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IntroductionPain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysisThe Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and disseminationThe trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

WHAT is your, expert opinion of the Government's handling of monetary affairs? Is the suggestion of panic...

Background The prognostic value of tumor‐associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c+ DC co–expressing the immunoinhibitory molecule PD‐L1 and their spatial relationship with CD8+ T‐cells in patients treated for stage III colon cancer. Methods Tissue microarrays containing representative cores of central tumor, leading edge, and adjacent normal tissue from 221 patients with stage III colon cancer were immunostained for CD8, CD11c, PD‐L1, and cytokeratin using immunofluorescent probes. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kaplan‐Meier estimates and Cox regression were used to assess survival. Results Intratumoral CD8+ cell density (HR = .52, 95% confidence interval [CI] .33‐.83, P = .007), stromal CD11c+ cell density (HR = .52, 95% CI .33‐.83, P = .006), intratumoral CD11c+PD‐L1+ cell density (HR = .57, 95% CI .35‐.92, P = .021), and stromal CD11c+PD‐L1+ cell density (HR = .48, 95% CI .30‐.77, P = .003) on leading‐edge cores were all significantly associated with good survival. CD8+ cell density was positively correlated with both CD11c+ cell density and CD11c+PD‐L1+ cell density in tumor epithelium and stromal compartments. Conclusion Here we showed that PD‐L1‐expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically “hot” tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by tumor‐associated DC may help to further elucidate their prognostic value. In this study, using immunofluorescence analysis of fixed surgical samples, we demonstrate that PD‐L1 expressing dendritic cells are associated with good prognosis in stage III colon cancer. However, densities of PD‐L1 expressing dendritic cells were correlated to CD8 T cell density, indicating that they may represent an immunologically “hot” tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by DC is required.

The structure and function of the anterolateral complex (ALC) of the knee has created much controversy since the ‘re-discovery’ of the anterolateral ligament (ALL) and its proposed role in aiding control of anterolateral rotatory laxity in the anterior cruciate ligament (ACL) injured knee. A group of surgeons and researchers prominent in the field gathered to produce consensus as to the anatomy and biomechanical properties of the ALC. The evidence for and against utilisation of ALC reconstruction was also discussed, generating a number of consensus statements by following a modified Delphi process. Key points include that the ALC consists of the superficial and deep aspects of the iliotibial tract with its Kaplan fibre attachments on the distal femur, along with the ALL, a capsular structure within the anterolateral capsule. A number of structures attach to the area of the Segond fracture including the capsule-osseous layer of the iliotibial band, the ALL and the anterior arm of the short head of biceps, and hence it is not clear which is responsible for this lesion. The ALC functions to provide anterolateral rotatory stability as a secondary stabiliser to the ACL. Whilst biomechanical studies have shown that these structures play an important role in controlling stability at the time of ACL reconstruction, the optimal surgical procedure has not yet been defined clinically. Concern remains that these procedures may cause constraint of motion, yet no clinical studies have demonstrated an increased risk of osteoarthritis development. Furthermore, clinical evidence is currently lacking to support clear indications for lateral extra-articular procedures as an augmentation to ACL reconstruction. The resulting statements and scientific rationale aim to inform readers on the most current thinking and identify areas of needed basic science and clinical research to help improve patient outcomes following ACL injury and subsequent reconstruction. Level of evidence V.

Coral reefs are the most biologically diverse of shallow water marine ecosystems but are being degraded worldwide by human activities and climate warming. Analyses of the geographic ranges of 3235 species of reef fish, corals, snails, and lobsters revealed that between 7.2% and 53.6% of each taxon have highly restricted ranges, rendering them vulnerable to extinction. Restricted-range species are clustered into centers of endemism, like those described for terrestrial taxa. The 10 richest centers of endemism cover 15.8% of the world's coral reefs (0.012% of the oceans) but include between 44.8 and 54.2% of the restricted-range species. Many occur in regions where reefs are being severely affected by people, potentially leading to numerous extinctions. Threatened centers of endemism are major biodiversity hotspots, and conservation efforts targeted toward them could help avert the loss of tropical reef biodiversity.

Treatment strategies for ACL injuries continue to evolve. Evidence supporting best practice guidelines to manage ACL injury is largely based on studies with low-level evidence. An international consensus group of experts was convened determine consensus regarding best available evidence on operative versus non-operative treatment for ACL injury. The purpose of this study is to report the consensus statements on operative versus non-operative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. Sixty-six international experts on the management of ACL injuries, representing 18 countries, convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the Scientific Organising Committee and Session Chairs. Panel participants reviewed preliminary statements prior to the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Eighty per cent agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus non-operative treatment of ACL injury reached consensus during the Symposium. Nine statements achieved unanimous support, two reached strong consensus, one did not achieve consensus, and one was removed due to redundancy in the information provided. In highly active patients engaged in jumping, cutting and pivoting sports, early anatomical ACL reconstruction is recommended due to the high risk of secondary meniscus and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight plane activities, non-operative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomical ACL reconstruction is indicated. The consensus statements derived from international leaders in the field may assist clinicians in deciding between operative and non-operative treatment with patients after an ACL injury. Level of evidence: Level V

A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sport and their previous activity level. The aim of the Panther Symposium ACL Injury Return to Sport Consensus Group was to provide a clear definition of RTS after ACL injury and a description of the RTS continuum as well as provide clinical guidance on RTS testing and decision-making. Consensus statement. An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Key points include that RTS is characterized by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS and, ultimately, return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum, with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors, and concomitant injuries. The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing, and methods for the biological assessment of healing and recovery.

The potential for conservation of individual species has been greatly advanced by the International Union for Conservation of Nature's (IUCN) development of objective, repeatable, and transparent criteria for assessing extinction risk that explicitly separate risk assessment from priority setting. At the IV World Conservation Congress in 2008, the process began to develop and implement comparable global standards for ecosystems. A working group established by the IUCN has begun formulating a system of quantitative categories and criteria, analogous to those used for species, for assigning levels of threat to ecosystems at local, regional, and global levels. A final system will require definitions of ecosystems; quantification of ecosystem status; identification of the stages of degradation and loss of ecosystems; proxy measures of risk (criteria); classification thresholds for these criteria; and standardized methods for performing assessments. The system will need to reflect the degree and rate of change in an ecosystem's extent, composition, structure, and function, and have its conceptual roots in ecological theory and empirical research. On the basis of these requirements and the hypothesis that ecosystem risk is a function of the risk of its component species, we propose a set of four criteria: recent declines in distribution or ecological function, historical total loss in distribution or ecological function, small distribution combined with decline, or very small distribution. Most work has focused on terrestrial ecosystems, but comparable thresholds and criteria for freshwater and marine ecosystems are also needed. These are the first steps in an international consultation process that will lead to a unified proposal to be presented at the next World Conservation Congress in 2012.

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Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury.