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Context. Observations of edge-on disks are an important tool for constraining general protoplanetary disk properties that cannot be determined in any other way. However, most radiative transfer models cannot simultaneously reproduce the spectral energy distributions (SEDs) and resolved scattered light and submillimeter observations of these systems, due to the differences in geometry and dust properties at different wavelengths. Aims. We simultaneously constrain the geometry of the edge-on protoplanetary disk HH 48 NE and the characteristics of the host star. HH 48 NE is part of the JWST early release science program Ice Age. This work serves as a stepping stone towards a better understanding of the disk physical structure and icy chemistry in this particular source. This kind of modeling lays the groundwork for studying other edge-on sources to be observed with the JWST. Methods. We fit a parameterized dust model to HH 48 NE by coupling the radiative transfer code RADMC-3D and an MCMC framework. The dust structure was fitted independently to a compiled SED, a scattered light image at 0.8 ${\mu}$m and an ALMA dust continuum observation at 890 ${\mu}$m. Results. We find that 90% of the dust mass in HH 48 NE is settled to the disk midplane, less than in average disks, and that the atmospheric layers of the disk contain exclusively large grains (0.3-10 ${\mu}$m). The exclusion of small grains in the upper atmosphere likely has important consequences for the chemistry due to the deep penetration of high-energy photons. The addition of a relatively large cavity (ca. 50 au in radius) is necessary to explain the strong mid-infrared emission, and to fit the scattered light and continuum observations simultaneously., Comment: 16 pages, 8 figures, accepted for publication in Astronomy & Astrophysics

Planetary systems such as our own are formed after a long process where matter condenses from diffuse clouds to stars, planets, asteroids, comets and residual dust, undergoing dramatic changes in physical and chemical state in less than a few million years. Several studies have shown that the chemical composition during the early formation of a Solar-type planetary system is a powerful diagnostic to track the history of the system itself. Among the approximately 270 molecules so far detected in the ISM, the so-called interstellar complex organic molecules (iCOMs) are of particular interest both because of their evolutionary diagnostic power and because they might be potential precursors of biomolecules, which are at the basis of terrestrial life. This Chapter focuses on the evolution of organic molecules during the early stages of a Solar-type planetary system, represented by the prestellar, Class 0/I and protoplanetary disk phases, and compares them with what is observed presently in Solar System comets. Our twofold goal is to review the processes at the base of organic chemistry during Solar-type star formation and, in addition, to possibly provide constraints on the early history of our own planetary system., Comment: Chapter for Protostars & Planets VII

Background: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ((177)Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the (177)Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the (177)Lu-Dotatate group versus 3% in the control group (PConclusions: Treatment with (177)Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the (177)Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

Biomarkers have been the mainstay in the diagnosis and follow-up of patients with neuroendocrine tumors (NETs) over the last few decades. In the beginning, secretory products from a variety of subtypes of NETs were regarded as biomarkers to follow during diagnosis and treatment: serotonin for small intestinal (SI) NETs, and gastrin and insulin for pancreatic NETs. However, it became evident that a large number of NETs were so-called nonfunctioning tumors without secreting substances that caused hormone-related symptoms. Therefore, it was necessary to develop so-called “general tumor markers.” The most important ones so far have been chromogranin A and neuron-specific enolase (NSE). Chromogranin A is the most important general biomarker for most NETs with a sensitivity and specificity somewhere between 60 and 90%. NSE has been a relevant biomarker for patients with high-grade tumors, particularly lung and gastrointestinal tract tumors. Serotonin and the breakdown product urinary 5-hydroxyindoleacetic acid (U-5-HIAA) is still an important marker for diagnosing and follow-up of SI NETs. Recently, 5-HIAA in plasma has been analyzed by high-performance liquid chromatography and fluorometric detection and has shown good agreement with U-5-HIAA analysis. In the future, we will see new tests including circulating tumor cells, circulating DNA and mRNA. Recently, a NET test has been developed analyzing gene transcripts in circulating blood. Preliminary data indicate high sensitivity and specificity for NETs. However, its precise role has to be validated in prospective randomized controlled trials which are ongoing right now.

ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas)

ENETS Consensus Guidelines for the Management of Patients with Liver and Other Distant Metastases from Neuroendocrine Neoplasms of Foregut, Midgut, Hindgut, and Unknown Primary

a Division of Hepatology and Gastroenterology, Department of Internal Medicine, Campus Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Berlin , Germany; b Department of Pathology, Universitatsspital, Zurich , Switzerland; c Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; d Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem , Israel; e Department of Internal Medicine, Philipps University, Marburg , Germany; f Hopital Sirio Libanes, Centro de Oncologia, Sao Paulo , Brazil; g Department of Radiology, Campus Virchow-Klinikum, Charite, University Medicine Berlin, Berlin , Germany; h Department of Oncology, Institut Catala d’Oncologia (IDIBELL), Barcelona , Spain; i Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford , UK

Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research. © 2014 Elsevier Ltd.

a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Oncology, Institut Catala d’Oncologia, Barcelona , Spain; c Department of Surgery, Verona University, Verona , Italy; d Department of Endocrinology and Metabolism, Genimatas Hospital, Athens , Greece; e Department of Gastroenterology, Beaujon Hospital, Clichy , France; f Department of Endocrinology, Erasmus MC University, Rotterdam , The Netherlands; g Department of Internal Medicine, Martin University, Martin , Slovakia; h Department of Propaedeutic Internal Medicine, Laiko Hospital, Athens , Greece; i Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; j Department of Gastroenterology, Beaujon Hospital, Clichy , France; k Department of Gastroenterology, Royal Free Hospital, London , UK; l Department of Cell Biology, National Institute of Health, Bethesda, Md. , USA; m Department of Endocrinology, University Hospital, Uppsala , Sweden

The goal of this paper is to update a more extensive review and guidelines paper published in 2012 [1] . Gen-erally, any pertinent update pertaining to the diagnosis and staging of individual prima ...

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : echocardiography.

a DRK Kliniken Westend, Berlin , Germany; b UFR Bichat-Beaujon-Louis Mourier, Service de Chirurgie Digestive, Hopital Louis Mourier, Colombes , France; c Medicine and Surgery, General Surgery Section, MED/18 – General Surgery and d Department of Pathology, University of Verona, Verona , Italy; e Netherlands Cancer Centre, Amsterdam , and f Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam , The Netherlands

Consensus guidelines for the management of patients with digestive neuroendocrine tumors : well-differentiated jejunal-ileal tumor/carcinoma

a Department of Pathology, Gothenburg University, Gothenburg , Sweden; b Department of Gastroenterology, Gasthuisberg University, Leuven , Belgium; c Department of Gastroenterology, Ospedale S. Andrea, Rome , Italy; d Department of Oncology, University of Texas, Houston, Tex. , USA; e Department of Endocrinology, Erlangen University, Erlangen , Germany; f Department of Oncology and Pathology, Royal Infirmary Hospital, Glasgow , UK; g Department of Oncology, Virgen de la Victoria Hospital, Malaga , Spain; h Department of Nuclear Medicine, Medizinische Hochschule Hannover, Hannover , Germany; i Department of Endocrinology, Erciyes University, Kayseri , Turkey; j Department of Surgery, Beaujon Hospital, Clichy , France; k Department of Nuclear Medicine, Catholique de Louvain University, Brussels , Belgium; l Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; m Department of Gastroenterology, Royal Free Hospital, London , UK

Ultraviolet (UV) ice photodesorption is an important non-thermal desorption pathway in many interstellar environments that has been invoked to explain observations of cold molecules in disks, clouds, and cloud cores. Systematic laboratory studies of the photodesorption rates, between 7 and 14 eV, from CO:N$_{2}$ binary ices, have been performed at the DESIRS vacuum UV beamline of the synchrotron facility SOLEIL. The photodesorption spectral analysis demonstrates that the photodesorption process is indirect, i.e., the desorption is induced by a photon absorption in sub-surface molecular layers, while only surface molecules are actually desorbing. The photodesorption spectra of CO and N$_{2}$ in binary ices therefore depend on the absorption spectra of the dominant species in the sub-surface ice layer, which implies that the photodesorption efficiency and energy dependence are dramatically different for mixed and layered ices compared with pure ices. In particular, a thin (1-2 ML) N$_{2}$ ice layer on top of CO will effectively quench CO photodesorption, while enhancing N$_{2}$ photodesorption by a factor of a few (compared with the pure ices) when the ice is exposed to a typical dark cloud UV field, which may help to explain the different distributions of CO and N$_{2}$H$^{+}$ in molecular cloud cores. This indirect photodesorption mechanism may also explain observations of small amounts of complex organics in cold interstellar environments.

Neuroendocrine gastro-entero-pancreatic tumors : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

a Digestive Diseases Branch, NIDDK, NIH, Bethesda, Md. , USA; b Dipartimento di Patologia e Medicina di Laboratorio, Universita di Parma, Parma , Italy; c Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps University, Marburg , Germany; d Department of Pathology, IPATIMUP Hospital, Porto , Portugal; e Dipartimento di Fisiopatologia Clinica, Universita di Firenze, Firenze , Italy; f Department of Surgery, Johann-Wolfgang-Goethe-Universitat, Frankfurt , Germany; g E. Christ, Department of Endocrinology, Inselspital, Bern , Switzerland; h Department of Oncology, Netherlands Cancer Centre, Amsterdam , The Netherlands; i Department of Surgery, Rigshospitalet Blegdamsvej Hospital, Copenhagen , Denmark; j Department of Surgery, Gothenburg University, Gothenburg , Sweden; k Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam , The Netherlands; l Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l’Appareil Digestif, Hopital Beaujon, Clichy , France

We present an easy to use, rapid fabrication platform for microfluidic systems, based on micro-molding of novel thiolene based polymer formulations. The novel fabrication platform addresses major drawbacks of PDMS by allowing large freedom in material and surface properties, including: (photo)patterning of stable surface modifications, bonding without plasma treatment, rapid UV or thermal curing, variable E-modulus, minimized leaching of uncured components [1] and suppressed non-specific binding of biomolecules [2]. This process is potentially suited for both rapid prototyping in the laboratory and medium-scale commercial production, bridging the “development gap”. QC 20140819 Intopsens