Whole-tumor apparent diffusion coefficient measurements in nephroblastoma: Can it identify blastemal predominance?

PURPOSE: To explore the potential relation between whole-tumor apparent diffusion coefficient (ADC) parameters in viable parts of tumor and histopathological findings in nephroblastoma. MATERIALS AND METHODS: Children (n = 52) with histopathologically proven nephroblastoma underwent diffusion-weighted magnetic resonance imaging (MRI) (1.5T) before preoperative chemotherapy. Of these, 25 underwent an additional MRI after preoperative chemotherapy, shortly before resection. An experienced reader performed the whole-tumor ADC measurements of all lesions, excluding nonenhancing areas. An experienced pathologist reviewed the postoperative specimens according to standard SIOP guidelines. Potential associations between ADC parameters and proportions of histological subtypes were assessed with Pearson's or Spearman's rank correlation coefficient depending on whether the parameters tested were normally distributed. In case the Mann-Whitney U-test revealed significantly different ADC values in a subtype tumor, this ADC parameter was used to derive a receiver operating characteristic (ROC) curve. RESULTS: The 25(th) percentile ADC at presentation was the best ADC metric correlated with proportion of blastema (Pearson's r = -0.303, P = 0.026). ADC after preoperative treatment showed moderate correlation with proportion stromal subtype at histopathology (r = 0.579, P = 0.002). By ROC analysis, the optimal threshold of median ADC for detecting stromal subtype was 1.362 × 10(-3) mm(2) /s with sensitivity and specificity of 100% (95% confidence interval [CI] 0.65-1.00) and 78.9% (95% CI 0.57-0.92), respectively. CONCLUSION: ADC markers in nephroblastoma are related to stromal subtype histopathology; however, identification of blastemal predominant tumors using whole-tumor ADC measurements is probably not feasible. Level of Evidence 3 J. Magn. Reson. Imaging 2016;00:000-000

Measuring vertebrate telomeres: applications and limitations

Telomeres are short tandem repeated sequences of DNA found at the ends of eukaryotic chromosomes that function in stabilizing chromosomal end integrity. In vivo studies of somatic tissue of mammals and birds have shown a correlation between telomere length and organismal age within species, and correlations between telomere shortening rate and lifespan among species. This result presents the tantalizing possibility that telomere length could be used to provide much needed information on age, ageing and survival in natural populations where longitudinal studies are lacking. Here we review methods available for measuring telomere length and discuss the potential uses and limitations of telomeres as age and ageing estimators in the fields of vertebrate ecology, evolution and conservation

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy

Time to tweak the TTO: results from a comparison of alternative specifications of the TTO

Abstract This article examines the effect that different specifications of the time trade-off (TTO) valuation task may have on values for EQ-5D-5L health states. The new variants of the TTO, namely lead-time TTO and lag-time TTO, along with the classic approach to TTO were compared using two durations for the health states (15 and 20 years). The study tested whether these methods yield comparable health-state values. TTO tasks were administered online. It was found that lag-time TTO produced lower values than lead-time TTO and that the difference was larger in the longer time frame. Classic TTO values most resembled those of the lag-time TTO in a 20-year time frame in terms of mean absolute difference. The relative importance of different domains of health was systematically affected by the duration of the health state. In the tasks with a 10-year health-state duration, anxiety/ depression had the largest negative impact on health-state values; in the tasks with a 5-year duration, the pain/discomfort domain had the largest negative impact

Truth Commissions after Economic Crises: Political Learning or Blame Game?

This article addresses an important but understudied aspect of the recent Great Recession in Europe: the institutional strategies political elites deployed to learn from past policy failures and address accountability, more specifically, truth commissions. We raise two overlapping puzzles. The first concerns the timing of the decision to adopt an economic truth commission: while Iceland established a truth commission at an early stage of the crisis, Greece and Ireland did so much later. What accounts for ‘early’ versus ‘delayed’ truth seekers? The second concerns variations in learning outcomes. Iceland’s commission paved the way for learning institutional lessons, but truth commissions in Greece and Ireland became overtly politicised. What accounts for these divergences? This article compares truth commissions in Iceland, Greece and Ireland and identifies two types of political learning – institutional and instrumental – related to the establishment of a truth commission. It argues that political elites in countries with higher pre-crisis levels of trust in institutions and public transparency are more likely to establish economic truth commissions quickly; this is the ‘institutional logic’ of learning. The ‘instrumental logic’ of learning, in contrast, leads governments interested in apportioning blame to their predecessors to establish commissions at a later date, usually proximal to critical elections

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

OBJECTIVES: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. RESULTS: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. CONCLUSIONS: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. KEY POINTS: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology

Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry-based national study

BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. ----- METHODS: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. ----- RESULTS: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. ----- CONCLUSIONS: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns