The Safety of Glycopeptide-Impregnated Calcium Sulphate Following Debridement, Antibiotics and Implant Retention (DAIR) for Infected Total Knee Replacement.

Background and objective The impact of prosthetic joint infection (PJI) stretches far beyond the physical nature of the disease. It can result in psychological and social consequences, with significant morbidity and mortality for patients. Calcium sulphate-based delivery agents are effective in the management of PJI, yet with associated risks of systemic adverse events. This study aims to evaluate the risk of systemic adverse events when using calcium-sulphate-based local antibiotic delivery agents in the management of PJIs. Methodology We identified 43 patients who underwent debridement, antibiotics and implant retention (DAIR) for infected total knee arthroplasty (TKA) between 2008 and 2014. Patients in the control groupunderwent conventional intravenous and then oral antibiotic administration, while those in the intervention groupunderwent additional local antibiotic therapy via a calcium sulphate alpha hemihydrate matrix. Case notes and laboratory results data were compiled to establish the safety and efficacy of local glycopeptide delivery. Results Serum vancomycin levels were within the safe therapeutic range for all patients in the intervention group with no difference in serum assays between treatment groups (intervention 7.7 mg/L; control 8.0 mg/L; P = 0.85). Renal function for the study cohort improved at every time point post-operatively when referenced against pre-operative renal function (P < 0.05). There was no difference in renal function between intervention and control groups on day 1, one week, six weeks or 12 weeks post-operatively (P = 0.78, 0.89, 0.20 and 0.50). Conclusions Local glycopeptide delivery via a calcium sulphate alpha hemihydrate matrix did not result in systemic adverse consequences specifically not raising the systemic level of glycopeptide, nor reducing renal function. Implications for future research Although demonstrates a safety profile and potential therapeutic benefit, the long-term efficacy of this approach needs to be established. Importantly, selection bias may contribute to masking clinically significant differences in post-operative outcomes.

Exploration biases forelimb reaching strategies.

The brain can generate actions, such as reaching to a target, using different movement strategies. We investigate how such strategies are learned in a task where perched head-fixed mice learn to reach to an invisible target area from a set start position using a joystick. This can be achieved by learning to move in a specific direction or to a specific endpoint location. As mice learn to reach the target, they refine their variable joystick trajectories into controlled reaches, which depend on the sensorimotor cortex. We show that individual mice learned strategies biased to either direction- or endpoint-based movements. This endpoint/direction bias correlates with spatial directional variability with which the workspace was explored during training. Model-free reinforcement learning agents can generate both strategies with similar correlation between variability during training and learning bias. These results provide evidence that reinforcement of individual exploratory behavior during training biases the reaching strategies that mice learn.

A single bout of vigorous intensity exercise enhances the efficacy of rituximab against human chronic lymphocytic leukaemia B-cells ex vivo.

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naïve CLL completed a bout of cycling 15 % above anaerobic threshold for âˆ¼ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3-CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells - independent of rituximab - was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy.

Focal resurfacing of the knee - A systematic review and meta-analysis.

PURPOSE: In order to assess the published validity of focal resurfacing of the knee, a systematic review and meta-analysis were conducted to (i) evaluate revision rates and implant survival of focal resurfacing of the knee; (ii) explore surgical complications; and (iii) evaluate patient reported clinical outcome measures. METHODS: PubMED, Cochrane Library and Medline databases were searched by 2 independent reviewers in February 2022 for prospective and retrospective cohort studies evaluating any of the following implant types: HemiCAP®, UniCAP®, Episealer® or BioBoly®. Data on incidence of revision, complications and various patient reported outcome measures, such as Knee Society Score (KSS) or Knee Injury and Osteoarthritis Outcome Score (KOOS) was sourced. RESULTS: A total of 24 published studies were identified with a total of 1465 enrolled patients. A revision rate of 12.97% over a 5.9 year weighted mean follow-up period was observed across all implant types. However, in one series a Kaplan-Meir survival as high as 92.6% at a 10-year follow-up period was noted. A statistically significant improvement was documented across multiple subjective clinical outcomes scores, for example a mean 4.56 point improvement of the VAS (0-10) pain score. The Kellgren-Lawrence score was used to evaluate the radiological progression of osteoarthritis and showed a small significant reduction in all anatomical locations, hence not supporting the hypothesis that focal femoral implants can lead to the progression of osteoarthritis in the affected compartment. There was a low reported incidence of post-operative complications such as aseptic loosening or deep wound infection. CONCLUSIONS: Focal femoral resurfacing appears to be a viable treatment option for focal symptomatic chondral lesions in patients beyond biological reconstruction, with low revision rates and high patient satisfaction especially at short and medium length follow-up.

