We previously reported the advantages of (18)F-fluorodeoxyglucose-positron emission tomography (PET) fused with CT for radiotherapy planning over CT alone in head and neck carcinoma (HNC). The ...purpose of this study was to evaluate clinical outcomes and the predictive value of PET for patients receiving PET/CT-guided definitive radiotherapy with or without chemotherapy.
From December 2002 to August 2006, 42 patients received PET/CT imaging as part of staging and radiotherapy planning. Clinical outcomes including locoregional recurrence, distant metastasis, death, and treatment-related toxicities were collected retrospectively and analyzed for disease-free and overall survival and cumulative incidence of recurrence.
Median follow-up from initiation of treatment was 32 months. Overall survival and disease-free survival were 82.8% and 71.0%, respectively, at 2 years, and 74.1% and 66.9% at 3 years. Of the 42 patients, seven recurrences were identified (three LR, one DM, three both LR and DM). Mean time to recurrence was 9.4 months. Cumulative risk of recurrence was 18.7%. The maximum standard uptake volume (SUV) of primary tumor, adenopathy, or both on PET did not correlate with recurrence, with mean values of 12.0 for treatment failures vs. 11.7 for all patients. Toxicities identified in those patients receiving intensity modulated radiation therapy were also evaluated.
A high level of disease control combined with favorable toxicity profiles was achieved in a cohort of HNC patients receiving PET/CT fusion guided radiotherapy plus/minus chemotherapy. Maximum SUV of primary tumor and/or adenopathy was not predictive of risk of disease recurrence.
We use data from the Meso‐America Subduction Experiment to detect and locate low‐frequency earthquakes (LFEs) in the Mexican subduction zone. We use visually‐identified templates to perform a network ...waveform correlation search that produced ~17,000 robustly detected LFEs that form 15 distinct families. Stacking an LFE family's corresponding detections results in seismograms with high signal‐to‐noise ratios and clear P and S wave arrivals; we use these travel times to locate the sources. The resulting locations superpose a previously identified region of permanent non‐volcanic tremor (NVT) activity. Husker et al. (2012) called this region a Sweet Spot, suggesting that the local conditions are adequate to continuously generate NVT. The LFE hypocenters have been located at a depth of 40–45 km in an area that is surrounding the upper slab‐plate interface. We characterize their focal mechanisms by comparing their stacked seismograms to synthetic seismograms. This analysis reveals a common low‐dipping focal mechanism.
Key Points
Detected and characterized 15 low‐frequency earthquake families in Mexico
Sources locate to a region known for constant non‐volcanic tremor activity
Focal mechanisms reflect shearing on the subducting plate interface
Urbanization strongly affects biodiversity, altering natural communities and often leading to a reduced species richness. Yet, despite its increasingly recognized importance, how urbanization impacts ...on the health of individual animals, wildlife populations and on disease ecology remains poorly understood. To test whether, and how, urbanization-driven ecosystem alterations influence pathogen dynamics and avian health, we use house sparrows (Passer domesticus) and Yersinia spp. (pathogenic for passerines) as a case study. Sparrows are granivorous urban exploiters, whose western European populations have declined over the past decades, especially in highly urbanized areas. We sampled 329 house sparrows originating from 36 populations along an urbanization gradient across Flanders (Belgium), and used isolation combined with 'matrix-assisted laser desorption ionization- time of flight mass spectrometry' (MALDI-TOF MS) and PCR methods for detecting the presence of different Yersinia species. Yersinia spp. were recovered from 57.43% of the sampled house sparrows, of which 4.06%, 53.30% and 69.54% were identified as Y. pseudotuberculosis, Y. enterocolitica and other Yersinia species, respectively. Presence of Yersinia was related to the degree of urbanization, average daily temperatures and the community of granivorous birds present at sparrow capture locations. Body condition of suburban house sparrows was found to be higher compared to urban and rural house sparrows, but no relationships between sparrows' body condition and presence of Yersinia spp. were found. We conclude that two determinants of pathogen infection dynamics, body condition and pathogen occurrence, vary along an urbanization gradient, potentially mediating the impact of urbanization on avian health.
The integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence ...both clonal expansion and persistence of infected cells. Methods based on short-read sequencing can identify viral insertion sites, but the sequence of the viral genomes within remains unobserved. We develop PCIP-seq, a method that leverages long reads to identify insertion sites and sequence their associated viral genome. We apply the technique to exogenous retroviruses HTLV-1, BLV, and HIV-1, endogenous retroviruses, and human papillomavirus.
