Multiple myeloma presenting as CEA-producing rectal cancer

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas

Fuel cycle modelling of open cycle thorium-fuelled nuclear energy systems

In this study, we have sought to determine the advantages, disadvantages, and viability of open cycle thorium–uranium-fuelled (Th–U-fuelled) nuclear energy systems. This has been done by assessing three such systems, each of which requires uranium enriched to ∼20% 235U, in comparison to a reference uranium-fuelled (U-fuelled) system over various performance indicators, spanning material flows, waste composition, economics, and proliferation resistance. The values of these indicators were determined using the UK National Nuclear Laboratory’s fuel cycle modelling code ORION. This code required the results of lattice-physics calculations to model the neutronics of each nuclear energy system, and these were obtained using various nuclear reactor physics codes and burn-up routines. In summary, all three Th–U-fuelled nuclear energy systems required more separative work capacity than the equivalent benchmark U-fuelled system, with larger levelised fuel cycle costs and larger levelised cost of electricity. Although a reduction of ∼6% in the required uranium ore per kWh was seen for one of the Th–U-fuelled systems compared to the reference U-fuelled system, the other two Th–U-fuelled systems required more uranium ore per kWh than the reference. Negligible advantages and disadvantages were observed for the amount and the properties of the spent nuclear fuel (SNF) generated by the systems considered. Two of the Th–U-fuelled systems showed some benefit in terms of proliferation resistance of the SNF generated. Overall, it appears that there is little merit in incorporating thorium into nuclear energy systems operating with open nuclear fuel cycles

Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America

The aim of the present study was to evaluate the association between history of tuberculosis and airflow obstruction.A population-based, multicentre study was carried out and included 5,571 subjects aged >= 40 yrs living in one of five Latin American metropolitan areas: São Paulo (Brazil); Montevideo (Uruguay); Mexico City (Mexico); Santiago (Chile); and Caracas (Venezuela). Subjects performed pre- and post-bronchodilator spirometry and were asked whether they had ever been diagnosed with tuberculosis by a physician.The overall prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity post-bronchodilator < 0.7) was 30.7% among those with a history of tuberculosis, compared with 13.9% among those without a history. Males with a medical history of tuberculosis were 4.1 times more likely to present airflow obstruction than those without such a diagnosis. This remained unchanged after adjustment for confounding by age, sex, schooling, ethnicity, smoking, exposure to dust and smoke, respiratory morbidity in childhood and current morbidity. Among females, the unadjusted and adjusted odds ratios were 2.3 and 1.7, respectively.In conclusion, history of tuberculosis is associated with airflow obstruction in Latin American middle-aged and older adults.Univ Fed Pelotas, BR-96020220 Pelotas, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilNatl Inst Resp Dis, Mexico City, DF, MexicoUniv Republica, Montevideo, UruguayCatholic Univ Chile, Santiago, ChileCent Univ Venezuela, Caracas, VenezuelaUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The new 14C chronology for the Palaeolithic site of La Ferrassie, France: the disappearance of Neanderthals and the arrival of Homo sapiens in France

The grand abri at La Ferrassie (France) has been a key site for Palaeolithic research since the early part of the 20th century. It became the eponymous site for one variant of Middle Palaeolithic stone tools, and its sequence was used to define stages of the Aurignacian, an early phase of the Upper Palaeolithic. Several Neanderthal remains, including two relatively intact skeletons, make it one of the most important sites for the study of Neanderthal morphology and one of the more important data sets when discussing the Neanderthal treatment of the dead. However, the site has remained essentially undated. Our goal here is to provide a robust chronological framework of the La Ferrassie sequence to be used for broad regional models about human behaviour during the late Middle to Upper Palaeolithic periods. To achieve this goal, we used a combination of modern excavation methods, extensive geoarchaeological analyses, and radiocarbon dating. If we accept that Neanderthals were responsible for the Châtelperronian, then our results suggest an overlap of ca. 1600 years with the newly arrived Homo sapiens found elsewhere in France

Hepatitis C virus NS5A is a direct substrate of casein kinase I-&#945;, a cellular kinase identified by inhibitor affinity chromatography using specific NS5A hyperphosphorylation inhibitors

The hepatitis C virus encodes a single polyprotein that is processed by host and viral proteases to yield at least 10 mature viral proteins. The nonstructural (NS) protein 5A is a phosphoprotein, and experimental data indicate that the phosphorylation state of NS5A is important for the outcome of viral RNA replication. We were able to identify kinase inhibitors that specifically inhibit the formation of the hyperphosphorylated form of NS5A (p58) in cells. These kinase inhibitors were used for inhibitor affinity chromatography in order to identify the cellular targets of these compounds. The kinases casein kinase I (CKI), p38 MAPK, CIT (Citron Rho-interacting kinase), GAK, JNK2, PKA, RSK1/2, and RIPK2 were identified in the high affinity binding fractions of two NS5A hyperphosphorylation inhibitors (NS5A-p58-i). Even though these kinases are targets of the NS5A-p58-i, the only kinase showing an effect on NS5A hyperphosphorylation was confirmed to be CKI-\u3b1. Although this finding does not exclude the possibility that other kinase(s) might be involved in basal or regulatory phosphorylation of NS5A, we show here that NS5A is a direct substrate of CKI-\u3b1. Moreover, in vitro phosphorylation of NS5A by CKI-\u3b1 resulted for the first time in the production of basal and hyperphosphorylated forms resembling those produced in cells. In vitro kinase reactions performed with NS5A peptides show that Ser-2204 is a preferred substrate residue for CKI-\u3b1 after pre-phosphorylation of Ser-2201

Back to Uluzzo – archaeological, palaeoenvironmental and chronological context of the Mid–Upper Palaeolithic sequence at Uluzzo C Rock Shelter (Apulia, southern Italy)

The tempo and mode of Homo sapiens dispersal in Eurasia and the demise of Neanderthals has sparked debate about the dynamics of Neanderthal extinction and its relationship to the arrival of H. sapiens. In Italy, the so-called ‘Transition’ from Neanderthals to H. sapiens is related to the Uluzzian technocomplex, i.e. the first archaeological evidence for modern human dispersal on the European continent. This paper illustrates the new chronology and stratigraphy of Uluzzo C, a rock shelter and Uluzzian key site located in the Uluzzo Bay in southern Italy, where excavations are ongoing, refining the cultural sequence known from previous excavations. Microstratigraphic investigation suggests that most of the deposit formed after dismantling of the vault of the rock shelter and due to wind input of loess deflated by the continental shelf. The occasional reactivation of the hydrology of the local karst system under more humid conditions further contributed to the formation of specific layers accumulating former Terra Rossa-type soil fragments. Superposed on sedimentary processes, strong bioturbation and the mobilization and recrystallization of calcite have been detected. Optically stimulated luminescence (OSL) ages from Uluzzo C Rock Shelter are congruent with previously published radiocarbon ages obtained on shell beads and tephrachronology from adjacent sites preserving the Uluzzian technocomplex such as Grotta del Cavallo, confirming the onset for the Uluzzian in the area to ca. 39.2–42.0 ka. The OSL chronology from Uluzzo C also provides a terminus post quem for the end of the Mousterian in the region, constraining the disappearance of the Neanderthals in that part of Italy to ≥46 ± 4 ka