An Analysis of Tax Incentives in the FDI Decision Process from Organisational Structural Perspectives: Evidence from UK Multinationals

This paper investigates the role of tax incentives in the FDI decision making process in a sample of UK multinational companies. The paper considers the relative importance of stages and determinants in the FDI decision making process. The determining factors in FDI decision process are examined from the organisational structure perspectives –FDI ownership form and market entry mode. The paper specifically identifies the role of tax in the strategic decisions of FDI organisational structure, as well as the stages of FDI decision making process. Relatively few prior empirical studies have examined the interface between tax strategy and corporate strategy in the context of FDI organisational structure and decision making process. This paper therefore attempts to examine the tax incentives for FDI decision process from the perspectives of the organisational structure

Dielectrophoresis of charged colloidal suspensions

We present a theoretical study of dielectrophoretic (DEP) crossover spectrum of two polarizable particles under the action of a nonuniform AC electric field. For two approaching particles, the mutual polarization interaction yields a change in their respective dipole moments, and hence, in the DEP crossover spectrum. The induced polarization effects are captured by the multiple image method. Using spectral representation theory, an analytic expression for the DEP force is derived. We find that the mutual polarization effects can change the crossover frequency at which the DEP force changes sign. The results are found to be in agreement with recent experimental observation and as they go beyond the standard theory, they help to clarify the important question of the underlying polarization mechanisms

Effective conductivity of composites of graded spherical particles

We have employed the first-principles approach to compute the effective response of composites of graded spherical particles of arbitrary conductivity profiles. We solve the boundary-value problem for the polarizability of the graded particles and obtain the dipole moment as well as the multipole moments. We provide a rigorous proof of an {\em ad hoc} approximate method based on the differential effective multipole moment approximation (DEMMA) in which the differential effective dipole approximation (DEDA) is a special case. The method will be applied to an exactly solvable graded profile. We show that DEDA and DEMMA are indeed exact for graded spherical particles.Comment: submitted for publication

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined the genetics of variation in concentrations of postprandial metabolites (t = 150 min) in response to a liquid mixed meal through genome-wide association studies (GWAS) performed in the Netherlands Epidemiology of Obesity (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (beta [SE] -0.23 [0.03], P = 2.15 x 10(-19)). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: beta [SE] 0.17 [0.03], P = 5.76 x 10(-10); XXLVLDL cholesterol ester: beta [SE] 0.17 [0.03], P = 9.74 x 10(-10)), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 x 10(-8)). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-beta, Matsuda insulin sensitivity index, and HbA(1c) in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate-corrected q <0.05). To conclude, genetic studies of metabolomics change after a liquid meal illuminate novel pathways for glucose and lipid metabolism. Further studies are warranted to corroborate biological pathways of the ANKRD55 locus underlying diabetes.Functional Genomics of Systemic Disorder

ACTIV-2: A Platform Trial for the Evaluation of Novel Therapeutics for the Treatment of Early COVID-19 in Outpatients

In April of 2020, the public-private partnership, Accelerating COVID-19 Therapeutics and Vaccine (ACTIV), a cross National Institutes of Health (NIH) initiative, was created to jumpstart the evaluation of new therapeutics and vaccines for coronavirus disease 2019 (COVID-19) in randomized clinical trials. The process through which the ACTIV trials were developed and the rationale for the use of a master protocol for this purpose has been previously described. The ACTIV-2 trial was initiated to address the need to evaluate monoclonal antibodies and other novel therapies for ambulatory patients with COVID-19, and the AIDS Clinical Trials Group (ACTG) was selected by the NIH and the ACTIV Therapeutics Working Group to lead the protocol development and study conduct. The goal was to develop a platform trial that could rapidly evaluate compounds that were prioritized for study by the ACTIV agent prioritization group. The clinical trial was sponsored by the NIH and designed and led by a team of investigators in the ACTG with funding to the ACTG UM1 awards. The time from concept submission for ACTIV-2 to the first participant enrolled was 2.5 months. The study team worked in collaboration with pharmaceutical companies who were developing the products; however, all aspects of the trial were under the primary sponsorship of the NIH. A clinical research organization (CRO), PPD, was contracted by the NIH to support the ACTG in the implementation of the trial. This supplement includes papers that describe selected key findings and study design and analysis challenges. In this overview, we provide a description of the ACTIV-2 trial and highlight key operational challenges

Pooling Different Placebos as a Control Group in a Randomized Platform Trial: Benefits and Challenges From Experience in the ACTIV-2 COVID-19 Trial

Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials. Clinical Trials Registration. NCT04518410

