The number of offspring weaned from ewe lambs is affected differently by liveweight and age at breeding

In this paper, we tested the hypothesis that ewe lambs that are heavier and older at breeding will wean more offspring, due to increased reproductive rate and offspring survival and lower maternal mortality. To test this hypothesis, we analyzed data from more than 11,500 maternal composite ewe lambs collected over eight years. The ewe lambs had full pedigree records including birth type, age and liveweight at breeding plus records of the birthweight and survival of their offspring and the dam. The average liveweight and age at breeding was 40.2 kg and 228 days. The reproductive rate and weaning rate responses to liveweight at breeding were curvilinear (p < 0.001), and if ewe lambs achieved 45 kg by the start of breeding, their reproductive rate and weaning rate were within 5% of their maximum. By contrast, the effects of age at breeding on weaning rate was linear and increased by 0.4% per day, despite a quadratic (p < 0.01) effect of age at breeding on reproductive rate which increased only marginally when ewe lambs were older than 8 months at breeding. Increasing liveweight (p < 0.05) or age (p < 0.001) at breeding increased survival of their offspring, however an extra 10 kg of liveweight or 30 days of age at breeding increased offspring survival by less than 5%. Both liveweight (p < 0.001) and age (p < 0.01) at breeding also influenced survival of the ewe lamb dam but survival rates exceeded 95% across the range in liveweights from 30 to 55 kg and ages from 6 to 9 months. This understanding of the trade-off between age and liveweight at breeding will assist farmers to optimize the management of their ewe lambs, given the earlier they can be bred successfully the easier they can be integrated with the breeding of the adult ewe flock the following year

Diversity of Agaricales (Basidiomycota) in the Reserva Biológica Walter Egler, Amazonas, Brazil

A study of the order Agaricales Clements (Hymenomycetes, Basidiomycotina), occurring in the Reserva Biológica Walter Egler was carried out from December 2000 to June 2001. The area of study is situated at Road AM-010, Manaus-Itacoatiara, km 64, Latitude 02° 43' S and Longitude 59° 47' W, Rio Preto da Eva, in the State of Amazonas, with a total area of 709 ha of terra firme rain forest. The fungi collected were identified based on traditional methodology for identification of Agaricales. A total of 39 species were studied, distributed in 13 genera and six families: Polyporaceae: Pleurotus sp.; Hygrophoraceae: Hygrocybe cf. megistospora, Hygrocybe aff. miniceps, Hygrocybe occidentalis var. scarletina and eight indeterminate species of Hygrocybe; Tricholomataceae: Clitocybe sp., Hydropus sp.1 and Hydropus sp.2, Macrocystidia sp., Marasmiellus sp., Marasmius bellus, Marasmius haedinus var. haedinus, Marasmius cf. leoninus, Marasmius cf. mazatecus, Marasmius cf. ruber, Marasmius cf. setulosifolius, Marasmius tageticolor, Marasmius cf. variabiliceps var. variabiliceps, Marasmius sp.1, Marasmius sp.2, Marasmius sp.3 and Marasmius sp.4, Tricholoma sp.; Agaricaceae: Agaricus sp.1 and Agaricus sp.2, Lepiota sp., Cystoderma sp.; Entolomataceae: Entoloma cf. azureoviride, Entoloma cf. cystidiophorum, Entoloma strigosissima, Entoloma sp.; Russulaceae: Lactarius panuoides. Entoloma azureoviride, Hygrocybe miniceps, Lactarius panuoides, Marasmius cf. mazatecus, Marasmius cf. setulosifolius and Marasmius variabiliceps var. variabiliceps, apparently are here cited for the first time from Brazil. With exception of Marasmius tageticolor, all species are cited here for the first time as occurring in Egler Forest. The tables with the species occurrence, in accordance with the topographical gradient (sand bank, incline, plateau) and its respective habitat, are supplied.", 'enFoi realizado um estudo dos representantes da Ordem Agaricales Clements (Hymenomycetes, Basidiomycotina), ocorrentes na Reserva Biológica Walter Egler, situada na Estrada AM-010, Manaus-Itacoatiara, Km 64, Latitude 02° 43' S e Longitude 59° 47' W, Rio Preto da Eva, Amazonas. A área abrange 709 ha de floresta de terra firme primária. As coletas foram realizadas no período de dezembro de 2000 a junho de 2001 e seguiu-se a metodologia usual para identificação de Agaricales. Foram estudadas um total de 39 espécies, distribuídas em 13 gêneros e seis famíliasPolyporaceaePleurotus sp.; HygrophoraceaeHygrocybe cf. megistospora, Hygrocybe aff. miniceps, Hygrocybe occidentalis var. scarletina, e mais oito espécies de Hygrocybe indeterminadas; TricholomataceaeClitocybe sp., Hydropus sp.1 e Hydropus sp.2, Macrocystidia sp., Marasmiellus sp., Marasmius bellus, Marasmius haedinus var. haedinus,Marasmius cf. leoninus, Marasmius cf. mazatecus, Marasmius cf. ruber,Marasmius cf. setulosifolius, Marasmius tageticolor, Marasmius cf. variabiliceps var. variabiliceps, Marasmius sp.1, Marasmius sp.2, Marasmius sp.3 e Marasmius sp.4, Tricholoma sp.; AgaricaceaeAgaricus sp.1 e Agaricus sp.2, Lepiota sp., Cystoderma sp.; EntolomataceaeEntoloma cf. azureoviride, Entoloma cf. cystidiophorum, Entoloma strigosissima, Entoloma sp.; RussulaceaeLactarius panuoides. Destas, Entoloma azureoviride, Hygrocybe miniceps, Lactarius panuoides, Marasmius cf. mazatecus, Marasmius cf. setulosifolius e Marasmius variabiliceps var. variabiliceps, provavelmente, estão sendo aqui citadas pela primeira vez, para o Brasil. Com exceção de Marasmius tageticolor, as demais espécies são citadas pela primeira vez, para a Reserva Egler. São fornecidas tabelas com a ocorrência das espécies de acordo com o gradiente topográfico (baixio, vertente, platô) e seus respectivos habitats

Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers

<p>Abstract</p> <p>Background</p> <p>There has been an increase in 'risk sharing' schemes for pharmaceuticals between healthcare institutions and pharmaceutical companies in Europe in recent years as an additional approach to provide continued comprehensive and equitable healthcare. There is though confusion surrounding the terminology as well as concerns with existing schemes.</p> <p>Methods</p> <p>Aliterature review was undertaken to identify existing schemes supplemented with additional internal documents or web-based references known to the authors. This was combined with the extensive knowledge of health authority personnel from 14 different countries and locations involved with these schemes.</p> <p>Results and discussion</p> <p>A large number of 'risk sharing' schemes with pharmaceuticals are in existence incorporating both financial-based models and performance-based/outcomes-based models. In view of this, a new logical definition is proposed. This is "<it>risk sharing' schemes should be considered as agreements concluded by payers and pharmaceutical companies to diminish the impact on payers' budgets for new and existing schemes brought about by uncertainty and/or the need to work within finite budgets</it>". There are a number of concerns with existing schemes. These include potentially high administration costs, lack of transparency, conflicts of interest, and whether health authorities will end up funding an appreciable proportion of a new drug's development costs. In addition, there is a paucity of published evaluations of existing schemes with pharmaceuticals.</p> <p>Conclusion</p> <p>We believe there are only a limited number of situations where 'risk sharing' schemes should be considered as well as factors that should be considered by payers in advance of implementation. This includes their objective, appropriateness, the availability of competent staff to fully evaluate proposed schemes as well as access to IT support. This also includes whether systematic evaluations have been built into proposed schemes.</p

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013–003413–18). Findings: Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92\ub78% (SE 2\ub76) in the abatacept group and 69\ub72% (4\ub77) in the placebo group. Kaplan–Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0\ub7044). The difference in restricted mean survival time between groups was 53 days (95% CI 28–78; p&lt;0\ub70001) at 12 months and 99 days (95% CI 38–161; p=0\ub70016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment. Interpretation: Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals. Funding: Bristol Myers Squibb