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Instrumental variable (IV) methods are widely used to address endogeneity concerns. Yet, a specific kind of endogeneity – spatial interdependence – is regularly ignored. We show that ignoring spatial interdependence in the outcome results in asymptotically biased estimates even when instruments are randomly assigned. The extent of this bias increases when the instrument is also spatially clustered, as is the case for many widely used instruments: rainfall, natural disasters, economic shocks, and regionally- or globally-weighted averages. Because the biases due to spatial interdependence and predictor endogeneity can offset, addressing only one can increase the bias relative to ordinary least squares. We demonstrate the extent of these biases both analytically and via Monte Carlo simulation. Finally, we discuss a general estimation strategy – S-2SLS – that accounts for both outcome interdependence and predictor endogeneity, thereby recovering consistent estimates of predictor effects.
Instruments based on realizations of the endogenous variable in other units—for instance, regional or global weighted averages—are commonly used in political science. Such spatial instruments have proved attractive: they are convenient to obtain, typically have power, and are plausibly exogenous. We argue that the assumptions underlying spatial instruments remain poorly understood and challenge whether spatial instruments can satisfy the conditions required for valid instruments. First, when cross-unit dependence exists in the endogenous predictor, other cross-unit relationships—spillovers and interdependence—likely exist as well and risk violations of the exclusion restriction. Second, spatial instruments produce simultaneity in the first-stage equation, as left-hand side outcomes are included as right-hand side predictors. Because the instrument and the endogenous variable are simultaneously determined, the exclusion restriction is, necessarily and by construction, violated. Taken together, these concerns lead us to conclude that spatial instruments are rarely, if ever, valid.
200 μm thick solution annealed AISI 316L stainless steel foils were implanted with Ar ions to produce a 0.25 at. % concentration-depth plateau extending from the near surface to a depth of ≈ 250 nm, and then annealed at 550°C for 2 hours to form small Ar bubbles and Ar-vacancy clusters. Distinct sets of samples (including control ones without Ar) were irradiated at the temperature of 550 °C with Au ions accelerated at 5 MeV to produce an average damage content about ≈36 dpa at the region containing the Ar plateau. These samples were investigated by transmission electron microscopy using plan-view specimens prepared by ion milling. In contrast with the control samples where the irradiation causes the formation of a high concentration of extended defects and large cavities, carbonite precipitation of 1:1 metal-carbon (MC) content with a cubic structure occurs only in the samples containing the Ar bubbles. This precipitation phenomenon is not commonly observed in the literature. The results are interpreted considering that the precipitate growth process requires the emission of vacancies which are synergistically absorbed by the growth of the Ar bubbles.
A Movement Disorder Society (MDS) taskforce recently proposed diagnostic criteria for Parkinson’s disease with features of mild cognitive impairment (PD-MCI). This study first examined the prevalence and nature of PD-MCI in a non-demented cohort using the MDS criteria. Using the generic Monte Carlo simulation method developed by Crawford and colleagues (2007), this study then estimated the base rate of the representative population who would demonstrate PD-MCI due to chance alone. A total of 104 participants with idiopathic PD underwent extensive motor and neuropsychological testing at baseline and 2 years later. The Unified Parkinson’s Disease Rating Scale (UPDRS) was used to assess motor symptoms of PD and a range of established neuropsychological tests was used to assess PD-MCI in accord with MDS criteria. In accord with MDS criteria, 38% of this cohort demonstrated PD-MCI at baseline and 48% at follow-up. Of the 36 participants in the multiple-domain PD-MCI subtype at time-1, 9 (25%) demonstrated no PD-MCI at follow up. Analysis revealed that approximately 13% of the representative population would demonstrate abnormally low scores for 2 of the 9 tests used, thereby meeting MDS criteria for PD-MCI. Clinicians and researchers need to approach a single diagnosis (i.e., based on one assessment) of PD-MCI with considerable caution. (JINS, 2015, 21, 137–145)
Chagas’ disease is a neglected tropical disease caused by Trypanosoma cruzi and constitutes a serious public health problem for Latin America. Its unsatisfactory chemotherapy stimulates the search for novel antiparasitic compounds. Amidines and related compounds exhibit well-known activity towards different microbes including T. cruzi. In this vein, our present aim was to evaluate the biological effect of 10 novel structurally related amidines in vitro against bloodstream and intracellular forms of the parasite as well as their potential toxicity on cardiac cell cultures. Our results show that although active against the extracellular forms, with some of them like DB2247 being 6-fold more effective than benznidazole and displaying very low toxicity (>96 μm), none presented superior trypanocidal effect against intracellular forms as compared with the reference drug. These results may be due to differences in susceptibility profiles related to distinct uptake/extrusion mechanisms and cellular targets between bloodstream and amastigote forms. The present study adds to the knowledge base for the future design of novel amidines that may provide promising activity against T. cruzi.
