Search

Sclerosing epithelioid fibrosarcoma (SEF) is a rare, malignant fibroblastic neoplasm, morphologically composed of cords, nests or sheets of monotonous epithelioid cells within a collagenous matrix. It has been recently characterized by recurrent pathogenic EWS-CREB3L1/2 or FUS-CREB3L2 fusions and common MUC4 protein expression by immunohistochemistry. Typically SEF occur in middle-aged adults and rarely have been reported within the abdominal cavity. Here we report an 18-year-old man with intraabdominal tumor and multiple disseminated liver metastases, presenting pure SEF histologic and immunophenotypic features. Fluorescence in situ hybridization analysis showed unbalanced rearrangement of Ewing sarcoma breakpoint region 1 (EWSR1) gene. Genomic profiling by array CGH, followed by RT-PCR and sequencing analysis, revealed a previously not reported EWSR1 translocation partner, cAMP-responsive element-binding protein 3-like 3 (CREB3L3). The novel EWSR1-CREB3L3 fusion further extends the range of fusion types involving EWSR1 that are characteristic for SEF.

Religious rituals are found all over the world. Some cultures engage in extreme religious rituals in which individuals take on forms of bodily harm to demonstrate their devotion. Such rituals entail excessive costs in terms of physical pain and effort, but the equivalent societal benefits remain unclear. The field experiment reported here examined the interplay between extreme rituals and moral behavior. Using a die-roll task to measure honest behavior, we tested whether engaging or observing others engaging in extreme ritual activities affects subsequent moral behavior. Strikingly, the results showed that extreme rituals promote moral behavior among ritual observers, but not among ritual performers. The discussion centres on the moral effects of rituals within the broader social context in which they occur. Extreme religious rituals appear to have a moral cleansing effect on the numerous individuals observing the rituals, which may imply that these rituals evolved to advance and maintain moral societies.

Camille Wingo, Pictures Making Beliefs: A Cognitive Technological Model for Ritual Efficacy (Durham, NC: Carolina Academic Press, 2012), 238 pp. $30.00 (pbk). ISBN: 978-1-59460-973-2.

Background The World Health Organization Essential Medicines List (WHO-EML) includes ‘access’ antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of ‘forgotten’ antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications. Objective To investigate which WHO-EML ‘access’ and ‘forgotten’ antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs). Methods The Scientific Committee used a consensus procedure to select 26 WHO-EML ‘access’ and 15 ‘forgotten’ antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market. Results Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML ‘access’ antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 ‘access’ antibiotics were approved in more than two-thirds of countries. Among the 15 ‘forgotten’ antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23–35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries. Conclusions WHO-EML ‘access’ antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the ‘forgotten’ antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria.

Objectives: With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. Methods: A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. Results: The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with >= 80% agreement; 20 elements and items were rephrased. Conclusions: This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Driver mutations occur in Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), and calreticulin (CALR) in BCR-ABL1 negative myeloproliferative neoplasms (MPNs). From mutations leading to one amino acid substitution in JAK2 or MPL, to frameshift mutations in CALR resulting in a protein with a different C-terminus, all the mutated proteins lead to pathologic and persistent JAK2-STAT5 activation. The most prevalent mutation, JAK2 V617F, is associated with the 3 entities polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), while CALR and MPL mutations are associated only with ET and MF. Triple negative ET and MF patients may harbor noncanonical mutations in JAK2 or MPL. One major fundamental question is whether the conformations of JAK2 V617F, MPL W515K/L/A, or CALR mutants differ from those of their wild type counterparts so that a specific treatment could target the clone carrying the mutated driver and spare physiological hematopoiesis. Of great interest, a set of epigenetic mutations can co-exist with the phenotypic driver mutations in 35%–40% of MPNs. These epigenetic mutations, such as TET2, EZH2, ASXL1, or DNMT3A mutations, promote clonal hematopoiesis and increased fitness of aged hematopoietic stem cells in both clonal hematopoiesis of indeterminate potential (CHIP) and MPNs. Importantly, the main MPN driver mutation JAK2 V617F is also associated with CHIP. Accumulation of several epigenetic and splicing mutations favors progression of MPNs to secondary acute myeloid leukemia. Another major fundamental question is how epigenetic rewiring due to these mutations interacts with persistent JAK2-STAT5 signaling. Answers to these questions are required for better therapeutic interventions aimed at preventing progression of ET and PV to MF, and transformation of these MPNs in secondary acute myeloid leukemia.

