Clinical relevance of circulating tumour cells in the bone marrow of patients with SCCHN

Background: Clinical outcome of patients with head and neck squamous cell carcinoma (SCCHN) depends on several risk factors like the presence of locoregional lymph node or distant metastases, stage, localisation and histologic differentiation of the tumour. Circulating tumour cells in the bone marrow indicate a poor prognosis for patients with various kinds of malignoma. The present study examines the clinical relevance of occult tumour cells in patients suffering from SCCHN. Patients and Methods: Bone marrow aspirates of 176 patients suffering from SCCHN were obtained prior to surgery and stained for the presence of disseminated tumour cells. Antibodies for cytokeratin 19 were used for immunohistochemical detection with APAAP on cytospin slides. Within a clinical follow-up protocol over a period of 60 months, the prognostic relevance of several clinicopathological parameters and occult tumour cells was evaluated. Results: Single CK19-expressing tumour cells could be detected in the bone marrow of 30.7% of the patients. There is a significant correlation between occult tumour cells in the bone marrow and relapse. Uni- and multivariate analysis of all clinical data showed the metastases in the locoregional lymph system and detection of disseminated tumour cells in the bone marrow to be statistically highly significant for clinical prognosis. Conclusion: The detection of minimal residual disease underlines the understanding of SCCHN as a systemic disease. Further examination of such cells will lead to a better understanding of the tumour biology, as well as to improvement of diagnostic and therapeutic strategies

How the First Stars Regulated Star Formation. II. Enrichment by Nearby Supernovae

Metals from Population III (Pop III) supernovae led to the formation of less massive Pop II stars in the early universe, altering the course of evolution of primeval galaxies and cosmological reionization. There are a variety of scenarios in which heavy elements from the first supernovae were taken up into second-generation stars, but cosmological simulations only model them on the largest scales. We present small-scale, high-resolution simulations of the chemical enrichment of a primordial halo by a nearby supernova after partial evaporation by the progenitor star. We find that ejecta from the explosion crash into and mix violently with ablative flows driven off the halo by the star, creating dense, enriched clumps capable of collapsing into Pop II stars. Metals may mix less efficiently with the partially exposed core of the halo, so it might form either Pop III or Pop II stars. Both Pop II and III stars may thus form after the collision if the ejecta do not strip all the gas from the halo. The partial evaporation of the halo prior to the explosion is crucial to its later enrichment by the supernova.Comment: Accepted to Ap

Toward a protocol for quantifying the greenhouse gas balance and identifying mitigation options in smallholder farming systems

Globally, agriculture is directly responsible for 14% of annual greenhouse gas (GHG) emissions and induces an additional 17% through land use change, mostly in developing countries (Vermeulen et al 2012). Agricultural intensification and expansion in these regions is expected to catalyze the most significant relative increases in agricultural GHG emissions over the next decade (Smith et al 2008, Tilman et al 2011). Farms in the developing countries of sub-Saharan Africa and Asia are predominately managed by smallholders, with 80% of land holdings smaller than ten hectares (FAO 2012). One can therefore posit that smallholder farming significantly impacts the GHG balance of these regions today and will continue to do so in the near future. However, our understanding of the effect smallholder farming has on the Earth's climate system is remarkably limited. Data quantifying existing and reduced GHG emissions and removals of smallholder production systems are available for only a handful of crops, livestock, and agroecosystems (Herrero et al 2008, Verchot et al 2008, Palm et al 2010). For example, fewer than fifteen studies of nitrous oxide emissions from soils have taken place in sub-Saharan Africa, leaving the rate of emissions virtually undocumented. Due to a scarcity of data on GHG sources and sinks, most developing countries currently quantify agricultural emissions and reductions using IPCC Tier 1 emissions factors. However, current Tier 1 emissions factors are either calibrated to data primarily derived from developed countries, where agricultural production conditions are dissimilar to that in which the majority of smallholders operate, or from data that are sparse or of mixed quality in developing countries (IPCC 2006). For the most part, there are insufficient emissions data characterizing smallholder agriculture to evaluate the level of accuracy or inaccuracy of current emissions estimates. Consequentially, there is no reliable information on the agricultural GHG budgets for developing economies. This dearth of information constrains the capacity to transition to low-carbon agricultural development, opportunities for smallholders to capitalize on carbon markets, and the negotiating position of developing countries in global climate policy discourse. Concerns over the poor state of information, in terms of data availability and representation, have fueled appeals for new approaches to quantifying GHG emissions and removals from smallholder agriculture, for both existing conditions and mitigation interventions (Berry and Ryan 2013, Olander et al 2013). Considering the dependence of quantification approaches on data and the current data deficit for smallholder systems, it is clear that in situ measurements must be a core part of initial and future strategies to improve GHG inventories and develop mitigation measures for smallholder agriculture. Once more data are available, especially for farming systems of high priority (e.g., those identified through global and regional rankings of emission hotspots or mitigation leverage points), better cumulative estimates and targeted actions will become possible. Greenhouse gas measurements in agriculture are expensive, time consuming, and error prone. These challenges are exacerbated by the heterogeneity of smallholder systems and landscapes and the diversity of methods used. Concerns over methodological rigor, measurement costs, and the diversity of approaches, coupled with the demand for robust information suggest it is germane for the scientific community to establish standards of measurements—'a protocol'—for quantifying GHG emissions from smallholder agriculture. A standard protocol for use by scientists and development organizations will help generate consistent, comparable, and reliable data on emissions baselines and allow rigorous comparisons of mitigation options. Besides enhancing data utility, a protocol serves as a benchmark for non-experts to easily assess data quality. Obviously many such protocols already exist (e.g., GraceNet, Parkin and Venterea 2010). None, however, account for the diversity and complexity of smallholder agriculture, quantify emissions and removals from crops, livestock, and biomass together to calculate the net balance, or are adapted for the research environment of developing countries; conditions that warrant developing specific methods. Here we summarize an approach being developed by the Consultative Group on International Agricultural Research's (CGIAR) Climate Change, Agriculture, and Food Security Program (CCAFS) and partners. The CGIAR-CCAFS smallholder GHG quantification protocol aims to improve quantification of baseline emission levels and support mitigation decisions. The protocol introduces five novel quantification elements relevant for smallholder agriculture (figure 1). First, it stresses the systematic collection of 'activity data' to describe the type, distribution, and extent of land management activities in landscapes cultivated by smallholder. Second, it advocates an informed sampling approach that concentrates measurement activities on emission hotspots and leverage points to capture heterogeneity and account for the diversity and complexity of farming activities. Third, it quantifies emissions at multiple spatial scales, whole-farm and landscape, to provide information targeted to household and communities decisions. Fourth, it encourages GHG research to document farm productivity and economics in addition to emissions, in recognition of the importance of agriculture to livelihoods. Fifth, it develops cost-differentiated measurement solutions that optimize the relationships among scale, cost, and accuracy. Each of the five innovations is further described in the main article

A systematic review of factors influencing treatment adherence in chronic inflammatory skin disease – strategies for optimizing treatment outcome

Adherence describes how a patient follows a medical regime recommended by a healthcare provider. Poor treatment adherence represents a complex and challenging problem of international healthcare systems, as it has a substantial impact on clinical outcomes and patient safety and constitutes an important financial burden. Since it is one of the most common causes of treatment failure, it is extremely important for physicians to reliably distinguish between non‐adherence and non‐response. This systematic review aims to summarize the current literature on treatment adherence in dermatology, focusing on chronic inflammatory skin diseases such as psoriasis, atopic dermatitis and acne. A systematic literature search was performed using the PubMed Database, including articles from 2008 to 2018. Low treatment adherence is a multidimensional phenomenon defined by the interplay of numerous factors and should under no circumstances be considered as the patient's fault alone. Factors influencing treatment adherence in dermatology include patient characteristics and beliefs, treatment efficacy and duration, administration routes, disease chronicity and the disease itself. Moreover, the quality of the physician‐patient relationship including physician‐time available for the patient plays an important role. Understanding patients’ adherence patterns and the main drivers of non‐adherence creates opportunities to improve adherence in the future. Strategies to increase treatment adherence range from reminder programs to simplifying prescriptions or educational interventions. Absolute adherence to treatment may not be realistically achievable, but efforts need to be made to raise awareness in order to maximize adherence as far as possible

Formation sites of Population III star formation: The effects of different levels of rotation and turbulence on the fragmentation behavior of primordial gas

We use the moving-mesh code arepo to investigate the effects of different levels of rotation and turbulence on the fragmentation of primordial gas and the formation of Population III stars. We consider 9 different combinations of turbulence and rotation and carry out 5 different realizations of each setup, yielding one of the largest sets of simulations of Population III star formation ever performed. We find that fragmentation in Population III star-forming systems is a highly chaotic process and show that the outcomes of individual realizations of the same initial conditions often vary significantly. However, some general trends are apparent. Increasing the turbulent energy promotes fragmentation, while increasing the rotational energy inhibits fragmentation. Within the ∼1000 yr period that we simulate, runs including turbulence yield flat protostellar mass functions while purely rotational runs show a more top-heavy distribution. The masses of the individual protostars are distributed over a wide range from a few 10−3 M⊙ to several tens of M⊙. The total mass growth rate of the stellar systems remains high throughout the simulations and depends only weakly on the degree of rotation and turbulence. Mergers between protostars are common, but predictions of the merger fraction are highly sensitive to the criterion used to decide whether two protostars should merge. Previous studies of Population III star formation have often considered only one realization per set of initial conditions. However, our results demonstrate that robust trends can only be reliably identified by considering averages over a larger sample of runs

Polyphyly of non-bioluminescent Vibrio fischeri sharing a lux-locus deletion

available in PMC 2013 May 16This study reports the first description and molecular characterization of naturally occurring, non-bioluminescent strains of Vibrio fischeri. These ‘dark’V. fischeri strains remained non-bioluminescent even after treatment with both autoinducer and aldehyde, substrate additions that typically maximize light production in dim strains of luminous bacteria. Surprisingly, the entire lux locus (eight genes) was absent in over 97% of these dark V. fischeri strains. Although these strains were all collected from a Massachusetts (USA) estuary in 2007, phylogenetic reconstructions allowed us to reject the hypothesis that these newly described non-bioluminescent strains exhibit monophyly within the V. fischeri clade. These dark strains exhibited a competitive disadvantage against native bioluminescent strains when colonizing the light organ of the model V. fischeri host, the Hawaiian bobtail squid Euprymna scolopes. Significantly, we believe that the data collected in this study may suggest the first observation of a functional, parallel locus-deletion event among independent lineages of a non-pathogenic bacterial species.National Institutes of Health (U.S.) (NIH Molecular Biosciences (5T32GM007215-35))National Institutes of Health (U.S.) (NIH Microbes in Health and Disease, training grant (2T32AI055397-07))Gordon and Betty Moore FoundationBroad Institute of MIT and Harvard (SPARC programme)National Science Foundation (U.S.) (NSF IOS 0841507)National Institutes of Health (U.S.) (NIH R01 RR12294)National Science Foundation (U.S.) (NSF Microbial Systems in the Biosphere programme)Woods Hole Center for Oceans & Human Healt

Immundefekte bei chronischer Rhinosinusitis : eine bedeutende und oft unterschätzte Ursache

Background Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. Methods A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. Results The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. Conclusion Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies

Microlocal analysis of quantum fields on curved spacetimes: Analytic wavefront sets and Reeh-Schlieder theorems

We show in this article that the Reeh-Schlieder property holds for states of quantum fields on real analytic spacetimes if they satisfy an analytic microlocal spectrum condition. This result holds in the setting of general quantum field theory, i.e. without assuming the quantum field to obey a specific equation of motion. Moreover, quasifree states of the Klein-Gordon field are further investigated in this work and the (analytic) microlocal spectrum condition is shown to be equivalent to simpler conditions. We also prove that any quasifree ground- or KMS-state of the Klein-Gordon field on a stationary real analytic spacetime fulfills the analytic microlocal spectrum condition.Comment: 31 pages, latex2

Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice.

Neural progenitor cells (NPC) represent potential cell transplantation therapies for CNS injuries. To understand how lesion environments influence transplanted NPC fate in vivo, we derived NPC expressing a ribosomal protein-hemagglutinin tag (RiboTag) for transcriptional profiling of transplanted NPC. Here, we show that NPC grafted into uninjured mouse CNS generate cells that are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, NPC transplanted into subacute CNS lesions after stroke or spinal cord injury in mice generate cells that share transcriptional, morphological and functional features with newly proliferated host astroglia that restrict inflammation and fibrosis and isolate lesions from adjacent viable neural tissue. Our findings reveal overlapping differentiation potentials of grafted NPC and proliferating host astrocytes; and show that in the absence of other interventions, non-cell autonomous cues in subacute CNS lesions direct the differentiation of grafted NPC towards a naturally occurring wound repair astroglial phenotype

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals