists of all equivalence classes of ≈, h maps each x i to [x i ] ≈ , the relations are interpreted as (∪ i≥0 H i )/ ≈ , and ρ is the image of under h. However, it is far less clear that a finite database D exists with the same properties. Intuitively, different classes of ≈ must be merged in order to obtain a finite domain, and this must be done consistently with the H i 's. We are able to show the following key result.
Recall that for a symbolic run = {(x i , H i , i , σ i )} i≥0 of Γ, we denote by ≈ the transitive closure of (∪ i≥0 i ) and by [x i ] ≈ the class of x i wrt ≈. Note that, because Γ is in linear propagation form, we can assume that [x i ] ≈ contains only variables x j. We define span([ x i ] ≈ ) = {j | x j ≈ x i }. Clearly, each span is an interval. Next, for x ∈ x we define lane(x) = {[x i ] ≈ | i ≥ 0} (totally ordered by [x i ] ≈ ≤ [x j ] ≈ iff i ≤ j). The remainder of the proof consists of defining certain finite characteristics of equivalence classes of ≈, so that different classes in a given lane can be collapsed if they share the same characteristics. This yields an enactment of the symbolic run over the finite database whose elements are the collapsed classes. We omit the rather involved technical details.
Universal test databases. The above results, notably Theorem 14, have some potentially significant benefits for verification. We can show the following rather surprising result. Theorem 16. Let Γ be a constant-free artifact system with k artifact variables. One can construct a database D * of size double exponential in |x| such that for every constant-free LTL-FO formula ξ over Γ, Γ |= ξ iff Runs D * (Γ) |= ξ. Proof. Consider an LTL-FO formula ξ over Γ. As shown in  [11]  (Lemma 3. 3), global variables can be easily eliminated, so one can assume that ξ = ϕ f. Let = {(x i , H i , i , σ i )} i≥0 be a symbolic run of Γ. Satisfaction of ξ by is defined similarly to actual runs, by evaluating each FO component of ϕ f on the consecutive H i / i. Consider an enactment (D, ρ, θ) of , where ρ = {(ρ i , σ i )} i≥0.
Because H i / i and D|(ρ i ∪ ρ i+1 ) are isomorphic, it is clear that |= ξ iff ρ |= ξ. This in conjunction with Lemma 13 and Theorem 14 shows that Γ |= ξ iff every symbolic run of Γ satisfies ξ. Because each symbolic run has an enactment on some database of size exponential in k, Runs k (Γ) = ∪{Runs D (Γ) | |D| ≤ exp(k)} are enactments of all symbolic runs of Γ. Thus, Γ |= ξ iff all runs in Runs k (Γ) satisfy ξ. Suppose Γ and ξ are constant free. There are finitely many non-isomorphic databases of size bounded by exp(k), and let D * be their disjoint union. Clearly, Γ |= ξ iff all runs over D * satisfy ξ. The size of D * is double exponential in k. Thus, D * acts as a universal test database (akin to an Armstrong relation) for satisfaction of constant-free LTL-FO properties of Γ. In particular, a fixed D * can be pre-computed and used to generate a counter-example run for every constant-free LTL-FO property violated by Γ.