Screening Regime Research Articles

Estimating latent, dynamic processes of breast cancer tumour growth and distant metastatic spread from mammography screening data.

We propose a framework for jointly modelling tumour size at diagnosis and time to distant metastatic spread, from diagnosis, based on latent dynamic sub-models of growth of the primary tumour and of distant metastatic detection. The framework also includes a sub-model for screening sensitivity as a function of latent tumour size. Our approach connects post-diagnosis events to the natural history of cancer and, once refined, may prove useful for evaluating new interventions, such as personalised screening regimes. We evaluate our model-fitting procedure using Monte Carlo simulation, showing that the estimation algorithm can retrieve the correct model parameters, that key patterns in the data can be captured by the model even with misspecification of some structural assumptions, and that, still, with enough data it should be possible to detect strong misspecifications. Furthermore, we fit our model to observational data from an extension of a case-control study of post-menopausal breast cancer in Sweden, providing model-based estimates of the probability of being free from detected distant metastasis as a function of tumour size, mode of detection (of the primary tumour), and screening history. For women with screen-detected cancer and two previous negative screens, the probabilities of being free from detected distant metastases 5 years after detection and removal of the primary tumour are 0.97, 0.89 and 0.59 for tumours of diameter 5, 15 and 35 mm, respectively. We also study the probability of having latent/dormant metastases at detection of the primary tumour, estimating that 33% of patients in our study had such metastases.

On nonlinearity in field-effect transistor-based binding assay response

Field-effect transistor (FET)-based biosensors have demonstrated highly sensitive label-free detection of a plethora of biomolecules as next-generation binding assays. While the dose–response curve of affinity-based binding assays generally has a nonlinear shape, any distortion contributed by the FET transducers has not been well understood. In this paper, we show that the signal transduction of FET sensors plays an important role in shaping their dose–response curves when operating in the nonlinear screening regime. We have found that the nonlinearity arising from the counterion screening in the electrical double layer could distort the relationship between the device flatband voltage shift and the analyte concentrations in (1) lowering its half-maximal response concentration as well as the sensitive detection range and (2) expanding its dynamic range. Negligence of such nonlinearity would introduce errors in the extracted affinity properties of the analyte–receptor pair. This work provides useful guidelines for designing FET-based binding assays and interpreting their measurement data.

About the force of electrostatic interaction between two spheroidal macroparticles in the Poisson-Boltzmann model

Electrostatic interaction of two charged spheroidal macroparticles is analyzed within the linearized Poisson-Botzmann model.Interparticle forces are calculated through finite-element method in the regimes of weak and moderate screening with constant surface potentials in the absence of external field. Keywords: linearized Poisson-Botzmann model, two charged macroparticles, spheroidal macroparticles, colloidal particles, dusty plasmas.

О силе электростатического взаимодействия двух сфероидальных макрочастиц в модели Пуассона-Больцмана

Еlectrostatic interaction of two charged spheroidal macroparticles is analyzed within the linearized Poisson–Botzmann model.Interparticle forces are calculated through finite-element method in the regimes of weak and moderate screening with constant surface potentials in the absence of external field.

FDI and Technological Development in Brazil: A New Regulatory Framework?

This paper analyses newly regulatory moves towards Foreign Direct Investment – FDI in Brazil. For that purpose, this paper explores the key economic rationale for regulating FDI and provides a legal baseline based on relevant FDI screening regimes already in force in mature jurisdictions. Later, this paper presents a brief assessment of the current Brazilian regulatory and governance scenario relating to FDI control, to demonstrate potential deficiencies that could emerge due to the lack of a structured FDI screening in the country, particularly the absence of quality control of FDI targeted to certain key areas, as well as risks of high political interference, which could generate undesirable effects on the country’s technological development and increase its level of dependence on technology developers.

A Robust Method for the Large-Scale Production of Spheroids for High-Content Screening and Analysis Applications.