Little research has addressed the impacts of invasive-species establishment on native forest insect communities. Such information is lacking even for gypsy moth, Lymantria dispar (L.) (Lepidoptera: Erebidae), the most thoroughly studied invasive forest insect. We investigated the ecological impacts of gypsy moth on native species at sites in north-central Ontario, Canada, with and without significant histories of gypsy moth defoliation over a 2-year period. Patterns in native forest caterpillar communities are described using measures of species diversity and multivariate analysis. We documented a transition from low-level to dominant gypsy moth populations. Sites with different gypsy moth outbreak histories exhibited differences in rank-abundance distributions and dominance structures in the first year of the study; by the second year, gypsy moth was dominant at sites of both types irrespective of their previous defoliation history. Contrary to our predictions, we found that gypsy moth outbreak history had no significant effects on native caterpillar community diversity or structure. However, sites with currently high gypsy moth abundance demonstrated significant shifts in late-season caterpillar community structure. Our results suggest that observed community differences were due to the presence of a highly abundant folivore, and not to permanent shifts in the native community because of the introduction of an invasive species.
We present observational and theoretical studies constraining Type Ia supernova progenitors.
First, we use a new observational technique to show that “prompt” SNe Ia that trace star-formation on cosmic timescales exhibit a significant delay time of 200-500 million years. This implies that either the majority of SNe Ia companion stars have main-sequence masses less than three solar masses, or that most SNe Ia arise from double-white dwarf binaries.
Second we present a comprehensive study of white dwarf collisions as an avenue for creating SNe Ia. Using a smooth particle hydrodynamics code with a 13-isotope nuclear network, we show that several combinations of white dwarf masses and impact parameters produce enough 56Ni to result in luminosities ranging from those of sub-luminous to super-luminous SNe Ia, depending on the parameters of the collision.
Finally, we conduct a simulation survey of double-degenerate white dwarf mergers with varying mass combinations. Unlike previous works, we do not add detonations by hand to our simulations, and we do not find any thermonuclear explosions during the mergers. Instead, all but one of our simulations forms a cold, degenerate core surrounded by a hot disk, while our least massive pair of stars forms only a hot disk. We characterize the remnants by core mass, rotational velocity, and half-mass radius, and discuss how we will evolve them further with simulations that incorporate dissipative processes. Such simulations may indeed lead to double-degenerate Type Ia explosions that occur many orbits after the mergers themselves.
We have begun new studies of the evolution of thermonuclear runaways (TNRs) in the accreted envelopes of white dwarfs (WDs). Here we focus on the recent outbursts of RS Oph (2006), U Sco (2010) and T Pyx (2011). U Sco explodes about every 10 years and the ejected material from the WD is helium rich. It has a short orbital period for recurrent novae (RNe) but the secondary is likely to be evolved. The WD is thought to be close in mass to the Chandrasekhar limit. T Pyx has just suffered its first outburst since 1966 and it was predicted to never experience another outburst. It has a short orbital period and has formed dust in the ejecta as this paper was being written. One important question is the secular evolution of the WD. Do the repeated outbursts cause the WD to gain or lose mass? If it is gaining mass, it could eventually reach the Chandrasekhar limit and become a Type Ia supernova (SNe Ia) if it can hide the hydrogen and helium in the system. Here, we report on our latest studies of TNRs in accreted envelopes on WDs using a variety of initial WD masses, luminosities, and mass accretion rates. Of great importance to our conclusions, we assume a solar composition (Lodders abundance distribution). We use our 1-D hydro code, NOVA, that includes the Hix and Thielemann nuclear reaction network, the Iliadis reaction rate library, the Timmes equation of state, OPAL opacities, and the new convection of Arnett, Meakin, and Young. We report on the amount of ejected mass, evolution time to explode, and whether or not the WD is growing or losing mass.
PbTe-based thermoelectric (TE) materials exhibit promising thermoelectric properties and have potential applications in waste heat recovery from sources such as truck engines and shipboard engines. TE components designed for these applications will be subject to mechanical/thermal loading and vibration as a result from in-service conditions, including mechanical vibration, mechanical and/or thermal cycling, and thermal shock.
In the current study, we present and discuss the mechanical properties of several PbTe-based compositions with different dopants and processing methods, including n-type and p-type specimens fabricated both by casting and by powder processing. Room temperature hardness and Young's modulus are studied by Vickers indentation and nanoindentation while fracture strength is obtained by biaxial flexure testing. Temperature dependent Young's modulus, shear modulus, and Poisson's ratio are studied via resonant ultrasound spectroscopy (RUS).
Electron backscatter diffraction (EBSD) analysis of monazite requires a comparison of empirically collected electron backscatter patterns (EBSPs) with theoretical diffraction data, or ‘match units’, derived from known crystallographic parameters. Published crystallographic data derived from compositionally varying natural and synthetic monazite are used to calculate ten different match units for monazite. These match units are used to systematically index EBSPs obtained from four natural monazite samples with different compositions. Analyses of EBSD data, derived from the indexing of five and six diffraction bands using each of the ten match units for 10,000 EBSPs from each of the four samples, indicate a large variation in the ability of the different match units to correctly index the different natural samples. However, the use of match units derived from either synthetic Gd or Eu monazite crystallographic data yield good results for three of the four analysed monazites. Comparison of sample composition with published monazite compositions indicates that these match units are likely to yield good results for the EBSD analysis of metamorphic monazite. The results provide a clear strategy for optimizing the acquisition and analysis of EBSD data from monazite but also indicate the need for the collection of new crystallographic structure data and the subsequent generation of more appropriate match units for natural monazite.
An extensive serological survey for rinderpest antibody in wildlife, principally buffalo (Syncerus caffer), and sheep and goats has been undertaken in the previously endemic region of Northern Tanzania to determine whether or not the virus has continued to cycle in susceptible species since the last occurrence of overt disease in 1982. The results show that infection but not disease has occurred at least until 1987 in buffalo in parts of the Serengeti National Park but not in the other game areas of Tanzania where samples were taken. Sero-positive sheep and goats were widely distributed and have been found in 10 of the 14 districts sampled but there have been no reports of disease. These findings bring into question the possibility of eradicating the disease from Africa and continuous annual monitoring of this and other similar ecological zones will be required.
This paper describes a new application for radiofrequency ablation in head and neck surgery. Two patients with extensive laryngeal papillomata were successfully treated using this technology. The technique is described in detail, highlighting the main benefits of this approach as compared with existing techniques. These advantages include limited damage to underlying tissues and a bloodless field.
S. Starrfield, Department of Physics and Astronomy, ASU, Tempe, AZ 85287–1504,
S. Dwyer, Department of Physics and Astronomy, ASU, Tempe, AZ 85287–1504,
F. X. Timmes, Center for Astrophysical Thermonuclear Flashes, University of Chicago, Chicago, IL 60637,
W. R. Hix, Physics Division, ORNL, Oak Ridge, TN 37831,
E. M. Sion, Department of Astronomy, Villanova University, Villanova, PA,
W. M. Sparks, X-4, LANL, Los Alamos, NM, 87545
The assumption commonly made is that Supernovae of Type Ia (SN Ia) are the result of thermonuclear runaways (TNR) in the cores of carbon-oxygen white dwarfs (WD) which are members of binary systems and have accreted material from a companion until their masses exceed the Chandrasekhar Limit (Leibundgut 2000, 2001). However, the binary star systems that end in this explosion are not yet known although there have been numerous proposals. Nevertheless, the importance of SN Ia, both to our understanding of the evolution of the Universe and to the formation of iron in the Galaxy, demands that we determine the progenitors of these explosions.
Originally proposed by Whelan and Iben (1973), virtually every type of close binary which contains a WD has been suggested at one time or another. However, based purely on observational concerns, most of the systems that have been proposed cannot be the progenitors (Starrfield 2003). For example, one of the first suggestions was a classical nova system (CN), but the amount of core material ejected during the outburst implies strongly that the WD is losing mass as a result of the outburst (Gehrz et al. 1998). Other suggestions such as Symbiotic Novae (T CrB or RS Oph, for example) can probably be ruled out.because there is too much hydrogen present in the system (the explosion takes place inside the outer layers of a red giant) and the defining characteristic of a SN Ia outburst is the absence of hydrogen in the spectrum (Filippenko 1997).
Twenty-nine patients (16 males, 13 females) with Joubert syndrome were identified from ophthalmology, neurology, and genetic databases covering a 15-year period at Great Ormond Street Hospital, London. Criteria for diagnosis included absent or markedly hypoplastic cerebellar vermis, abnormal eye movements, and developmental delay. Five patients had died. Scans and notes were available for 22 patients, and 18 cases were clinically reviewed. The median age was 10 years 10 months (range 3mo to 19y) and the median follow-up was 8 years 5 months (range 3mo to 19y, with one new patient seen at 3mo of age). Cerebellar vermis hypoplasia/aplasia with ‘molar tooth sign’ in the axial plane was present in 22 of 22 patients, coloboma in 6 of 22, and polydactyly in 6 of 22. In the 18 clinically reviewed, apnoea occurred in 13 patients. Five had renal problems with cysts and 4 of 5 had abnormal electroretinograms (ERGs). Visual electrophysiology was abnormal in 14 of 18 patients, and in 6 there was evidence of deterioration in the ERG. Blood investigations of organic acids, phytanic acid, very-long-chain fatty acid, and transferrin were normal in 12 patients tested. Developmental assessment showed that 6 of 15 patients aged more than 5 years were at mainstream school, and 12 of 18 had started walking between 22 months and 10 years. Speech difficulties and behavioural problems were prominent.
The extracellular matrix (ECM) contains a variety of structural proteins which include collagens, proteoglycans and glycoproteins. These proteins act as a cellular ‘skeleton’ allowing cell to cell interactions.
Physiologically, matrix remodelling requires the synthesis of matrix which is balanced by degradation mediated via the production of active matrix metalloproteinases (MMPs). When this balance of synthesis and degradation is uncontrolled, inadequate or increased amounts of ECM are deposited. Reduced levels of matrix are associated with unstable angina whereas elevated levels of matrix are found in alcoholic cirrhosis, pulmonary fibrosis and left ventricular hypertrophy (LVH).
To date, 17 MMPs have been characterized (Table 37.1). MMPs were originally classified in terms of their substrate specificity, but this view has now been superseded and a numbering system introduced when it was appreciated that each MMP could hydrolyse a variety of substrates, including the degradation of other MMPs.
MMPs have a variety of domains, but all MMPs share three: (i) a predomain which targets the MMP for extracellular excretion; (ii) a prodomain which maintains the MMP in an inactive form called the proMMP; and (iii) a zinc-dependent catalytic domain which becomes activated on hydrolysis of the prodomain. With the exception of MMP7, all the MMPs have a haemopexin domain which enhances the binding of substrates and inhibitors. MMPs contain two conserved motifs: the prodomain and catalytic domain. MMP14, 15, 16 and 17 have a transmembrane domain and MMP14 activates proMMP2 into its biologically active form .