Search

Arrestin-1, or visual arrestin, exhibits an exquisite selectivity for light-activated phosphorylated rhodopsin (P-Rh*) over its other functional forms. That selectivity is believed to be mediated by two well-established structural elements in the arrestin-1 molecule, the activation sensor detecting the active conformation of rhodopsin and the phosphorylation sensor responsive to the rhodopsin phosphorylation, which only active phosphorylated rhodopsin can engage simultaneously. However, in the crystal structure of the arrestin-1–rhodopsin complex there are arrestin-1 residues located close to rhodopsin, which do not belong to either sensor. Here we tested by site-directed mutagenesis the functional role of these residues in wild type arrestin-1 using a direct binding assay to P-Rh* and light-activated unphosphorylated rhodopsin (Rh*). We found that many mutations either enhanced the binding only to Rh* or increased the binding to Rh* much more than to P-Rh*. The data suggest that the native residues in these positions act as binding suppressors, specifically inhibiting the arrestin-1 binding to Rh* and thereby increasing arrestin-1 selectivity for P-Rh*. This calls for the modification of a widely accepted model of the arrestin–receptor interactions.

As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET.1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's discretion. The primary endpoint was pathologic partial response (pPR) and secondary endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Clinical benefit was defined as having a pPR or stable disease (SD) with NET.Overall, 94.4% of patients with genomically (g) Luminal A-Type (50.0% pPR and 44.4% SD) and 95.0% with Luminal B-Type tumors (55.0% pPR and 40.0% SD) exhibited clinical benefit. At 5 years, patients with gLuminal B tumors had significantly worse DMFS (75.6%, 95% CI 50.8-89.1) than patients with gLuminal A (91.1%; 95% CI 74.8-97.1; p = 0.047), with a similar trend for OS, albeit not significant (81.0%, 95% CI 56.9-92.4 and 91.1%, 95% CI 74.8-97.1, respectively; p = 0.13).Genomic assays offer a broader understanding of the underlying tumor biology, which adds precision to pathology as a preoperative risk classifier. Patients with 70-gene signature Low Risk, gLuminal A tumors treated with endocrine therapy alone have excellent 5-year outcomes. Most patients with genomically-defined Luminal A- and B-Type tumors respond well to NET, suggesting these patients may be safely treated with NET, while those with gLuminal B tumors will also require post-operative chemotherapy or CDK4/6 inhibitors to improve long-term outcomes. Overall, these findings demonstrate that genomic classification, defined by the combined 70- and 80-gene signatures, is associated with tumor response and prognostic of long-term outcomes.

A number of technologies would benefit from developing inorganic compounds and materials with specific electronic and magnetic exchange properties. Unfortunately, designing compounds with these properties is difficult because metal⋅⋅⋅metal coupling schemes are hard to predict and control. Fully characterizing communication between metals in existing compounds that exhibit interesting properties could provide valuable insight and advance those predictive capabilities. One such class of molecules are the series of Lindqvist iron-functionalized and hexavanadium polyoxovanadate-alkoxide clusters, which we characterized here using V K-edge X-ray absorption spectroscopy. Substantial changes in the pre-edge peak intensities were observed that tracked with the V 3d-electron count. The data also suggested substantial delocalization between the vanadium cations. Meanwhile, the FeIII cations were electronically isolated from the polyoxovanadate core.

Alkali atoms trapped in solid hydrogen matrices have demonstrated ultralong electron spin coherence times, and are promising as quantum sensors. Their spin coherence is limited by magnetic noise from naturally-occurring orthohydrogen molecules in the parahydrogen matrix. In the gas phase, the orthohydrogen component of hydrogen can be converted to parahydrogen by flowing it over a catalyst held at cryogenic temperatures, with lower temperatures giving a lower orthohydrogen fraction. In this work, we use a single cryostat to reduce the orthohydrogen fraction of hydrogen gas and grow a solid matrix from the resulting high-purity parahydrogen. We demonstrate operation of the catalyst down to a temperature of 8 K, and we spectroscopically verify that orthohydrogen impurities in the resulting solid are at a level < 1e-6. We also find that, at sufficiently low temperatures, the cryogenic catalyst provides isotopic purification, reducing the HD fraction., 7 pages, 8 figures

It is known from ensemble measurements that rubidium atoms trapped in solid parahydrogen have favorable properties for quantum sensing of magnetic fields. To use a single rubidium atom as a quantum sensor requires a technique capable of efficiently measuring the internal state of a single atom, such as laser-induced fluorescence. In this work we search for laser-induced fluorescence from ensembles of rubidium atoms trapped in solid parahydrogen and, separately, in solid neon. In parahydrogen we find no evidence of fluorescence over the range explored, and we place upper limits on the radiative branching ratio. In neon, we observe laser-induced fluorescence, measure the spectrum of the emitted light, and measure the excited-state lifetime in the matrix. Bleaching of atoms from the excitation light is also reported.

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

In this work, we measure the properties of ensembles of rubidium atoms trapped in solid neon that are relevant for use as quantum sensors of magnetic fields: the spin coherence of the trapped atoms and the ability to optically control and measure their spin state. We use the rubidium atoms as an AC magnetometer (by employing an appropriate dynamical decoupling sequence) and demonstrate NMR detection of Ne-21 atoms co-trapped in the neon matrix., Comment: 7 pages, 9 figures

Coherence time is an essential parameter for quantum sensing, quantum information, and quantum computation. In this work, we demonstrate electron spin coherence times as long as 0.1 s for an ensemble of rubidium atoms trapped in a solid parahydrogen matrix. We explore the underlying physics limiting the coherence time. The properties of these matrix isolated atoms are very promising for future applications, including quantum sensing of nuclear spins. If combined with efficient single-atom readout, this would enable NMR and magnetic resonance imaging of single molecules cotrapped with alkali-metal atom quantum sensors within a parahydrogen matrix.

We have produced a cryogenic buffer-gas cooled beam of the diatomic molecular radical CH (methylidyne). This molecule is of interest for studying cold chemical reactions and fundamental physics measurements. Its light mass and ground-state structure make it a promising candidate for electrostatic guiding and Stark deceleration, which allows for control over its kinetic energy. This control can facilitate studies of reactions with tuneable collision energies and trapping for precise spectroscopic studies. Here, we have demonstrated electrostatic guiding of CH with fluxes up to $10^9$ molecules per steradian per pulse, 10 pages, 10 figures

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Risk perception is an important construct in many health behavior theories. Smoking risk perceptions are thoughts and feelings about the harms associated with cigarette smoking. Wide variation in the terminology, definition, and assessment of this construct makes it difficult to draw conclusions about the associations of risk perceptions with smoking behaviors. To understand optimal methods of assessing adults’ cigarette smoking risk perceptions (among both smokers and nonsmokers), we reviewed best practices from the tobacco control literature, and where gaps were identified, we looked more broadly to the research on risk perceptions in other health domains. Based on this review, we suggest assessments of risk perceptions (1) about multiple smoking-related health harms, (2) about harms over a specific timeframe, and (3) for the person affected by the harm. For the measurement of perceived likelihood in particular (ie, the perceived chance of harm from smoking based largely on deliberative thought), we suggest including (4) unconditional and conditional items (stipulating smoking behavior) and (5) absolute and comparative items and including (6) comparisons to specific populations through (7) direct and indirect assessments. We also suggest including (8) experiential (ostensibly automatic, somatic perceptions of vulnerability to a harm) and affective (emotional reactions to a potential harm) risk perception items. We also offer suggestions for (9) response options and (10) the assessment of risk perception at multiple time points. Researchers can use this resource to inform the selection, use, and future development of smoking risk perception measures. Implications Incorporating the measurement suggestions for cigarette smoking risk perceptions that are presented will help researchers select items most appropriate for their research questions and will contribute to greater consistency in the assessment of smoking risk perceptions among adults.

We present a deep convolutional neural network for breast cancer screening exam classification, trained and evaluated on over 200,000 exams (over 1,000,000 images). Our network achieves an AUC of 0.895 in predicting whether there is a cancer in the breast, when tested on the screening population. We attribute the high accuracy of our model to a two-stage training procedure, which allows us to use a very high-capacity patch-level network to learn from pixel-level labels alongside a network learning from macroscopic breast-level labels. To validate our model, we conducted a reader study with 14 readers, each reading 720 screening mammogram exams, and find our model to be as accurate as experienced radiologists when presented with the same data. Finally, we show that a hybrid model, averaging probability of malignancy predicted by a radiologist with a prediction of our neural network, is more accurate than either of the two separately. To better understand our results, we conduct a thorough analysis of our network's performance on different subpopulations of the screening population, model design, training procedure, errors, and properties of its internal representations., Comment: MIDL 2019 [arXiv:1907.08612]

Cryogenic buffer-gas beams are important sources of cold molecules. In this work we explore the use of a converging-diverging nozzle with a buffer-gas beam. We find that, under appropriate circumstances, the use of a nozzle can produce a beam with improved collimation, lower transverse temperatures, and higher fluxes per solid angle.

