A partial dependence factorial analysis to deal with selection bias in observational studis

This thesis presents a creative and practical approach to dealing with the problem of selection bias. Selection bias may be the most important vexing problem in program evaluation or in any line of research that attempts to assert causality. Some of the greatest minds in economics and statistics have scrutinized the problem of selection bias, with the resulting approaches – Rubin’s Potential Outcome Approach(Rosenbaum and Rubin,1983; Rubin, 1991,2001,2004) or Heckman’s Selection model (Heckman, 1979) – being widely accepted and used as the best fixes. These solutions to the bias that arises in particular from self selection are imperfect, and many researchers, when feasible, reserve their strongest causal inference for data from experimental rather than observational studies. The innovative aspect of this thesis is to propose a data transformation that allows measuring and testing in an automatic and multivariate way the presence of selection bias. The approach involves the construction of a multi-dimensional conditional space of the X matrix in which the bias associated with the treatment assignment has been eliminated. Specifically, we propose the use of a partial dependence analysis of the X-space as a tool for investigating the dependence relationship between a set of observable pre-treatment categorical covariates X and a treatment indicator variable T, in order to obtain a measure of bias according to their dependence structure. The measure of selection bias is then expressed in terms of inertia due to the dependence between X and T that has been eliminated. Given the measure of selection bias, we propose a multivariate test of imbalance in order to check if the detected bias is significant, by using the asymptotical distribution of inertia due to T (Estadella et al. 2005) , and by preserving the multivariate nature of data. Further, we propose the use of a clustering procedure as a tool to find groups of comparable units on which estimate local causal effects, and the use of the multivariate test of imbalance as a stopping rule in choosing the best cluster solution set. The method is non parametric, it does not call for modeling the data, based on some underlying theory or assumption about the selection process, but instead it calls for using the existing variability within the data and letting the data to speak. The idea of proposing this multivariate approach to measure selection bias and test balance comes from the consideration that in applied research all aspects of multivariate balance, not represented in the univariate variable- by-variable summaries, are ignored. The first part contains an introduction to evaluation methods as part of public and private decision process and a review of the literature of evaluation methods. The attention is focused on Rubin Potential Outcome Approach, matching methods, and briefly on Heckman’s Selection Model. The second part focuses on some resulting limitations of conventional methods, with particular attention to the problem of how testing in the correct way balancing. The third part contains the original contribution proposed , a simulation study that allows to check the performance of the method for a given dependence setting and an application to a real data set. Finally, we discuss, conclude and explain our future perspectives.

"Daring to be foolish". L'opera poetica di Robert Kroetsch dal 2001 al 2010

La presente dissertazione si pone come oggetto di analisi la produzione poetica di Robert Kroetsch (1927-2011), scrittore e critico letterario canadese nativo dell’Alberta (Canada), che tra il 1960 e il 2010 ha pubblicato un numero notevole di opere (nove romanzi, più di venti opere poetiche tra componimenti singoli e in raccolta, due volumi di saggi e diverse interviste). In particolare si è scelto di focalizzare l’attenzione sulle ultime tre raccolte di poesia – rispettivamente The Hornbooks of Rita K (2001), The Snowbird Poems (2004) e Too Bad: Sketches Toward a Self-Portrait (2010) – che, se confrontate con la produzione precedente, forniscono prova di alcuni elementi di novità all’interno della prospettiva poetica di Kroetsch. L’ipotesi dalla quale trae origine il presente studio è infatti che, a partire dalla raccolta The Hornbooks of Rita K, Kroetsch abbia imboccato un percorso di evoluzione stilistica che corre in parallelo con la formulazione di una nuova poetica. Nello specifico, si osserva che, negli ultimi dieci anni, da un punto di vista formale i componimenti si frammentano progressivamente, passando da una forma lunga – quella del long poem – a una breve – lo sketch, che risulta più adatta a rappresentare sul piano espressivo una mutata percezione dell’Io poetico. A un simile aspetto si aggiunge poi il fatto che la raffigurazione della propria vicenda umana diventa, con sempre maggiore evidenza, motivo di riflessione su una condizione universale dell’umano e sulla dimensione etica del suo agire.

