HO<inf>2</inf>NO<inf>2</inf> and HNO<inf>3</inf> in the coastal Antarctic winter night: A lab-in-the-field experiment

Abstract. Observations of peroxynitric acid (HO2NO2) and nitric acid (HNO3) were made during a 4 month period of Antarctic winter darkness at the coastal Antarctic research station, Halley. Mixing ratios of HNO3 ranged from instrumental detection limits to ~8 parts per trillion by volume (pptv), and of HO2NO2 from detection limits to ~5 pptv; the average ratio of HNO3 : HO2NO2 was 2.0(± 0.6) : 1, with HNO3 always present at greater mixing ratios than HO2NO2 during the winter darkness. An extremely strong association existed for the entire measurement period between mixing ratios of the respective trace gases and temperature: for HO2NO2, R2 = 0.72, and for HNO3, R2 = 0.70. We focus on three cases with considerable variation in temperature, where wind speeds were low and constant, such that, with the lack of photochemistry, changes in mixing ratio were likely to be driven by physical mechanisms alone. We derived enthalpies of adsorption (ΔHads) for these three cases. The average ΔHads for HNO3 was −42 ± 2 kJ mol−1 and for HO2NO2 was −56 ± 1 kJ mol−1; these values are extremely close to those derived in laboratory studies. This exercise demonstrates (i) that adsorption to/desorption from the snow pack should be taken into account when addressing budgets of boundary layer HO2NO2 and HNO3 at any snow-covered site, and (ii) that Antarctic winter can be used as a natural "laboratory in the field" for testing data on physical exchange mechanisms. This study is part of the British Antarctic Survey Polar Science for Planet Earth Programme. It was funded by The Natural Environment Research Council (NERC).This is the final published version. It first appeared at http://www.atmos-chem-phys.net/14/11843/2014/acp-14-11843-2014.html

In the face of threat: neural and endocrine correlates of impaired facial emotion recognition in cocaine dependence.

The ability to recognize facial expressions of emotion in others is a cornerstone of human interaction. Selective impairments in the recognition of facial expressions of fear have frequently been reported in chronic cocaine users, but the nature of these impairments remains poorly understood. We used the multivariate method of partial least squares and structural magnetic resonance imaging to identify gray matter brain networks that underlie facial affect processing in both cocaine-dependent (n = 29) and healthy male volunteers (n = 29). We hypothesized that disruptions in neuroendocrine function in cocaine-dependent individuals would explain their impairments in fear recognition by modulating the relationship with the underlying gray matter networks. We found that cocaine-dependent individuals not only exhibited significant impairments in the recognition of fear, but also for facial expressions of anger. Although recognition accuracy of threatening expressions co-varied in all participants with distinctive gray matter networks implicated in fear and anger processing, in cocaine users it was less well predicted by these networks than in controls. The weaker brain-behavior relationships for threat processing were also mediated by distinctly different factors. Fear recognition impairments were influenced by variations in intelligence levels, whereas anger recognition impairments were associated with comorbid opiate dependence and related reduction in testosterone levels. We also observed an inverse relationship between testosterone levels and the duration of crack and opiate use. Our data provide novel insight into the neurobiological basis of abnormal threat processing in cocaine dependence, which may shed light on new opportunities facilitating the psychosocial integration of these patients.This work was funded by a research grant from the Medical Research Council (G0701497) and supported by the infrastructure of the Behavioural and Clinical Neuroscience Institute (which is supported by a joint award from the Medical Research Council and the Wellcome Trust). This study was jointly sponsored by the Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. KD Ersche, CC Hagan, and PS Jones are supported by the Medical Research Council, and DG Smith by the Cambridge Overseas Trust.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.5

Effects of treatment withdrawal on brachial and central aortic pressure after direct renin inhibition or angiotensin receptor blockade

Whilst sustained lowering of brachial systolic blood pressure (Br-SBP) and central aortic systolic pressure (CASP) have been demonstrated in patients with hypertension, effects of treatment withdrawal on these parameters have not been investigated. The ASSERTIVE study previously reported more sustained control of Br-SBP with aliskiren versus telmisartan in patients with hypertension, following 7-days treatment withdrawal. In this ASSERTIVE sub-study, we hypothesised that aliskiren would similarly exert more sustained control of CASP than telmisartan during treatment withdrawal

The economic burden of cancer in the UK: a study of survivors treated with curative intent.

OBJECTIVE: We aim to describe the economic burden of UK cancer survivorship for breast, colorectal and prostate cancer patients treated with curative intent, 1 year post-diagnosis. METHODS: Patient-level data were collected over a 3-month period 12-15 months post-diagnosis to estimate the monthly societal costs incurred by cancer survivors. Self-reported resource utilisation data were obtained via the electronic Patient-reported Outcomes from Cancer Survivors system and included community-based health and social care, medications, travel costs and informal care. Hospital costs were retrieved through data linkage. Multivariate regression analysis was used to examine cost predictors. RESULTS: Overall, 298 patients were included in the analysis, including 136 breast cancer, 83 colorectal cancer and 79 prostate cancer patients. The average monthly societal cost was $US409 (95$US316-$US502) [mean: £260, 95$US279, 95%CI: $US207-$US351) [mean: £177, 95%CI: £131-£224], patients' out-of-pocket (OOP) expenses (mean: $US40, 95$US15-$US65) [mean: £25, 95$US110, 95%CI: $US57-$US162) [mean: £70, 95%CI: £38-£102]. The distribution of costs was skewed with a small number of patients incurring very high costs. Multivariate analyses showed higher societal costs for breast cancer patients. Significant predictors of OOP costs included age and socioeconomic deprivation. CONCLUSIONS: This study found the economic burden of cancer survivorship is unevenly distributed in the population and that cancer survivors may still incur substantial costs over 1 year post-diagnosis. In addition, this study illustrates the feasibility of using an innovative online data collection platform to collect patient-reported resource utilisation information. Copyright © 2015 John Wiley & Sons, Ltd

Cognitive architectures as Lakatosian research programmes: two case studies

Cognitive architectures - task-general theories of the structure and function of the complete cognitive system - are sometimes argued to be more akin to frameworks or belief systems than scientific theories. The argument stems from the apparent non-falsifiability of existing cognitive architectures. Newell was aware of this criticism and argued that architectures should be viewed not as theories subject to Popperian falsification, but rather as Lakatosian research programs based on cumulative growth. Newell's argument is undermined because he failed to demonstrate that the development of Soar, his own candidate architecture, adhered to Lakatosian principles. This paper presents detailed case studies of the development of two cognitive architectures, Soar and ACT-R, from a Lakatosian perspective. It is demonstrated that both are broadly Lakatosian, but that in both cases there have been theoretical progressions that, according to Lakatosian criteria, are pseudo-scientific. Thus, Newell's defense of Soar as a scientific rather than pseudo-scientific theory is not supported in practice. The ACT series of architectures has fewer pseudo-scientific progressions than Soar, but it too is vulnerable to accusations of pseudo-science. From this analysis, it is argued that successive versions of theories of the human cognitive architecture must explicitly address five questions to maintain scientific credibility

