The clinical Transferability of Raman Micro-Spectroscopic Systems for Cervical Cytopathology

The clinical potential for Raman microscopic systems is well established for early diagnosis via cytology. Although Raman systems offer a complementary diagnostic tool providing molecular information, it is not yet utilised substantially in clinics. A few challenges for the clinical implementation of Raman spectroscopy are system and user variability. In this study, we asked how much variability occurs due to different Raman systems or users. To address these questions, we measured the same set of cells using two different Raman microscopes and by two different users. And classification models were generated using multivariate partial least squares discriminant analysis (PLS-DA) and analysed for clinical implementation. Raman spectra were measured from single exfoliated cells (n=400) from ThinPrep samples with negative cytology (n=10) and high-grade cytology (n=10). Raman spectra were acquired from the same set of cells via two identical HORIBA Jobin Yvon XploRATM systems (Villeneuve d\u27Ascq, France), as well as two different users. The Raman data was subjected to PLS-DA and cross-validated via leave-one-patient out. The study\u27s findings suggest that the data acquired from the two Raman systems are 99% identical. However, the observed classification accuracy for the data obtained by user-1 was 92%, whereas by user-2 was 99%

Discrete time measures versus trajectories of drinking frequency across adolescence as predictors of binge drinking in young adulthood: a longitudinal investigation

OBJECTIVES: We compared discrete time measures with trajectories of adolescent drinking frequency as predictors of sustained binge drinking in young adulthood. DESIGN: Prospective longitudinal study. SETTING: 10 high schools in Montreal, Canada. PARTICIPANTS: 1293 high-school students followed from mean (SD) age 12 (0.6) to 24 (0.7) years. PRIMARY OUTCOME MEASURES: Patterns of drinking frequency (self-reports every 3 months from ages 12 to 17) identified using group-based trajectory modelling. Sustained binge drinking was defined as binging monthly or more often at both ages 20 and 24. ANALYSES: Using logistic regression, sustained binge drinking was regressed on trajectory group membership and on four discrete time measures (frequency of drinking at age 12; frequency of drinking at age 17; age at drinking onset; age at onset of drinking monthly or more often). RESULTS: We identified seven drinking trajectories: late triers (15.2%), decreasers (9.5%), late escalators (10.4%), early slow escalators (16.5%), steady drinkers (14.4%), early rapid escalators (15.8%) and early frequent drinkers (18.2%). Sustained binge drinking was reported by 260 of 787 participants (33.0%) with complete data at both ages 20 and 24. Decreasers did not differ from late triers; all other patterns were associated with higher odds of sustained binge drinking (adjusted ORs: AORs=1.4-17.0). All discrete time measures were associated with sustained binge drinking, notably frequency at age 12 (a bit to try and drinking monthly: (AORs=2.6 (1.7; 3.9) and 2.8 (1.3; 6.1), respectively), age of drinking onset \u3c 13 years (AOR=7.6 (3.0; 24.1)), and any age of onset of drinking monthly or more often (AORs=5.1-8.2). CONCLUSION: Youth at risk of sustained binge drinking as young adults can be identified with indicators of early drinking as early as 7th grade (aged 12-13 years). Identification of easy-to-obtain indicators can facilitate screening and intervention efforts

Climate as a risk factor for armed conflict

This is the author accepted manuscriptResearch findings on the relationship between climate and conflict are diverse and contested. Here we assess the current understanding of the relationship between climate and conflict, based on the structured judgments of experts from diverse disciplines. These experts agree that climate has affected organized armed conflict within countries. However, other drivers, such as low socioeconomic development and low capabilities of the state, are judged to be substantially more influential, and the mechanisms of climate–conflict linkages remain a key uncertainty. Intensifying climate change is estimated to increase future risks of conflict.European Research Counci

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS

Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases

Strengthening fairness, transparency and accountability in health care priority setting at district level in Tanzania