Mechanical microcontacts of powder particles studied with the quartz crystal microbalance

Within this work, a particle-polymer surface system is studied with respect to the particle-surface interactions. The latter are governed by micromechanics and are an important aspect for a wide range of industrial applications. Here, a new methodology is developed for understanding the adhesion process and measure the relevant forces, based on the quartz crystal microbalance, QCM. rnThe potential of the QCM technique for studying particle-surface interactions and reflect the adhesion process is evaluated by carrying out experiments with a custom-made setup, consisting of the QCM with a 160 nm thick film of polystyrene (PS) spin-coated onto the quartz and of glass particles, of different diameters (5-20µm), deposited onto the polymer surface. Shifts in the QCM resonance frequency are monitored as a function of the oscillation amplitude. The induced frequency shifts of the 3rd overtone are found to decrease or increase, depending on the particle-surface coupling type and the applied oscillation (frequency and amplitude). For strong coupling the 3rd harmonic decreased, corresponding to an “added mass” on the quartz surface. However, positive frequency shifts are observed in some cases and are attributed to weak-coupling between particle and surface. Higher overtones, i.e. the 5th and 7th, were utilized in order to derive additional information about the interactions taking place. For small particles, the shift for specific overtones can increase after annealing, while for large particle diameters annealing causes a negative frequency shift. The lower overtones correspond to a generally strong-coupling regime with mainly negative frequency shifts observed, while the 7th appears to be sensitive to the contact break-down and the recorded shifts are positive.rnDuring oscillation, the motion of the particles and the induced frequency shift of the QCM are governed by a balance between inertial forces and contact forces. The adherence of the particles can be increased by annealing the PS film at 150°C, which led to the formation of a PS meniscus. For the interpretation, the Hertz, Johnson-Kendall-Roberts, Derjaguin-Müller-Toporov and the Mindlin theory of partial slip are considered. The Mindlin approach is utilized to describe partial slip. When partial slip takes place induced by an oscillating load, a part of the contact ruptures. This results in a decrease of the effective contact stiffness. Additionally, there are long-term memory effects due to the consolidation which along with the QCM vibrations induce a coupling increase. However, the latter can also break the contact, lead to detachment and even surface damage and deformation due to inertia. For strong coupling the particles appear to move with the vibrations and simply act as added effective mass leading to a decrease of the resonance frequency, in agreement with the Sauerbrey equation that is commonly used to calculate the added mass on a QCM). When the system enters the weak-coupling regime the particles are not able to follow the fast movement of the QCM surface. Hence, they effectively act as adding a “spring” with an additional coupling constant and increase the resonance frequency. The frequency shift, however, is not a unique function of the coupling constant. Furthermore, the critical oscillation amplitude is determined, above which particle detach. No movement is detected at much lower amplitudes, while for intermediate values, lateral particle displacement is observed. rnIn order to validate the QCM results and study the particle effects on the surface, atomic force microscopy, AFM, is additionally utilized, to image surfaces and measure surface forces. By studying the surface of the polymer film after excitation and particle removal, AFM imaging helped in detecting three different meniscus types for the contact area: the “full contact”, the “asymmetrical” and a third one including a “homocentric smaller meniscus”. The different meniscus forms result in varying bond intensity between particles and polymer film, which could explain the deviation between number of particles per surface area measured by imaging and the values provided by the QCM - frequency shift analysis. The asymmetric and the homocentric contact types are suggested to be responsible for the positive frequency shifts observed for all three measured overtones, i.e. for the weak-coupling regime, while the “full contact” type resulted in a negative frequency shift, by effectively contributing to the mass increase of the quartz..rnThe interplay between inertia and contact forces for the particle-surface system leads to strong- or weak-coupling, with the particle affecting in three mentioned ways the polymer surface. This is manifested in the frequency shifts of the QCM system harmonics which are used to differentiate between the two interaction types and reflect the overall state of adhesion for particles of different size.rn