The relationship between residual depressive symptoms, cognition and functioning in patients with euthymic bipolar disorder is a subject of debate.
To assess whether cognition mediates the ...association between residual depressive symptoms and functioning in patients with bipolar disorder who were euthymic.
We included 241 adults with euthymic bipolar disorder in a multicentre cross-sectional study. We used a battery of tests to assess six cognition domains. A path analysis was then used to perform a mediation analysis of the relationship between residual depressive symptoms, cognitive components and functioning.
Only verbal and working memory were significantly associated with better functioning. Residual depressive symptoms were associated with poorer functioning. No significant relationship was found between residual depressive symptoms and any cognitive component.
Cognition and residual depressive symptoms appear to be two independent sources of variation in the functioning of people with euthymic bipolar disorder.
Spatiotemporal variations of natural selection may influence the evolution of various features of organisms such as local adaptation or specialisation. This article develops a method for inferring ...how selection varies between locations and between generations from phenotypic data. It is assumed that generations are non-overlapping and that individuals reproduce by selfing or asexually. A quantitative genetics model taking account of the effects of stabilising natural selection, the environment and mutation on phenotypic means and variances is developed. Explicit results on the evolution of populations are derived and used to develop a Bayesian inference method. The latter is applied to simulated data and to data from a wheat participatory plant breeding programme. It has some ability to infer evolutionary parameters, but estimates may be sensitive to prior distributions, for example when phenotypic time series are short and when environmental effects are large. In such cases, sensitivity to prior distributions may be reported or more data may be collected.
We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn ...variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.
Objectives Our purpose was to evaluate the efficacy of antiarrhythmic drugs (AADs) in recurrent ventricular fibrillation (VF) associated with inferolateral early repolarization pattern on the ...electrocardiogram. Background Although an implantable cardioverter-defibrillator is the treatment of choice, additional AADs may be necessary to prevent frequent episodes of VF and reduce implantable cardioverter-defibrillator shock burden or as a lifesaving therapy in electrical storms. Methods From a multicenter cohort of 122 patients (90 male subjects, age 37 ± 12 years) with idiopathic VF and early repolarization abnormality in the inferolateral leads, we selected all patients with more than 3 episodes of VF (multiple) including those with electrical storms (≥3 VF in 24 h). The choice of AAD was decided by individual physicians. Follow-up data were obtained for all patients using monitoring with implantable defibrillator. Successful oral AAD was defined as elimination of all recurrences of VF with a minimal follow-up period of 12 months. Results Multiple episodes of VF were observed in 33 (27%) patients. Electrical storms (34 ± 47 episodes) occurred in 16 and were unresponsive to beta-blockers (11 of 11), lidocaine/mexiletine (9 of 9), and verapamil (3 of 3), while amiodarone was partially effective (3 of 10). In contrast, isoproterenol infusion immediately suppressed electrical storms in 7 of 7 patients. Over a follow-up of 69 ± 58 months, oral AADs were poorly effective in preventing recurrent VF: beta-blockers (2 of 16), verapamil (0 of 4), mexiletine (0 of 4), amiodarone (1 of 7), and class 1C AADs (2 of 9). Quinidine was successful in 9 of 9 patients, decreasing recurrent VF from 33 ± 35 episodes to nil for 25 ± 18 months. In addition, quinidine restored a normal electrocardiogram. Conclusions Multiple recurrences of VF occurred in 27% of patients with early repolarization abnormality and may be life threatening. Isoproterenol in acute cases and quinidine in chronic cases are effective AADs.
•Genes rather than environment contribute to family resemblance in academic motivation.•Environmental influences stemmed entirely from individual specific experiences.•Attending same vs. different ...classes did not affect twin similarity in motivation.•Results are similar across ages, countries and academic subjects.
Little is known about why people differ in their levels of academic motivation. This study explored the etiology of individual differences in enjoyment and self-perceived ability for several school subjects in nearly 13,000 twins aged 9–16 from 6 countries. The results showed a striking consistency across ages, school subjects, and cultures. Contrary to common belief, enjoyment of learning and children’s perceptions of their competence were no less heritable than cognitive ability. Genetic factors explained approximately 40% of the variance and all of the observed twins’ similarity in academic motivation. Shared environmental factors, such as home or classroom, did not contribute to the twin’s similarity in academic motivation. Environmental influences stemmed entirely from individual specific experiences.