Line Extension Research Articles

Design and commissioning of the Beam Test Facility at the Spallation Neutron Source

Abstract The Beam Test Facility (BTF) originally built to verify the spare RFQs at the Spallation Neutron Source (SNS) possesses the additional capability to carry out high intensity beam experiments with unique capabilities. These capabilities include a full 6D phase space measurement system, and a beam line extension for studying the propagate beam dynamics including halo development under different match conditions. A phase space density plot method that characterizes beam halo is utilized in the design of the beamline. Simulations demonstrate that the beamline design meets the requirements for conducting beam halo research. Installation and commissioning of the BTF has been completed in stages, with the first stage demonstrating that the RFQ achieves the design parameters. Commissioning of the beamline extension has begun, and a high transmission efficiency has been achieved. More work, e.g. analysis of beam halo formation under different match conditions, will be done in the future.

Sustainability Development of Knowledge-Intensive Business Services: Strategic Actions and Business Performance

The recognition of the relevance of knowledge-intensive business services (KIBS) is becoming especially acute in the European Union and even more important for many emerging economies. The objective of the present study is twofold: (1) to examine whether an empirically-based typology of sustainability development can be constructed for KIBS; (2) to identify whether different development patterns are associated with different business performance outcomes. The empirical evidence is based on quantitative and firm-level data gathered through an email questionnaire which yielded 128 qualified responses from KIBS in the Czech Republic. The analysis is based on exploratory factor and cluster analysis to identify the cluster membership and to assess the relationship with performance outcomes it has been used the parametric test one-way ANOVA. Data analysis revealed that three distinct patterns types of KIBS exist, which were associated with different performance outcomes. With regard to the level of sustainable development, we found the conservative KIBS following market extension through a repositioning of existing and revised services, innovating KIBS following a new service development strategy focusing mainly on complements or line extension to existing services based on changes in technology and middle-ranged KIBS focusing on traditional strategy of comprehensiveness of services or “more services under one roof”. Innovating KIBS outperform other types of KIBS in all financial and non-financial parameters. The results have implications for practices involved in strategy development in services and useful for government efforts. The limitation of the research is done by focus on small companies, operating mainly in ICT and architectural and engineering services.

Analytical solutions for material line and plane in triple slip, with inverse solutions for the slips from a finite deformation experiment on iron crystals

Triple-slip analytical solutions are derived for rotation and extension of crystal material lines and planes relative to the underlying lattice, applicable to any crystal class. An algebraic inverse solution is then developed for the amounts of slip on the three systems (two collinear) in terms of initial and final positions of material line and plane. The solutions are applied to a finite deformation experiment (from the recent literature) on a bcc iron crystal in uniaxial compression, considering both {110} and {112} slip-planes. The respective slips and areal and length changes are determined from the initial and final experimental positions of the compression plane and an edge line. Such analyses can assist in assessment of relative hardening rates of the slip systems.

Preface: Celebration of the Career of Robert Nathan Ginsburg

Preface: Celebration of the Career of Robert Nathan Ginsburg

DISCRETE METRIC SPACES: STRUCTURE, ENUMERATION, AND 0-1 LAWS

AbstractFix an integer $r \ge 3$. We consider metric spaces on n points such that the distance between any two points lies in $\left\{ {1, \ldots ,r} \right\}$. Our main result describes their approximate structure for large n. As a consequence, we show that the number of these metric spaces is $\left\lceil {{{r + 1} \over 2}} \right\rceil ^{\left( {\matrix{ n \cr 2 \cr } } \right) + o\left( {n^2 } \right)} .$Related results in the continuous setting have recently been proved by Kozma, Meyerovitch, Peled, and Samotij [34]. When r is even, our structural characterization is more precise and implies that almost all such metric spaces have all distances at least $r/2$. As an easy consequence, when r is even, we improve the error term above from $o\left( {n^2 } \right)$ to $o\left( 1 \right)$, and also show a labeled first-order 0-1 law in the language ${\cal L}_r $, consisting of r binary relations, one for each element of $[r]$ . In particular, we show the almost sure theory T is the theory of the Fraïssé limit of the class of all finite simple complete edge-colored graphs with edge colors in $\left\{ {r/2, \ldots ,r} \right\}$.Our work can be viewed as an extension of a long line of research in extremal combinatorics to the colored setting, as well as an addition to the collection of known structures that admit logical 0-1 laws.