Apathy and impulsivity in frontotemporal lobar degeneration syndromes

Apathy and impulsivity are common and disabling consequences of frontotemporal lobar degeneration. They cause substantial carer distress, but their aetiology remains elusive. There are critical limitations to previous studies in this area including (i) the assessment of either apathy or impulsivity alone, despite their frequent co-existence; (ii) the assessment of behavioural changes within single diagnostic groups; and (iii) the use of limited sets of tasks or questions that relate to just one aspect of these multifactorial constructs. We proposed an alternative, dimensional approach that spans behavioural and language variants of frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome. This accommodates the commonalities of apathy and impulsivity across disorders and reveals their cognitive and anatomical bases. The ability to measure the components of apathy and impulsivity and their associated neural correlates across diagnostic groups would provide better novel targets for pharmacological manipulations, and facilitate new treatment strategies and strengthen translational models. We therefore sought to determine the neurocognitive components of apathy and impulsivity in frontotemporal lobar degeneration syndromes. The frequency and characteristics of apathy and impulsivity were determined by neuropsychological and behavioural assessments in 149 patients and 50 controls from the PIck’s disease and Progressive supranuclear palsy Prevalence and INcidence study (PiPPIN). We derived dimensions of apathy and impulsivity using principal component analysis and employed these in volumetric analyses of grey and white matter in a subset of 70 patients (progressive supranuclear palsy, n = 22; corticobasal syndrome, n = 13; behavioural variant, n = 14; primary progressive aphasias, n = 21) and 27 control subjects. Apathy and impulsivity were present across diagnostic groups, despite being criteria for behavioural variant frontotemporal dementia alone. Measures of apathy and impulsivity frequently loaded onto the same components reflecting their overlapping relationship. However, measures from objective tasks, patient-rated questionnaires and carer-rated questionnaires loaded onto separate components and revealed distinct neurobiology. Corticospinal tracts correlated with patients’ self-ratings. In contrast, carer ratings correlated with atrophy in established networks for goal-directed behaviour, social cognition, motor control and vegetative functions, including frontostriatal circuits, orbital and temporal polar cortex, and the brainstem. Components reflecting response inhibition deficits correlated with focal frontal cortical atrophy. The dimensional approach to complex behavioural changes arising from frontotemporal lobar degeneration provides new insights into apathy and impulsivity, and the need for a joint therapeutic strategy against them. The separation of objective tests from subjective questionnaires, and patient from carer ratings, has important implications for clinical trial design

Randomised, double-blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial study

Objectives To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Design Double blind, placebo controlled study. Setting Eighteen UK hospitals. Participants 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV1) 50% of predicted normal. Interventions Inhaled fluticasone propionate 500 ìg twice daily from a metered dose inhaler or identical placebo. Main outcome measures Efficacy measures: rate of decline in FEV1 after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. Results There was no significant difference in the annual rate of decline in FEV1 (P = 0.16). Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P &lt; 0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P = 0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P = 0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v19%, P = 0.034). Conclusions Fluticasone propionate 500 ìg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1. Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease

Disrupted iron regulation in the brain and periphery in cocaine addiction

Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction

Some pioneers of European human genetics

Some of the pioneers of human genetics across Europe are described, based on a series of 100 recorded interviews made by the author. These interviews, and the memories of earlier workers in the field recalled by interviewees, provide a vivid picture, albeit incomplete, of the early years of human and medical genetics. From small beginnings in the immediate post-World War 2 years, human genetics grew rapidly across many European countries, a powerful factor being the development of human cytogenetics, stimulated by concerns over the risks of radiation exposure. Medical applications soon followed, with the recognition of human chromosome abnormalities, the need for genetic counselling, the possibility of prenatal diagnosis and later, the applications of human molecular genetics. The evolution of the field has been strongly influenced by the characters and interests of the relatively small number of founding workers in different European countries, as well as by wider social, medical and scientific factors in the individual countries

Spectral Classification; Old and Contemporary

Beginning with a historical account of the spectral classification, its refinement through additional criteria is presented. The line strengths and ratios used in two dimensional classifications of each spectral class are described. A parallel classification scheme for metal-poor stars and the standards used for classification are presented. The extension of spectral classification beyond M to L and T and spectroscopic classification criteria relevant to these classes are described. Contemporary methods of classifications based upon different automated approaches are introduced.Comment: To be published in "Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars: Ed Aruna Goswami & Eswar Reddy, Springer Verlag, 2009, 17 pages, 10 figure