Feasibility randomised controlled trial comparing TRAK-ACL digital rehabilitation intervention plus treatment as usual versus treatment as usual for patients following anterior cruciate ligament reconstruction

Objectives: To evaluate the feasibility of trialling taxonomy for the rehabilitation of knee conditions-ACL (TRAK-ACL), a digital health intervention that provides health information, personalised exercise plans and remote clinical support combined with treatment as usual (TAU), for people following ACL reconstruction. Methods: The study design was a two-arm parallel randomised controlled trial (RCT). Eligible participants were English-speaking adults who had undergone ACL reconstruction within the last 12 weeks, had access to the internet and could provide informed consent. Recruitment took place at three sites in the UK. TRAK-ACL intervention was an interactive website informed by behaviour change technique combined with TAU. The comparator was TAU. Outcomes were: recruitment and retention; completeness of outcome measures at follow-up; fidelity of intervention delivery and engagement with the intervention. Individuals were randomised using a computer-generated random number sequence. Blinded assessors allocated groups and collected outcome measures. Results: Fifty-nine people were assessed for eligibility at two of the participating sites, and 51 were randomised; 26 were allocated to TRAK-ACL and 25 to TAU. Follow-up data were collected on 44 and 40 participants at 3 and 6 months, respectively. All outcome measures were completed fully at 6 months except the Client Service Receipt Inventory. Two patients in each arm did not receive the treatment they were randomised to. Engagement with TRAK-ACL intervention was a median of 5 logins (IQR 3-13 logins), over 18 weeks (SD 12.2 weeks). Conclusion: TRAK-ACL would be suitable for evaluation of effectiveness in a fully powered RCT

Early-life exposure to gut microbiota from disease protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice

The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible non-obese diabetic (NOD) mice have been shown to harbour a distinct microbiota to disease protected mice. We hypothesised that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6 derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before birth, resulted in moderate changes to the gut microbiota, whereas initiating co-housing at weaning only led to minimal changes. Terminating cohousing at weaning reduced the changes in the microbiota composition. However, diabetes onset was not significantly delayed and there was no reduction in intestinal inflammation or the proportion of regulatory T cells in the co-housed NOD mice. However, insulin but not IGRP-specific CD8+ T cells were reduced by co-housing suggesting an epitope-specific modulation of the autoreactive response by the gut microbiota. These results suggest that the T1D susceptible genetic background of the NOD mouse was resistant to the introduction of a C57BL/6 derived microbiota. This article is protected by copyright. All rights reserved

The resurrection of group selection as a theory of human cooperation

Two books edited by members of the MacArthur Norms and Preferences Network (an interdisciplinary group, mainly anthropologists and economists) are reviewed here. These books in large part reflect a renewed interest in group selection that has occurred among these researchers: they promote the theory that human cooperative behavior evolved via selective processes which favored biological and/or cultural group-level adaptations as opposed to individual-level adaptations. In support of this theory, an impressive collection of cross-cultural data are presented which suggest that participants in experimental economic games often do not behave as self-interested income maximizers; this lack of self-interest is regarded as evidence of group selection. In this review, problems with these data and with the theory are discussed. On the data side, it is argued that even if a behavior seems individually-maladaptive in a game context, there is no reason to believe that it would have been that way in ancestral contexts, since the environments of experimental games do not at all resemble those in which ancestral humans would have interacted cooperatively. And on the theory side, it is argued that it is premature to invoke group selection in order to explain human cooperation, because more parsimonious individual-level theories have not yet been exhausted. In summary, these books represent ambitious interdisciplinary contributions on an important topic, and they include unique and useful data; however, they do not make a convincing case that the evolution of human cooperation required group selection

APC-targeted proinsulin expression inactivates insulin-specific memory CD8+ T cells in NOD mice

Type 1 diabetes (T1D) results from T-cell-mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β-cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β-cell destructive effector and memory T-cell responses has the potential to prevent disease progression and recurrence. Targeting antigen expression to antigen-presenting cells inactivates cognate CD8+ effector and memory T-cell responses and has therapeutic potential. Here we investigated this in the context of insulin-specific responses in the non-obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. Insulin-specific CD8+ memory T cells transferred to mice expressing proinsulin in antigen-presenting cells proliferated in response to transgenically expressed proinsulin and the majority were rapidly deleted. A small proportion of transferred insulin-specific Tmem remained undeleted and these were antigen-unresponsive, exhibited reduced T cell receptor (TCR) expression and H-2Kd/insB15-23 tetramer binding and expressed co-inhibitory molecules. Expression of proinsulin in antigen-presenting cells also abolished the diabetogenic capacity of CD8+ effector T cells. Therefore, destructive insulin-specific CD8+ T cells are effectively inactivated by enforced proinsulin expression despite tolerance defects that exist in diabetes-prone NOD mice. These findings have important implications in developing immunotherapeutic approaches to T1D and other T-cell-mediated autoimmune diseases

Fragilaria radians (Kützing) D.M.Williams et Round, the correct name for F. gracilis (Fragilariaceae, Bacillariophyta): a critical analysis of this species complex in Europe

Fragilaria gracilis is one of the most reported Fragilaria species in Europe, observed in a broad range of water bodies, ranging from (ultra)oligotrophic rivers to even eutrophic lakes. A revision of this im-portant taxon based on the analysis of the morphology of a large number of historic and recent populations was highly needed. In the present study, type material of Fragilaria gracilis and several related taxa such as Synedra radians, Fragilaria pseudolaevissima, S. utermoehlii, F. aquaplus, F. boreomongolica and F. tridentina together with more than 10 modern populations were investigated using LM and SEM observations. The results based on these comparisons show that Fragilaria (Synedra) radians is the name for the taxon formerly known as F. gracilis. Moreover, detailed analysis demonstrated that F. pseudolaevissima and Synedra utermoehlii are conspecific with F. radians and should be considered as heterotypic synonyms. The observations made in this study also resulted in the description of several new species, often with distinct ecologies and distribution ar-eas: Fragilaria huerlimannii Van de Vijver sp. nov., F. acerosa Van de Vijver, C.E.Wetzel, Jarlman et Ector sp. nov., F. neglecta Van de Vijver, C.E.Wetzel, Jarlman et Ector sp. nov., F. heudreana Van de Vijver, C.E.Wetzel et Ector sp. nov., F. eutraphenta Van de Vijver, Kusber et D.M.Williams sp. nov., and F. mertensiana Van de Vijver, C.E.Wetzel et Ector sp. nov. Using an analysis of the associated diatom flora, the ecological preferences of each taxon are briefly discussed

The Otterbein Miscellany - December 1976

https://digitalcommons.otterbein.edu/miscellany/1020/thumbnail.jp

Idd9.2 and Idd9.3 Protective Alleles Function in CD4+ T-Cells and Nonlymphoid Cells to Prevent Expansion of Pathogenic Islet-Specific CD8+ T-Cells

OBJECTIVE - Multiple type 1 diabetes susceptibility genes have now been identified in both humans and mice, yet mechanistic understanding of how they impact disease pathogenesis is still minimal. We have sought to dissect the cellular basis for how the highly protective mouse Idd9 region limits the expansion of autoreactive CD8 T-cells, a key cell type in destruction of the islets. RESEARCH DESIGN AND METHODS - We assess the endogenous CD8 T-cell repertoire for reactivity to the islet antigen glucose-6-phosphatase-related protein (IGRP). Through the use of adoptively transferred T-cells, bone marrow chimeras, and reconstituted severe combined immunodeficient mice, we identify the protective cell types involved. RESULTS - IGRP-specific CD8 T-cells are present at low frequency in the insulitic lesions of Idd9 mice and could not be recalled in the periphery by viral expansion. We show that Idd9 genes act extrinsically to the CD8 T-cell to prevent the massive expansion of pathogenic effectors near the time of disease onset that occurs in NOD mice. The subregions Idd9.2 and Idd9.3 mediated this effect. Interestingly, the Idd9.1 region, which provides significant protection from disease, did not prevent the expansion of autoreactive CD8 T-cells. Expression of Idd9 genes was required by both CD4 T-cells and a nonlymphoid cell to induce optimal tolerance. CONCLUSIONS - Idd9 protective alleles are associated with reduced expansion of IGRP-specific CD8 T-cells. Intrinsic expression of protective Idd9 alleles in CD4 T-cells and nonlymphoid cells is required to achieve an optimal level of tolerance. Protective alleles in the Idd9.2 congenic subregion are required for the maximal reduction of islet-specific CD8 T-cells

The meaning of life in a developing universe

The evolution of life on Earth has produced an organism that is beginning to model and understand its own evolution and the possible future evolution of life in the universe. These models and associated evidence show that evolution on Earth has a trajectory. The scale over which living processes are organized cooperatively has increased progressively, as has its evolvability. Recent theoretical advances raise the possibility that this trajectory is itself part of a wider developmental process. According to these theories, the developmental process has been shaped by a larger evolutionary process that involves the reproduction of universes. This evolutionary process has tuned the key parameters of the universe to increase the likelihood that life will emerge and develop to produce outcomes that are successful in the larger process (e.g. a key outcome may be to produce life and intelligence that intentionally reproduces the universe and tunes the parameters of ‘offspring’ universes). Theory suggests that when life emerges on a planet, it moves along this trajectory of its own accord. However, at a particular point evolution will continue to advance only if organisms emerge that decide to advance the evolutionary process intentionally. The organisms must be prepared to make this commitment even though the ultimate nature and destination of the process is uncertain, and may forever remain unknown. Organisms that complete this transition to intentional evolution will drive the further development of life and intelligence in the universe. Humanity’s increasing understanding of the evolution of life in the universe is rapidly bringing it to the threshold of this major evolutionary transition