A semi-Markov model for stroke with piecewise-constant hazards in the presence of left, right and interval censoring.

This paper presents a parametric method of fitting semi-Markov models with piecewise-constant hazards in the presence of left, right and interval censoring. We investigate transition intensities in a three-state illness-death model with no recovery. We relax the Markov assumption by adjusting the intensity for the transition from state 2 (illness) to state 3 (death) for the time spent in state 2 through a time-varying covariate. This involves the exact time of the transition from state 1 (healthy) to state 2. When the data are subject to left or interval censoring, this time is unknown. In the estimation of the likelihood, we take into account interval censoring by integrating out all possible times for the transition from state 1 to state 2. For left censoring, we use an Expectation-Maximisation inspired algorithm. A simulation study reflects the performance of the method. The proposed combination of statistical procedures provides great flexibility. We illustrate the method in an application by using data on stroke onset for the older population from the UK Medical Research Council Cognitive Function and Ageing Study

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital

Preventive Therapy for Child Contacts of Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

BACKGROUND: Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome. METHODS: In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause. RESULTS: One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age <1 year (rate ratio [RR], 10.1; 95% confidence interval [CI], 1.65-105.8; P = .009), HIV-positive status (RR, 10.6; 95% CI, 1.01-64.9; P = .049), exposure to multiple source cases (RR, 6.75; 95% CI, 1.11-70.9; P = .036) and poor adherence (RR, 7.50; 95% CI, 1.23-78.7; P = .026). CONCLUSIONS: This 3-drug preventive therapy regimen was well tolerated and few children developed tuberculosis or died if adherent to therapy. The provision of preventive therapy to vulnerable children following exposure to MDR tuberculosis should be considered

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

Orbital Kondo effect in carbon nanotubes

Progress in the fabrication of nanometer-scale electronic devices is opening new opportunities to uncover the deepest aspects of the Kondo effect, one of the paradigmatic phenomena in the physics of strongly correlated electrons. Artificial single-impurity Kondo systems have been realized in various nanostructures, including semiconductor quantum dots, carbon nanotubes and individual molecules. The Kondo effect is usually regarded as a spin-related phenomenon, namely the coherent exchange of the spin between a localized state and a Fermi sea of electrons. In principle, however, the role of the spin could be replaced by other degrees of freedom, such as an orbital quantum number. Here we demonstrate that the unique electronic structure of carbon nanotubes enables the observation of a purely orbital Kondo effect. We use a magnetic field to tune spin-polarized states into orbital degeneracy and conclude that the orbital quantum number is conserved during tunneling. When orbital and spin degeneracies are simultaneously present, we observe a strongly enhanced Kondo effect, with a multiple splitting of the Kondo resonance at finite field and predicted to obey a so-called SU(4) symmetry.Comment: 26 pages, including 4+2 figure

Kondo effect in an integer-spin quantum dot

The Kondo effect is a key many-body phenomenon in condensed matter physics. It concerns the interaction between a localised spin and free electrons. Discovered in metals containing small amounts of magnetic impurities, it is now a fundamental mechanism in a wide class of correlated electron systems. Control over single, localised spins has become relevant also in fabricated structures due to the rapid developments in nano-electronics. Experiments have already demonstrated artificial realisations of isolated magnetic impurities at metallic surfaces, nanometer-scale magnets, controlled transitions between two-electron singlet and triplet states, and a tunable Kondo effect in semiconductor quantum dots. Here, we report an unexpected Kondo effect realised in a few-electron quantum dot containing singlet and triplet spin states whose energy difference can be tuned with a magnetic field. This effect occurs for an even number of electrons at the degeneracy between singlet and triplet states. The characteristic energy scale is found to be much larger than for the ordinary spin-1/2 case.Comment: 12 page

Yours ever (well, maybe): Studies and signposts in letter writing

Electronic mail and other digital communications technologies seemingly threaten to end the era of handwritten and typed letters, now affectionately seen as part of snail mail. In this essay, I analyze a group of popular and scholarly studies about letter writing-including examples of pundits critiquing the use of e-mail, etiquette manuals advising why the handwritten letter still possesses value, historians and literary scholars studying the role of letters in the past and what it tells us about our present attitudes about digital communications technologies, and futurists predicting how we will function as personal archivists maintaining every document including e-mail. These are useful guideposts for archivists, providing both a sense of the present and the past in the role, value and nature of letters and their successors. They also provide insights into how such documents should be studied, expanding our gaze beyond the particular letters, to the tools used to create them and the traditions dictating their form and function. We also can discern a role for archivists, both for contributing to the literature about documents and in using these studies and commentaries, suggesting not a new disciplinary realm but opportunities for new interdisciplinary work. Examining a documentary form makes us more sensitive to both the innovations and traditions as it shifts from the analog to the digital; we can learn not to be caught up in hysteria or nostalgia about one form over another and archivists can learn about what they might expect in their labors to document society and its institutions. At one time, paper was part of an innovative technology, with roles very similar to the Internet and e-mail today. It may be that the shifts are far less revolutionary than is often assumed. Reading such works also suggests, finally, that archivists ought to rethink how they view their own knowledge and how it is constructed and used. © 2010 Springer Science+Business Media B.V

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Two-channel Kondo effect and renormalization flow with macroscopic quantum charge states

Many-body correlations and macroscopic quantum behaviors are fascinating condensed matter problems. A powerful test-bed for the many-body concepts and methods is the Kondo model which entails the coupling of a quantum impurity to a continuum of states. It is central in highly correlated systems and can be explored with tunable nanostructures. Although Kondo physics is usually associated with the hybridization of itinerant electrons with microscopic magnetic moments, theory predicts that it can arise whenever degenerate quantum states are coupled to a continuum. Here we demonstrate the previously elusive `charge' Kondo effect in a hybrid metal-semiconductor implementation of a single-electron transistor, with a quantum pseudospin-1/2 constituted by two degenerate macroscopic charge states of a metallic island. In contrast to other Kondo nanostructures, each conduction channel connecting the island to an electrode constitutes a distinct and fully tunable Kondo channel, thereby providing an unprecedented access to the two-channel Kondo effect and a clear path to multi-channel Kondo physics. Using a weakly coupled probe, we reveal the renormalization flow, as temperature is reduced, of two Kondo channels competing to screen the charge pseudospin. This provides a direct view of how the predicted quantum phase transition develops across the symmetric quantum critical point. Detuning the pseudospin away from degeneracy, we demonstrate, on a fully characterized device, quantitative agreement with the predictions for the finite-temperature crossover from quantum criticality.Comment: Letter (5 pages, 4 figures) and Methods (10 pages, 6 figures