Social and labour movements need a coherent critique of science and technology, it was argued at a meeting on “Radical Science and Alternative Technology”, held in London on 11 April 2015. On a pra...

Dear Editor, Myeloproliferative neoplasms (MPNs) are rare diseases in children [1] when compared to adults [2]. Targeted sequencing revealed differences in the mutational landscape of pediatric and adult MPNs [1]. Children exhibit a lower frequency of mutations in the MPN driver genes JAK2, MPL, and CALR, and a much higher proportion of children exhibit no mutation among the 104 classically involved genes; these children exhibiting a trend towards essential thrombocythemia (ET) [1]. We were surprised to read about an activating thrombopoietin receptor (TpoR/Mpl) S505A transmembrane domain (TM) mutation in childhood hereditary thrombocytosis (HT) and ET [3–5]. [...]

Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation. Female mice received a single 4 Gy whole-brain radiation dose on postnatal day (PND) 21 and were randomized to 0.24% Li2CO3 chow or normal chow from PND 49 to 77. Hippocampal neurogenesis was assessed on PND 77, 91, and 105. We found that lithium treatment had a pro-proliferative effect on neural progenitors, but neuronal integration occurred only after it was discontinued. Also, the treatment ameliorated deficits in spatial learning and memory retention observed in irradiated mice. Gene expression profiling and DNA methylation analysis identified two novel factors related to the observed effects, Tppp, associated with microtubule stabilization, and GAD2/65, associated with neuronal signaling. Our results show that lithium treatment reverses irradiation-induced loss of hippocampal neurogenesis and cognitive impairment even when introduced long after the injury. We propose that lithium treatment should be intermittent in order to first make neural progenitors proliferate and then, upon discontinuation, allow them to differentiate. Our findings suggest that pharmacological treatment of cognitive so-called late effects in childhood cancer survivors is possible.

Unavailability of old antibiotics threatens effective treatment for common bacterial infections

Summary Background The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. Methods We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. Findings We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa , and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus . Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori , and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae , and Salmonella typhi were included in the high-priority tier. Interpretation Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae , and H pylori . Funding World Health Organization.

Few biologists have studied the evolutionary processes at work in indoor environments. Yet indoor environments comprise approximately 0.5% of ice-free land area--an area as large as the subtropical coniferous forest biome. Here we review the emerging subfield of 'indoor biome' studies. After defining the indoor biome and tracing its deep history, we discuss some of its evolutionary dimensions. We restrict our examples to the species found in human houses--a subset of the environments constituting the indoor biome--and offer preliminary hypotheses to advance the study of indoor evolution. Studies of the indoor biome are situated at the intersection of evolutionary ecology, anthropology, architecture, and human ecology and are well suited for citizen science projects, public outreach, and large-scale international collaborations.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare, malignant fibroblastic neoplasm, morphologically composed of cords, nests or sheets of monotonous epithelioid cells within a collagenous matrix. It has been recently characterized by recurrent pathogenic EWS-CREB3L1/2 or FUS-CREB3L2 fusions and common MUC4 protein expression by immunohistochemistry. Typically SEF occur in middle-aged adults and rarely have been reported within the abdominal cavity. Here we report an 18-year-old man with intraabdominal tumor and multiple disseminated liver metastases, presenting pure SEF histologic and immunophenotypic features. Fluorescence in situ hybridization analysis showed unbalanced rearrangement of Ewing sarcoma breakpoint region 1 (EWSR1) gene. Genomic profiling by array CGH, followed by RT-PCR and sequencing analysis, revealed a previously not reported EWSR1 translocation partner, cAMP-responsive element-binding protein 3-like 3 (CREB3L3). The novel EWSR1-CREB3L3 fusion further extends the range of fusion types involving EWSR1 that are characteristic for SEF.

According to Deborah Tollefsen, from the analytic perspective called “interpretivism”, there is a reasonable way in which groups can be said to have mental states. She bases her argument on the every-day use of language, where people speak as if groups have states such as intentions, desires and wishes. Such propositional attitudes form the basis of any account of truth-conditional semantics, the rules by which people grasp the conditions under which an utterance is true. If groups (abstract units of people) have mental states, perhaps superhuman agents have them too. One argument that may contradict this premise is one that says that, whereas groups exist, superhuman agents do not. However, if groups exist on the basis of normative narratives about them and the institutionalized actions they carry out in the world, the same can be said for superhuman agents. They are like legal fictions: fictional but real. Superhuman agents are fictional and real in a similar sense as groups.1

Norenzayan's book is an ambitious attempt to integrate recent research from behavioral economics and social psychology, particularly priming studies, into a book about religion. If the account is meant as an explanation of religion or big religion, it does not succeed. If it has more modest aims, namely to describe how surveillance institutions, of which big religion is one important class, can sometimes lead to cooperation and conflict, then it is quite successful in doing so.

Infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacilli are increasingly challenging to manage in hospitals and long term-care facilities worldwide. As the therapeutic options are limited, the International Society of Chemotherapy in collaboration with the Asia-Pacific Society of Clinical Microbiology and Immunology organised a consensus conference as part of the 13th Asia-Pacific Congress of Clinical Microbiology and Infection. A panel of international experts from Europe, the Americas and Asia were convened to discuss the issues of therapeutic options for the management of these difficult-to-treat pathogens.

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased during the past 10 years. Its detection is frequently difficult, because they do not always show a minimum inhibitory concentration (MIC) value for carbapenems in the resistance range. Both broth microdilution and agar dilution methods are more sensitive than disk diffusion method, Etest and automated systems. Studies on antimicrobial treatment are based on a limited number of patients; therefore, the optimal treatment is not well established. Combination therapy with two active drugs appears to be more effective than monotherapy. Combination of a carbapenem with another active agent--preferentially an aminoglycoside or colistin--could lower mortality provided that the MIC is ≤4 mg/l and probably ≤8 mg/l, and is administered in a higher-dose/prolonged-infusion regimen. An aggressive infection control and prevention strategy is recommended, including reinforcement of hand hygiene, using contact precautions and early detection of CPE through use of targeted surveillance.

The book is made up of a series of conference papers and previously published essays. No attempt is made at relating the essays, so the reader gets no real sense of structure for the book as a whole or sense of what the author intends the book to accomplish, other than a kind of Bruce Lincoln’s “Recent Hits.” This is not necessarily a critique, unless one thinks that explicitly stated coherence is a requirement of scholarly books. If a red thread can be traced in this very rich assortment it must be found already (and perhaps only) in the title, where we find that the book is about the relationship between Gods, demons, priests, and scholars. The book is very much about the discursive positionality of scholars of religion in relation to their object they study.

La Sociedad Argentina de Infectología convocó a otras sociedades científicas para elaborar una guía práctica y actualizada para el manejo del tratamiento antibiótico de las bronquitis agudas (BA) y los episodios de reagudización de enfermedad pulmonar obstructiva crónica (EPOC), con el objetivo de promover el uso racional de los recursos diagnósticos y terapéuticos. La BA se caracteriza por la inflamación del árbol bronquial que afecta tanto a adultos como a niños sin enfermedades pulmonares crónicas, siendo de origen viral en la mayoría de los casos. El diagnóstico es clínico, debiéndose diferenciar de los episodios de neumonía adquirida en la comunidad. El tratamiento de los episodios de BA es fundamentalmente sintomático. En huéspedes inmunocomprometidos, con enfermedades crónicas respiratorias o cardíacas y en adultos mayores con comorbilidades debe evaluarse el requerimiento de tratamiento antibiótico caso por caso. Se define como exacerbación de la EPOC al cambio agudo en la situación clínica basal del paciente más allá de la variabilidad diaria, que cursa con aumento de la disnea, aumento de la expectoración, expectoración purulenta, o cualquier combinación de estos tres síntomas, y que precisa un cambio terapéutico. La presencia de uno de estos síntomas se define como episodio leve, dos como moderado y tres como grave. En un 50 a 75% de las exacerbaciones de EPOC se aísla en el esputo un agente infeccioso. En los episodios moderados y graves debe iniciarse tratamiento antibiótico. Amoxicilina-inhibidor de betalactamasas, macrólidos y fluoroquinolonas se encuentran entre las opciones terapéuticas.

