Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial.

BACKGROUND: Estimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs. METHODS: Data from the UK Lung Cancer Screening trial were analysed. Multivariable logistic regression models were used to identify independent predictors and to develop a parsimonious model to estimate the probability of lung cancer in lung nodules detected at baseline and at 3-month and 12-month repeat screening. RESULTS: Of 1994 participants who underwent CT scan, 1013 participants had a total of 5063 lung nodules and 52 (2.6%) of the participants developed lung cancer during a median follow-up of 4 years. Covariates that predict lung cancer in our model included female gender, asthma, bronchitis, asbestos exposure, history of cancer, early and late onset of family history of lung cancer, smoking duration, FVC, nodule type (pure ground-glass and part-solid) and volume as measured by semiautomated volumetry. The final model incorporating all predictors had excellent discrimination: area under the receiver operating characteristic curve (AUC 0.885, 95% CI 0.880 to 0.889). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected AUC 0.882, 95% CI 0.848 to 0.907). The risk model had a good calibration (goodness-of-fit χ[8] 8.13, p=0.42). CONCLUSIONS: Our model may be used in estimating the probability of lung cancer in nodules detected at baseline and at 3 months and 12 months from baseline, allowing more efficient stratification of follow-up in population-based lung cancer screening programmes. TRIAL REGISTRATION NUMBER: 78513845.National Institute for Health Research Health Technology Assessment (NIHR HTA) (reference number HTA 09/61/01)

Turing's Genius - Defining an apt microcosm.

Alan Turing (1912–1954) is widely acknowledged as a genius. As well as codebreaking during World War II and taking a pioneering role in computer hardware design and software after the War, he also wrote three important foundational papers in the fields of theoretical computer science, artificial intelligence, and mathematical biology. He has been called the father of computer science, but he also admired by mathematicians, philosophers, and perhaps more surprisingly biologists, for his wide-ranging ideas. His influence stretches from scientific to cultural and even political impact. For all these reasons, he was a true polymath. This paper considers the genius of Turing from various angles, both scientific and artistic. The four authors provide position statements on how Turing has influenced and inspired their work, together with short biographies, as a starting point for a panel session and visual music performance

A study on text-score disagreement in online reviews

In this paper, we focus on online reviews and employ artificial intelligence tools, taken from the cognitive computing field, to help understanding the relationships between the textual part of the review and the assigned numerical score. We move from the intuitions that 1) a set of textual reviews expressing different sentiments may feature the same score (and vice-versa); and 2) detecting and analyzing the mismatches between the review content and the actual score may benefit both service providers and consumers, by highlighting specific factors of satisfaction (and dissatisfaction) in texts. To prove the intuitions, we adopt sentiment analysis techniques and we concentrate on hotel reviews, to find polarity mismatches therein. In particular, we first train a text classifier with a set of annotated hotel reviews, taken from the Booking website. Then, we analyze a large dataset, with around 160k hotel reviews collected from Tripadvisor, with the aim of detecting a polarity mismatch, indicating if the textual content of the review is in line, or not, with the associated score. Using well established artificial intelligence techniques and analyzing in depth the reviews featuring a mismatch between the text polarity and the score, we find that -on a scale of five stars- those reviews ranked with middle scores include a mixture of positive and negative aspects. The approach proposed here, beside acting as a polarity detector, provides an effective selection of reviews -on an initial very large dataset- that may allow both consumers and providers to focus directly on the review subset featuring a text/score disagreement, which conveniently convey to the user a summary of positive and negative features of the review target.Comment: This is the accepted version of the paper. The final version will be published in the Journal of Cognitive Computation, available at Springer via http://dx.doi.org/10.1007/s12559-017-9496-

A Terminal Velocity on the Landscape: Particle Production near Extra Species Loci in Higher Dimensions

We investigate particle production near extra species loci (ESL) in a higher dimensional field space and derive a speed limit in moduli space at weak coupling. This terminal velocity is set by the characteristic ESL-separation and the coupling of the extra degrees of freedom to the moduli, but it is independent of the moduli's potential if the dimensionality of the field space is considerably larger than the dimensionality of the loci, D >> d. Once the terminal velocity is approached, particles are produced at a plethora of nearby ESLs, preventing a further increase in speed via their backreaction. It is possible to drive inflation at the terminal velocity, providing a generalization of trapped inflation with attractive features: we find that more than sixty e-folds of inflation for sub-Planckian excursions in field space are possible if ESLs are ubiquitous, without fine tuning of initial conditions and less tuned potentials. We construct a simple, observationally viable model with a slightly red scalar power-spectrum and suppressed gravitational waves; we comment on the presence of additional observational signatures originating from IR-cascading and individual massive particles. We also show that moduli-trapping at an ESL is suppressed for D >> d, hindering dynamical selection of high-symmetry vacua on the landscape based on this mechanism.Comment: 46 pages, 6 figures. V3: typos corrected compared to JHEP version, conclusions unchange

