The interaction between sheep and the nematode Teladorsagia circumcincta is one of the best understood of all host-parasite interactions. Following infection, there is considerable variation among lambs in the number of nematode eggs produced, the number of early fourth-stage larvae and the number of adult worms in the mucosa. These traits have a high variance to mean ratio (i.e. they are overdispersed or aggregated among hosts), they are skewed and approximately negative binomially distributed. The sources of overdispersion are differences among lambs in the ingestion of infective larvae and the immune response. Both forces can produce aggregation but their relative importance is unknown. The key components of variation can be identified by variance analysis. The sum of the average effects of polymorphic genes is known as additive genetic variation and this increases essentially from zero at one month of age to quite high values at six months of age. The major mechanism underlying genetic variation appears to be the differences among individuals in immune responses. Two of the major sources of variation in immune responses are differences in antigen recognition and differences in the type of cytokines produced. Genes that influence both these sources of variation are associated with differences in resistance to nematode infection. Therefore, much of the heterogeneity among animals in parasite transmission appears to be due to genetic variation in immune responsiveness.

As schizophrenia is a chronic disorder, it is important that treatment be given over a long period of time to avoid relapse. Quetiapine, an atypical antipsychotic, has established efficacy and good tolerability in the short-term treatment of schizophrenia. This study investigated the long-term efficacy and safety of quetiapine in 674 patients with schizophrenia using combined data from the open-label extension phase of four Phase IIIa trials. The results showed that quetiapine, at a mean daily dose of 472.4 mg, provided progressive improvement and maintenance in the Brief Psychiatric Rating Scale total, positive- and negative-symptoms cluster, Clinical Global Impression Severity of Illness, and Scale for the Assessment of Negative Symptoms total scores over 208 weeks and beyond. Furthermore, quetiapine was well tolerated throughout the study period, with a low incidence of extrapyramidal symptom-related adverse events. In conclusion, quetiapine may be a suitable therapy in the long-term treatment of schizophrenia.

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Nicolas Coldstream once marked an undergraduate essay of mine (on the function of the so-called 'Lustral Basins' at Knossos) 'Very level-headed'. I could not, then or since, have asked for any more satisfying comment, and would wish always to be thought level-headed by Nicolas, whose opinion I value deeply, and to whom I owe a great deal. This essay is a very small contribution to a muchdeserved tribute: its subject may be thought appropriate since Charles Newton became, in 1880, the first Yates Professor of Archaeology at University College, London.The British Museum holds neither the largest nor the most important collection of Greek Bronze Age material in the world, nor were its curators amongst those pioneers in the field who brought such material to light. Nonetheless, the onlooker sometimes sees most of the game. The Museum was already a venerable institution when, a mere one hundred and twenty years ago or so, Schliemann first sank his several spades into the soils of Troy and of Mycenae: moreover, it already contained material of great significance for those seeking the truth about the earliest age of Greece.Charles Newton, Keeper of Greek and Roman antiquities from 1861 to 1886, became acquainted with Schliemann, and from 1872 onwards, the year of the first full-scale excavation at Troy, the two were in regular correspondence.' They also met from time to time, usually when Schliemann was in London to lecture on his discoveries. The extraordinary Schliemann, who was energetically wresting from the earth large quantities of material of unfamiliar type, not to mention golden treasures of a most dramatic sort, felt deeply the need to discuss his finds with established scholars, and his discovery of, as he put it, 'a whole new world'. He was himself convinced that this was the world described by Homer, the heroic age of Greece, but he wanted to know how it was related to other known periods and cultures, how, in other words, it fitted into the established picture of the past. Thus he turned to Newton and other scholars to discuss his finds, and thus it was that Newton interested himself in what we now know as the Greek Bronze Age. Newton was extremely helpful. Few scholars greeted the new finds with such an open mind, or such enthusiasm, and few had the broadly-based knowledge that enabled him very quickly to make significant connections. His contribution is generally unregarded, and he would probably not have minded: the discoverer of the Mausoleum at Halicarnassus perhaps needs no other monument. The Bronze Age only ever formed a minor part of his Nevertheless, he was in the forefront of the interpretation ' The surviving correspondence is published in J.L. Fitton, Heinrich Schliemann and the British Museum. British Museum Occasional Paper 83 (London 1991). A brief account of Newton's life appears in JHS 14 (1894) xlix-liv. See also Dictionary of National Biography, Supplement iii, 224.

Background Olorofim, the first orotomide antifungal, selectively inhibits fungal dihydroorotate dehydrogenase (DHODH), a key enzyme in fungal pyrimidine biosynthesis. Olorofim is active against Aspergillus (including azole-resistant and cryptic species), resistant moulds (e.g., Lomentospora prolificans, Scopulariopsis) and dimorphic fungi (e.g., Coccidioides). The drug is given orally and cleared by multiple CYP450 isoenzymes. Serial images via bronchoscope of Scopulariopsis infection at the anastamosis in a lung transplant patient, pre- and post-olorofim therapy. After lung transplant, airway obstruction at the anastomosis due to Scopulariopsis was unresponsive to available antifungal agents. The airway was clear by day 10 on olorofim monotherapy. Infection was cured with 84 days of olorofim. Methods Patients with limited or no treatment options for proven invasive mycoses or probable pulmonary invasive aspergillosis (IA, as per 2020 EORTC-MSGERC criteria) received olorofim (loading dose of 150mg BID on day 1, followed by 90mg BID) for up to 90 days, with extended therapy beyond day 90 allowed. The primary endpoint was DRC-adjudicated overall response rate by pathogen at day 42 using the EORTC-MSG response criteria. Results At database lock for the first 100 cases, infecting fungi were Aspergillus species (53, including 13 azole-resistant species), L. prolificans (17), Scedosporium (11), Coccidioides (11), and other fungi (8). Success (complete or partial response) was 44% at day 42 and 39% at day 84. When stable disease was counted as success, the success rate was 69% and 59% respectively. Response was seen in patients with highly active, uncontrolled infection (Figure). Overall all-cause mortality was 14% and 19% at day 42 and 84 respectively (IA: 23% and 30%; non-IA infections 4% and 6% respectively). Safety: Olorofim was well tolerated over the 84d median dosing duration (max 722 days). Altered hepatic biochemistry possibly due to olorofim was seen in 8% of study subjects and managed by dose reduction/pause and led to discontinuation in 2%. Mild, self-limiting GI intolerance was noted in 2%. Conclusion Olorofim is an oral, mechanistically novel anti-mould agent with activity against a range of mould infections which are difficult to treat. Olorofim has a positive risk-benefit profile in a well-defined population of patients with infections due to moulds including species considered resistant to all approved antifungals. Disclosures Johan A. Maertens, MD PhD, F2G Ltd: Advisor/Consultant|Gilead Sciences Ltd: Advisor/Consultant|Mundipharma: Advisor/Consultant|Pfizer Inc: Advisor/Consultant George R. 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