Sonographically Guided Knee Meniscus Injections: Feasibility, Techniques, and Validation

BackgroundThere is a growing interest in the use of biologic agents such as platelet‐rich plasma and mesenchymal stem/stromal cells to treat musculoskeletal injuries, including meniscal tears. Although previous research has documented the role of diagnostic ultrasound to evaluate meniscal tears, sonographically guided (SG) techniques to specifically deliver therapeutic agents into the meniscus have not been described.ObjectiveTo describe and validate SG injection techniques for the body and posterior horn of the medial and lateral meniscus.DesignProspective, cadaveric laboratory investigation.SettingAcademic institution procedural skills laboratory.SubjectsFive unenbalmed cadaveric knee‐ankle‐foot specimens from 5 donors (3 female and 2 male) ages 33‐92 years (mean age 74 years) with body mass indices of 21.1‐32.4 kg/m2 (mean 24.1 kg/m2).MethodsA single, experienced operator completed SG injections into the bodies and posterior horns of the medial and lateral menisci of 5 unenbalmed cadaveric knees using colored latex and a 22‐gauge, 38‐mm needle. After injection, coinvestigators dissected each specimen to assess latex distribution within the menisci and identify injury to intra‐articular and periarticular structures.Main Outcome MeasuresLatex location within the target region of meniscus (accurate/inaccurate), and iatrogenic injury to “at risk” intra‐ and periarticular structures (present/absent).ResultsSeventeen of 20 injections were accurate. Two of 3 inaccurate injections infiltrated the posterior horn of the medial meniscus instead of the targeted meniscal body. One inaccurate lateral meniscus injection did not contain latex despite sonographically accurate needle placement. No specimen exhibited injury to regional neurovascular structures or intra‐articular hyaline cartilage.ConclusionsSG meniscus injections are feasible and can accurately and safely deliver injectates such as regenerative agents into bodies and posterior horns of the medial and lateral menisci. The role of SG intrameniscal injections in the treatment of patients with degenerative and traumatic meniscal disorders warrants further exploration.Level of EvidenceNot applicable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147070/1/pmr2998.pd

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

PDRs4All IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar

(Abridged) Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 $\mu$m. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR, the atomic PDR, and the HII region. We use JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extract five template spectra to represent the morphology and environment of the Orion Bar PDR. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. While the spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 $\mu$m, a wealth of weaker features and sub-components are present. We report trends in the widths and relative strengths of AIBs across the five template spectra. These trends yield valuable insight into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 $\mu$m AIB emission from class B$_{11.2}$ in the molecular PDR to class A$_{11.2}$ in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a "weeding out" of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called 'grandPAHs'.Comment: 25 pages, 10 figures, to appear in A&

PDRs4All II: JWST's NIR and MIR imaging view of the Orion Nebula

The JWST has captured the most detailed and sharpest infrared images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). We investigate the fundamental interaction of far-ultraviolet photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of 0.1-1" (0.0002-0.002 pc or 40-400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. A complex, structured, and folded DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate

PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar

(Abridged) We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the HII region to the atomic PDR (crossing the ionisation front (IF)), and the subsequent transition to the molecular PDR (crossing the dissociation front (DF)). We use high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science Program. The NIRSpec data reveal a forest of lines including, but not limited to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. We observe numerous smaller scale structures whose typical size decreases with distance from Ori C and IR lines from CI, if solely arising from radiative recombination and cascade, reveal very high gas temperatures consistent with the hot irradiated surface of small-scale dense clumps deep inside the PDR. The H2 lines reveal multiple, prominent filaments which exhibit different characteristics. This leaves the impression of a "terraced" transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star- and planet formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&

CORDAP R&D Technology Roadmap for Understanding the Natural Adaptation and Assisted Evolution of Corals to Climate Change

Experts release a roadmap for harnessing the potential of assisted evolution to help save corals. The IPCC predicts that if warming reaches 2°C, 99% of all coral reefs will be lost in less than 30 years. It is clear that to ensure the future of corals, the highest priority must be reducing global greenhouse gas emissions. However, even with swift and substantial reductions in emissions, corals will continue to face increasing temperatures for the foreseeable future, which can result in extensive coral mortality and local extinction of some coral species. While recent studies have shown that corals may exhibit some degree of adaptation to ocean warming, it is unclear whether corals are able to survive the rate of temperature change during heat waves that will become more frequent under several climate change scenarios. If corals lack what it takes to naturally rapidly adapt to new environmental regimes, they may fail to survive a warming ocean. This is where assisted evolution could be a game-changer. Growing our understanding of the power of adaptation In January 2023, we held a workshop on assisted evolution co-organized with the Australian Institute of Marine Sciences (AIMS) as part of CORDAP’s Scoping Studies (a series of planning sessions and technology roadmap studies to shape our funding priorities). Our aim was to develop a visionary roadmap, offering recommendations on how to prioritise assisted evolution in R&D investment in the future. Assisted evolution is the use of human interventions to speed up the natural evolutionary process. It may allow coral species to adapt faster than they would if left unaided, allowing reefs and corals to keep better pace with the ocean’s environmental changes. The first step in creating this strategy was to pinpoint where we are now in our understanding regarding the potential and impacts of assisted evolution on enhancing coral tolerance to stress conditions like ocean warming. Our experts unanimously agreed that assisted evolution methods cannot be understood and evaluated without a solid foundational understanding of natural adaptation, and identified some knowledge gaps that can be closed with relatively minimal effort and others that will require substantial investment of time and resources. Key Findings: - Standardising methods, experimental designs, species selection guidelines, and terminologies will help to understand natural adaptation and assisted evolution more rapidly. - Long-term funding is critical to facilitate multigenerational studies, which are needed to deliver essential but largely missing information about coral evolution. Building the best pathway for research and investment This roadmap sets out tangible recommendations for future investment and research, to help fill critical knowledge gaps that could assist natural adaptation and evolution of coral reefs in a warming world. Overall, the roadmap recommends investment in a mixed portfolio of R&D, ranging from technologies with lower perceived risks to those with higher percieved risks and longer R&D horizons. This strategy is advised because of the uncertainty around future heating trajectories and thus requirements for enhancement of tolerance. The roadmap outlined four main areas of work that need to be undertaken: 1. Leading global coordination and synthesis. Recommendation: Building global infrastructure to support research would dramatically accelerate the generation of knowledge around the natural and assisted evolution of corals. This could include compiling and committing to a set of standards and methods that will allow more studies to be used in predictive models, as well as establishing a global resource-sharing network and database to facilitate meta-analysis and synthesis. 2. Optimising generation and use of knowledge. Recommendation: Make sure new studies are well designed and timely. Optimize published and future studies by characterizing relationships between heat stress metrics and other facets of coral fitness. Having funding set aside to be able to quickly respond to bleaching events will ensure vital knowledge is captured rather than lost if and when those events occur. 3. Filling critical knowledge gaps in multigenerational coral data in the laboratory and field. Recommendation: Given the slow-growing nature of coral, longer-term funding would allow researchers to gain critical knowledge needed to estimate the multi-generational benefits and risks of implementing assisted evolution methods in the wild. Standardised approaches repeated in different parts of the world would add confidence to generalise those results. 4. Supporting the advance of existing and new technologies. Recommendation: Methods that may yield a larger effect (e.g., gene editing, hybridisation between species, and assisted migration) are also potentially of greater risk and would need considerable R&D. Expanding support for some of the riskier long-term projects currently being overlooked, could potentially offer a greater return on investment, but should be balanced with continued investment in less risky technologies. CORDAP will be using these recommendations to prepare new accelerator program and we believe that they will assist academia in understanding gaps and needs for future research as well as helping to guide funding agencies on where their money will be most effective. The roadmap identifies the funding structures and research priorities that are most likely to yield the knowledge needed to ensure that assisted evolution methods can be implemented effectively. Ultimately, conserving and restoring coral reefs in warming climates will require an inclusive infrastructure involving many partners at a local, national, and international level

Endurance Sports Medicine : A Clinical Guide

Endurance Sports Medicin

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility