New insights into the ∼74ka Toba eruption from sulfur isotopes of polar ice cores

Abstract. The ∼74 ka Toba eruption was one of the largest volcanic events of the Quaternary. There is much interest in determining the impact of such a large event, particularly on the climate and hominid populations at the time. Although the Toba eruption has been identified in both land and marine archives as the Youngest Toba Tuff, its precise place in the ice core record is ambiguous. Several volcanic sulfate signals have been identified in both Antarctic and Greenland ice cores and span the Toba eruption 40Ar/39Ar age uncertainty. Here, we measure sulfur isotope compositions in Antarctic ice samples from the Dome C (EDC) and Dronning Maud Land (EDML) ice cores at high temporal resolution across 11 of these potential Toba sulfate peaks to identify candidates with sulfur mass-independent fractionation (S-MIF), indicative of an eruption whose plume reached altitudes at or above the stratospheric ozone layer. Using this method, we identify several candidate sulfate peaks that contain stratospheric sulfur. We further narrow down potential candidates based on the isotope signatures by identifying sulfate peaks that are due to a volcanic event at tropical latitudes. In one of these sulfate peaks at 73.67 ka, we find the largest ever reported magnitude of S-MIF in volcanic sulfate in polar ice, with a Δ33S value of −4.75 ‰. As there is a positive correlation between the magnitude of the S-MIF signal recorded in ice cores and eruptive plume height, this could be a likely candidate for the Toba super-eruption, with a plume top height in excess of 45 km. These results support the 73.7±0.3 ka (1σ) 40Ar/39Ar age estimate for the eruption, with ice core ages of our candidates with the largest magnitude S-MIF at 73.67 and 73.74 ka. Finally, since these candidate eruptions occurred on the transition into Greenland Stadial 20, the relative timing suggests that Toba was not the trigger for the large Northern Hemisphere cooling at this time although we cannot rule out an amplifying effect. Royal Societ

Underutilization of information and knowledge in everyday medical practice: Evaluation of a computer-based solution

<p>Abstract</p> <p>Background</p> <p>The medical history is acknowledged as the <it>sine qua non </it>for quality medical care because recognizing problems is pre-requisite for managing them. Medical histories typically are incomplete and inaccurate, however. We show here that computers are a solution to this issue of information gathering about patients. Computers can be programmed to acquire more complete medical histories with greater detail across a range of acute and chronic issues than physician histories.</p> <p>Methods</p> <p>Histories were acquired by physicians in the usual way and by a computer program interacting directly with patients. Decision-making of what medical issues were queried by computer were made internally by the software, including determination of the chief complaint. The selection of patients was from admissions to the Robert-Bosch-Hospital, Stuttgart, Germany by convenience sampling. Physician-acquired and computer-acquired histories were compared on a patient-by-patient basis for 45 patients.</p> <p>Results</p> <p>The computer histories reported 160 problems not recorded in physician histories or slightly more than 3.5 problems per patient. However, physicians but not the computer reported 13 problems. The data show that computer histories reported problems across a range of organ systems, that the problems detected by computer but not physician histories were both acute and chronic and that the computer histories detected a significant number of issues important for preventing further morbidity.</p> <p>Conclusion</p> <p>A combination of physician and computer-acquired histories, in non-emergent situations, with the latter available to the physician at the time he or she sees the patient, is a far superior method for collecting historical data than the physician interview alone.</p

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Lorentzian and Euclidean Quantum Gravity - Analytical and Numerical Results

We review some recent attempts to extract information about the nature of quantum gravity, with and without matter, by quantum field theoretical methods. More specifically, we work within a covariant lattice approach where the individual space-time geometries are constructed from fundamental simplicial building blocks, and the path integral over geometries is approximated by summing over a class of piece-wise linear geometries. This method of ``dynamical triangulations'' is very powerful in 2d, where the regularized theory can be solved explicitly, and gives us more insights into the quantum nature of 2d space-time than continuum methods are presently able to provide. It also allows us to establish an explicit relation between the Lorentzian- and Euclidean-signature quantum theories. Analogous regularized gravitational models can be set up in higher dimensions. Some analytic tools exist to study their state sums, but, unlike in 2d, no complete analytic solutions have yet been constructed. However, a great advantage of our approach is the fact that it is well-suited for numerical simulations. In the second part of this review we describe the relevant Monte Carlo techniques, as well as some of the physical results that have been obtained from the simulations of Euclidean gravity. We also explain why the Lorentzian version of dynamical triangulations is a promising candidate for a non-perturbative theory of quantum gravity.Comment: 69 pages, 16 figures, references adde

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Childhood adversity, mental ill-health and aggressive behavior in an African orphanage: Changes in response to trauma-focused therapy and the implementation of a new instructional system

