Quantile Models with Endogeneity

In this article, we review quantile models with endogeneity. We focus on models that achieve identification through the use of instrumental variables and discuss conditions under which partial and point identification are obtained. We discuss key conditions, which include monotonicity and full-rank-type conditions, in detail. In providing this review, we update the identification results of Chernozhukov & Hansen (2005). We illustrate the modeling assumptions through economically motivated examples. We also briefly review the literature on estimation and inference

Optical Structural Analysis of Individual alpha-Synuclein Oligomers

Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species have proved difficult to study due to the lack of suitable methods capable of resolving these heterogeneous aggregates, which are smaller than the optical diffraction limit. We demonstrate here an all‐optical fluorescence microscopy method to characterise the structure of individual protein aggregates based on the fluorescence anisotropy of dyes such as thioflavin‐T, and show that this technology is capable of studying oligomers in human biofluids such as cerebrospinal fluid. We first investigated in vitro the structural changes in individual oligomers formed during the aggregation of recombinant α‐synuclein. By studying the diffraction‐limited aggregates we directly evaluated their structural conversion and correlated this with the potential of aggregates to disrupt lipid bilayers. We finally characterised the structural features of aggregates present in cerebrospinal fluid of Parkinson's disease patients and age‐matched healthy controls

High Energy Neutrino Astronomy: Towards Kilometer-Scale Detectors

Of all high-energy particles, only neutrinos can directly convey astronomical information from the edge of the universe---and from deep inside the most cataclysmic high-energy processes. Copiously produced in high-energy collisions, travelling at the velocity of light, and not deflected by magnetic fields, neutrinos meet the basic requirements for astronomy. Their unique advantage arises from a fundamental property: they are affected only by the weakest of nature's forces (but for gravity) and are therefore essentially unabsorbed as they travel cosmological distances between their origin and us. Many of the outstanding mysteries of astrophysics may be hidden from our sight at all wavelengths of the electromagnetic spectrum because of absorption by matter and radiation between us and the source. For example, the hot dense regions that form the central engines of stars and galaxies are opaque to photons. In other cases, such as supernova remnants, gamma ray bursters, and active galaxies, all of which may involve compact objects or black holes at their cores, the precise origin of the high-energy photons emerging from their surface regions is uncertain. Therefore, data obtained through a variety of observational windows---and especially through direct observations with neutrinos---may be of cardinal importance. In this talk, the scientific goals of high energy neutrino astronomy and the technical aspects of water and ice Cherenkov detectors are examined, and future experimental possibilities, including a kilometer-square deep ice neutrino telescope, are explored.Comment: 13 pages, Latex, 6 postscript figures, uses aipproc.sty and epsf.sty. Talk presented at the International Symposium on High Energy Gamma Ray Astronomy, Heidelberg, June 200

Association between Knops blood group polymorphisms and susceptibility to malaria in an endemic area of the Brazilian Amazon

Complement receptor 1 (CR1) gene polymorphisms that are associated with Knops blood group antigens may influence the binding of Plasmodium parasites to erythrocytes, thereby affecting susceptibility to malaria. The aim of this study was to evaluate the genotype and allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) of Knops blood group antigens and examine their association with susceptibility to malaria in an endemic area of Brazil. One hundred and twenty-six individuals from the Brazilian Amazon were studied. The CR1-genomic fragment was amplified by PCR and six SNPs and haplotypes were identified after DNA sequence analysis. Allele and haplotype frequencies revealed that the Knb allele and H8 haplotype were possibly associated with susceptibility to Plasmodium falciparum. The odds ratios were reasonably high, suggesting a potentially important association between two Knops blood antigens (Knb and KAM+) that confer susceptibility to P. falciparum in individuals from the Brazilian Amazon

Health care use and costs of adverse drug events emerging from outpatient treatment in Germany: A modelling approach