High-content screening (HCS) and high-content analysis (HCA) are technologies that provide researchers with the ability to extract large-scale quantitative phenotypic measurements from cells. This approach has proved powerful for deepening our understanding of a wide range of both fundamental and applied events in cell biology. To date, the majority of applications for this technology have relied on the use of cells grown in monolayers, although it is increasingly realized that such models do not recapitulate many of the interactions and processes that occur in tissues. As such, there has been an emergence in the development and use of 3-dimensional (3D) cell assemblies, such as spheroids and organoids. Although these 3D models are particularly powerful in the context of cancer biology and drug delivery studies, their production and analysis in a reproducible manner suitable for HCS and HCA present a number of challenges. The protocol detailed here describes a method for the generation of multicellular tumor spheroids (MCTS), and demonstrates that it can be applied to three different cell lines in a manner that is compatible with HCS and HCA. The method facilitates the production of several hundred spheroids per well, providing the specific advantage that when used in a screening regime, data can be obtained from several hundred structures per well, all treated in an identical manner. Examples are also provided, which detail how to process the spheroids for high-resolution fluorescence imaging and how HCA can extract quantitative features at both the spheroid level as well as from individual cells within each spheroid. This protocol could easily be applied to answer a wide range of important questions in cell biology.

The Center Cannot Hold: A Comparison of the FDI Screening Regimes of the United States and European Union in Addressing the West's China Problem

Whether or not current U.S.-China strategic competition may be properly named a new Cold War, it is useful to compare the regimes of the United States and the European Union to better understand how domestic FDI screening mechanisms are growing in importance as a foreign policy tool (e.g. national defense strategies). Section II provides a contextual background weighing China’s own restrictive FDI policies against its increased technology and market access acquisitions in the U.S. and Europe. Section III outlines the U.S. FDI screening review by the Committee on Foreign Investment in the United States (CFIUS) with particular focus the broadening of its review powers by the Foreign Investment Risk Review Modernization Act of 2019 (FIRRMA). Section IV outlines the European Union’s Regulation 2019/452 which provides both a framework for FDI screening by Member States on the grounds of “security or public order” and a cooperation mechanism between Member States, as well as Member States and the Commission. Section V considers whether the increased use of FDI screening as a foreign policy tool potentially (1) undermines other multilateral efforts, in areas such as international trade, to address concerns related to the influence of Chinese state-owned enterprises, and (2) is ineffective given the difficulties faced by national authorities to fully appreciate organizational structures related to foreign government-supported investment. Looking to the “geographical pivot of history,” this paper concludes that “multilateralism still matters” and calls for renewed efforts to realize an International Convention on Foreign Investment.

Foreign direct investment rules in selected European countries – an overview

Purpose To provide an overview of the national foreign direct investment (“FDI”) screening mechanisms in place across Europe including in France, Germany, Italy, the Netherlands, Spain and the UK. Design/methodology/approach This article summarizes the key elements of the national FDI screening regimes of some of the leading European economies. This includes setting out the relevant investment thresholds, protected sectors, lengths of review periods, standstill obligations and potential sanctions in each jurisdiction. Findings Many of Europe’s leading economies are following the wider global trend towards stricter reviews of foreign investment ahead of the EU Screening Regulation coming into force in October 2020. However, the approach taken to FDI screening can vary significantly at a country level in terms of both process and substance and the applicable laws are evolving rapidly, not least as a response to concerns related to the impact of COVID-19. Practical implications Investors looking to make acquisitions in Europe will need to consider whether national FDI screening will apply to their proposed investments. Depending on the jurisdiction, FDI screening can introduce lengthy review periods and require detailed information gathering as well as uncertainty as to the final outcome. Potential investors also need to consider the risk of sanctions, including criminal sanctions, for non-compliance with the screening regimes. Originality/value This article offers a summary and comparison of national FDI screening regimes across Europe.

