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OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.
This article presents a novel analysis of Negative Auxiliary Inversion (NAI) constructions such as didn't many people eat, in which a negated auxiliary appears in pre-subject position. NAI, found in varieties including Appalachian, African American, and West Texas English, has a word order identical to a yes/no question, but is pronounced and interpreted as a declarative. We propose that NAI subjects are negative DPs, and that the negation raises from the subject DP to adjoin to Fin (a functional head in the left periphery). Three properties of NAI motivate this analysis: (i) scope freezing effects, (ii) the various possible and impossible NAI subject types, and (iii) the incompatibility of NAI constructions with true Double-Negation interpretations. Implications for theories of Negative Concord, Negative Polarity Items, and the representation of negation are discussed.
Collins & Postal (2014) argue that English NPIs have two distinct syntactic structures: a unary NEG structure and a binary NEG structure. They suggest that this distinction is generally valid for natural languages. This formal difference was taken to reconstruct the common distinction in NPI studies between strong and weak NPIs. The present analysis of Ewe NPIs seeks to provide cross-linguistic support for this dual conception of NPIs by showing that the ke-NPIs in this language are all properly analyzed exclusively as unary NEG structures.
Collins and Postal (2014) postulate that English NPIs represent two distinct structures: a unary NEG structure and a binary NEG structure. Some NPIs, such as any and ever expressions, can instantiate either of these two structures in different contexts. Others (such as one use of jackshit) have only unary NEG structures. The present article seeks to provide cross-linguistic support for this hypothesis by showing that the two series of NPIs in Serbian/Croatian (Progovac 1994) should be analyzed in terms of the two structure types postulated for English NPIs.
Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.
Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.
While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.
This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.
Overwintered cover crops mechanically terminated into mulch can be a weed management tool for reduced-tillage organic agriculture. However, the impacts of management options for cover cropping are not well understood, including cover crop variety, termination timing and termination method. In a field experiment, conducted in 2012 and 2013 in Western Washington, we examined three grains, four vetches and one barley–vetch mix terminated with two mechanical methods and at two different times. We determined the influence of cover crop variety and termination time on cover crop biomass production and tissue nitrogen (N), effectiveness of cover crop termination, soil nitrate–N and percent weed cover. We also determined the influence of termination method on percent weed cover. Cover crop biomass ranged between 3 and 9 Mg ha−1 and was not influenced by termination time; the greatest production was from three varieties of grain. Rye varieties were more effectively terminated with a roller–crimper than barley. Mean soil nitrate–N levels ranged from 1.9 to 18 mg kg−1 and were the greatest with vetches. Post-termination weed cover was greater in 2013 than in 2012 and the cover crop variety influenced weed cover at the Late termination time only. Neither plant N concentration in the cover crop mulch nor soil nitrate influenced weed cover. The results of this study indicate that cover crop biomass and termination timing are important factors influencing weed cover and termination effectiveness in cover crop mulch.
Claims of a significant underdensity or void in the density distribution on scales out to ≃ 300 Mpc have recently been made using samples of galaxies. We present the results of an alternative test of the matter distribution on these scales using clusters of galaxies, which provide an independent and powerful probe of large-scale structure. We study the density distribution of X-ray clusters from the ROSAT-based REFLEX II catalogue, which covers a contiguous area of 4.24 steradians in the southern hempsphere (34% of the entire sky). Using the normalised comoving number density of clusters we find evidence for an underdensity (30-40%), out to z∼ 0.04, equivalent to ≃170 Mpc and with a significance of 3.4σ. On scales between 300 Mpc and 1 Gpc the distribution of REFLEX II clusters is consistent with being uniform. We also confirm recent results that the underdensity has a large contribution from the direction of the South Galactic Cap region, but is not significant in the direction of the Northern Galactic Cap as viewed from the southern sky. Both the limited size of the detected underdensity and its lack of isotropy, argue against the idea that the Type Ia supernovae data can be explained without the need for dark energy.
Small scale explosively driven fragmentation experiments have been performed on Aluminum (Al)-Tungsten (W) granular composite rings processed using cold isostatic compression of Al and W powders with a particle size of 4-30 microns. Fragments collected from the experiments had a maximum size of the order of a few hundred micrometers. This is a dramatic reduction in the fragment size when compared to the 1-10 mm typical for a homogeneous material such as solid aluminum under similar loading conditions. Numerical simulations of the experiment were performed to elucidate the mechanisms of fragmentation that were responsible for this shift in fragmentation size scales. Simulations were performed with a significantly stronger explosive driver to examine how the mechanisms of fragmentation change when the detonation pressure increases.
The Security Needs Assessment Profile (SNAP) was developed to provide a detailed description of individual patient's security requirements in the then Trent Region of England. A national survey of secure units was undertaken to examine the content validity of the item structure of SNAP and revise the item definitions to reflect more broadly based clinical practice. A follow-up survey sought views on the usefulness of SNAP in clinical practice.
Thirty-five secure units from National Health Service and independent sector providers participated. No new security items were generated. All the item definitions were reviewed, many amended, and a small number revised extensively. Units' security profiles were rated on the original and revised instruments.
The revised SNAP has been shown to be generalisable across secure services in England; 92% of respondents agreed or strongly agreed that SNAP would be useful in providing a structured security needs assessment.
This chapter provides an overview of Earth system models, the various model ‘flavours’, their state of development including model evaluation, benchmarking and optimization against observational data and their application to climate change issues.
The Earth system can be conceptualized as a suite of interacting physical, chemical, biological and anthropogenic processes that regulate the planet’s low of matter and energy. Earth system models (ESMs; Box 5.1 ) are built to mirror these processes. In fact, ESMs are the only tool available to the scientific community to investigate the system properties of the Earth, as we do not have an alternative planet to manipulate that could serve as a scientist’s laboratory.
The term ‘Earth system model’ is commonly used to describe coupled land–ocean–atmosphere models that include interactive biogeochemical components. Such models have developed progressively from the physical climate models first created in the 1960s and 1970s. Conventional climate models apply physical laws to simulate the general circulation of atmosphere and ocean. As our understanding of the natural and anthropogenic controls on climate has grown, and given the steady advances in computing power, global climate models have been extended to include more comprehensive representations of biological and geochemical processes, involving the addition of the various interacting components of the Earth system with their own feedback mechanisms. Figure 5.1 shows the conceptual differences between a conventional global coupled atmosphere–ocean general circulation model (AOGCM) and an ESM. In terms of the coupling between components, ESMs are more complex, and they have correspondingly higher computational demands.
A large fraction of the stellar mass in galaxy clusters is thought to be contained in the diffuse low surface brightness intracluster light (ICL). Being bound to the gravitational potential of the cluster rather than any individual galaxy, the ICL contains much information about the evolution of its host cluster and the interactions between the galaxies within. However due its low surface brightness it is notoriously difficult to study. We present the first detection and measurement of the flux contained in the ICL at z ~ 1. We find that the fraction of the total cluster light contained in the ICL may have increased by factors of 2–4 since z ~ 1, in contrast to recent findings for the lack of mass and scale size evolution found for brightest cluster galaxies. Our results suggest that late time build-up in cluster cores may occur more through stripping than merging and we discuss the implications of our results for hierarchical simulations.
There is considerable evidence that pro-cholinergic agents can cause depressed mood. However, there are also published case reports of a rare association between cholinesterase inhibitors and mood elevation in patients with pre-existing major functional psychiatric disorders, or organic disorders other than dementia. This report adds to the literature by describing a case of mood elevation in a patient without pre-existing psychiatric disorder.
This paper describes the consonant inventory of the endangered southern African language Nǀuu. Our novel approach to segment classification accounts for all 73 Nǀuu consonants with just four phonetic dimensions (place, manner, phonation, airstream) and does away with the phonetically empty category click accompaniment. We provide ultrasound data showing that the posterior constrictions in clicks are not produced at the ‘velar’ place of articulation, and that posterior place differs with anterior place. We therefore argue for a terminological shift from velaric to lingual airstream mechanism. Our data also show that the posterior place of articulation is the same in Nǀuu's five lingual ([⊙ ǀ ǃ ǁ ǂ]) and linguo-pulmonic () stops. We argue that the difference between these segment classes is best captured in terms of airstream, not place. Plain clicks use only the lingual airstream, while linguo-pulmonic segments are airstream contours, in which the transition to the pulmonic airstream occurs within the segment rather than at its boundary. Our evidence suggests that the contrast between ‘velar’ and ‘uvular’ clicks proposed for the related language ǃXóõ is likely also one of airstream and that a contrast solely in terms of posterior place would be articulatorily impossible.
This article challenges two tenets of Falla scholarship: that the composer made use of a system of chord generation based on the harmonic series, and that he learnt this technique from Louis Lucas's L'acoustique nouvelle (Paris, 1854). The author demonstrates that Lucas's theories are largely unconcerned with the harmonic series and that Falla's use of ‘natural resonance’ has been misunderstood. Study of Falla's work, including manuscripts and writings (published and unpublished), reveals the true nature of Lucas's influence. Consideration is also given to Falla's role in the creation of this false orthodoxy.
Dementia with Lewy bodies (DLB) is a common cause of the dementia syndrome. Symptomatic treatment of the fluctuating cognition, visual hallucinations, and sleep distrubance that characterize this condition is challenging; neuroleptics are relatively contraindicated. We describe eight patients fulfilling the consensus diagnostic criteria for probable DLB who were treated with rivastigmine. Clinical features rated were: cognition by the Modified Mini-Mental State Examination (3MS); and behavioral and psychiatric symptoms by the Neuropsychiatric Inventory (NPI). Additional information was obtained from family and nursing reports. Seven patients showed resolution or improvement in cognition and neuropsychiatric symptoms as demonstrated by improvement in their 3MS and NPI scores. They also became more independent in mobility and activities of daily living, and the majority returned to live in their own home. Of the seven patients with sleep disruption, six improved. One case had no improvement in his symptomatology and the rivastigmine was stopped. Outcomes in this case series suggest that rivastigmine is well tolerated in clinical practice.
Contrary to common belief the technology associated with components and systems for operation in the millimetre and submillimetre or Terahertz (THz) region of the electromagnetic spectrum is mature. However, it has largely been developed for use in the fields of radio astronomy and remote sensing, two areas where size and cost have not been the driving issues. This is changing, both fields now have ambitious plans to put large complex systems into space in experiments such as NASA'a EOS MLS and ESA'a FIRST amongst others. Also, ground based systems such as ALMA are planned where the total number of receivers exceeds 1000. For such instruments cost and size now becomes important. Taking these factors into account for the last decade or so there has been a concerted drive towards smaller and cheaper instrumentation. Initially, the use of quasi-optical systems was implemented in place of waveguide mainly because of its prohibitive manufacturing cost. Quas-ioptical systems are still being developed but waveguide has recently seen a revival due to the use of new micromachining techniques for its fabrication. Planar or integrated circuitry mounted in waveguide has now demonstrated state of the art performance to 2.5THz. Combining these factors means that for the first time the cost of manufacturing high performance RF electronics in the THz region has finally become affordable thereby making it available to new areas of research, material science is one of many. This paper describes how new devices and systems may be implemented to realise the basic building blocks of such instrumentation, namely, detectors and sources.
We present an overview of recent results for hydrogen interactions with amorphous silicon (a-Si), based on first- principles calculations. We review the current understanding regarding molecular hydrogen, and show that H2 molecules are far less inert than previously assumed. We then discuss results for motion of hydrogen through the material, as relating to diffusion and defect formation. We present a microscopic mechanism for hydrogen-hydrogen exchange, and examine the metastable ≠ SiH2 complex formed during the exchange process. We also discuss the enhanced stability of Si-D compared to Si-H bonds, which may provide a means of suppressing light-induced defect generation.
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