Practical Method of Predicting Slope Failure Based on Velocity Value (SLO Method) From Slope Stability Radar

Predicting slope failure is one of the most sought after feature from Slope Stability Radar (SSR). An accurate slope failure prediction will potentially give an ample time to manage risk related with slope stability, wherein the evacuation ofequipment or personal would be executed on a timely manner. The renownedmethod to predict failure among geo-mechanical practitioner is utilizing inversevelocity method, in which collapse will be predicted to happen when the extension of inverse velocity line is intercepted at predefined value that is usually only fractal above zero. The tenet of this method is, if one has acquired the knowledge of inverse velocity value from previous collapses, the next collapse could be predicted based on it with the pretext that both share the same nature and geological feature. The same can be said for predicting collapse based on velocity value. Set of maximum velocity value from several previous collapses will be averaged to determine predefined assumption to predict the next collapse. This paper will demonstrate an alternative method to predict collapse that will use velocity value instead of inverse velocity. This method is called SLO method as proposed by Azania Mufundirwa.This paper will specifically exemplify the practical steps to produce the failureprediction from slope stability radar data, and discuss the characteristic of theprediction yield by this method. Velocity chart with velocity calculation period of60 minutes is first established from particular pixel deemed as the one that showing the most distinguished progressive deformation trend. The velocity data will then be an exported and reprocess as such that the time data will be converted into unit time stamp number. The designated time stamp will then be accumulated, in which the onset of failure, will be regarded as time 0 reference. Log linear chart will be generated in which X-axis will be occupied by velocity value, while Y-axis will depict Velocity x Accumulated time (SLO chart). Collapse can subsequently be predicted by intercepting the predefined assumption of velocity during collapse with the log linear curve from the SLO chart. Two methods, mathematical & graphical, will be presented in this paper in order to give in depth understanding as to how one can predict collapse event with velocity value. Taking account on the study case from iron ore mining, SLO method yielded prediction of failuretime on 10:58 PM 31st January 2016, meanwhile the real failure occur on 11:32 PM 31st January 2016.

Characterization of local morphology and availability of triple-phase boundaries in solid oxide cell electrodes

The performance of solid oxide cells is known to be dependent upon the density of three phase boundaries (TPB), but the potential for improving their effective electrocatalytic activity by morphological adjustments is imprecisely known. A spilling algorithm was developed to characterize the surfaces available for diffusion at TPBs. It scans each slice in a 3-D imaging dataset to measure the interfaces between the solid and the pore phases at each TPB. Because of the stereological approach, these surfaces are defined as “available lengths” (LA). The measurement was tested on artificial packed spheres structures with controlled properties and a percolation theory-based model before application to a real Ni-YSZ. The LA distributions cover 2 orders of magnitude. The subset shorter than the extent of diffusion profiles reported in the literature is in the range of 3% and 20% for Ni and YSZ, respectively, suggesting possible limitations of their effective electrocatalytic properties. The average LA is larger on YSZ than on Ni, which is a trend opposite to the phase diameter. The available length analysis revealed microstructural characteristics that stem from the manufacturing route and cannot be identified by the inspection of standard metric and topological properties. A strong correlation between the available length and the extension of TPB lines is observed for Ni but not for YSZ, despite the predominance of convex shapes, which likely originates from the Ni reduction. This suggests possibilities for controlling the available length by the manufacturing route, depending specifically on the electrocatalytic properties of the phases in composite materials.

Do extra ingredients on the package lead to extra calorie estimates?

PurposeThis paper aims to address how adding food ingredients to a packaged base food affects consumers’ calorie estimation of the new augmented product.Design/methodology/approachThe four performed experiments and analyses of variance demonstrate an underlying psychological mechanism, explained below.FindingsResults show that the healthiness of the added food ingredient (AFI) does not matter if the base food is healthy, and consumers’ calorie estimates of the augmented packaged food product are accurate. When, however, the food base is unhealthy, and the AFI is healthy, consumers underestimate the new product calories. This underestimation effect increases further when the healthy ingredients multiply. This underestimation effect endures when these ingredients are presented in a visual form, but it becomes smaller when these ingredients are presented in a verbal form. A justification mechanism is relevant.Research limitations/implicationsFurther research should test across the broader range of the food product matrix. There is a great diversity of AFI presentations, and further research may deal with the impact of AFIs of these different forms on consumers’ calorie estimation and healthiness perceptions. Research may also test sensory-arousing mechanisms that can help understand how consumers perceive the calories of the augmented food.Practical implicationsThe findings suggest that consumers should be cautious of the judgment bias caused by the presence of an AFI on food packages and raise their awareness regarding nutrition implications and dietary effects. From the perspective of food manufacturers, although adding healthy AFIs to unhealthy base foods may increase consumers’ purchase intention and bring higher profits, it may not be sustainable as a marketing strategy in the long term and has immediate ethical implications.Social implicationsPolicymakers should introduce voluntary schemes to monitor and restrict the improper presentation of AFIs, aiming to rule out the abuse of healthy AFIs on unhealthy packaged food.Originality/valueThis work offers three major original and valuable contributions. It explains the effects of AFIs on calorie estimation and consumer healthiness perceptions in a context not studied before, namely, packaged food products. Next, it advances the literature on consumer judgment error and heuristics concerning product package attributes. As adding ingredients is integral to product line extension decisions, the results also clarify how marketing can safeguard firm social responsibility in combating obesity.

Percolation transitions of physically and hydrogen bonded clusters in supercritical water

Molecular Dynamics simulations were employed to locate the densities and pressures at which infinitely spanning networks form for both physically and hydrogen bonded water clusters along the 650, 700, 750 and 800 K supercritical isotherms. The SPC/E water model was used and the percolation thresholds were determined by examining the cluster size distributions. Average hydrogen bond numbers for the entire system are reported and are near the critical number of 1.55 expected at the hydrogen bonded percolation threshold. Percolating physical clusters appeared at lower densities than infinite hydrogen bonded networks. Physical and hydrogen bonded percolation thresholds were plotted on the P-ρ and P-T planes. Neither of the lines of percolation transitions match the extension of the vapor-liquid coexistence line into the supercritical region. Empirical relationships were obtained for each transition threshold as functions of temperature as well as density. Activation volumes of diffusion increase rapidly until they reach their maximum at the threshold densities where water molecules are connected via percolating network of hydrogen bonds.

Posterior malleolar fracture morphology determines outcome in rotational type ankle fractures

IntroductionRotational type ankle fractures with a concomitant fracture of the posterior malleolus are associated with a poorer clinical outcome as compared to ankle fractures without. However, clinical implications of posterior malleolar (PM) fracture morphology and pattern have yet to be established. Many studies on this subject report on fragment size, rather than fracture morphology based on computed tomography (CT). The overall purpose of the current study was to elucidate the correlation of PM fracture morphology and functional outcome, assessed with CT imaging and not with –unreliable- plain radiographs. MethodsBetween January 2010 and May 2014, 194 patients with an operatively (ORIF) treated ankle fracture, were prospectively included in the randomized clinical EF3X-trial at our Level-I trauma center. The current study retrospectively included 73 patients with rotational type ankle fractures and concomitant fractures of the posterior malleolus. According to the CT-based Haraguchi fracture morphology, all patients were divided into three groups: 20 Type I (large posterolateral-oblique), 21 Type II (transverse medial-extension) and 32 Type III (small-shell fragment). At 12 weeks, 1 year and 2 years postoperatively the Foot and Ankle Outcome Scores (FAOS) and SF-36 scores were obtained, with the FAOS domain scores at two years postoperative as primary study outcome. Statistical analysis included a multivariate regression and secondary a mixed model analysis. ResultsHaraguchi Type II PM ankle fractures demonstrated significantly poorer outcome scores at two years follow-up compared to Haraguchi Types I and III. Mean FAOS domain scores at two years follow-up showed to be significantly worse in Haraguchi Type II as compared to Type III, respectively: Symptoms 48.2 versus 61.7 (p = 0.03), Pain 58.5 versus 84.4 (p < 0.01), Activities of Daily Living (ADL) 64.1 versus 90.5 (p < 0.01). ConclusionPosterior malleolar ankle fractures with medial extension of the fracture line (i.e. Haraguchi Type II) are associated with significantly poorer functional outcomes. The current dogma to fix PM fractures that involve at least 25–33% of the tibial plafond may be challenged, as posterior malleolar fracture pattern and morphology - rather than fragment size - seem to determine outcome.

