Invitation Only Research Event

Invitation Only Research Event

Event participants

Dr Robin Niblett CMG, Director, Chatham House  
Toshiro Mutoh, Honorary Chairman, Daiwa Institute of Research; CEO, Tokyo Organising Committee of the Olympic and Paralympic Game
José Manuel Barroso, Senior Adviser, Chatham House; President of the European Commission (2004-14); Prime Minister of Portugal (2002-04)
Akihiko Tanaka, President, National Graduate Institute for Policy Studies

The aim of this project is to provide a space to explore creative/disruptive ideas in order to make headway on perspectives concerning deterrence. This will encourage ‘responsible disruption’ in the nuclear field.

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by ¹⁸F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.

Data independent acquisition (DIA) is an attractive alternative to standard shotgun proteomics methods for quantitative experiments. However, most DIA methods require collecting exhaustive, sample-specific spectrum libraries with data dependent acquisition (DDA) to detect and quantify peptides. In addition to working with non-human samples, studies of splice junctions, sequence variants, or simply working with small sample yields can make developing DDA-based spectrum libraries impractical. Here we illustrate how to acquire, queue, and validate DIA data without spectrum libraries, and provide a workflow to efficiently generate DIA-only chromatogram libraries using gas-phase fractionation (GPF). We present best-practice methods for collecting DIA data using Orbitrap-based instruments, and develop an understanding for why DIA using an Orbitrap mass spectrometer should be approached differently than when using time-of-flight instruments. Finally, we discuss several methods for analyzing DIA data without libraries.

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

JW Baynes
Jan 1, 1999; 48:1-9
Articles

Invitation Only Research Event

Event participants

Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign Affairs
Chair: Dr Robin Niblett, Director; Chief Executive, Chatham House

Invitation Only Research Event

Imagine that you are waiting in line to be born . . . Presently, you are scheduled to be born white. However, you are offered an alternative arrangement. In exchange for a cash gift, to be deposited in a bank account for you when you are born, you can choose to instead be born black.

As European policymakers and publics continue to grapple with the migration crisis, this conversation offers an opportunity to reflect on the role and responsibility of experts in these politically sensitive debates.

Jennifer M. Perkins
Apr 1, 2007; 25:57-62
Feature Articles

How does your genetic inheritance, culture and history influence your health? Biological anthropologist Lara Durgavich discusses the field of evolutionary medicine as a gateway to understanding the quirks of human biology -- including why a genetic mutation can sometimes have beneficial effects -- and emphasizes how unraveling your own evolutionary past could glean insights into your current and future health.

Policy Analysis for California Education has been a premier ed policy organization for three decades. As Daisy Gonzales writes, it is in the forefront of shaping current reforms and interpreting them for audiences such as 'On California.'

"Aloha" isn't just a greeting; in a way it is their way of life, and when you distort that sacred word, you distort their way of life.

Advertising -- Psychological aspects.

Psychoanalysis.

Rockville, Maryland : National Institute on Drug Abuse, 1985.

Rockville, Maryland : National Institute on Drug Abuse, 1988.

Beverly Hills : Sage Publications, 1976.

Pac-12 Networks' Yogi Roth and Ashley Adamson talk with Hall of Fame player and Pac-12 Networks talent Bill Walton during Thursday's Pac-12 Perspective podcast.

Patrick L. Combettes, Christian L. Müller.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 207--238.

Abstract:
We introduce a flexible optimization model for maximum likelihood-type estimation (M-estimation) that encompasses and generalizes a large class of existing statistical models, including Huber’s concomitant M-estimator, Owen’s Huber/Berhu concomitant estimator, the scaled lasso, support vector machine regression, and penalized estimation with structured sparsity. The model, termed perspective M-estimation, leverages the observation that convex M-estimators with concomitant scale as well as various regularizers are instances of perspective functions, a construction that extends a convex function to a jointly convex one in terms of an additional scale variable. These nonsmooth functions are shown to be amenable to proximal analysis, which leads to principled and provably convergent optimization algorithms via proximal splitting. We derive novel proximity operators for several perspective functions of interest via a geometrical approach based on duality. We then devise a new proximal splitting algorithm to solve the proposed M-estimation problem and establish the convergence of both the scale and regression iterates it produces to a solution. Numerical experiments on synthetic and real-world data illustrate the broad applicability of the proposed framework.

Daniel Ahlberg.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 397--401.

Abstract:
We study the rate of convergence in the celebrated Shape Theorem in first-passage percolation, obtaining the precise asymptotic rate of decay for the probability of linear order deviations under a moment condition. Our results are presented from a temporal perspective and complement previous work by the same author, in which the rate of convergence was studied from the standard spatial perspective.