P128 The implications of SARS-CoV-2 on a Cardiothoracic unit

IntroductionThe effort to prevent healthcare systems becoming overrun during the 2020 COVID-19 pandemic has come at the cost of delaying operations and with that bringing difficult risk analysis to help decide which operations should go ahead. With COVID-19 being a novel disease there is limited evidence for guidance on this issue. We have previously presented work highlighting the high risk of mortality associated with a perioperative cardiothoracic patient becoming COVID-19 positive and thus decided to implement a series of changes to departmental perioperative practice. This work presents these interventions and compares the infection and the mortality rate with those before the intervention was put in place.MethodTwo retrospective loops were performed. Pre intervention, 5/3/20 – 20/4/20, and post intervention, 21/4/20- 23/6/20. Inclusion criteria: patients who had received cardiothoracic surgery at University Hospital of Wales within 4 weeks of the positive COVID-19 PCR (1st loop n = 53, 2nd loop n = 40). Exclusion criteria included re-admissions from greater than 4 weeks (n = 2). Interventions included 14 day pre op isolation, a strict multifaceted screening regime, reverse barrier nursing and delaying operations if diagnostic uncertainty.Results9/51 patients from the pre intervention loop and 2/40 from post intervention loop tested +ve for COVID-19. The pre intervention mortality was 5/9 and post intervention mortality was 0/2.ConclusionOur data suggest that simple changes to perioperative practice can decrease the transmission of COVID-19 during this period. Thus, allowing surgical services to run at a reduced risk

EU의 외국인직접투자(FDI)에 대한 심사체계에 대하여 - Regulation EU 2019/452를 중심으로 -

EU는 최근 COVID-19 팬데믹 발발이 기폭제가 되면서 적극적으로 외국인투자에 대한 심사를 강화하는 일련의 대응책을 마련했는데 그러한 대응책이 바로 외국인직접투자심사체제 확립에 관한 규칙 EU 2019/452다.<BR> 외국인투자와 공동체 및 회원국의 중요 인프라, 기술 등 보호와 외국인투자 사이에서 균형을 맞추는 것을 목표로 하는 본 규정은 이미 심사제도를 갖춘 회원국의 그것을 대체하지는 않으며 반대로 심사제도를 갖추지 않은 회원국은 본 규정에 맞춘 심사규정을 제정 혹은 수립할 의무를 지지 않는다. 하지만 한 회원국에 대한 투자가 공동체 혹은 다른 회원국의 안전 혹은 공공질서에 위협이 된다고 여겨지는 경우 다른 회원국의 판단에 따라 작성된 의견 혹은 견해에 대해 해당 회원국의 권한 있는 심사기관은 심사를 행할 시, 이를 고려해야만 하는 요소로 작용하기 때문에 국가적 결정절차에서 상당한 정치적 비중을 가질 수 있으며 중국과 같은 안보에 민감한 역외국의 투자에 대한 중요한 통제수단으로 부상할 수 있는 우려를 내포하고 있다. EU의 접근법은 FDI를 규제하는 정부의 권한을 증진하려는 광범위한 추세와 일치한다고 할 수 있는데 이는 2019년, 미국의 외국인투자위원회 절차(United States to the Committee on Foreign Investment in the United States; CFIUS)에 대한 입법변경은 물론 독일과 프랑스의 최근 개혁을 포함하여 특정 회원국의 강화된 FDI 심사제도와 해당 법률의 채택을 들 수 있다. 이러한 배경을 바탕으로 본 논문은 2019년 4월 10일 공식적으로 발효된 FDIR 2019/452의 내용 전반에 대한 검토와 함께 그로부터 도출되는 시사점에 대해 논하고자 하는 것이 그 목적이라고 할 수 있다. 공동체 이익을 위한 FDI 심사규정은 미국의 CFIUS와 유사하게 투자자들에게 불확실성을 유발할 수 있는데 그 이유로서 집행위원회가 투자를 검토하고 차단할 권한이 있으며 패쇄된 투자거래를 해소할 권한이 있을 것으로 예상하고 있기 때문이다. 넓게는 외국투자에 대한 평가는 EU의 무역협상과 제3국과의 무역분쟁은 물론 공동체 차원에서의 무역정책목표에 상당히 영향을 받을 가능성을 비추고 있다. 본 논문은 선행연구에서 제기하고 있는 집행위원회의 실질적 권한의 확대 여부와 외국투자에 미칠 영향에 대해 FDIR 2019/452 규정분석을 통하여 알아보고자 한다.<BR> 결과적으로 FDIR 2019/452에서 특히 강조하고 있는 부분은 ‘안전’ 그리고 ‘공공질서’인데 이러한 안전 및/또는 공공질서에 위협이 될 가능성이 있는 FDI의 예의 열거는 불완전한 것이며, 따라서 위와 같은 안전 및/또는 공공질서가 될 수 있는 요소들에 제한이 없어 투자자들이 예상할 수 있는 범위를 넘어선 불확실성이 확실시된다. 하지만 이로써 집행위원회의 권한이 미국의 CFIUS와 같은 수준의 투자에 대한 직접차단이나 중지를 명할 수 있는 권한은 없으며 그러한 권한은 최종적으로 해당 회원국에게 있음을 명문화하고 있다. 다만, 실질적으로 집행위원회와 다른 회원국이 해당 회원국의 최종결정에 어떠한 영향을 미칠지는 아직 해당 제도가 완전히 시행된 지 불과 몇 개월 전이기 때문에 이에 대한 전망은 지켜봐야 할 것으로 보이며, 따라서 본 논문에서 강조하고자 하는 부분은 향후 회원국의 심사제도(screening regimes)의 강화, 수정 그리고 도입에 따라 거래업체와 외국인 투자자는 신고요건의 증가(notification requirements), 늘어난 심사절차일정, 그리고 중요한 기술 및 외국 정부의 개입과 같은 추가된 요소를 고려해야만 할 것이며 특히 그러한 요소가 규정상 예시적인 것에 불과하여 변수로써 작용하는 다른 제 요소들에 대한 예상이 불투명하다는 점에 더욱 주의가 필요하다는 것을 강조하고자 한다.

Optimal Timing for Cancer Screening and Adaptive Surveillance Using Mathematical Modeling.

Cancer screening and early detection efforts have been partially successful in reducing incidence and mortality, but many improvements are needed. Although current medical practice is informed by epidemiologic studies and experts, the decisions for guidelines are ultimately ad hoc. We propose here that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain "window of opportunity" for intervention when early cancer development may be observable. Alternative to a strictly empirical approach or microsimulations of a multitude of possible scenarios, biologically based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett's esophagus, these methods were applied for a model of esophageal adenocarcinoma that was previously calibrated to U.S. cancer registry data. Optimal screening ages for patients with symptomatic gastroesophageal reflux disease were older (58 for men and 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Collectively, our framework captures critical aspects of cancer evolution within patients with Barrett's esophagus for a more personalized screening design. SIGNIFICANCE: This study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes, with the added potential to improve surveillance regimes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/4/1123/F1.large.jpg.

Theoretical Estimate of the Glass Transition Line of Yukawa One-Component Plasmas.

The mode coupling theory of supercooled liquids is combined with advanced closures to the integral equation theory of liquids in order to estimate the glass transition line of Yukawa one-component plasmas from the unscreened Coulomb limit up to the strong screening regime. The present predictions constitute a major improvement over the current literature predictions. The calculations confirm the validity of an existing analytical parameterization of the glass transition line. It is verified that the glass transition line is an approximate isomorphic curve and the value of the corresponding reduced excess entropy is estimated. Capitalizing on the isomorphic nature of the glass transition line, two structural vitrification indicators are identified that allow a rough estimate of the glass transition point only through simple curve metrics of the static properties of supercooled liquids. The vitrification indicators are demonstrated to be quasi-universal by an investigation of hard sphere and inverse power law supercooled liquids. The straightforward extension of the present results to bi-Yukawa systems is also discussed.

Kondo screening regimes in multi-Dirac and Weyl systems

We have investigated the Kondo physics of a single magnetic impurity embedded in multi-Dirac (Weyl) node fermionic systems. By using a generic effective model for the host material and employing a numerical renormalization group approach we access the low temperature behavior of the system, identifying the existence of Kondo screening in single-, double-, and triple-Dirac (Weyl) node models. We find that in any multi-Dirac node systems the low-energy regime lies within one of the known classes of pseudogap Kondo problem, extensively studied in the literature. Kondo screening is also observed for time reversal symmetry broken Weyl systems. This is, however, possible only in the particle-hole symmetry broken regime obtained for finite chemical potential $\mu$. Although weakly, breaking time-reversal symmetry suppresses the Kondo resonance, especially in the single-node Weyl semimetals. More interesting Kondo screening regimes are obtained for inversion symmetry broken multi-Weyl fermions. In these systems the Kondo regimes of double- and triple-Weyl node models are much richer than in the single-Weyl node model. While in the single-Weyl node model the Kondo temperature increases monotonically with $|\mu|$ regardless the value of the inversion symmetry breaking parameter $Q_0$, in double- and triple-Weyl node models there are two distinct regimes: (i) For $Q_0< |\mu|$ the Kondo temperature depends strongly on $\mu$, while (ii) for $Q_0 > |\mu|$ the Kondo temperature depends very weakly on $\mu$, resembling the flat-band single impurity Anderson model.

National security and FDI policy ambiguity: A commentary

From Germany’s chipmaker Infineon’s proposed takeover of US-based Wolfspeed being blocked in 2017 to China’s Huawei being banned in the USA and other countries in 2020; from the UK’s new National Security and Investment Bill being announced in the Queen’s Speech on December 19, 2019, to the EU’s FDI Screening Regulation fully entering into force on October 11, 2020, inward foreign direct investments are increasingly scrutinized by host-country governments on the grounds of national security concerns. While FDI policy and screening regimes work differently in different countries, they share something in common, that is, ambiguity and obscurity have become key features of FDI policies for most countries when concerned with national security. Drawing on securitization and balance-of-power theories, I contend that the ambiguity in FDI policy is intentionally constructed to leave room for power struggles. I argue that ambiguity is an important prerequisite for politicians and other political and corporate actors to engage in the securitization of FDI to support their political and commercial agendas. This commentary contributes to a better understanding of the prevailing trend of ambiguity in relation to inward FDI policy, a reality that differs from that advocated by Cuervo-Cazurra (2018).

Theaters, TV and the Microwave: Screening Regimes in Pablo Larraín’s Trilogy

The medium is socially the message — Marshall McLuhan— Dictator Augusto Pinochet was pushed out of power by the victory of the “No” vote in the 1988 plebiscite, but the economic regime remained. In...

Safeguarding Croatian Strategic Industries Within the Scope of the EU Foreign Direct Investment Regime

A European Union (EU)-wide screening regime entered into force in October 2020, marking the turning point in the Member States’ investment relations with third countries, most notably, the emerging economies of the Far East. Most Central and Eastern European (CEE) states have recently embraced novel screening solutions; some legislative proposals are still pending in a few states. These regulatory changes are the result of the socio-economic turmoil caused by the COVID-19 epidemic, which threatens a major fire sale of resources that are deemed critical for the Member States’ national security and public order. In this paper, the authors examine the existing screening mechanisms regarding foreign direct investment (FDI) in five EU countries: Austria, Germany, Hungary, Slovenia, and Poland. Given the apparent lack of comprehensive FDI screening mechanisms in Croatia, the authors consider that the findings of this comparative analysis could help Croatian legislator establish a comprehensive legal regime for FDI pouring into Croatian strategic industries. This paper argues that Croatia should introduce novel screening mechanisms along the lines of the Germanic legal tradition, most notably, the CEE and the German foreign trade and payments law. The authors suggest potential solutions de lege ferenda that would fit the scope and objectives of the screening regulation. Following the introduction, the second section of the paper glances through FDI screening mechanisms in four CEE countries. In the third section, the paper revisits the existing Croatian legislation on FDI control. The fourth section considers possible amendments thereof within the context of the German foreign trade and payments law. The fifth section summarises and concludes the paper.

Equilibrium field theory of magnetic monopoles in degenerate square spin ice: Correlations, entropic interactions, and charge screening regimes

We describe degenerate square spin as an ensemble of magnetic monopoles coupled via an emergent entropic field that subsumes the effect of the underlying spin vacuum. We compute their effective free energy, entropic interaction, correlations, screening, and structure factors that coincide with the experimental ones. Unlike in pyrochlore ices, a dimensional mismatch between real and entropic interactions leads to weak singularities at the pinch points and algebraic correlations at long distance. This algebraic screening can be, however, camouflaged by a pseudo-screening regime.

Anomalous exciton Rydberg series in two-dimensional semiconductors on high- κ dielectric substrates

Engineering of the dielectric environment represents a powerful strategy to control the electronic and optical properties of two-dimensional (2D) materials without compromising their structural integrity. Here we show that the recent development of high-$\kappa$ 2D materials present new opportunities for dielectric engineering. By solving a 2D Mott-Wannier exciton model for WSe$_2$ on different substrates using a screened electron-hole interaction obtained from first principles, we demonstrate that the exciton Rydberg series changes qualitatively when the dielectric screening within the 2D semiconductor becomes dominated by the substrate. In this regime, the distance dependence of the screening is reversed and the effective screening increases with exciton radius, which is opposite to the conventional 2D screening regime. Consequently, higher excitonic states become underbound rather than overbound as compared to the Hydrogenic Rydberg series. Finally, we derive a general analytical expression for the exciton binding energy of the entire 2D Rydberg series

Re-evaluation of indications for prenatal diagnosis of advanced pregnant women under the new screening regime

To assess the value of non-invasive prenatal testing (NIPT) for women with advanced gestational age but normal measurement for nuchal translucency (NT). A total of 9371 singleton pregnancies with negative NT screening at early pregnancy were reviewed. Among these, 8627 cases were selected to be screened again by NIPT, and their indications and results were analyzed. The results were compared with those of with other high risk factors and young gestational age. The incidence of fetal aneuploidies increased in women with advanced gestational age and ultrasound soft markers, in particular among those who were negative for NT screening but over the age of 37. The detection rate of pathological or likely pathological copy number variations was 1.88% among women who directly underwent invasive prenatal diagnosis because of the advanced age, but there was no correlation with the increase of age. 0.68% of the women where with negative NT screening and NIPT still need to undergo invasive prenatal diagnosis. After NT screening in early pregnancy, NIPT can replace invasive prenatal diagnosis for those below the age of 37, though there is still a possibility of missed detection of pathogenic copy number variation. It is necessary to strengthen ultrasonic monitoring in later period.

Breast-iRRISC: a novel model for predicting the individualised lifetime risk of radiation-induced breast cancer from a single screening event.

This work establishes the prototype of a new innovative risk model that aims to evaluate the total risk involved with screening mammography for each individual female. This has been specifically designed to accommodate any combination of lifetime screening regimes, using only the information gathered from a single mammographic examination. This model prototype was developed with the aid of a large dataset of images from the Cancer Institute New South Wales (CINSW) with over 30,000 images from over 7000 examinations. Each examination is derived from a separate female. This prototype which we have called Breast Individualised Risk of Radiation-Induced Screening Cancer (Breast-iRRISC) is a novel tool for the assessment of the lifetime risk involved with screening mammography. The results demonstrate the applicability of this approach to the various screening regimes utilised around the globe, in addition to the personalised screening frequency patterns females have undergone and are likely to receive in the future. This unique tailored approach to risk assessment will further empower females and clinicians towards a more informed clinical decision process regarding future imaging pathways. It will also inform health policy decisions regarding alternate screening durations and intervals. Breast-iRRISC is a novel tool that provides females, clinicians and health policymakers around the globe with the ability to quantify the lifetime risk of radiation-induced breast cancer from screening mammography on an individual level from a single exposure.