<p>Abstract</p> <p>Background</p> <p>This study's aim was to develop a first quantification of the frequency and costs of adverse drug events (ADEs) originating in ambulatory medical practice in Germany.</p> <p>Methods</p> <p>The frequencies and costs of ADEs were quantified for a base case, building on an existing cost-of-illness model for ADEs. The model originates from the U.S. health care system, its structure of treatment probabilities linked to ADEs was transferred to Germany. Sensitivity analyses based on values determined from a literature review were used to test the postulated results.</p> <p>Results</p> <p>For Germany, the base case postulated that about 2 million adults ingesting medications have will have an ADE in 2007. Health care costs related to ADEs in this base case totalled 816 million Euros, mean costs per case were 381 Euros. About 58% of costs resulted from hospitalisations, 11% from emergency department visits and 21% from long-term care. Base case estimates of frequency and costs of ADEs were lower than all estimates of the sensitivity analyses.</p> <p>Discussion</p> <p>The postulated frequency and costs of ADEs illustrate the possible size of the health problems and economic burden related to ADEs in Germany. The validity of the U.S. treatment structure used remains to be determined for Germany. The sensitivity analysis used assumptions from different studies and thus further quantified the information gap in Germany regarding ADEs.</p> <p>Conclusions</p> <p>This study found costs of ADEs in the ambulatory setting in Germany to be significant. Due to data scarcity, results are only a rough indication.</p

Transmission of MDR and XDR Tuberculosis in Shanghai, China

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are global health problems. We sought to determine the characteristics, prevalence, and relative frequency of transmission of MDR and XDR TB in Shanghai, one of the largest cities in Asia. Methods: TB is diagnosed in district TB hospitals in Shanghai, China. Drug susceptibility testing for first-line drugs was performed for all culture positive TB cases, and tests for second-line drugs were performed for MDR cases. VNTR-7 and VNTR-16 were used to genotype the strains, and prior treatment history and treatment outcomes were determined for each patient. Results: There were 4,379 culture positive TB cases diagnosed with drug susceptibility test results available during March 2004 through November 2007. 247 (5.6%) were infected with a MDR strain of M. tuberculosis and 11 (6.3%) of the 175 MDR patients whose isolate was tested for susceptibility to second-line drugs, were XDR. More than half of the patients with MDR and XDR were newly diagnosed and had no prior history of TB treatment. Nearly 57 % of the patients with MDR were successfully treated. Discussion: Transmission of MDR and XDR strains is a serious problem in Shanghai. While a history of prior anti-TB treatment indicates which individuals may have acquired MDR or XDR TB, it does not accurately predict which TB patients have disease caused by transmission of MDR and XDR strains. Therefore, universal drug susceptibility testing i

Cost effectiveness of total knee arthroplasty from a health care providers' perspective before and after introduction of an interdisciplinary clinical pathway - is investment always improvement?

<p>Abstract</p> <p>Background</p> <p>Total knee arthroplasty (TKA) is an effective, but also cost-intensive health care intervention for end stage osteoarthritis. This investigation was designed to evaluate the cost-effectiveness of TKA before versus after introduction of an interdisciplinary clinical pathway from a University Orthopedic Surgery Department's cost perspective as an interdisciplinary full service health care provider.</p> <p>Methods</p> <p>A prospective trial recruited two sequential cohorts of 132 and 128 consecutive patients, who were interviewed by means of the WOMAC questionnaire. Direct process costs from the health care providers' perspective were estimated according to the German DRG calculation framework. The health economic evaluation was based on margiual cost-effectveness ratios (MCERs); an individual marginal cost effectiveness relation ≤ 100 € per % WOMAC index increase was considered as primary endpoint of the confirmatory cohort comparison. The interdisciplinary clinical pathway under consideration primarily consisted of a voluntary preoperative personal briefing of patients concerning postoperatively expectable progess in health status and optimum use of walking aids after surgery. All patients were supplied with written information on these topics, attendance of the personal briefing also included preoperative training for postoperative mobilisation by the Department's physiotherapeutic staff.</p> <p>Results</p> <p>An individual marginal cost effectiveness relation ≤ 100 €/% WOMAC index increase was found in 38% of the patients in the pre pathway implementation cohort versus in 30% of the post pathway implementation cohort (Fisher p = 0.278). Both cohorts showed substantial improvement in WOMAC scores (39 versus 35% in median), whereas the cohort did not differ significantly in the median WOMAC score before surgery (41% for the pre pathway cohort versus 44% for the post pathway cohort). Despite a locally significant decrease in costs (4303 versus 4194 € in median), the individual cost/benefit relation became worse after introduction of the pathway: for the first cohort the MCER was estimated 108 € per gained % WOMAC index increase (86 - 150 €/%) versus 118 €/% WOMAC gain (93 - 173 €/%) in the second cohort after pathway implementation. In summary, the proposed critical pathway for TKA could be shown to be significantly cost efficient, but not cost effective concerning functional outcome, when the above individual marginal cost effectiveness criterion was concentrated on.</p> <p>Conclusions</p> <p>The introduction of an interdisciplinary clinical pathway does not necessarily improve patient related outcomes. On the contrary, cost effectiveness from the health care providers' perspective may even turn out remarkably reduced in the setting considered here (functional outcome assessment after treatment by a full service health care provider).</p

The evolution of rapid optical/X-ray timing correlations in the initial hard state of MAXI J1820+070

We report on a multiepoch campaign of rapid optical/X-ray timing observations of the superbright 2018 outburst of MAXI J1820+070, a black hole low-mass X-ray binary system. The observations spanned 80 d in the initial hard state and were taken with NTT/ULTRACAM and GTC/HiPERCAM in the optical (usgsrsiszs filters at time resolutions of 8-300 Hz) and with ISS/NICER in X-rays. We find (i) a growing anticorrelation between the optical and X-ray light curves, (ii) a steady, positive correlation at an optical lag of ~0.2 s (with a longer lag at longer wavelengths) present in all epochs, and (iii) a curious positive correlation at negative optical lags in the last, X-ray softest epoch, with longer wavelengths showing a greater correlation and a more negative lag. To explain these, we postulate the possible existence of two synchrotron-emitting components - a compact jet and a hot flow. In our model, the significance of the jet decreases over the outburst, while the hot flow remains static (thus, relatively, increasing in significance). We also discuss a previously discovered quasi-periodic oscillation and note how it creates coherent optical time lags, stronger at longer wavelengths, during at least two epochs.</p

Identification of Limited English Proficient Patients in Clinical Care

BackgroundStandardized means to identify patients likely to benefit from language assistance are needed.ObjectiveTo evaluate the accuracy of the U.S. Census English proficiency question (Census-LEP) in predicting patients' ability to communicate effectively in English.DesignWe investigated the sensitivity and specificity of the Census-LEP alone or in combination with a question on preferred language for medical care for predicting patient-reported ability to discuss symptoms and understand physician recommendations in English.ParticipantsThree hundred and two patients &gt; 18 who spoke Spanish and/or English recruited from a cardiology clinic and an inpatient general medical-surgical ward in 2004-2005.ResultsOne hundred ninety-eight (66%) participants reported speaking English less than "very well" and 166 (55%) less than "well"; 157 (52%) preferred receiving their medical care in Spanish. Overall, 135 (45%) were able to discuss symptoms and 143 (48%) to understand physician recommendations in English. The Census-LEP with a high-threshold (less than "very well") had the highest sensitivity for predicting effective communication (100% Discuss; 98.7% Understand), but the lowest specificity (72.6% Discuss; 67.1% Understand). The composite measure of Census-LEP and preferred language for medical care provided a significant increase in specificity (91.9% Discuss; 83.9% Understand), with only a marginal decrease in sensitivity (99.4% Discuss; 96.7% Understand).ConclusionsUsing the Census-LEP item with a high-threshold of less than "very well" as a screening question, followed by a language preference for medical care question, is recommended for inclusive and accurate identification of patients likely to benefit from language assistance