The U.S. training institute for dissemination and implementation research in health

Abstract Background The science of dissemination and implementation (D&I) is advancing the knowledge base for how best to integrate evidence-based interventions within clinical and community settings and how to recast the nature or conduct of the research itself to make it more relevant and actionable in those settings. While the field is growing, there are only a few training programs for D&I research; this is an important avenue to help build the field’s capacity. To improve the United States’ capacity for D&I research, the National Institutes of Health and Veterans Health Administration collaborated to develop a five-day training institute for postdoctoral level applicants aspiring to advance this science. Methods We describe the background, goals, structure, curriculum, application process, trainee evaluation, and future plans for the Training in Dissemination and Implementation Research in Health (TIDIRH). Results The TIDIRH used a five-day residential immersion to maximize opportunities for trainees and faculty to interact. The train-the-trainer-like approach was intended to equip participants with materials that they could readily take back to their home institutions to increase interest and further investment in D&I. The TIDIRH curriculum included a balance of structured large group discussions and interactive small group sessions. Thirty-five of 266 applicants for the first annual training institute were accepted from a variety of disciplines, including psychology (12 trainees); medicine (6 trainees); epidemiology (5 trainees); health behavior/health education (4 trainees); and 1 trainee each from education & human development, health policy and management, health services research, public health studies, public policy and social work, with a maximum of two individuals from any one institution. The institute was rated as very helpful by attendees, and by six months after the institute, a follow-up survey (97% return rate) revealed that 72% had initiated a new grant proposal in D&I research; 28% had received funding, and 77% had used skills from TIDIRH to influence their peers from different disciplines about D&I research through building local research networks, organizing formal presentations and symposia, teaching and by leading interdisciplinary teams to conduct D&I research. Conclusions The initial TIDIRH training was judged successful by trainee evaluation at the conclusion of the week’s training and six-month follow-up, and plans are to continue and possibly expand the TIDIRH in coming years. Strengths are seen as the residential format, quality of the faculty and their flexibility in adjusting content to meet trainee needs, and the highlighting of concrete D&I examples by the local host institution, which rotates annually. Lessons learned and plans for future TIDIRH trainings are summarized

Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), occurs in 1 in 800 live births and is the most common human aneuploidy. DS results in multiple phenotypes, including craniofacial dysmorphology, which is characterised by midfacial hypoplasia, brachycephaly and micrognathia. The genetic and developmental causes of this are poorly understood. Using morphometric analysis of the Dp1Tyb mouse model of DS and an associated mouse genetic mapping panel, we demonstrate that four Hsa21-orthologous regions of mouse chromosome 16 contain dosage-sensitive genes that cause the DS craniofacial phenotype, and identify one of these causative genes as Dyrk1a. We show that the earliest and most severe defects in Dp1Tyb skulls are in bones of neural crest (NC) origin, and that mineralisation of the Dp1Tyb skull base synchondroses is aberrant. Furthermore, we show that increased dosage of Dyrk1a results in decreased NC cell proliferation and a decrease in size and cellularity of the NC-derived frontal bone primordia. Thus, DS craniofacial dysmorphology is caused by an increased dosage of Dyrk1a and at least three other genes

Medicine Posters - 2019

Medicine Posters - 2019https://scholarlycommons.libraryinfo.bhs.org/research_education/1004/thumbnail.jp

The continuum limit of the static-light meson spectrum

We investigate the continuum limit of the low lying static-light meson spectrum using Wilson twisted mass lattice QCD with N_f = 2 dynamical quark flavours. We consider three values of the lattice spacing a ~ 0.051 fm, 0.064 fm, 0.080 fm and various values of the pion mass in the range 280 MeV < m_PS < 640 MeV. We present results in the continuum limit for light cloud angular momentum j = 1/2, 3/2, 5/2 and for parity P = +, -. We extrapolate our results to physical quark masses, make predictions regarding the spectrum of B and B_s mesons and compare with available experimental results.Comment: 18 pages, 3 figure

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes

Objective: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging (‘‘LDI FLARE area’’) in type 1 diabetes and in healthy volunteers. Research and Methods: Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm 2) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity. Results: Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70 % for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDIFLARE area. Conclusions: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of earl