A Geometrically Simple Compact Wideband Circularly Polarized Antenna

A compact broadband wide-slot circular polarization (CP) antenna is proposed. An inverted L-shaped parasitic strip at the open end of a microstrip line extension and a slot modification is applied to attain wideband CP. The advantage of this technique is simplicity, which makes it readily redesignable for different frequency bands. To demonstrate the concept, three designs working at different frequencies are obtained. The redesign procedure is straightforward and only requires a recalculation of the selected physical dimensions followed by electromagnetic-based parameter tuning. A compact size of 0.09 λ 0 is achieved when measured at the lowest CP frequency. The optimized designs are validated experimentally in terms of | S 11|, axial ratio, realized gain, and radiation patterns. For the design corresponding to the lowest operating frequency, a total impedance bandwidth of ∼89% (3.2–8.4 GHz), axial-ratio bandwidth (ARBW) ≤3 dB of 82% (3.2–7.65 GHz), average in-band realized gain of 3.3 dBi, and a bidirectional radiation pattern with a dual sense of polarization are achieved. A thorough benchmarking indicates the superiority of the proposed antenna over the state-of-the-art designs in terms of all major performance figures.

Immune checkpoint inhibitors (ICI): An analysis of FDA’s and EMA’s decision patterns and times for initial approvals and extensions of indication.

e14062 Background: In certain clinical settings ICI have demonstrated unprecedented patterns of efficacy, resulting since 2011 in regulatory approvals worldwide in a variety of cancer indications. As immuno-oncology (IO) drugs constitute today an intense area of oncology drug development, we sought to analyze and compare the regulatory approval decisions for ICI, issued until end of 2018 by the US FDA and the European Medicines Agency (EMA). Methods: We reviewed the biological license applications (BLA) of the 7 (EU: 6) ICI, for which marketing approval decisions for were granted so far. Together with parallel and extension of indication applications, 43 (FDA) respectively 23 (EMA) approval procedures were finalized between March 2011 and December 2018. We analyzed agency decision outcomes and timeline patterns; approval decisions issued for novel non-IO cancer drugs served as benchmarks. The primary variable for analysis was median approval time (MAT). Results: MAT for initial BLA applications for ICI in the USA were with 189 days [Interquartile range (IQR) 154-209] shorter than MAT for BLA and NDA approvals for non-IO drugs: for the 51 novel oncology drugs approved 2011-2018 by the FDA, MAT was 227 days [IQR 159-303]. With 181 days [IQR 155-184], FDA’s MAT for ICI line extensions did not differ from MAT for initial ICI approvals. For the EU, MAT for initial ICI marketing applications were with 373 days (IQR 326-413) also shorter than MAT for the 51 non-IO drugs approved 2011-18 (422 days [IQR 368-450]); for ICI line extensions, MAT was 254 days [IQR 187-293). Conclusions: For ICI as for novel non-IO cancer drugs, initial regulatory approvals are usually issued in the USA first. Regulatory approval times for initial approvals are shorter in the USA, compared to Europe, the same applies for ICI extensions of indication. FDA’s extensive granting of breakthrough therapy designations (BTD) helped to bring US MAT for initial ICI BLA down to 6 months – i.e. to the same time, FDA requires for its priority review of extensions of indication. For some ICI extensions of indication, the granting of BTD supported approval decisions within 3 months, supporting patients’ rapid access to novel therapies.

Probabilistic assessment of tunneling-induced building damage

This paper presents a rational and efficient probabilistic framework to address the uncertainties of geotechnical properties and the stratigraphic profile in a tunneling-induced building damage assessment. The probabilistic approach is based on the application of a hybrid point estimation method that employs a reduced number of computations without losing accuracy. The framework also relies on sensitivity analyses using tornado diagrams. Analyses of ground movements and building displacements are considered prior to the building damage assessment. The proposed approach was applied to the recently constructed extension of Line 5 of the São Paulo Metro. Two-dimensional (2D) and three-dimensional (3D) numerical analyses were carried out using a commercial finite element code by considering the Mohr-Coulomb and linear elastic constitutive models. Three probabilistic scenarios based on the lower, mean, and upper bound values of the coefficient of variation of input variables were considered. The results obtained using the proposed framework allowed estimating the probabilistic scenario that better provides an ideal coefficient of variation to adopt for input variables. The ground elastic properties and upper layer thickness had the greatest influence on ground movements and building displacements. Finally, the building damage analysis showed good agreement with the settlement data measured in the field.