Interactions of inhaled nanoparticles with the alveolar-capillary barrier of the human respiratory tract

In dieser Arbeit wurden zytotoxische Effekte sowie die inflammatorische Reaktionen des distalen respiratorischen Traktes nach Nanopartikelexposition untersucht. Besondere Aufmerksamkeit lag auch auf der Untersuchung unterschiedlicher zellulärer Aufnahmewege von Nanopartikeln wie z.B. Clathrin- oder Caveolae-vermittelte Endozytose oder auch Clathrin- und Caveolae-unabhängige Endozytose (mit möglicher Beteiligung von Flotillinen). Drei unterschiedliche Nanopartikel wurden hierbei gewählt: amorphes Silica (aSNP), Organosiloxan (AmorSil) und Poly(ethyleneimin) (PEI). Alle unterschiedlichen Materialien gewinnen zunehmend an Interesse für biomedizinische Forschungsrichtungen (drug and gene delivery). Insbesondere finden aSNPs auch in der Industrie vermehrt Anwendung, und stellen somit ein ernstzunehmendes Gesundheitsrisiko dar. Dieser wird dadurch zu einem begehrten Angriffsziel für pharmazeutische Verabreichungen von Medikamenten über Nanopartikel als Vehikel aber bietet zugleich auch eine Angriffsfläche für gesundheitsschädliche Nanomaterialien. Aus diesem Grund sollten die gesundheitsschädigenden Risiken, sowie das Schicksal von zellulär aufgenommenen NPs sorgfältig untersucht werden. In vivo Studien an der alveolaren-kapillaren Barriere sind recht umständlich. Aus diesem Grund wurde in dieser Arbeit ein Kokulturmodel benutzt, dass die Alveolar-Kapillare Barrier in vivo nachstellt. Das Model besteht aus dem humanen Lungenepithelzelltyp (z.B. NCI H441) und einem humanen microvasculären Endothelzelltyp (z.B. ISO-HAS-1), die auf entgegengesetzten Seiten eines Transwell-Filters ausgesät werden und eine dichte Barriere ausbilden. Die NP Interaktion mit Zellen in Kokultur wurde mit denen in konventioneller Monokultur verglichen, in der Zellen 24h vor dem Experiment ausgesät werden. Diese Studie zeigt, dass nicht nur die polarisierte Eigenschaft der Zellen in Kokultur sondern auch die unmittelbare Nähe von Epithel und Endothelzelle ausschlaggebend für durch aSNPs verursachte Effekte ist. Im Hinblick auf inflammatorische Marker (sICAM, IL-6, IL8-Ausschüttung), reagiert die Kokultur auf aSNPs empfindlicher als die konventionelle Monokultur, wohingegen die Epithelzellen in der Kokultur auf zytotoxikologischer Ebene (LDH-Ausschüttung) unempfindlicher auf aSNPs reagierten als die Zellen in Monokultur. Aufnahmestudien haben gezeigt, dass die Epithelzellen in Kokultur entschieden weniger NPs aufnehmen. Somit zeigen die H441 in der Kokultur ähnliche epitheliale Eigenschaften einer schützenden Barriere, wie sie auch in vivo zu finden sind. Obwohl eine ausreichende Aufnahme von NPs in H441 in Kokultur erreicht werden konnte, konnte ein Transport von NPs durch die epitheliale Schicht und eine Aufnahme in die endotheliale Schicht mit den gewählten Inkubationszeiten nicht gezeigt werden. Eine Clathrin- oder Caveolae-vermittelte Endozytose von NPs konnte mittels Immunfluoreszenz weder in der Mono- noch in der Kokultur nachgewiesen werden. Jedoch zeigte sich eine Akkumulation von NPs in Flotillin-1 und-2 enthaltende Vesikel in Epithelzellen aus beiden Kultursystemen. Ergebnisse mit Flotillin-inhibierten (siRNA) Epithelzellen, zeigten eine deutlich geringere Aufnahme von aSNPs. Zudem zeigte sich eine eine reduzierte Viabilität (MTS) von aSNP-behandelten Zellen. Dies deutet auf eine Beteiligung von Flotillinen an unbekannten (Clathrin oder Caveolae -unabhängig) Endozytosemechanismen und (oder) endosomaler Speicherung. Zusammenfassend waren die Aufnahmemechanismen für alle untesuchten NPs in konventioneller Monokultur und Kokultur vergleichbar, obwohl sich die Barriereeigenschaften deutlich unterscheiden. Diese Arbeit zeigt deutlich, dass sich die Zellen in Kokultur anders verhalten. Die Zellen erreichen hierbei einen höheren Differenzierungsgrad und eine Zellkommunikation mit anderen relevanten Zelltypen wird ermöglicht. Durch das Einbringen eines dritten relevanten Zelltyps in die Kokultur, des Alveolarmakrophagen (Zelllinie THP-1), welcher die erste Verteidigungsfront im Alveolus bildet, wird diese Aussage weiter bekräftigt. Erste Versuche haben gezeigt, dass die Triplekultur bezüglich ihrer Barriereeigenschaften und IL-8-Ausschüttung sensitiver auf z.B. TNF- oder LPS-Stimulation reagiert als die Kokultur. Verglichen mit konventionellen Monokulturen imitieren gut ausgebildete, multizelluräre Kokulturmodelle viel präziser das zelluläre Zusammenspiel im Körper. Darum liefern Nanopartikelinteraktionen mit dem in vitro-Triplekulturmodel aufschlussreichere Ergebnisse bezüglich umweltbedingter oder pharmazeutischer NP-Exposition in der distalen Lung als es uns bisher möglich war.