We present a joint experimental and theoretical study of spin coherence properties of 39K, 85Rb, 87Rb, and 133Cs atoms trapped in a solid parahydrogen matrix. We use optical pumping to prepare the spin states of the implanted atoms and circular dichroism to measure their spin states. Optical pumping signals show order-of-magnitude differences depending on both matrix growth conditions and atomic species. We measure the ensemble transverse relaxation times (T2*) of the spin states of the alkali-metal atoms. Different alkali species exhibit dramatically different T2* times, ranging from sub-microsecond coherence times for high mF states of 87Rb, to ~100 microseconds for 39K. These are the longest ensemble T2* times reported for an electron spin system at high densities (n > 10^16 cm^-3). To interpret these observations, we develop a theory of inhomogenous broadening of hyperfine transitions of ^2S atoms in weakly-interacting solid matrices. Our calculated ensemble transverse relaxation times agree well with experiment, and suggest ways to longer coherence times in future work.

BACKGROUND: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. METHODS: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. FINDINGS: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0-3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3-2·9) for those with diabetes, 2·8 kg (2·5-3·2) for those with prediabetes, and 3·3 kg (2·6-4·0) for those with normoglycaemia (p

We discuss the use of optical cavities as tools to search for dark matter (DM) composed of virialized ultra-light fields (VULFs). Such fields could lead to oscillating fundamental constants, resulting in oscillations of the length of rigid bodies. We propose searching for these effects via differential strain measurement of rigid and suspended-mirror cavities. We estimate that more than two orders of magnitude of unexplored phase space for VULF DM couplings can be probed at VULF Compton frequencies in the audible range of 0.1-10 kHz., 6 pages, 4 figures, title updated

BACKGROUND Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. METHODS Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. RESULTS Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P

People display unrealistic optimism in their predictions about countless events, believing that their personal future outcomes will be more desirable than can possibly be true. We summarize the vast literature on unrealistic optimism by focusing on four broad questions: What is unrealistic optimism, when does it occur, why does it occur, and what are its consequences? Unrealistic optimism can be operationalized in multiple ways; is commonplace yet has well-established boundary conditions; occurs for a variety of reasons; and has consequences for affect, decision making, and behavior.

At present there is no therapy for Alzheimer's Disease which completely stops the progressive dementia effecting late onset Alzheimer's Disease (AD) patients. It is felt that the main reason for this failure is that AD appears to be a disease caused by four major pathological processes. To date, efforts to develop treatments have addressed only one or another of these four etiologies. However, even a partially effective therapy against one cause allows the others, untreated, to continue their inexorable destruction of the neurons of the brain. It is suggested that a therapy is required which inhibits all four causes of the disease. Just such a therapy is proposed here with four specific drugs and a vitomer together in a combination treatment. The four major pathologic processes causing AD are: I. vascular hypoperfusion of the brain with associated mitochondrial dysfunction. II. destructive protein occlusions. III. uncontrolled oxidate stress and IV: pro-inflammatory immune processes secondary to microglial and astrocytic dysfunction in the brain. A detailed literature search has provided four drugs and a B6 vitomer which together provide an ideal combination to treat the four etiologies of AD. All four drugs are used clinically for various indications and would be used "off label" in combination to treat AD. The drugs have been used in preliminary studies to treat dementia with favorable indications in all of them inhibiting dementia with only modest side effects. In in vitro studies all five of the combination have been shown effective in inhibiting one or more of the four disease etiologies and together they are effective against all four. The four drugs are Trental, Nicergoline, Nilotinib, and Methylene blue. The vitamer is B6 pyridoxamine. The cumulative benefits of this combination should provide an effective treatment to completely stop the progressive dementia of AD, measured in 12-18months. The use of an endpoint of complete cessation of progressive dementia rather than the standard of a statistical determination of the slowing of progressive dementia allows the study to be conducted with a cohort of only 15 patients (no statistics and no placebo patients) as every AD patient would otherwise show progressive dementia without the effective treatment.