Urban transport and social inequities in neighbourhoods near underground stations in Greater London

ABSTRACTSocial equity, and the contribution that transport planning can make to social equity, are increasingly attracting the attention of transport planners and researchers. This perhaps reflects the heightened levels of social inequity in cities and the concern over differential access to transport and participation in activities. This paper considers these issues by applying the Capabilities Approach to transport, in order to examine an individual’s opportunities to travel and engage in activities (capabilities) and their actual day to day travel and engagement in activities (functionings). London is selected as a case study using analysis from three Underground stations on the Jubilee Line Extension. The findings show that there are statistically significant differences in terms of capabilities and functionings across the socio-demographic characteristics of individuals, and also across different neighbourhoods in London. It is argued that unless local residents’ potential travel opportunities and actual activities, and the gaps between them, are better understood and responded to, the problem of transport-related social inequity is likely to persist in London. Therefore, we suggest that the findings from this research, including the multi-dimensional social indicators and understanding of the barriers to accessibility, could be used alongside existing approaches such as accessibility planning.

Understanding Cultural Differences in Consumers’ Reactions to Foreign-Market Brand Extensions: The Role of Thinking Styles

One popular strategy for brands to grow outside of their home markets is to use line extensions. Although extensive research has examined how factors such as culture influence product acceptance across markets, far less is known regarding how such factors influence parent brand perceptions in response to an extension. This article investigates the role of one aspect of culture, consumers’ thinking styles, in terms of postextension parent brand spillover effects, and considers potential implications for firms’ global brand strategies, including the extension’s direction (upward or downward) and parent brand concept (functional or prestige). Through two studies, one using consumer panels in the United States and India and the other set in the United States, the authors examine consumer-level differences by measuring thinking styles. Results based on both studies indicate that vertical line extension type affects analytic thinkers’ reactions more than those of holistic thinkers, and parent brand image benefits (suffers) when a vertical line extension is for a functional (prestige) brand, regardless of consumers’ thinking style. The authors find interesting differences in the role of thinking styles based on the particular dimension examined.

Ophthalmic medicine regulatory approvals through the European Centralised Procedure, 1999-2017: Clinical efficacy considerations.

Regulatory approval of new medicines requires a thorough assessment of the potential clinical benefits and risks. Study end-points are expected to demonstrate a clinically relevant treatment effect that will translate into direct patient benefits. This study sought to review the ophthalmic medicines with European Union-wide approval granted via the Centralised Procedure and characterise the key efficacy end-points underpinning the demonstration of clinical benefit. This study was a retrospective review of published data pertaining to the European regulatory authorisation of centrally approved ophthalmic products between 1999 and 2017, inclusive. All sources and data consulted are in the public domain. European Public Assessment Reports published by the European Medicines Agency were consulted for data concerning the pivotal clinical efficacy studies supporting the applications. Data analyses were descriptive. The European Medicines Agency have authorised 30 products via the Centralised Procedure between 1999 and 2017. For these products, a total of 24 additional approvals for line extensions or additional therapeutic indications were granted. Four products have been approved for orphan indications, including one approval 'under exceptional circumstances' and one 'Conditional Marketing Authorisation'. Approvals for products in retina (36%) and glaucoma (28%) indications together accounted for the majority of authorisations, with trial end-points predominantly based on visual acuity and intraocular pressure parameters, respectively. Products were also approved for indications in ocular surface disease, inflammation, optic neuropathy and surgical adjuncts, with a range of functional and anatomical end-points. Approvals for ophthalmic medicines have been granted for a range of clinical indications, representing a considerable portion of available major therapeutics for practitioners. Benefit-risk assessments rely on clinical trial data demonstrating a clearly relevant patient benefit.

Disaster Management Dynamics – An Analysis of Chaos from the Flash Flood (2013) in the Fragile Himalayan System

Abstract Managing a disaster is a very complex issue in which both the people and the affected region of the particular country are involved. In disasters, the vision of reality entails proper understanding of complexity, uncertainty and instability in the backdrop of nonlinear dynamics. Decision making in case of disasters is a nonlinear thread which has to wind its way through various rhythms and systems that range from ground reality to management operations. The Uttarakhand disaster of 2013 is not a simple straight line extension of a house fire or an automobile accident. It is a mixed web of complexity, nonlinearity, instability and chaos. Maintaining hierarchy in decision making and managing a disaster of such magnitude in public domain has been found to be ineffective in operations. The theory of chaos and the science of complexity can lead to better disaster management options. In fact, chaos theory provides viable framework for management of natural disasters. Chaos theory describes how the human society influences the reality. Indeed, in some degrees, the society relevant for the region creates it. In the Indian Himalayas in Uttarakhand state, during the third week of June 2013, intermittent and unprecedented precipitation covering large area led to flash floods and landslides. They carried away everything resulting in colossal loss of life and property. Incoherencies in management occurred mainly because of lack of understanding of nonlinear dynamics and deterministic chaos in natural phenomena and a fixed approach i.e. ‘mode lock-in’ approach in decision making. In this article, the disaster situation is established to have been initiated due to forces of deterministic chaos. On this basis, some suggestions are formulated where help of the chaos theory may prove congenial to decision making.

Impact of vertical line extensions on brand attitudes and new extensions

PurposeCompanies often extend brands to higher or lower quality tiers to access different market segments. However, the impact of such extensions on the brand and its subsequent offerings is not yet conclusive. While some studies found an “averaging” pattern (all models contribute equally to the overall perception of the brand: a symmetric effect), others found a “best-of-brand” pattern (the positive impact of an upstream extension is much greater than the negative impact of a downstream extension: an asymmetric effect). This paper aims to reconcile these seemingly conflicting findings by assessing the conditions under which each pattern is likely to emerge.Design/methodology/approachThree experimental studies are presented to test the conditions under which a symmetric or asymmetric pattern of brand evaluation would merge. Study 1 examined the impact of judgment focus (quality vs expertise) on the pattern of brand evaluations. Study 2 tested the impact of having a comparative set on the assessment of specific brand dimensions. Study 3 examined the impact of the informativeness of price positioning on product quality expectations.FindingsBrand evaluations and attitudes are determined by the presence of a comparative brand and judgment focus. When brands are evaluated without a comparison, a symmetric pattern emerges, as a low-tier extension hurts a brand as much as a high-tier extension helps it. In contrast, when brands are evaluated with a comparison, focusing the assessment on quality leads to a symmetric pattern, while focusing it on expertise leads to an asymmetric one.Research limitations/implicationsThe present research specifies conditions under which a low-tier model may hurt brand perceptions. We used hypothetical brands to avoid the impact of preexisting attitudes. While we expect our results to generalize to real brands, this may be considered a limitation of the present research.Practical implicationsThe current research delineates the circumstances under which vertical line extensions have positive, neutral or negative impact on brand perceptions and future product expectations. We introduce the presence of a comparison set as a key variable and show how it interacts with assessment focus to affect brand evaluations. When thinking about the impact of extensions on brand perceptions, marketers need to consider which assessment focus is likely to be triggered by environmental cues and whether comparisons are salient.Originality/valueBrand extension is an important area of investigation as evidenced by the vast literature dedicated to the subject. The present paper advances knowledge in this area by identifying key factors affecting the impact of vertical extensions on brand perceptions.

History-Dependent Demand in Chronic Drug Markets: Evidence and Implications

History-dependence in drug demand can lead to higher drug prices, encourage entry deterrence, and worsen health outcomes. I use temporal discontinuities in choice sets to identify history-dependence, and find large and long-term effects. Quasi-randomly assigning a patient to a newly launched drug today produces a 54 percentage point increase in the probability of the patient choosing the same drug four years later. History-dependence is stronger in patients who take medications for multiple conditions and weaker in drugs that are significantly more effective than substitutes. It is also weaker in generics and line extensions, driven by switching from the reference branded drug. I capture these patterns by estimating a pair-specific switching-cost model of demand. Finally, I use the model to highlight the entry incentive created by demand and provide suggestive evidence that firms respond to these incentives when making entry-timing decisions.

The year's new drugs and biologics 2018: Part I.

Sixty-four new drugs and biologics reached their first global markets in 2018, the greatest number in at least a decade. In addition, 19 important new line extensions (new indications, new combinations or new formulations of previously marketed drugs) were introduced over the course of 2018. Twenty-three other new products and new line extensions were approved but not launched before December 31. As has been the trend in recent years, oncology was the most active therapeutic area in terms of new launches, with cancer drugs accounting for 25% of all novel drugs and biologics introduced worldwide last year. Eight first-in-class agents were launched for the first time in 2018, including the first RNA interference agent as well as the photo-finish approval and rollout of the first three members of a radically different class of non-vasoconstricting antimigraine agents, the anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies. Twenty-nine of the drugs launched last year were designated orphan drugs, reflecting the continued upswing in investment in the area of neglected diseases. This is especially true in the U.S., which welcomed 25 of the newly launched orphan drugs. Overall, the U.S. was the most active market for new drugs and biologics, accounting for two-thirds of all new launches in 2018.