Measurement of the distributions of event-by-event flow harmonics in lead-lead collisions at = 2.76 TeV with the ATLAS detector at the LHC

The distributions of event-by-event harmonic flow coefficients v_n for n=2-4 are measured in sqrt(s_NN)=2.76 TeV Pb+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using charged particles with transverse momentum pT> 0.5 GeV and in the pseudorapidity range |eta|<2.5 in a dataset of approximately 7 ub^-1 recorded in 2010. The shapes of the v_n distributions are described by a two-dimensional Gaussian function for the underlying flow vector in central collisions for v_2 and over most of the measured centrality range for v_3 and v_4. Significant deviations from this function are observed for v_2 in mid-central and peripheral collisions, and a small deviation is observed for v_3 in mid-central collisions. It is shown that the commonly used multi-particle cumulants are insensitive to the deviations for v_2. The v_n distributions are also measured independently for charged particles with 0.51 GeV. When these distributions are rescaled to the same mean values, the adjusted shapes are found to be nearly the same for these two pT ranges. The v_n distributions are compared with the eccentricity distributions from two models for the initial collision geometry: a Glauber model and a model that includes corrections to the initial geometry due to gluon saturation effects. Both models fail to describe the experimental data consistently over most of the measured centrality range.

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at √s=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton-proton collision data at s√=8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t~→tχ~01 or t~→bχ~±1→bW(∗)χ~01, where χ~01 (χ~±1) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t~→tχ~01. For a branching fraction of 100%, top squark masses in the range 270-645 GeV are excluded for χ~01 masses below 30 GeV. For a branching fraction of 50% to either t~→tχ~01 or t~→bχ~±1, and assuming the χ~±1 mass to be twice the χ~01 mass, top squark masses in the range 250-550 GeV are excluded for χ~01 masses below 60 GeV.

Smoke free restaurant ordinance, compliance with the regulation to reduce exposure to environmental tobacco smoke while dining at local restaurants in San Antonio, Texas

This study is a secondary analysis of a survey developed by Dr. Jimmy Perkins and administered by San Antonio/Bexar County Metropolitan Health District. The survey was developed subsequent to the implementation of the city smoking ordinance effective January 1, 2004. The survey had a multi-purpose plan to establish the number of restaurants having smoke free status prior to and following the ordinance, determine compliance as it relates to a necessary smoking section and proper signage, and expose the rationale for restaurants to become smoke free. The data resulting from the survey was presented to the San Antonio/Bexar County Metropolitan Health District. The summary presented the types of establishments surveyed, smoking status of the establishment, reasons for the establishment becoming smoke free, compliance with smoking sections, compliance with signage requirements, awareness of ordinance, and chain status of the establishment. ^ The results of this study display the relationships among the variables previously mentioned. The following relationships have been examined and the outcomes have determined whether each is significant. After careful analysis, knowledge translates into compliance with signage regulations, which then translate into ordinance compliance. Size does matter as it relates to an establishment's number of employees and seating capacity. The smaller the establishment the more likely the establishment is to have become smoke free before the ordinance went into effect. Restaurants, rather than fast food establishments most commonly cited their reason for becoming smoke free was to comply with the ordinance and only ten percent of restaurants gave policy as the main reason for becoming smoke free. ^ This study is important for public health because the negative health effects of environmental tobacco smoke (ETS) are still an overwhelming problem in the United States (3). ETS is a Known Human Group A Carcinogen (5). The Environmental Protection Agency (EPA) has estimated that around 3,000 non-smoking Americans die every year from lung cancer caused by ETS (6). This information illustrates the importance of providing smoke free establishments, especially to non-smoking patrons. ^

Factors associated with the retention of HIV-infected children in care in Botswana

Lost to follow up (LTFU) in the care and treatment of HIV/AIDS represents a particularly problematic aspect when evaluating the success of treatment programs. Identifying modifiable factors that lead to LTFU would be important if we are to design effective retention interventions. The purpose of this study was to identify the challenges faced by children seeking care and treatment at a large HIV Clinic in Botswana. In order to identify those factors, we used mixed methods from different sources of information available at the Baylor Clinic. The first method involved a case-control study through which we interviewed a select representation of children 1-18 years who, at some point in time, have attended clinic at Baylor Clinic in Gaborone, Botswana. We document this in detail using the first journal article. We defined LTFU as patients who had not attended clinic for more than 6 months at the onset of the study; the comparison group was recruited from among those who have attended clinic at any point in the 6 months leading to the start of study. Factors were compared between the cases and controls. The second methodology involved conducting in-depth interviews with health providers to elicit their opinions and experiences dealing with patients at the at the Baylor clinic in general and the LTFU patients in particular. We document this methodology and its findings in the second journal article. ^ We found that most patients that are LTFU failed to engage with the clinic. Most of the LTFU made only one visit to the clinic (47.66%) as compared to less than 1% in the control group (P<0.01, 2-tailed Fisher's exact test). Among the interviewed patients, psychosocial factors such as stigma, religious beliefs, child rebellion and disclosure of HIV status concerns were characteristic of the LTFU population, but psychosocial issues were not cited among the comparison group. We also found that these psychosocial aspects of the patients point towards a bigger problem of mental health that needs to be addressed. Socioeconomic factors such as lack of transport, school-related activities and forgetting check-up dates were cited predominantly by the controls than cases. ^ From these findings, there is need to target interventions towards engaging pediatric patients at their initial clinic visit. Such interventions would focus on psychosocial support, as well as involving faith-based organizations in planning joint responses.^

Application of Independent Components Analysis with the JADE algorithm and NIR hyperspectral imaging for revealing food adulteration

In recent years, Independent Components Analysis (ICA) has proven itself to be a powerful signal-processing technique for solving the Blind-Source Separation (BSS) problems in different scientific domains. In the present work, an application of ICA for processing NIR hyperspectral images to detect traces of peanut in wheat flour is presented. Processing was performed without a priori knowledge of the chemical composition of the two food materials. The aim was to extract the source signals of the different chemical components from the initial data set and to use them in order to determine the distribution of peanut traces in the hyperspectral images. To determine the optimal number of independent component to be extracted, the Random ICA by blocks method was used. This method is based on the repeated calculation of several models using an increasing number of independent components after randomly segmenting the matrix data into two blocks and then calculating the correlations between the signals extracted from the two blocks. The extracted ICA signals were interpreted and their ability to classify peanut and wheat flour was studied. Finally, all the extracted ICs were used to construct a single synthetic signal that could be used directly with the hyperspectral images to enhance the contrast between the peanut and the wheat flours in a real multi-use industrial environment. Furthermore, feature extraction methods (connected components labelling algorithm followed by flood fill method to extract object contours) were applied in order to target the spatial location of the presence of peanut traces. A good visualization of the distributions of peanut traces was thus obtained

4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor γ

The estrogen-related receptors (ERRα, ERRβ, and ERRγ) form a family of orphan nuclear receptors that share significant amino acid identity with the estrogen receptors, but for which physiologic roles remain largely unknown. By using a peptide sensor assay, we have identified the stilbenes diethylstilbestrol (DES), tamoxifen (TAM), and 4-hydroxytamoxifen (4-OHT) as high-affinity ligands for ERRγ. In direct binding assays, 4-OHT had a Kd value of 35 nM, and both DES and TAM displaced radiolabeled 4-OHT with Ki values of 870 nM. In cell-based assays, 4-OHT binding caused a dissociation of the complex between ERRγ and the steroid receptor coactivator-1, and led to an inhibition of the constitutive transcriptional activity of ERRγ. ERRα did not bind 4-OHT, but replacing a single amino acid predicted to be in the ERRα ligand-binding pocket with the corresponding ERRγ residue allowed high-affinity 4-OHT binding. These results demonstrate the existence of high-affinity ligands for the ERR family of orphan receptors, and identify 4-OHT as a molecule that can regulate the transcriptional activity of ERRγ.

The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1.

The transmembrane protein-tyrosine-phosphatases (PTPases) LAR, PTP delta, and PTP sigma each contain two intracellular PTPase domains and an extracellular region consisting of Ig-like and fibronectin type III-like domains. We describe the cloning and characterization of human PTP sigma (HPTP sigma) and compare the structure, alternative splicing, tissue distribution, and PTPase activity of LAR, HPTP delta, and HPTP sigma, as well their ability to associate with the intracellular coiled-coil LAR-interacting protein LIP.1. Overall, these three PTPases are structurally very similar, sharing 64% amino acid identity. Multiple isoforms of LAR, HPTP delta, and HPTP sigma appear to be generated by tissue-specific alternative splicing of up to four mini-exon segments that encode peptides of 4-16 aa located in both the extracellular and intracellular regions. Alternative usage of these peptides varies depending on the tissue mRNA analyzed. Short isoforms of both HPTP sigma and HPTP delta were also detected that contain only four of the eight fibronectin type III-like domains. Northern blot analysis indicates that LAR and HPTP sigma are broadly distributed whereas HPTP delta expression is largely restricted to brain, as is the short HPTP sigma isoform containing only four fibronectin type III-like domains. LAR, HPTP delta, and HPTP sigma exhibit similar in vitro PTPase activities and all three interact with LIP.1, which has been postulated to recruit LAR to focal adhesions. Thus, these closely related PTPases may perform similar functions in various tissues.

Rethinking Migration Distribution in the EU: Shall we start with the facts? CEPS Essay 23/22 January 2016

Sound policy-making about migration –how to distribute responsibility for asylum seekers, how to deal with the issue of secondary movement (when asylum seekers move from one state to another within the EU) and whether migrants are welcome or not – needs to be based on solid evidence. On 16 November 2015, EUROSTAT published comprehensive statistics on the issue of first-residence permits by member states. This CEPS Essay closely examines these data and reports some surprising findings, some of which vary considerably from the impression promoted by the European media.

The correspondence between the commissioners of the state of So. Ca. to the government at Washington and the President of the United States; together with the statement of Messrs. Miles and Keitt. Printed by order of the Convention.

Commissioners: R.W. Barnwell, J.H. Adams, James L. Orr.

Plaque with the Journey to Emmaus and Noli Me Tangere

Ivory, Spanish, 12C; 10 5/8 in.x 5 9/32 in.x 3/4 in.; ivory, traces of gilding

Plaque with the Journey to Emmaus and Noli Me Tangere: top

Ivory, Spanish, 12C; ivory, traces of gilding