Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women

IMPORTANCE: Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. OBJECTIVE: To determine whether rotating night shift work is associated with CHD risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). EXPOSURES: Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). MAIN OUTCOMES AND MEASURES: Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. RESULTS: During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] CONCLUSIONS AND RELEVANCE: Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics

Solar fusion cross sections. II. The pp chain and CNO cycles

We summarize and critically evaluate the available data on nuclear fusion cross sections important to energy generation in the Sun and other hydrogen-burning stars and to solar neutrino production. Recommended values and uncertainties are provided for key cross sections, and a recommended spectrum is given for 8B solar neutrinos. We also discuss opportunities for further increasing the precision of key rates, including new facilities, new experimental techniques, and improvements in theory. This review, which summarizes the conclusions of a workshop held at the Institute for Nuclear Theory, Seattle, in January 2009, is intended as a 10-year update and supplement to Reviews of Modern Physics 70 (1998) 1265.Comment: 54 pages, 20 figures, version to be published in Reviews of Modern Physics; various typos corrected and several updates mad

Finality revived: powers and intentionality

Proponents of physical intentionality argue that the classic hallmarks of intentionality highlighted by Brentano are also found in purely physical powers. Critics worry that this idea is metaphysically obscure at best, and at worst leads to panpsychism or animism. I examine the debate in detail, finding both confusion and illumination in the physical intentionalist thesis. Analysing a number of the canonical features of intentionality, I show that they all point to one overarching phenomenon of which both the mental and the physical are kinds, namely finality. This is the finality of ‘final causes’, the long-discarded idea of universal action for an end to which recent proponents of physical intentionality are in fact pointing whether or not they realise it. I explain finality in terms of the concept of specific indifference, arguing that in the case of the mental, specific indifference is realised by the process of abstraction, which has no correlate in the case of physical powers. This analysis, I conclude, reveals both the strength and weakness of rational creatures such as us, as well as demystifying (albeit only partly) the way in which powers work

The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report

BACKGROUND: Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. CASE PRESENTATION: Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. CONCLUSION: The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts

Vault changes after cyclopentolate instillation in eyes with posterior chamber phakic intraocular lens

Posterior chamber phakic intraocular lens (pIOL) implantation is a common option for correcting moderate-to-high ocular refractive defects. Because this pIOL is implanted on ciliary sulcus, the distance between the back surface of the pIOL and the anterior surface of the crystalline lens, that it is known as vault, should be measured in different conditions to ensure the technique's safety. Cyclopentolate is a drug that dilates the pupil and relaxes accommodation (cycloplegia). It is often used for different ocular examinations and for other medical purposes. However, there is no evidence of the effect of this drug on vault. This study quantified central vault changes associated with cyclopentolate instillation. We measured the vault under normal conditions (pre-cycloplegic instillation) and after instilling cyclopentolate on 39 eyes of 39 patients with implanted pIOL. Our results suggest that cyclopentolate instillation may induce changes to vault in eyes with implanted pIOL. These changes seem safe and are mainly associated with vault under normal conditions, but also with anterior chamber depth, pupillary diameter and pIOL size.- European Fund for Regional Development (FEDER) through the COMPETE Program and the Portuguese Foundation for Science and Technology (FCT) provided financial support in the framework of projects PTDC/SAU-BEB/098391/2008, PTDC/SAU-BEB/098392/2008 and the Strategic Project PEST-C/FIS/UI607/2011

The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.National Science Foundation (U.S.). Science and Technology Center (Award CCF-1231216)National Science Foundation (U.S.) (Grant NSF-0640097)National Science Foundation (U.S.) (Grant NSF-0827427)United States. Air Force Office of Scientific Research (Grant FA8650-05-C-7262)Eugene McDermott Foundatio

The combined effects of obesity, abdominal obesity and major depression/anxiety on health-related quality of life: The lifelines cohort study

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