Research has found that patient-subjects in early phase cancer trials exhibit unrealistic optimism regarding the risks and possible benefits of trial participation. Unrealistic optimism is associated with therapeutic misconception and failures to appreciate research-related information. This is the first study to assess whether those who decline to participate in these trials also exhibit unrealistic optimism. It is also the first study to assess whether there are significant differences in appreciation of research-related risks/benefits and therapeutic misconception between these two groups. We approached 261 patients at two academic medical centers who were offered enrollment in a Phase I, II, or I/II cancer trial (between 2012 and 2016). Two hundred thirty-three patients agreed to enroll in an early phase cancer trial, 171 of whom agreed to be interviewed for the study. Twenty-eight patients declined the offer to enroll, 15 of whom agreed to be interviewed for the study. Subjects participated in a structured face-to-face interview with a research associate trained to administer the study questionnaires. Acceptors demonstrated a significantly higher level of unrealistic optimism than decliners ( p.05). Decliners had significantly less therapeutic misconception than acceptors (3.37 [ SD = 0.85] vs. 3.79 [ SD = 0.77], p = .042). There was a significant difference on one of the appreciation questions between acceptors and decliners ( p = .009). Comparative assessment of acceptors and decliners to early phase cancer trials casts light on whether unrealistic optimism is consequential for the decision to participate in these trials. The different levels of unrealistic optimism exhibited by these groups suggest that it may be a factor that affects the decision to participate.

In this article we examine intuitive dimensions of personal cancer risk likelihood, which theory and empirical evidence indicate may be important elements in the risk perception process. We draw on data from a study of risk perceptions in three social groups, university students, men living in the community, and primary care patients living in urban area. The study took place in 2007-2011, in New York State (Garden City and New York City) and Boston, Massachusetts. This study used items developed from categories identified in prior qualitative research specifying emotions and attitudes activated in cancer risk determination to examine perception of cancer risks. Across three samples - university students (N=568), community men (N=182), and diverse, urban primary care patients (N=127) - we conducted exploratory factor and construct analyses. We found that the most reliable two factors within the five-factor solution were Cognitive Causation, tapping beliefs that risk thoughts may encourage cancer development, and Negative Affect in Risk, assessing negative feelings generated during the risk perception process. For these factors, there were high levels of item endorsement, especially in minority groups, and only modest associations with established cancer risk perception and worry assessments, indicating novel content. These items may prove useful in measuring and comparing intuitive cancer risk perceptions across diverse population subgroups.

Researchers have used terms such as unrealistic optimism and optimistic bias to refer to concepts that are similar but not synonymous. Drawing from 3 decades of research, we discuss critically how researchers define unrealistic optimism, and we identify four types that reflect different measurement approaches: unrealistic absolute optimism at the individual and group levels and unrealistic comparative optimism at the individual and group levels. In addition, we discuss methodological criticisms leveled against research on unrealistic optimism and note that the criticisms are primarily relevant to only one type: the group form of unrealistic comparative optimism. We further clarify how the criticisms are not nearly as problematic as they might seem, even for unrealistic comparative optimism. Finally, we note boundary conditions on the different types of unrealistic optimism and reflect on five broad questions that deserve further attention.

Using helium buffer gas cooling, we have prepared dense samples of ground-state molecular calcium monohydride (CaH X 2Σ) at cryogenic temperatures. We have used optical pumping to polarise the spin state of the CaH molecules and we have measured the inelastic collisions of molecular CaH with atomic helium at temperatures from 2 to 7 K. The measured CaH electronic spin depolarisation rate coefficient increases rapidly with increasing temperature, increasing from 2 × 10−13 cm3 s−1 to over 10−11 cm3 s−1. The strong dependence of rate coefficient on temperature is attributed to the CaH population in the first excited rotational state.

Background The PCSK 9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol ( LDL ‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL ‐C target levels were not met. The primary efficacy endpoint was LDL ‐C percentage change from baseline to W24. Mean baseline LDL ‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL ‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P LDL ‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events. Conclusions Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL ‐C. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02023879.

PurposeRecent research has found unrealistic optimism (UO) among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism.MethodsA study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the bias in other contexts.ResultsOne hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators (p=0.024) and mental image (p=0.022), were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism (pConclusionPatient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing.

