You had to be there: Anachronism and the limits of laughing at the Middle Ages

Comic medievalism is one of the most widespread but least examined forms of postmedieval response. Its combination of comic modality, modern sensibility and historical vision captures what postmedieval audiences have deemed amusing about medieval society. But some instances have been less successful. ‘You had to be there,’ the phrase marking the failure of a comic attempt, and the relationship of that failure to the loss of immediacy, is realized in comic medievalism through the temporal fragility of laughter, historical mediation and temporal paradox. This essay explores some limitpoints to the comic reception of the Middle Ages, focusing especially on its use of anachronism

Immunoblotting for the serodiagnosis of alveolar echinococcosis in alive and dead Eurasian beavers (Castor fiber)

A novel species-specific anti-beaver-IgG-alkaline-phosphatase conjugate was synthesized for the development of a new serological test for echinococcosis in beavers. Two different ELISAs conventionally used for human Echinococcus multilocularis serology (Em18-ELISA and Em2-ELISA) yielded diagnostic sensitivities of 0% and 46%, respectively. In contrast, the subsequently developed immunoblotting assay gave an 85% diagnostic sensitivity (11 out of 13 beavers with alveolar echinococcosis were immunoblotting-positive, i.e. showed reactivity with a specific 21 Mr band), and maximal specificity. In conclusion, this immunoblotting assay should be the method of choice for use in serological studies on E. multilocularis in Eurasian beavers, and the test proved suitable to investigate both animals alive and post-mortem

The 2018 Lake Louise Acute Mountain Sickness Score.

Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score

External ballistics of Pleistocene hand-thrown spears: experimental performance data and implications for human evolution

The appearance of weaponry - technology designed to kill - is a critical but poorly established threshold in human evolution. It is an important behavioural marker representing evolutionary changes in ecology, cognition, language and social behaviours. While the earliest weapons are often considered to be hand-held and consequently short-ranged, the subsequent appearance of distance weapons is a crucial development. Projectiles are seen as an improvement over contact weapons, and are considered by some to have originated only with our own species in the Middle Stone Age and Upper Palaeolithic. Despite the importance of distance weapons in the emergence of full behavioral modernity, systematic experimentation using trained throwers to evaluate the ballistics of thrown spears during fight and at impact is lacking. This paper addresses this by presenting results from a trial of trained javelin athletes, providing new estimates for key performance parameters. Overlaps in distances and impact energies between hand-thrown spears and spearthrowers are evidenced, and skill emerges as a signifcant factor in successful use. The results show that distance hunting was likely within the repertoire of hunting strategies of Neanderthals, and the resulting behavioural flexibility closely mirrors that of our own specie

Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission

A significant proportion of chronic myeloid leukemia (CML) patients achieve a major cytogenetic remission (MCR) to imatinib therapy after failing interferon (IFN) alpha-based protocols. We sought to determine levels of residual disease in patients with MCR using various molecular methods and to establish a relation between residual BCR-ABL transcript levels and rate of relapse in complete cytogenetic remission (CCR). Response was measured by conventional cytogenetic analysis, hypermetaphase and interphase fluorescence in situ hybridization (HM-FISH, IP-FISH) of bone marrow (BM) cells, qualitative nested and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts. We investigated 323 peripheral blood (PB) and BM samples from 48 CML patients who achieved a complete (Ph+ 0%; n=41) or partial (Ph+ 1-34%; n=7) cytogenetic remission after 3-20 months of imatinib therapy. Prior to imatinib, 35 patients were in chronic phase (CP), eight in accelerated phase (AP), four in myeloid and one in lymphoid blast crisis. HM-FISH results correlated with ratios BCR-ABL/ABL in PB and BM. In patients with CCR, residual disease was detectable by HM-FISH (31%), IP-FISH (18%), and RT-PCR (100%). During follow-up, BCR-ABL became undetectable in two patients (one CP, one AP) by both nested and quantitative RT-PCR. CCR is ongoing in 30 evaluable patients, 11 patients have relapsed. At the time of best response, median ratios BCR-ABL/ABL were 2.1% (range 0.82-7.8) in patients with subsequent relapse and 0.075% (range 0-3.9) in patients with ongoing remission (P=0.0011). All 16 CP patients, who achieved ratios BCR-ABL/ABL <0.1% as best molecular response are in continuous remission, while 6/13 patients (46%) with ratios >/=0.1% have relapsed (P=0.0036). We conclude that: (i) in patients with CCR to imatinib, HM-FISH and RT-PCR usually reveal residual BCR-ABL+ cells; (ii) RT-PCR results derived from PB and BM are comparable in CP CML; and (iii) low levels of residual disease with ratios BCR-ABL/ABL &<0.1% are associated with continuous remission

Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha

The degree of tumor load reduction as measured by cytogenetic response is an important prognostic factor for chronic myelogenous leukemia (CML) patients on therapy. We sought to determine whether BCR-ABL transcript levels can predict chromosomal response. Residual disease was evaluated in 120 CML patients in chronic phase (CP) treated with the selective tyrosine kinase inhibitor imatinib after resistance or intolerance to interferon (IFN). Median time of therapy was 401 days (range 111-704). BCR-ABL and total ABL transcripts were measured in 486 peripheral blood (PB) specimens with a real time RT-PCR approach using fluorescent-labeled hybridization probes (LightCycler technology) and results were expressed as the ratio BCR-ABL/ABL. Cytogenetic response was determined in 3-monthly intervals: From 101 evaluable patients, 42 achieved a complete (CR, 0% Philadelphia chromosome (Ph)- positive metaphases), 18 a partial (PR, 1-34% Ph+), 13 a minor (MR, 35-94% Ph+), and 26 no response (NR, >94% Ph+). All PB samples were RT-PCR positive. The proportion of Ph+ metaphases and simultaneous BCR-ABL/ABL ratios correlated with r = 0.74, P < 0.0001. In order to investigate whether early molecular analysis may predict cytogenetic response, quantitative RT-PCR data obtained after 1 and 2 months of therapy were compared with cytogenetic response at 6 months. BCR-ABL/ABL ratios after 1 month were not predictive, but results after 2 months correlated with the consecutive cytogenetic response (P = 0.0008). The probability for a major cytogenetic response was significantly higher in patients with a BCR-ABL/ABL ratio <20% after 2 months of imatinib therapy. We conclude that: (1) quantitative determination of residual disease with real time RT-PCR is a reliable and sensitive method to monitor CML patients on imatinib therapy; (2) BCR-ABL/ABL ratios correlate well with cytogenetic response; (3) in IFN-pretreated patients all complete responders to imatinib have evidence of residual disease with the limited follow-up available; and (4) cytogenetic response at 6 months of therapy in CP patients is predictable with real time RT-PCR at 2 months