Health care systems are faced with the challenge of resource scarcity and have insufficient resources to respond to all health problems and target groups simultaneously. Hence, priority setting is an inevitable aspect of every health system. However, priority setting is complex and difficult because the process is frequently influenced by political, institutional and managerial factors that are not considered by conventional priority-setting tools. In a five-year EU-supported project, which started in 2006, ways of strengthening fairness and accountability in priority setting in district health management were studied. This review is based on a PhD thesis that aimed to analyse health care organisation and management systems, and explore the potential and challenges of implementing Accountability for Reasonableness (A4R) approach to priority setting in Tanzania. A qualitative case study in Mbarali district formed the basis of exploring the sociopolitical and institutional contexts within which health care decision making takes place. The study also explores how the A4R intervention was shaped, enabled and constrained by the contexts. Key informant interviews were conducted. Relevant documents were also gathered and group priority-setting processes in the district were observed. The study revealed that, despite the obvious national rhetoric on decentralisation, actual practice in the district involved little community participation. The assumption that devolution to local government promotes transparency, accountability and community participation, is far from reality. The study also found that while the A4R approach was perceived to be helpful in strengthening transparency, accountability and stakeholder engagement, integrating the innovation into the district health system was challenging. This study underscores the idea that greater involvement and accountability among local actors may increase the legitimacy and fairness of priority-setting decisions. A broader and more detailed analysis of health system elements, and socio-cultural context is imperative in fostering sustainability. Additionally, the study stresses the need to deal with power asymmetries among various actors in priority-setting contexts

Experimental study of dense pyroclastic density currents using sustained, gas-fluidized granular flows

© 2014, Springer-Verlag Berlin Heidelberg. We present the results of laboratory experiments on the behaviour of sustained, dense granular flows in a horizontal flume, in which high-gas pore pressure was maintained throughout the flow duration by continuous injection of gas through the flume base. The flows were fed by a sustained (0.5–30 s) supply of fine (75 ± 15 μm) particles from a hopper; the falling particles impacted an impingement surface at concentrations of ~3 to 45 %, where they densified rapidly to generate horizontally moving, dense granular flows. When the gas supplied through the flume base was below the minimum fluidization velocity of the particles (i.e. aerated flow conditions), three flow phases were identified: (i) an initial dilute spray of particles travelling at 1–2 m s−1, followed by (ii) a dense granular flow travelling at 0.5–1 m s−1, then by (iii) sustained aggradation of the deposit by a prolonged succession of thin flow pulses. The maximum runout of the phase 2 flow was linearly dependent on the initial mass flux, and the frontal velocity had a square-root dependence on mass flux. The frontal propagation speed during phase 3 had a linear relationship with mass flux. The total mass of particles released had no significant control on either flow velocity or runout in any of the phases. High-frequency flow unsteadiness during phase 3 generated deposit architectures with progradational and retrogradational packages and multiple internal erosive contacts. When the gas supplied through the flume base was equal to the minimum fluidization velocity of the particles (i.e. fluidized flow conditions), the flows remained within phase 2 for their entire runout, no deposit formed and the particles ran off the end of the flume. Sustained granular flows differ significantly from instantaneous flows generated by lock-exchange mechanisms, in that the sustained flows generate (by prolonged progressive aggradation) deposits that are much thicker than the flowing layer of particles at any given moment. The experiments offer a first attempt to investigate the physics of the sustained pyroclastic flows that generate thick, voluminous ignimbrites

Scale and Translation Invariant Methods for Enhanced Time-Frequency Pattern Recognition

Time-frequency (t-f) analysis has clearly reached a certain maturity. One can now often provide striking visual representations of the joint time-frequency energy representation of signals. However, it has been difficult to take advantage of this rich source of information concerning the signal, especially for multidimensional signals. Properly constructed time-frequency distributions enjoy many desirable properties. Attempts to incorporate t-f analysis results into pattern recognition schemes have not been notably successful to date. Aided by Cohen's scale transform one may construct representations from the t-f results which are highly useful in pattern classification. Such methods can produce two dimensional representations which are invariant to time-shift, frequency-shift and scale changes. In addition, two dimensional objects such as images can be represented in a like manner in a four dimensional form. Even so, remaining extraneous variations often defeat the pattern classification approach. This paper presents a method based on noise subspace concepts. The noise subspace enhancement allows one to separate the desired invariant forms from extraneous variations, yielding much improved classification results. Examples from sound classification are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47350/1/11045_2004_Article_181150.pd

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty