Hypercalcemia Caused by Metastatic Adamantinoma: Response to Radiotherapy

Purpose. To describe successful palliation of a patient with metastatic adamantinoma presenting with lung metastases and hypercalcemia resulting from a parathormone-like substance released from the tumor

Stratigraphic distributions of genera and species of Neogene to Recent Caribbean reef corals

To document evolutionary patterns in late Cenozoic Caribbean reef corals, we compiled composite stratigraphic ranges of 49 genera and 175 species using Neogene occurrences in the Cibao Valley sequence of the northern Dominican Republic and faunal lists for 24 Miocene to Recent sites across the Caribbean region. This new compilation benefits in particular from increased sampling at late Miocene to early Pleistocene sites and from increased resolution and greater taxonomic consistency provided by the use of morphometric procedures in species recognition. Preliminary examination and quantitative analysis of origination and extinction patterns suggest that a major episode of turnover took place between 4 and 1 Ma during Plio-Pleistocene time. During the episode, extinctions were approximately simultaneous in species of all reef-building families, except the Mussidae. Most strongly affected were the Pocilloporidae (Stylophora and Pocillopora), Agariciidae (Pavona and Gardineroseris), and free-living members of the Faviidae and Meandrinidae. At the genus level, mono- and paucispecific as well as more speciose genera became regionally extinct. Many of the extinct genera live today in the Indo-Pacific region, and some are important components of modern eastern Pacific reefs. Global extinctions were concentrated in free-living genera. During the turnover episode, no new genera or higher taxa arose. Instead, new species originated within the surviving Caribbean genera at approximately the same time as the extinctions, including many dominant modern Caribbean reef-building corals (e.g., Acropora palmata and the Montastraea annularis complex). Excluding this episode, the taxonomic composition of the Caribbean reef-coral fauna remained relatively unchanged during the Neogene. Minor exceptions include: 1) high originations in the Agariciidae and free-living corals during late Miocene time; and 2) regional or global extinctions of several important Oligocene Caribbean reef builders during early to middle Miocene tim

Durable Near-Complete Response to Anti-PD-1 Checkpoint Immunotherapy in a Refractory Malignant Solitary Fibrous Tumor of the Pleura

Solitary fibrous tumor of the pleura is a rare and usually benign primary neoplasm arising from mesenchymal cells of the submesothelial tissue. We present here the case of a patient diagnosed with CD34-positive advanced malignant solitary fibrous tumor of the pleura whose disease failed to respond to combination cytotoxic chemotherapy agents, but demonstrated a prompt near-complete response to checkpoint blockade treatment using the anti-programmed death (PD)-1 monoclonal antibody pembrolizumab, based on tumor molecular profiling revealing tumoral expression positivity for both programmed death-ligand 1 (PD-L1) and PD-1. The patient experienced minimal adverse effects from the treatment with durable favorable response lasting up to cycle 26

The origin of green icebergs in Antarctica

A comparison of samples from a translucent green iceberg with a core from the Ronne Ice Shelf revealed an excellent agreement in isotopic composition, crystal structure, and incorporated sediment particles. Marine shelf ice which constitutes the basal portion of some ice shelves is considered to be the source of green icebergs. It most likely results from "ice pump" processes which produce large amounts of ice platelets in the water column beneath ice shelves. These subsequently accumulate and become compacted into bubble-free, desalinated ice. Iceberg and drift-buoy trajectories indicate that green icebergs observed in the Weddell Sea originate from the Amery Ice Shelf rather than from the Ronne Ice Shelf, although the latter ice shelf is also a potential source

Weddell Sea iceberg drift: Five years of observations

Since 1999, 52 icebergs have been tagged with GPS buoys in the Weddell Seato enable monitoring of their position. The chosen icebergs were of small tomedium size, with a few icebergs larger than 10 km associatedwith the calving of icebergs A38 and A43 from the Ronne Ice Shelf.The majority of icebergs were tagged off Neumayer Station (8E, 70S).It was found that smaller bergs with edges shorter than 200 m had the shortestlife cycle (< 0.5 yr). Iceberg and thus freshwater export out of theWeddell Sea was found to be highly variable. In one year the majority of buoysdeployed remained in the Weddell Sea, constituting about 40 % of the NCEP P-Efreshwater input, whereas in other years all of the tagged icebergs were exported.The observed drifts of icebergs and sea-ice showed a remarkably coherent motion.The analysis of an iceberg - sea-ice buoy array in the western Weddell Seaand an iceberg array in the eastern Weddell Sea showed a coherent sea-iceiceberg drift in sea-ice concentrations above 86 %. Dynamic kinematic parameter(DKP) during the course of coherent movement were low and deviations from the meancourse associated with the passage of low-pressure system. The length scale ofcoherent movement was estimated to be less than 250km; about half the value found forthe Arctic Ocean

Machine learning outperforms clinical experts in classification of hip fractures

Hip fractures are a major cause of morbidity and mortality in the elderly, and incur high health and social care costs. Given projected population ageing, the number of incident hip fractures is predicted to increase globally. As fracture classification strongly determines the chosen surgical treatment, differences in fracture classification influence patient outcomes and treatment costs. We aimed to create a machine learning method for identifying and classifying hip fractures, and to compare its performance to experienced human observers. We used 3659 hip radiographs, classified by at least two expert clinicians. The machine learning method was able to classify hip fractures with 19% greater accuracy than humans, achieving overall accuracy of 92%

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence

<p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of <it>HER2</it>+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients.</p> <p>Methods</p> <p>A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in <it>HER2</it>+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in <it>HER2</it>+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI).</p> <p>Results</p> <p>TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 <it>HER2</it>+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 <it>HER2</it>+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts.</p> <p>Conclusions</p> <p>Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in <it>HER2+ </it>breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with <it>HER2 </it>targeted therapy.</p