Interstitial Nitrogen in Diamond – Optical and EPR Studies

Nitrogen is one of the most common impurities in diamond. On a substitutional site it acts as a deep donor, approximately 1.7 eV below the conduction band. Irradiation of nitrogen containing diamond and subsequent annealing creates the nitrogen vacancy centre, which has recently attracted much attention for quantum information processing application. Another possible product of irradiation and annealing of nitrogen containing diamond is interstitial nitrogen. Presumably, a mobile carbon interstitial migrates to a substitutional nitrogen to produce an interstitial nitrogen complex which may or may not be mobile. The configuration(s) of interstitial nitrogen related defects (e.g. bond centred, [001]-split) are not known. An infra-red (IR) absorption peak at 1450 cm-1 labelled H1a has been associated with an nitrogen interstitial complex. [1] Theoretical modelling suggested that this IR local mode is due to a bond centred nitrogen interstitial [2]. However, more recent modelling [3] suggests that this defect is mobile at temperatures were H1a is stable and instead assign H1a to two nitrogen atoms occupying a single lattice site in a [001]-split configuration. To date no electron paramagnetic resonance (EPR) spectra have been conclusively associated with an interstitial nitrogen defect.

In this study we present data from new EPR and optical absorption studies in combination with uniaxial stress of nitrogen interstitial related defects in electron irradiated and annealed nitrogen doped diamond. These measurements yield symmetry information about the defects allowing us to determine which of the proposed models are possible. EPR spectra of nitrogen interstitial related defects in samples isotopically enriched with 15N are reported and we show that these explain the lack of previous EPR data for these defects. Correlations between the IR absorbance and the integrated intensity of the new EPR defects are studied for varying irradiation doses and annealing temperatures.

Relationship between socioeconomic deprivation or urban/rural residence and visual acuity before cataract surgery in Northern Scotland

Purpose: To evaluate the influence of socioeconomic factors on visual acuity before cataract surgery. ?Methods: The medical case notes of 240 consecutive patients listed for cataract surgery from January 1, 2010, at Grampian University Hospital, Aberdeen, were reviewed retrospectively. Patients with ocular comorbidity were excluded. Demographics, postal codes, and visual acuity were recorded. Scottish Index of Multiple Deprivation was used to determine the deprivation rank. Home location was classified as urban or rural. The effect of these parameters on preoperative visual acuity was investigated using chi-square tests or Fisher exact test as appropriate. ?Results: A total of 184 patients (mean 75 years) were included. A total of 127 (69%) patients had visual acuity of 6/12 or better. An association was found between affluence and preoperative visual acuity of 6/12 or better (?2trend = 4.97, p = 0.03), with a significant rising trend across quintile of deprivation. There was no evidence to suggest association between geographical region and preoperative visual acuity (p = 0.63). ?Conclusion: Affluence was associated with good visual acuity (6/12 or better) before cataract surgery. There was no difference in preoperative visual acuity between rural and urban populations.

A multiconfigurational time-dependent Hartree-Fock method for excited electronic states. I. General formalism and application to open-shell states

The solution of the time-dependent Schrodinger equation for systems of interacting electrons is generally a prohibitive task, for which approximate methods are necessary. Popular approaches, such as the time-dependent Hartree-Fock (TDHF) approximation and time-dependent density functional theory (TDDFT), are essentially single-configurational schemes. TDHF is by construction incapable of fully accounting for the excited character of the electronic states involved in many physical processes of interest; TDDFT, although exact in principle, is limited by the currently available exchange-correlation functionals. On the other hand, multiconfigurational methods, such as the multiconfigurational time-dependent Hartree-Fock (MCTDHF) approach, provide an accurate description of the excited states and can be systematically improved. However, the computational cost becomes prohibitive as the number of degrees of freedom increases, and thus, at present, the MCTDHF method is only practical for few-electron systems. In this work, we propose an alternative approach which effectively establishes a compromise between efficiency and accuracy, by retaining the smallest possible number of configurations that catches the essential features of the electronic wavefunction. Based on a time-dependent variational principle, we derive the MCTDHF working equation for a multiconfigurational expansion with fixed coefficients and specialise to the case of general open-shell states, which are relevant for many physical processes of interest. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3600397]

Analog of Rabi oscillations in resonant electron-ion systems

Quantum coherence between electron and ion dynamics, observed in organic semiconductors by means of ultrafast spectroscopy, is the object of recent theoretical and computational studies. To simulate this kind of quantum coherent dynamics, we have introduced in a previous article [L. Stella, M. Meister, A. J. Fisher, and A. P. Horsfield, J. Chem. Phys. 127, 214104 (2007)] an improved computational scheme based on Correlated Electron-Ion Dynamics (CEID). In this article, we provide a generalization of that scheme to model several ionic degrees of freedom and many-body electronic states. To illustrate the capability of this extended CEID, we study a model system which displays the electron-ion analog of the Rabi oscillations. Finally, we discuss convergence and scaling properties of the extended CEID along with its applicability to more realistic problems. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3589165]

ESTIMATION OF PURITY FOR A QUANTUM HARMONIC OSCILLATOR INITIALLY PREPARED IN A DISPLACED THERMAL STATE

We address the estimation of purity for a quantum oscillator initially prepared in a displaced thermal state and probed by a suitably prepared qubit interacting with the oscillator via Jaynes-Cummings Hamiltonian without the rotating-wave approximation. We evaluate the quantum Fisher information (QFI) and show that optimal estimation of purity can be achieved by measuring the population of the qubit after a properly chosen interaction time. We also address the estimation of purity at fixed total energy and show that the corresponding precision is independent of the presence of a coherent amplitude.

Evaluating Many Treatments and Biomarkers in Oncology: A New Design

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.

Effect of interparticle interaction in a free-oscillation atomic interferometer

We investigate the dynamics of two interacting bosons repeatedly scattering off a beam-splitter in a free oscillation atom interferometer. Using the interparticle scattering length and the beam-splitter probabilites as our control parameters, we show that even in a simple setup like this a wide range of strongly correlated quantum states can be created. This in particular includes the NOON state, which maximizes the quantum Fisher information and is a foremost state in quantum metrology. DOI: 10.1103/PhysRevA.87.043630

Prevalence and risk factors of depressive symptoms in a Canadian palliative home care population: a cross-sectional study

Background: Depression in palliative care patients is important because of its intrinsic burden and association with elevated physical symptoms, reduced immunity and increased mortality risk. Identifying risk factors associated with depression can enable clinicians to more readily diagnose it, which is important since depression is treatable. The purpose of this cross-sectional study was to determine the prevalence of depressive symptoms and risk factors associated with them in a large sample of palliative home care patients.

Methods: The data come from interRAI Palliative Care assessments completed between 2006 and 2012. The sample (n = 5144) consists of adults residing in Ontario (Canada), receiving home care services, classified as palliative, and not experiencing significant cognitive impairment. Logistic regression identified the risk factors associated with depressive symptoms. The dependent variable was the Depression Rating Scale (DRS) and the independent variables were functional indicators from the interRAI assessment and other variables identified in the literature. We examined the results of the complete case and multiple imputation analyses, and found them to be similar.

Results: The prevalence of depressive symptoms was 9.8%. The risk factors associated with depressive symptoms were (pooled estimates, multiple imputation): low life satisfaction (OR = 3.01 [CI = 2.37-3.82]), severe and moderate sleep disorders (2.56 [2.05-3.19] and 1.56 [1.18-2.06]), health instability (2.12 [1.42-3.18]), caregiver distress 2.01 [1.62-2.51]), daily pain (1.73 [1.35-2.22]), cognitive impairment (1.45 [1.13-1.87]), being female (1.37 [1.11-1.68]), and gastrointestinal symptoms (1.27 [1.03-1.55]). Life satisfaction mediated the effect of prognostic awareness on depressive symptoms.

Conclusions: The prevalence of depressive symptoms in our study was close to the median of 10-20% reported in the palliative care literature, suggesting they are present but by no means inevitable in palliative patients. Most of the factors associated with depressive symptoms in our study are amenable to clinical intervention and often targeted in palliative care programs. Designing interventions to address them can be challenging, however, requiring careful attention to patient preferences, the spectrum of comorbid conditions they face, and their social supports. Life satisfaction was one of the strongest factors associated with depressive symptoms in our study, and is likely to be among the most challenging to address.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

Background: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.

Patients and methods: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.

Results: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.

Conclusions: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

The Engine of Thought Is a Hybrid: Roles of Associative and Structured Knowledge in Reasoning

Across a range of domains in psychology different theories assume different mental representations of knowledge. For example, in the literature on category-based inductive reasoning, certain theories (e.g., Rogers & McClelland, 2004; Sloutsky & Fisher, 2008) assume that the knowledge upon which inductive inferences are based is associative, whereas others (e.g., Heit & Rubinstein, 1994; Kemp & Tenenbaum, 2009; Osherson, Smith, Wilkie, López, & Shafir, 1990) assume that knowledge is structured. In this article we investigate whether associative and structured knowledge underlie inductive reasoning to different degrees under different processing conditions. We develop a measure of knowledge about the degree of association between categories and show that it dissociates from measures of structured knowledge. In Experiment 1 participants rated the strength of inductive arguments whose categories were either taxonomically or causally related. A measure of associative strength predicted reasoning when people had to respond fast, whereas causal and taxonomic knowledge explained inference strength when people responded slowly. In Experiment 2, we also manipulated whether the causal link between the categories was predictive or diagnostic. Participants preferred predictive to diagnostic arguments except when they responded under cognitive load. In Experiment 3, using an open-ended induction paradigm, people generated and evaluated their own conclusion categories. Inductive strength was predicted by associative strength under heavy cognitive load, whereas an index of structured knowledge was more predictive of inductive strength under minimal cognitive load. Together these results suggest that associative and structured models of reasoning apply best under different processing conditions and that the application of structured knowledge in reasoning is often effortful.

A multiconfigurational time-dependent Hartree-Fock method for excited electronic states. II. Coulomb interaction effects in single conjugated polymer chains

Conjugated polymers have attracted considerable attention in the last few decades due to their potential for optoelectronic applications. A key step that needs optimisation is charge carrier separation following photoexcitation. To understand better the dynamics of the exciton prior to charge separation, we have performed simulations of the formation and dynamics of localised excitations in single conjugated polymer strands. We use a nonadiabatic molecular dynamics method which allows for the coupled evolution of the nuclear degrees of freedom and of multiconfigurational electronic wavefunctions. We show the relaxation of electron-hole pairs to form excitons and oppositely charged polaron pairs and discuss the modifications to the relaxation process predicted by the inclusion of the Coulomb interaction between the carriers. The issue of charge photogeneration in conjugated polymers in dilute solution is also addressed. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3600404]

Robust nonadiabatic molecular dynamics for metals and insulators

We present a new formulation of the correlated electron-ion dynamics (CEID) scheme, which systematically improves Ehrenfest dynamics by including quantum fluctuations around the mean-field atomic trajectories. We show that the method can simulate models of nonadiabatic electronic transitions and test it against exact integration of the time-dependent Schrodinger equation. Unlike previous formulations of CEID, the accuracy of this scheme depends on a single tunable parameter which sets the level of atomic fluctuations included. The convergence to the exact dynamics by increasing the tunable parameter is demonstrated for a model two level system. This algorithm provides a smooth description of the nonadiabatic electronic transitions which satisfies the kinematic constraints (energy and momentum conservation) and preserves quantum coherence. The applicability of this algorithm to more complex atomic systems is discussed.

Optimization by quantum annealing: Lessons from simple cases

We investigate the basic behavior and performance of simulated quantum annealing (QA) in comparison with classical annealing (CA). Three simple one-dimensional case study systems are considered: namely, a parabolic well, a double well, and a curved washboard. The time-dependent Schrodinger evolution in either real or imaginary time describing QA is contrasted with the Fokker-Planck evolution of CA. The asymptotic decrease of excess energy with annealing time is studied in each case, and the reasons for differences are examined and discussed. The Huse-Fisher classical power law of double-well CA is replaced with a different power law in QA. The multiwell washboard problem studied in CA by Shinomoto and Kabashima and leading classically to a logarithmic annealing even in the absence of disorder turns to a power-law behavior when annealed with QA. The crucial role of disorder and localization is briefly discussed.