<p>Abstract</p> <p>Background</p> <p>The number of orphans in Sub-Saharan Africa is constantly rising. While it is known that family or community care is preferable over institutional care of African orphans, little is known about the quality of care in orphanages and possibilities of improvement.</p> <p>Study 1</p> <p>Methods</p> <p>Exposure to traumatic stress, experiences of violence in the home, school and orphanage, as well as mental ill-health and aggression of 38 children (mean age of <it>M </it>= 8.64 years) living in an orphanage in rural Tanzania were assessed at two time points. The severity of post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and internalizing and externalizing problems were used as indicators of mental ill-health.</p> <p>Results</p> <p>Violence experienced in the orphanage correlated more strongly with all indicators of mental ill-health than violence in the former home, school or neighborhood at time point 1. Additionally, violence experienced in the orphanage had a positive relationship with the aggressive behavior of the children at time point 2.</p> <p>Study 2</p> <p>Methods</p> <p>With the help of the pre-post assessment of Study 1, the implementation of a new instructional system and psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.</p> <p>Results</p> <p>In response to both, a change in the instructional system and psychotherapeutic treatment of PTSD, a massive decline in experienced violence and in the severity of PTSD-symptoms was found, whereas depressive symptoms and internalizing and externalizing problems exhibited little change.</p> <p>Conclusions</p> <p>These studies show that violence, especially in the orphanage, can severely contribute to mental ill-health in orphans and that mental health can be improved by implementing a new instructional system and psychotherapeutic treatment in an orphanage. Moreover, the results indicate that the experience of violence in an orphanage also plays a crucial role in aggressive behavior of the orphans.</p

Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data

<p>Abstract</p> <p>Background</p> <p>Molecular studies of breast cancer revealed biological heterogeneity of the disease and opened new perspectives for personalized therapy. While multiple gene expression-based systems have been developed, current clinical practice is largely based upon conventional clinical and pathologic criteria. This gap may be filled by development of combined multi-IHC indices to characterize biological and clinical behaviour of the tumours. Digital image analysis (DA) with multivariate statistics of the data opens new opportunities in this field.</p> <p>Methods</p> <p>Tissue microarrays of 109 patients with breast ductal carcinoma were stained for a set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16). Aperio imaging platform with the Genie, Nuclear and Membrane algorithms were used for the DA. Factor analysis of the DA data was performed in the whole group and hormone receptor (HR) positive subgroup of the patients (n = 85).</p> <p>Results</p> <p>Major factor potentially reflecting aggressive disease behaviour (i-Grade) was extracted, characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α. The i-Grade factor scores revealed bimodal distribution and were strongly associated with higher Nottingham histological grade (G) and more aggressive intrinsic subtypes. In HR-positive tumours, the aggressiveness of the tumour was best defined by positive Ki67 and negative ER loadings. High Ki67/ER factor scores were strongly associated with the higher G and Luminal B types, but also were detected in a set of G1 and Luminal A cases, potentially indicating high risk patients in these categories. Inverse relation between HER2 and PR expression was found in the HR-positive tumours pointing at differential information conveyed by the ER and PR expression. SATB1 along with HIF-1α reflected the second major factor of variation in our patients; in the HR-positive group they were inversely associated with the HR and BCL2 expression and represented the major factor of variation. Finally, we confirmed high expression levels of p16 in Triple-negative tumours.</p> <p>Conclusion</p> <p>Factor analysis of multiple IHC biomarkers measured by automated DA is an efficient exploratory tool clarifying complex interdependencies in the breast ductal carcinoma IHC profiles and informative value of single IHC markers. Integrated IHC indices may provide additional risk stratifications for the currently used grading systems and prove to be useful in clinical outcome studies.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/1512077125668949</url></p

Common Avian Infection Plagued the Tyrant Dinosaurs

Background: Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name 'Sue') has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids

Establishing an implementation network: lessons learned from community-based participatory research

<p>Abstract</p> <p>Background</p> <p>Implementation of evidence-based mental health assessment and intervention in community public health practice is a high priority for multiple stakeholders. Academic-community partnerships can assist in the implementation of efficacious treatments in community settings; yet, little is known about the processes by which these collaborations are developed. In this paper, we discuss our application of community-based participatory research (CBPR) approach to implementation, and we present six lessons we have learned from the establishment of an academic-community partnership.</p> <p>Methods</p> <p>With older adults with psychosis as a focus, we have developed a partnership between a university research center and a public mental health service system based on CBPR. The long-term goal of the partnership is to collaboratively establish an evidence-based implementation network that is sustainable within the public mental healthcare system.</p> <p>Results</p> <p>In building a sustainable partnership, we found that the following lessons were instrumental: changing attitudes; sharing staff; expecting obstacles and formalizing solutions; monitoring and evaluating; adapting and adjusting; and taking advantage of emerging opportunities. Some of these lessons were previously known principles that were modified as the result of the CBPR process, while some lessons derived directly from the interactive process of forming the partnership.</p> <p>Conclusion</p> <p>The process of forming of academic-public partnerships is challenging and time consuming, yet crucial for the development and implementation of state-of-the-art approaches to assessment and interventions to improve the functioning and quality of life for persons with serious mental illnesses. These partnerships provide necessary organizational support to facilitate the implementation of clinical research findings in community practice benefiting consumers, researchers, and providers.</p