90 research outputs found
Economies in transition : ageing, markups and place-based policies
Defence date: 11 May 2023Examining Board: Prof. Philipp Kircher, (Cornell University, supervisor); Prof. Thomas Crossley, (European University Institute, co-supervisor); Prof. Leena Rudanko, (Federal Reserve Bank of Philadelphia); Prof. Anna Salomons, (Utrecht University)In the first chapter, joint with Daniele Angelini, we analyze the effect of a change in the age composition of consumers on growth through competition. To identify the effect coming from the demand side of the economy, we instrument changes in the age composition of demand with unexpected foreign demographics shocks. We find that middle-aged consumers reduce competition. We rationalize our results in a general equilibrium heterogeneous agent model. Focusing on the USA, we estimate that changes in the age composition of consumers have contributed to a reduction in GDP growth of 8.7% in the period 1995-2004 and an increase of 10.3% in the period 2005-2019. In the second chapter, joint with Philipp Kircher and David Koll, we estimate labor market responses to local sector-level shocks as proxies for place-based policies. We show that local policy maker could face a trade-off between subsidising low-growth sectors with large short-term employment benefits or subsidising high growth sectors with initially smaller but persistent labor market improvements. Finally, in the third chapter, I present a model of consumer search that captures firms’ endogenous growth along two margins: customer capital and product range. The model provides micro-foundations for the existence of within-firm heterogeneity in terms of prices, sales and markups. Consistent with recent empirical evidence, firms do not increase markups over their growth path; instead, I show that they achieve a higher surplus from each match by increasing their product range and, therefore, buyer’s loyalty. Nevertheless, as a firm grows larger, its share of incumbent buyers increases and demand spreads more homogeneously across goods, mechanically reducing its average markup. I called this novel mechanism the curse of the large firm.1. The effect of a change in the age composition of consumers on the market structures
and growth --
2. Future versus present labor markets: the trade-off of place-based policies --
3. Customer loyalty and firm dynamics over their intensive and extensive margins --
References --
A. Appendix to chapter 1 --
B. Appendix to chapter 2 --
C. Appendix to chapter
A Case–Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection
Background: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). Methods: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. Results: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62–0.76 for ALU and 0.80, 95% CI: 0.73–0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. Conclusions: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker
Applications of Mathematical Models in Engineering
The most influential research topic in the twenty-first century seems to be mathematics, as it generates innovation in a wide range of research fields. It supports all engineering fields, but also areas such as medicine, healthcare, business, etc. Therefore, the intention of this Special Issue is to deal with mathematical works related to engineering and multidisciplinary problems. Modern developments in theoretical and applied science have widely depended our knowledge of the derivatives and integrals of the fractional order appearing in engineering practices. Therefore, one goal of this Special Issue is to focus on recent achievements and future challenges in the theory and applications of fractional calculus in engineering sciences. The special issue included some original research articles that address significant issues and contribute towards the development of new concepts, methodologies, applications, trends and knowledge in mathematics. Potential topics include, but are not limited to, the following: Fractional mathematical models; Computational methods for the fractional PDEs in engineering; New mathematical approaches, innovations and challenges in biotechnologies and biomedicine; Applied mathematics; Engineering research based on advanced mathematical tools
Doença de Fabry e o coração
Tese de doutoramento em MedicinaA doença de Fabry (DF) é uma causa de miocardiopatia hipertrófica (MCH), mas a sua prevalência na
MCH não está esclarecida. O nosso rastreio enzimático e genético de DF em 150 doentes adultos com
MCH da região Portuguesa de Guimarães revelou 25 casos de DF (16.6%) e a mutação GLA c.337T>C
(p.F113L) em 21 deles. O nosso estudo genealógico por historiadores revelou uma árvore familiar com
12 gerações e um ancestral comum aos doentes p.F113L, demonstrando um efeito fundador de DF com
400 anos. O rastreio familiar revelou disseminação desta mutação por muitos países no mundo.
A história natural dos fenótipos tardios de DF não é completamente conhecida. Nos nossos estudos, um
protocolo diagnóstico foi realizado no momento basal em 120 doentes consecutivos para caraterização
do fenótipo associado à mutação p.F113L e, subsequentemente, em 203 doentes (79 homens) (idade
46±18 anos) para caraterização da sua história natural. O envolvimento cardíaco teve o maior impacto
prognóstico, incluindo hipertrofia ventricular esquerda (HVE) (40.8%), taquicardia ventricular não
sustentada (TVNS) (12.5%), bloqueio auriculoventricular (AV) (18.3%) e bloqueio bifascicular (13.4%). Foi
implantado pacemaker em 5.8%. Nos homens, a HVE e o realce tardio (RT) surgiram a partir dos 30
anos; a insuficiência cardíaca, a TVNS e as perturbações da condução cardíaca a partir dos 40 anos; e
os bloqueios bifascicular e AV completo a partir dos 50 anos. Nas mulheres, as manifestações cardíacas
ocorreram menos frequentemente e 1-2 décadas depois. A frequência e a gravidade das manifestações
cardíacas aumentaram com a idade. As manifestações extracardíacas incluíram albuminuria aumentada
(36.1%), lesões da substância branca cerebral (54.4%) e surdez neurossensorial (44.5%) e surgiram antes
dos 30 anos em ambos os géneros na ausência de comorbilidades. Foram encontradas inclusões
lisossómicas em podócitos de doentes jovens p.F113L com proteinuria, mas a doença renal crónica
estadio ≥3 ocorreu em 7.6% (≈ população geral). Os eventos cerebrovasculares foram raros (3.3%).
O nosso rastreio multicêntrico de 780 doentes adultos com MCH revelou uma prevalência de DF,
ajustada para o efeito fundador, de 0.9%. O bloqueio bifascicular (OR 10.909, CI95% 2.377-50.059) e o
RT inferolateral basal (OR 10.677, CI95% 3.633-31.380) foram os preditores mais fortes de DF na MCH.
Na sua ausência, segundo o score ID FABRY-HCM, a DF é uma causa menos provável de MCH. Novas
variantes GLA c.286A>G (p.M96V) e c.607G>T (p.E203X) foram associadas à DF clássica.
Desde a nossa primeira descrição de não-compactação do ventrículo esquerdo (NCVE) num doente de
Fabry, permanece por esclarecer se a NCVE é uma manifestação de DF. O nosso rastreio multicêntrico
de DF em 78 doentes com NCVE não encontrou casos adicionais, argumentando contra esta hipótese.Fabry disease (FD) is a cause of hypertrophic cardiomyopathy (HCM), but its prevalence in HCM is not
clearly established. Our enzymatic and genetic screening of FD in 150 adult patients with HCM from the
Portuguese region of Guimarães found 25 Fabry cases (16.6%) and the GLA mutation c.337T>C
(p.F113L) in 21 of them. Our genealogy study by historians revealed a 12-generation family tree with a
common ancestor to p.F113L patients, demonstrating a founder effect of FD with 400 years. Family
screening revealed that this mutation has been spread to many countries around the world.
The natural history of late-onset phenotypes of FD is not completely known. In our studies, a diagnostic
protocol was performed at baseline in 120 consecutive patients for characterization of the phenotype
associated to the p.F113L mutation and, subsequently, in 203 patients (79 males) (age 46±18 years)
for characterization of its natural history. Cardiac involvement carried the highest prognostic impact,
including left ventricular hypertrophy (LVH) (40.8%), non-sustained ventricular tachycardia (NSVT)
(12.5%), atrioventricular (AV) block (18.3%) and bifascicular block (13.4%). Pacemaker implantation
occurred in 5.8%. In males, LVH and late gadolinium enhancement (LGE) arose over 30 years; heart
failure, NSVT and cardiac conduction disorders over 40 years; and bifascicular block and complete AV
block beyond 50 years of age. In females, cardiac manifestations occurred less commonly and 1-2
decades later. The frequency and severity of cardiac manifestations increased with age. Extracardiac
manifestations included increased albuminuria (36.1%), brain white matter lesions (54.4%) and
sensorineural deafness (44.5%) and arose before 30 years of age in both genders in the absence of
comorbidities. Lysosomal inclusions were found on podocytes of young p.F113L patients with proteinuria,
but chronic kidney disease stage ≥3 occurred in only 7.6% (≈ general population). Cerebrovascular events
were rare (3.3%).
Our multicentre FD screening in 780 adult patients with HCM revealed a FD prevalence, adjusted for the
founder effect, of 0.9%. Bifascicular block (OR 10.909, CI95% 2.377-50.059) and basal inferolateral LGE
(OR 10.677, CI95% 3.633-31.380) were the most powerful predictors of FD in HCM. In their absence,
according to the score ID FABRY-HCM, FD is a less probable cause of HCM. Novel GLA variants c.286A>G
(p.M96V) and c.607G>T (p.E203X) were shown to be associated with a FD classical phenotype.
Since our first report of left ventricular noncompaction (LVNC) in a FD patient, it remains to be clarified
whether LVNC is a manifestation of FD. Our multicentre FD screening in 78 patients diagnosed with LVNC
found no additional cases, arguing against this hypothesis
Plasma Cell-Free DNA Integrity Assessed by Automated Electrophoresis Predicts the Achievement of Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
PURPOSE The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression. RESULTS cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. CONCLUSION cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies
Network Modeling for Walking Infrastructure: Developing Pedestrian Traffic Assignment Methodologies for Large-Scale Footpath Networks
This dissertation focuses on exploring network-wide pedestrian bidirectional dynamics, developing frameworks for both static and
dynamic pedestrian network traffic assignment models, and estimating an empirical pedestrian route choice model using revealed
preference (RP) data from Sydney, Australia. To capture the bidirectional impact (e.g. lane formation and congestion due to flows
from counter direction), four different types of pedestrian volume delay functions (pVDFs) are proposed and calibrated against
controlled experimental data. The proposed pVDF is an essential component to develop a user equilibrium traffic assignment
problem (UE-pTAP) framework. The proposed UE-pTAP framework has been applied to both a small-scale toy network and a largescale
real-world network to demonstrate the impact of the bidirectionality of walking streams on the network assignment solution.
To capture the pedestrian travel behavior in a dynamic context, this dissertation also proposes a pedestrian dynamic network traffic
assignment (DTA) model based on the link transmission model (LTM). The formulated dynamic UE (DUE) adopts a bidirectional
fundamental diagram that takes into account properties of bidirectional pedestrian streams such as self-organization. The
applicability and validity of the model are demonstrated in a small grid network, a long corridor, and a large-scale real-world network.
To better understand the pedestrian route choice decision-making in an urban environment, four types of logit-based route choice
models, C-logit (CL), path size logit (PSL), and error component (EC), are also estimated using revealed preference (RP) data
passively collected from smartphones in Sydney, Australia. The cross-validation results show that the four route choice models
perform equally well. However, the PSL has a slight edge over other models because it has the least variability and requires much
less computational resources than the EC models. Overall, the quantitative values for various attributes e.g., distance, the number of
turns, maximum gradient, the number of points of interest (POI) along a path, and green view index (GVI), are comparable to
previous findings in the literature.
Overall, this dissertation offers valuable and new insights into the study of pedestrian bidirectional dynamics and the development of
pedestrian network models in both static and dynamic contexts. The development of stochastic route choice models using
smartphone data also provides an in-depth knowledge of decision-making behavior influenced by various built environment factors
beyond travel distance. Results of this research help with the strategic planning of walking infrastructure in cities as well as
estimating foot traffic across footpath networks for operational purposes
Designing Business Forms to Pursue Social Goals
The long-standing debate about the purpose and role of business firms has recently regained momentum. Business firms face growing pressure to pursue social goals and benefit corporation statutes proliferate across many U.S. states. This trend is largely based on the idea that firms increase long-term shareholder value when they contribute (or appear to contribute) to society. Contrary to this trend, this Article argues that the pressing issue is whether policies to create social impact actually generate value for third-party beneficiaries—rather than for shareholders. Because it is difficult to measure social impact with precision, the design of legal forms for firms that pursue social missions should incorporate organizational structures that generate both the incentives and competence to pursue such missions effectively. Specifically, firms that have a commitment to transacting with different types of disadvantaged groups demonstrate these attributes and should thus serve as the basis for designing legal forms.
While firms with such a commitment may be created using a variety of control and contractual mechanisms, the related transaction costs tend to be very high. This Article develops a social enterprise legal form that draws on the legal regime for community development financial institutions (CDFIs) and European legal forms for work-integration social enterprises (WISEs). This form would certify to investors, consumers, and governments that designated firms have a commitment as social enterprises. By obviating the need for costly social impact measurement, this form would facilitate the provision of subsidy-donations to social enterprises from multiple groups, particularly investors (through below-market investment) and consumers (via premiums over market prices). Thus, this social enterprise form would be to altruistic investors and consumers what the nonprofit form is to donors.
Moreover, the proposal could facilitate the flow of investments by foundations in social enterprises (known as program-related investments, “PRIs”) because it would help foundations verify the social impact of their investees. In addition, by giving subsidy-providers greater assurance that social enterprises pursue social missions effectively, the proposed legal form could facilitate public markets for social enterprises
Activity analysis of thermal imaging videos using a difference imaging approach
Infrared thermal imaging is a passive imaging technique that captures the emitted radiation from an object to estimate surface temperature, often for inference of heat transfer. Infrared thermal imaging offers the potential to detect movement without the challenges of glare, shadows, or changes in lighting associated with visual digital imaging or active infrared imaging. In this paper, we employ a frame subtraction algorithm for extracting the pixel-by-pixel relative change in signal from a fixed focus video file, tailored for use with thermal imaging videos. By summing the absolute differences across an entire video, we are able to assign quantitative activity assessments to thermal imaging data for comparison with simultaneous recordings of metabolic rates. We tested the accuracy and limits of this approach by analyzing movement of a metronome and provide an example application of the approach to a study of Darwin's finches. In principle, this “Difference Imaging Thermography” (DIT) would allow for activity data to be standardized to energetic measurements and could be applied to any radiometric imaging system
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