Comparative Pharmacokinetics of Tixagevimab/Cilgavimab (AZD7442) Administered Intravenously Versus Intramuscularly in Symptomatic SARS-CoV-2 Infection

AZD7442 (Evusheld) is a combination of two human anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs), tixagevimab (AZD8895) and cilgavimab (AZD1061). Route of administration is an important consideration to improve treatment access. We assessed pharmacokinetics (PKs) of AZD7442 absorption following 600 mg administered intramuscularly (i.m.) in the thigh compared with 300 mg intravenously (i.v.) in ambulatory adults with symptomatic COVID-19. PK analysis included 84 of 110 participants randomized to receive i.m. AZD7442 and 16 of 61 randomized to receive i.v. AZD7442. Serum was collected prior to AZD7442 administration and at 24 hours and 3, 7, and 14 days later. PK parameters were calculated using noncompartmental methods. Following 600 mg i.m., the geometric mean maximum concentration (Cmax) was 38.19 μg/mL (range: 17.30–60.80) and 37.33 μg/mL (range: 14.90–58.90) for tixagevimab and cilgavimab, respectively. Median observed time to maximum concentration (Tmax) was 7.1 and 7.0 days for tixagevimab and cilgavimab, respectively. Serum concentrations after i.m. dosing were similar to the i.v. dose (27–29 μg/mL each component) at 3 days. The area under the concentration-time curve (AUC)0–7d geometric mean ratio was 0.9 for i.m. vs. i.v. Participants with higher weight or body mass index were more likely to have lower concentrations with either route. Women appeared to have higher interparticipant variability in concentrations compared with men. The concentrations of tixagevimab and cilgavimab after administration i.m. to the thigh were similar to those achieved with i.v. after 3 days from dosing. Exposure in the i.m. group was 90% of i.v. over 7 days. Administration to the thigh can be considered to provide consistent mAb exposure and improve access

Evolution of deformation and recrystallization textures in high-purity Ni and the Ni-5 at. pct W alloy

An attempt has been made to study the evolution of texture in high-purity Ni and Ni-5 at. pct W alloy prepared by the powder metallurgy route followed by heavy cold rolling (∼95 pct deformation) and recrystallization. The deformation textures of the two materials are of typical pure metal or Cu-type texture. Cube-oriented ({001} {100}) regions are present in the deformed state as long thin bands, elongated in the rolling direction (RD). These bands are characterized by a high orientation gradient inside, which is a result of the rotation of the cube-oriented cells around the RD toward the RD-rotated cube ({013} {100}). Low-temperature annealing produces a weak cube texture along with the {013} {100} component, with the latter being much stronger in high-purity Ni than in the Ni-W alloy. At higher temperatures, the cube texture is strengthened considerably in the Ni-W alloy; however, the cube volume fraction in high-purity Ni is significantly lower because of the retention of the {013} {100} component. The difference in the relative strengths of the cube, and the {013} {100} components in the two materials is evident from the beginning of recrystallization in which more {013} {100} -oriented grains than near cube grains form in high-purity Ni. The preferential nucleation of the near cube and the {013} {100} grains in these materials seems to be a result of the high orientation gradients associated with the cube bands that offer a favorable environment for early nucleation

Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection

Non-neoclassical up/down asymmetry of impurity emission on Alcator C-Mod

We demonstrate that existing theories are insufficient to explain up/down asymmetries of argon x-ray emission in Alcator C-Mod ohmic plasmas. Instead of the poloidal variation, ñ[subscript z]/〈n[subscript z]〉, being of order the inverse aspect ratio, ϵ, and scaling linearly with B[subscript t][superscript _ over n][subscript e]/I[2 over p], it is observed over 0.8 < r/a < 1.0 to be of order unity and exhibits a threshold behaviour between 3.5 <B[subscript t][superscript _ over n][subscript e]/I[subscript p] < 4.0 (T10[superscript 20] m[superscript −3] MA[superscript −1]). The transition from a poloidally symmetric to asymmetric impurity distribution is shown to occur at densities just below those that trigger a reversal of the core toroidal rotation direction, thought to be linked to the transition between the linear and saturated ohmic confinement regimes. A possible drive is discussed by which anomalous radial transport might sustain the impurity density asymmetry as the ratio of the perpendicular to parallel equilibration times, τ[subscript ⊥,z]/τ[subscript ∥,z], approaches unity. This explanation requires a strong up/down asymmetry in radial flux which, while not observable on C-Mod, has been measured in TEXT and Tore Supra ohmic plasmas.United States. Dept. of Energy (Contract DE-FC02-99ER54512)United States. Dept. of Energy (Fusion Research Postdoctoral Research Program