A new independent trade union, set up to represent employees in higher education, is challenging wide-ranging reforms proposed by the Russian government.

I discuss problems importing evolutionary language into the study of religion. It is not impossible to do, but it is difficult to carry out properly in practice. I suggest five criteria for scholarship in the study of religion to amount to good science when incorporating such language. They are 1) avoiding just-so storytelling as much as possible 2) the requirement to add a compelling level of explanation beyond the historical narrative 3) clearly distinguishing between proximate and ultimate forms of causation and explanation, and favoring proximate causes where possible 4) addressing the specific content of religion directly as part of the narrative 5) being explicit about the genre of scholarship undertaken, whether science-writing, humanistic exploration, or some mix of the two. Wiebe and Martin’s arguments do not end up rising to the challenge that they themselves have instigated to have a truly scientific study of religion.

International audience; The Antibiotic Stewardship and Resistance Working Groups of the International Society for Chemotherapy propose ten key points for the appropriate use of antibiotics in hospital settings. (i) Get appropriate microbiological samples before antibiotic administration and carefully interpret the results: in the absence of clinical signs of infection, colonisation rarely requires antimicrobial treatment. (ii) Avoid the use of antibiotics to ‘treat’ fever: use them to treat infections, and investigate the root cause of fever prior to starting treatment. (iii) Start empirical antibiotic treatment after taking cultures, tailoring it to the site of infection, risk factors for multidrug-resistant bacteria, and the local microbiology and susceptibility patterns. (iv) Prescribe drugs at their optimal dosing and for an appropriate duration, adapted to each clinical situation and patient characteristics. (v) Use antibiotic combinations only where the current evidence suggests some benefit. (vi) When possible, avoid antibiotics with a higher likelihood of promoting drug resistance or hospital-acquired infections, or use them only as a last resort. (vii) Drain the infected foci quickly and remove all potentially or proven infected devices: control the infection source. (viii) Always try to de-escalate/streamline antibiotic treatment according to the clinical situation and the microbiological results. (ix) Stop unnecessarily prescribed antibiotics once the absence of infection is likely. And (x) Do not work alone: set up local teams with an infectious diseases specialist, clinical microbiologist, hospital pharmacist, infection control practitioner or hospital epidemiologist, and comply with hospital antibiotic policies and guidelines. © 2016

Abstract I elaborate the idea first proposed by Hans Penner that religious language is patently false in a rereading of Donald Davidson’s essay, “What Metaphors Mean.” I explore a Davidsonian paradigm concerning the semantics of superhuman agents. Religious language is meaningful because it is patently false or trivially true. Patency entails a breakdown at the surface that runs counter to the normative meaning of words. Since no special form of cognition or semantics is necessary to account for religious language, following Nancy Frankenberry’s argument about how metaphor and religious language are used, I explore the possibility that false reasoning is a kind of costly signal. Finally I suggest that literacy alters this matrix because it focuses attention on the literal instantiation of sentences in the form of inscriptions, thus exaggerating the role of false reasoning in relation to religion.

Students of religion should learn about integrationism for at least two reasons. The first concerns the proper way to understand the relation between orality and literacy, between speaking and writing. The second concerns the proper way to approach religious language. Harris is challenging because his argument has both methodogical and theoretical consequences for how we understand religious language and history. I explore possible ways of understanding religion from an integrationist perspective, and Judaism in particular. Harris has argued that we must have a broader view of what constitutes language; for this reason the first part of the essay goes into some detail about the cultural and cognitive context of rabbinic language. I then describe some of the consequences of literacy, incorporating some insights from integrationism and its approach to written language. I conclude the essay with some sections on the consequences of integrationism for the study of religious language.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. volumen 13; número 12