Norbert Hirschauer, Sven Grüner, Oliver Mußhoff, Claudia Becker.

Source: Statistics Surveys, Volume 12, 136--172.

Abstract:
Data on how many scientific findings are reproducible are generally bleak and a wealth of papers have warned against misuses of the $p$-value and resulting false findings in recent years. This paper discusses the question of what we can(not) learn from the $p$-value, which is still widely considered as the gold standard of statistical validity. We aim to provide a non-technical and easily accessible resource for statistical practitioners who wish to spot and avoid misinterpretations and misuses of statistical significance tests. For this purpose, we first classify and describe the most widely discussed (“classical”) pitfalls of significance testing, and review published work on these misuses with a focus on regression-based “confirmatory” study. This includes a description of the single-study bias and a simulation-based illustration of how proper meta-analysis compares to misleading significance counts (“vote counting”). Going beyond the classical pitfalls, we also use simulation to provide intuition that relying on the statistical estimate “$p$-value” as a measure of evidence without considering its sample-to-sample variability falls short of the mark even within an otherwise appropriate interpretation. We conclude with a discussion of the exigencies of informed approaches to statistical inference and corresponding institutional reforms.

George Karabatsos, Fabrizio Leisen.

Source: Statistics Surveys, Volume 12, 66--104.

Abstract:
We are living in the big data era, as current technologies and networks allow for the easy and routine collection of data sets in different disciplines. Bayesian Statistics offers a flexible modeling approach which is attractive for describing the complexity of these datasets. These models often exhibit a likelihood function which is intractable due to the large sample size, high number of parameters, or functional complexity. Approximate Bayesian Computational (ABC) methods provides likelihood-free methods for performing statistical inferences with Bayesian models defined by intractable likelihood functions. The vastity of the literature on ABC methods created a need to review and relate all ABC approaches so that scientists can more readily understand and apply them for their own work. This article provides a unifying review, general representation, and classification of all ABC methods from the view of approximate likelihood theory. This clarifies how ABC methods can be characterized, related, combined, improved, and applied for future research. Possible future research in ABC is then outlined.

Zhuang Ma, Xiaodong Li.

Source: Bernoulli, Volume 26, Number 1, 432--470.

Abstract:
Canonical correlation analysis (CCA) is a fundamental statistical tool for exploring the correlation structure between two sets of random variables. In this paper, motivated by the recent success of applying CCA to learn low dimensional representations of high dimensional objects, we propose two losses based on the principal angles between the model spaces spanned by the sample canonical variates and their population correspondents, respectively. We further characterize the non-asymptotic error bounds for the estimation risks under the proposed error metrics, which reveal how the performance of sample CCA depends adaptively on key quantities including the dimensions, the sample size, the condition number of the covariance matrices and particularly the population canonical correlation coefficients. The optimality of our uniform upper bounds is also justified by lower-bound analysis based on stringent and localized parameter spaces. To the best of our knowledge, for the first time our paper separates $p_{1}$ and $p_{2}$ for the first order term in the upper bounds without assuming the residual correlations are zeros. More significantly, our paper derives $(1-lambda_{k}^{2})(1-lambda_{k+1}^{2})/(lambda_{k}-lambda_{k+1})^{2}$ for the first time in the non-asymptotic CCA estimation convergence rates, which is essential to understand the behavior of CCA when the leading canonical correlation coefficients are close to $1$.

Alessandro Rinaldo, Ryan J. Tibshirani, Larry Wasserman.

Source: Statistical Science, Volume 34, Number 4, 599--603.

Abstract:
What is the meaning of a regression parameter? Why is this the de facto standard object of interest for statistical inference? These are delicate issues, especially when the model is misspecified. We argue that focusing on predictive quantities may be a desirable alternative.

A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning.

SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner.

A museum director looks to the past to explain why 'Aloha' is as necessary as ever

By Dr. Grazie Pozo Christie

Coronavirus is only the latest iteration of an age-old human affliction. Even now, with the benefit of advanced medical science, our reaction – our confusion, our fear – is not so different from how our ancestors experienced recurrent and terrifying onslaughts of plague, cholera, and yellow fever across the ages. We can learn from the courage and ingenuity of those who travelled this road before us.
 
Consider the work of Dr. Carlos Finlay in Cuba. In 1880 he hypothesized, and then worked to prove his hypothesis, that yellow fever, a disease that regularly decimated coastal populations up and down the Americas, was spread by infected mosquitos. Those mosquitos came to our shores in the 17th century on African slave ships and attacked portal communities in the tropics as well as cities like New Orleans and Philadelphia. The resulting epidemics occurred with oppressive regularity in the summer months, to the people’s great dread, with mortality rates as high as 50 percent. The impact was tremendous – not only in the milllions of lives lost and the wretchedness this caused, but in economic gains and opportunities wiped out or delayed (the Panama Canal).
 
Connecting the transmission of the deadly virus to its source or vector was a decisive step forward in the long struggle against yellow fever. It preceded the development of a vaccine by more than 60 years. Here's how it happened: A young doctor, Carlos Finlay, returned to his home in Havana one night, exhausted, after caring for a Carmelite priest dying of yellow fever. Realizing he had forgotten to say his daily rosary, he sat in his armchair, sweating in the oppressive heat, fingering his beads and swatting at a bothersome mosquito. Suddenly, inspiration pierced his depression and weariness: Could the mosquito, like the one annoying him that moment, be transmitting the infection from person to person? If so, this was marvelous. One could not fight the brutal steamy summer air – the miasma – but one could fight mosquitos.
 
Inspiration, however, was not enough to proceed. Courage and even heroism would be needed to prove Finlay’s hypothesis. These were at hand, thanks to 57 young Jesuit priests and brothers who volunteered as experimental subjects. As each arrived from Spain to staff the Colegio de Belen, newly founded by Queen Isabel II of Spain, he was met by Finlay, carrying a test tube filled with mosquitos that had just fed on a patient sick with yellow fever. Taking their lives in their hands, these Jesuits allowed themselves to be bitten for the sake of their fellow human beings. Three died of the bite, but all 57 were willing to do the same.
 
Subsequent experiments supported Finlay’s hypothesis. Although a vaccine to definitively eradicate the disease would not come for decades, Finlay’s insight helped man to co-exist safely with yellow fever until that time. The incidence of yellow fever in Cuba dropped precipitously through mosquito control. Standing water, a breeding ground for the noxious pests, was eliminated where possible or treated aggressively with insecticides where not. Panama, where tens of thousands of workers had already died of the disease while building the canal followed Cuba’s lead. The last Panama Canal worker to die of yellow fever came in 1906.
 
There are important lessons for us here -- first and foremost, lessons in resourcefulness and valor. 
 
Already, thousands of human minds are, today, tenaciously working to find a solution to Covid-19. They’re persisting without respite, persisting through depression and fatigue, to find a way forward. Just as Dr. Finlay did.
 
And, you can depend on it, inspiration is sure to strike again.
 
You can also see today the same kind of valor that animated the Jesuit volunteers who let the infected mosquitos bite them. You see it in the countless men and women who keep showing up for work at nursing homes or crowded food production lines. Their examples help us all to keep up and increase our courage so we can join them as we ease back into our normal daily lives.
 
As we face the moment when we too realize that we have no choice but to go back out into the world of work and personal interactions, we can take hope from contemplating our predecessors’ success in confronting yellow fever. Like us, they dreamed of a vaccine. But they didn’t lock themselves away until it was developed. They found a way to steel themselves and then to steal the deadly efficiency away from the virus that plagued them. A century later, we can do the same.

Taking differentiation to mean "everything all the time" isn’t a sustainable model, warns English teacher Chad Towarnicki.

The policy implications of the ESEA, and its most recent reauthorization, the No Child Left Behind Act, have been at the heart of an enduring public debate.

Many patient and family demographic characteristics are well-known risk factors for nonurgent emergency-department use. No previous study has examined the primary care physician perspective on parental decisions regarding specific nonurgent emergency-department visits by children.

When discussing specific instances when families in their practices sought nonurgent care for children in the emergency department, physicians believed that parents acted appropriately. Neither parents nor primary care physicians saw nonurgent emergency-department visits as a significant enough problem to warrant change. (Read the full article)

In 2011, the Accreditation Council on Graduate Medical Education increased restrictions on resident duty-hours. Further changes have been considered, including greater work-hour restrictions and lengthening residency. Residents’ views about these policies are unclear.

This is the first systematic, national inquiry into resident opinions on reduced work-hours and longer residency. More pediatric residents support than oppose reduced hours, and a minority would add a year to residency to achieve them. (Read the full article)

Higher-hazard, no-benefit research involving children may be approved by local institutional review boards only when the protocol enrolls children with the medical condition under study. The ethics of this distinction have been debated, but parental opinions have not been explored.

We found that parental opinions support federal regulations. We discuss parental motivations for and against research participation and the extent to which enrolling a child in higher-hazard, no-benefit research reflects appropriate surrogate decision-making. (Read the full article)