We have grown crystals of solid parahydrogen using a single closed-cycle cryostat. We have doped the crystals with rubidium atoms at densities on the order of ${10}^{17}\text{ }\text{ }{\mathrm{cm}}^{\ensuremath{-}3}$ and used optical pumping to polarize the spin state of the implanted atoms. The optical spectrum of the rubidium atoms shows larger broadening than previous work in which the rubidium was implanted in solid argon or neon. However, the optical pumping behavior is significantly improved, with both a larger optical pumping signal and a longer longitudinal relaxation time. The spin relaxation time shows a strong dependence on orthohydrogen impurity levels in the crystal, as well as the applied magnetic field. Current performance is comparable to state-of-the-art solid state systems at comparable spin densities, with potential for improvement at higher parahydrogen purities.

Graphite nanofibers (GNFs) embedded in paraffin phase change material are found to settle to the bottom of the sample when subjected to repeated thermal cycling. The majority of this settling is found to occur over the first heating/cooling cycle. A method is developed to prevent GNF settling by creating a shape stabilized phase change material using high density polyethylene (HDPE) as a stabilizing polymer. The shape stabilized samples reduced or eliminated GNF settling over repeated thermal cycles with as little as 10% HDPE by weight.

Three types of as prepared and treated graphite nanofibers (GNFs) were used as catalysts in the decomposition of isopropanol to propene and acetone in the presence of oxygen to evaluate the surface chemistry of the fibers. As prepared herringbone fibers were found to produce higher selectivity for propene compared to the as prepared platelet and ribbon fibers at all temperatures explored. Herringbone fibers that had undergone oxidative treatment with nitric acid, phosphoric acid, ruthenium tetroxide or potassium permanganate were also evaluated at a 290 °C. Effects of oxidation treatments on fiber structure were evaluated using a host of analytical techniques including BET, SEM/EDS, TGA, XPS, and fluorescence labeling of surface species. Selectivity for acetone dehydrogenation product or propene dehydration product could be achieved by the appropriate surface treatment. Nitric acid was the mildest treatment and the treated fibers showed minimal changes. (Potassium permanganate was a harsh treatment that almost completely degraded fiber structure, creating amorphous carbon.) Phosphoric acid treated fibers were found to produce very high conversions and almost pure selectivity for propene. Ruthenium tetroxide did not appear to have a large affect on fiber morphology; however, selectivity for acetone was much higher when GNFs were treated with ruthenium tetroxide.

In 2007 the authors presented a view of planning to confront the challenges for post-conflict and developing environments called Environment Shaping. In 2008, under contract to the US Army Corp of Engineers, the authors and their colleagues set about advancing the Environment Shaping concept into a detailed but practicable systems-based methodology and process for ‘real world’ planners in a project called Stake-Holder Asset-Based Planning Environment, or SHAPE. This article describes research and development efforts that traversed three primary avenues, each concerning different aspects of creating a workable process. First, it documents how the need to define what is meant by ‘system’ in post-conflict and development contexts requires identifying key descriptive characteristics and behaviors of the place of interest. To do so it relies on concepts from wicked problems, systems-of-systems approaches, and the authors’ own social-ecological systems perspective. Secondly, the authors discovered that one cons...

The thermal performance and energy storage capabilities of a 54 °C organic paraffin wax is be tested and directly compared using three common different thermal conductivity enhancement methods (TCE). These include the use of graphite foam with infiltrated PCM, aluminum foam with infiltrated PCM, and PCM with 10 wt% graphite nanofibers. The applied heat flux varies from 1.93 W/cm 2 to 19.3 W/cm 2 . This allows the study of higher heat flux conditions than any previously studied and the first direct comparison of the effectiveness of these three different methods on the control of the heated base temperature. The performance of the PCM in both the solid and liquid phase as well as the motion of the melt front between the two phases is examined for each TCE configuration. It is found that the selection of enhancement method has a significant effect on the thermal response of the system. The base paraffin consistently shows the development of a superheated liquid layer at the base and Rayleigh-Benard convection currents in the melt region. With the addition of 11 wt% GNF the convection currents at the base are suppressed and the PCM is coupled more closely to the module. The GNF/PCM was more effective at controlling the base temperature than the base paraffin at low power loads, but this effect decreased with increased power loading. The GNF/PCM mixture was less effective at base temperature control when compared to the aluminum or graphite foams. However, the foams are found to improve the heat sink abilities of the system without exhibiting any significant delay to steady-state through effective use of the PCM mass. The results provide much needed valuable insight into the comparative effectiveness of different TCE designs for high power configurations.