Cryogen-free 400-MHz nuclear magnetic resonance spectrometer as a versatile tool for pharmaceutical process analytical technology.

The discovery of new ceramic materials containing Ba-La-Cu oxides in 1986 that exhibited superconducting properties at high temperatures in the range of 35 K or higher, recognized with the Nobel Prize in Physics in 1987, opened a new world of opportunities for nuclear magnetic resonance (NMRs) and magnetic resonance imaging (MRIs) to move away from liquid cryogens. This discovery expands the application of high temperature superconducting (HTS) materials to fields beyond the chemical and medical industries, including electrical power grids, energy, and aerospace. The prototype 400-MHz cryofree HTS NMR spectrometer installed at Amgen's chemistry laboratory has been vital for a variety of applications such as structure analysis, reaction monitoring, and CASE-3D studies with RDCs. The spectrometer has been integrated with Amgen's chemistry and analytical workflows, providing pipeline project support in tandem with other Kinetic Analysis Platform technologies. The 400-MHz cryofree HTS NMR spectrometer, as the name implies, does not require liquid cryogens refills and has smaller footprint that facilitates installation into a chemistry laboratory fume hood, sharing the hood with a process chemistry reactor. Our evaluation of its performance for structural analysis with CASE-3D protocol and for reaction monitoring of Amgen's pipeline chemistry was successful. We envision that the HTS magnets would become part of the standard NMR and MRI spectrometers in the future. We believe that while the technology is being developed, there is room for all magnet options, including HTS, low temperature superconducting (LTS) magnets, and low field benchtop NMRs with permanent magnets, where utilization will be dependent on application type and costs.

Understanding Clinician EHR Data Quality for Reuse in Predictive Modelling.

It is imperative to build clinician trust to reuse ever-growing amounts of rich clinical data. Utilising a proprietary, structured electronic health record, we address data quality by assessing the plausibility of chiropractors, physical therapists and osteopaths' data entry to help determine if the data is fit for use in predicting outcomes of work-related musculoskeletal disorders using machine learning. For most variables assessed, individual clinician data entry positively correlated to the clinician group's data entry, indicating data is fit for reuse. However, from the clinician's perspective, there were inconsistencies, which could lead to data mistrust. When assessing data quality in EHR studies, it is crucial to engage clinicians with their deep understanding of EHR use, as improvement suggestions could be made. Clinicians should be considered local knowledge experts.

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study.

INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774.

Passive exposure to task-relevant stimuli enhances categorization learning.

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.

Dynamic lid domain of Chloroflexus aurantiacus Malonyl-CoA reductase controls the reaction.

Malonyl-Coenzyme A Reductase (MCR) in Chloroflexus aurantiacus, a characteristic enzyme of the 3-hydroxypropionate (3-HP) cycle, catalyses the reduction of malonyl-CoA to 3-HP. MCR is a bi-functional enzyme; in the first step, malonyl-CoA is reduced to the free intermediate malonate semialdehyde by the C-terminal region of MCR, and this is further reduced to 3-HP by the N-terminal region of MCR. Here we present the crystal structures of both N-terminal and C-terminal regions of the MCR from C. aurantiacus. A catalytic mechanism is suggested by ligand and substrate bound structures, and structural and kinetic studies of MCR variants. Both MCR structures reveal one catalytic, and one non-catalytic SDR (short chain dehydrogenase/reductase) domain. C-terminal MCR has a lid domain which undergoes a conformational change and controls the reaction. In the proposed mechanism of the C-terminal MCR, the conversion of malonyl-CoA to malonate semialdehyde is based on the reduction of malonyl-CoA by NADPH, followed by the decomposition of the hemithioacetal to produce malonate semialdehyde and coenzyme A. Conserved arginines, Arg734 and Arg773 are proposed to play key roles in the mechanism and conserved Ser719, and Tyr737 are other essential residues forming an oxyanion hole for the substrate intermediates.

A covalent fragment-based strategy targeting a novel cysteine to inhibit activity of mutant EGFR kinase.

Several generations of ATP-competitive anti-cancer drugs that inhibit the activity of the intracellular kinase domain of the epidermal growth factor receptor (EGFR) have been developed over the past twenty years. The first-generation of drugs such as gefitinib bind reversibly and were followed by a second-generation such as dacomitinib that harbor an acrylamide moiety that forms a covalent bond with C797 in the ATP binding pocket. Resistance emerges through mutation of the T790 gatekeeper residue to methionine, which introduces steric hindrance to drug binding and increases the Km for ATP. A third generation of drugs, such as osimertinib were developed which were effective against T790M EGFR in which an acrylamide moiety forms a covalent bond with C797, although resistance has emerged by mutation to S797. A fragment-based screen to identify new starting points for an EGFR inhibitor serendipitously identified a fragment that reacted with C775, a previously unexploited residue in the ATP binding pocket for a covalent inhibitor to target. A number of acrylamide containing fragments were identified that selectively reacted with C775. One of these acrylamides was optimized to a highly selective inhibitor with sub-1 µM activity, that is active against T790M, C797S mutant EGFR independent of ATP concentration, providing a potential new strategy for pan-EGFR mutant inhibition.

Biomechanical Comparison of the Simple Suture Technique, Meniscal Matrix-Assisted Repair, and a Novel Meniscus Cap Suture Technique for Complex Meniscal Repair.

Background: Meniscal repair is the gold standard for simple morphology tears. However, when the morphology and chronicity of the tear are less favorable, the success of the standard techniques is reduced. Purpose/Hypothesis: To compare meniscal repair augmented by a new bioresorbable implant (Meniscus Cap) versus a traditional simple suture technique and the currently available augmented repair collagen matrix meniscus wrapping technique. It was hypothesized that the Meniscus Cap suture technique would increase ultimate failure load and less displacement during cyclic loading. Study Design: Controlled laboratory study. Methods: A total of 80 fresh porcine menisci were harvested. Complex tears were created in 60 menisci, and 20 intact menisci were tested as the control group. Repairs were performed on the 60 meniscal tears using 1 of the 3 techniques (20 menisci each): an inside-out H-suture group (SS), the collagen matrix wrapping technique (CMW), and the Meniscus Cap bioresorbable implant group (CM). The menisci were subjected to 500 loading cycles from 4 to 20 N at a frequency of 1 Hz, and the total displacement was recorded. Then, the specimens underwent load to failure testing at a rate of 3.15 mm/s, and the failure mode was noted. Results: After 500 cycles of cyclic loading, there were no significant differences in displacement between the controls and CM group (0.524 vs 0.448 mm; P = .95). The displacement after the CM was significantly smaller compared with the CMW and the SS (0.448 vs 1.077 mm [P = .0009] and 0.448 vs 0.848 mm [P = .04], respectively). The ultimate load to failure was significantly greater for the controls and the CM group compared with the SS and CMW groups (controls, 1278.7 N and CM, 628.5 N vs CMW, 380.1 N and SS, 345.1 N; P < .05). The failure mode was suture breakage (suture failure) for all repairs. Conclusion: In a porcine specimen meniscal repair model, the biomechanical properties of a novel Meniscus Cap repair technique were superior to that of the simple suture and CMW techniques. Clinical Relevance: The results suggest that the Meniscal Cap repair technique may provide sufficient primary stability of the meniscal fixation even in the cases of complex meniscal tears.

Snakebite epidemiology, outcomes and multi-cluster risk modelling in Eswatini.

BACKGROUND: Halving snakebite morbidity and mortality by 2030 requires countries to develop both prevention and treatment strategies. The paucity of data on the global incidence and severity of snakebite envenoming causes challenges in prioritizing and mobilising resources for snakebite prevention and treatment. In line with the World Health Organisation's 2019 Snakebite Strategy, this study sought to investigate Eswatini's snakebite epidemiology and outcomes, and identify the socio-geographical factors associated with snakebite risk. METHODOLOGY: Programmatic data from the Ministry of Health, Government of Eswatini 2019-2021, was used to assess the epidemiology and outcomes of snakebite in Eswatini. We developed a snake species richness map from the occurrence data of all venomous snakes of medical importance in Eswatini that was subjected to niche modelling. We formulated four risk indices using snake species richness, various geospatial datasets and reported snakebites. A multivariate cluster modelling approach using these indices was developed to estimate risk of snakebite and the outcomes of snakebite in Eswatini. PRINCIPAL FINDINGS: An average of 466 snakebites was recorded annually in Eswatini. Bites were recorded across the entire country and peaked in the evening during summer months. Two cluster risk maps indicated areas of the country with a high probability of snakebite and a high probability of poor snakebite outcomes. The areas with the highest rate of snakebite risk were primarily in the rural and agricultural regions of the country. SIGNIFICANCE: These models can be used to inform better snakebite prevention and treatment measures to enable Eswatini to meet the global goal of reducing snakebite morbidity and mortality by 50% by 2030. The supply chain challenges of antivenom affecting southern Africa and the high rates of snakebite identified in our study highlight the need for improved snakebite prevention and treatment tools that can be employed by health care workers stationed at rural, community clinics.

Impact of Aerobic Training on Cardiovascular Function, Fitness, and Patient Reported Outcomes During Anthracycline Chemotherapy: A Case Series in Women With Breast Cancer.

BACKGROUND: Chemotherapy for breast cancer can increase the risk of cancer therapy related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD, however, research to date has indicated high degrees of individual variability following exercise interventions in this population. AIM: This study aimed to explore the impact of regular, individualized aerobic exercise on CTRCD incidence (defined by global longitudinal strain [GLS]) during and immediately upon the completion of dose-dense anthracycline (DDAC) chemotherapy in 5 women with breast cancer. METHODS: Five women receiving DDAC with stage I-III breast cancer enrolled. Participants underwent resting echocardiography and exercise testing before, during, upon the completion of, and 3 months after the completion of DDAC treatment to measure GLS and aerobic fitness (VO2peak). Participants opted-in to an individualized 8-week aerobic exercise intervention (3 sessions per week, 24 sessions total) or standard care for the duration of their DDAC treatment. Data for each participant were presented descriptively. RESULTS: Four of the 5 participants completed the exercise intervention during DDAC treatment (adherence 79.2%-91.7%). Mild asymptomatic CTRCD occurred in 2 of the 4 exercising participants, of whom both were at an increased risk (one was >65 years of age and diagnosed with hypertension, with the other receiving trastuzumab prior to DDAC treatment). Varied responses in VO2peak were observed and did not align with changes in GLS. The only participant not to complete the exercise intervention reported poorer health related quality of life and increased cancer related fatigue at all measurement timepoints. CONCLUSION: This study details the individual variability in cardiovascular responses to exercise that can occur during DDAC treatment in women with breast cancer, which can inform exercise professionals and researchers when designing individualized exercise programs for this population.

VarLOCK: sequencing-independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance.

The COVID-19 pandemic demonstrated the need for rapid molecular diagnostics. Vaccination programs can provide protection and facilitate the opening of society, but newly emergent and existing viral variants capable of evading the immune system endanger their efficacy. Effective surveillance for Variants of Concern (VOC) is therefore important. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. Here we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to provide rapid and sensitive discrimination of SARS-CoV-2 VOCs that can be used at point of care, implemented in the pipelines of small or large testing facilities, and even determine the proportion of VOCs in pooled population-level wastewater samples. This technology complements sequencing efforts to allow facile and rapid identification of individuals infected with VOCs to help break infection chains. We show the optimisation of our VarLOCK assays (Variant-specific SHERLOCK) for multiple specific mutations in the S gene of SARS-CoV-2 and validation with samples from the Cardiff University Testing Service. We also show the applicability of VarLOCK to national wastewater surveillance of SARS-CoV-2 variants and the rapid adaptability of the technique for new and emerging VOCs.

Engineering Nitrogenases for Synthetic Nitrogen Fixation: From Pathway Engineering to Directed Evolution.

Globally, agriculture depends on industrial nitrogen fertilizer to improve crop growth. Fertilizer production consumes fossil fuels and contributes to environmental nitrogen pollution. A potential solution would be to harness nitrogenases-enzymes capable of converting atmospheric nitrogen N2 to NH3 in ambient conditions. It is therefore a major goal of synthetic biology to engineer functional nitrogenases into crop plants, or bacteria that form symbiotic relationships with crops, to support growth and reduce dependence on industrially produced fertilizer. This review paper highlights recent work toward understanding the functional requirements for nitrogenase expression and manipulating nitrogenase gene expression in heterologous hosts to improve activity and oxygen tolerance and potentially to engineer synthetic symbiotic relationships with plants.

How do practitioners prescribe exercise to patients with breast cancer? Professional perspectives on the key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy.

OBJECTIVES: This study aimed to understand the key factors experienced accredited exercise physiologists (AEPs) and medical professionals consider when prescribing/recommending aerobic exercise to patients with breast cancer undergoing chemotherapy. DESIGN: Modified Delphi Survey. METHODS: A four-round, two-phase survey was conducted. Following a Delphi approach, four cancer-specific AEPs, four oncologists, and one breast cancer surgeon (median 13-yr breast-cancer-specific experience) completed phase one. Eighty-four AEPs (median 5-yr experience) completed phase two. Phase one participants answered open- and close-ended questions regarding key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy, and what information should be collected to guide exercise prescription. All questions and considerations agreed upon in phase one (>70 % rating 7-9 on a 0-9 Likert Scale) were rated by AEPs in phase two. RESULTS: Key considerations for exercise assessment and prescription aligned closely with exercise guidelines for cancer survivors. Common strategies for exercise individualisation were identified by AEPs, including separating aerobic exercise into 5-to--9-minute bouts when required and avoiding exercising to complete exhaustion. Exercise intensity and duration should be adjusted throughout chemotherapy to improve tolerance and adherence. Novel considerations for subjective questioning and objective assessments to tailor exercise prescription were outlined. CONCLUSIONS: This study identifies how professionals approach exercise assessment and prescription in patients with breast cancer undergoing chemotherapy. Findings can guide AEPs in practice when prescribing tailored exercise to breast cancer patients undergoing chemotherapy and inform future guidelines.

Modelling how plant cell-cycle progression leads to cell size regulation.

Populations of cells typically maintain a consistent size, despite cell division rarely being precisely symmetrical. Therefore, cells must possess a mechanism of "size control", whereby the cell volume at birth affects cell-cycle progression. While size control mechanisms have been elucidated in a number of other organisms, it is not yet clear how this mechanism functions in plants. Here, we present a mathematical model of the key interactions in the plant cell cycle. Model simulations reveal that the network of interactions exhibits limit-cycle solutions, with biological switches underpinning both the G1/S and G2/M cell-cycle transitions. Embedding this network model within growing cells, we test hypotheses as to how cell-cycle progression can depend on cell size. We investigate two different mechanisms at both the G1/S and G2/M transitions: (i) differential expression of cell-cycle activator and inhibitor proteins (with synthesis of inhibitor proteins being independent of cell size), and (ii) equal inheritance of inhibitor proteins after cell division. The model demonstrates that both these mechanisms can lead to larger daughter cells progressing through the cell cycle more rapidly, and can thus contribute to cell-size control. To test how these features enable size homeostasis over multiple generations, we then simulated these mechanisms in a cell-population model with multiple rounds of cell division. These simulations suggested that integration of size-control mechanisms at both G1/S and G2/M provides long-term cell-size homeostasis. We concluded that while both size independence and equal inheritance of inhibitor proteins can reduce variations in cell size across individual cell-cycle phases, combining size-control mechanisms at both G1/S and G2/M is essential to maintain size homeostasis over multiple generations. Thus, our study reveals how features of the cell-cycle network enable cell-cycle progression to depend on cell size, and provides a mechanistic understanding of how plant cell populations maintain consistent size over generations.

Diathermy and bone sawing are high aerosol yield procedures.

Aims: Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians' health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations. Methods: The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 µm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures. Results: Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s-1). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s-1). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields. Conclusion: This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure.

Arthroscopic Matrix-Based Meniscus Repair Surgical Technique With "Goat" Instrument.

Human meniscal treatment with an arthroscopic matrix-based meniscal repair technique is a promising procedure. Heretofore, the procedure has required a skilled surgeon with a great amount of experience in knee arthroscopic surgery and meniscal suturing. A surgical technique using a "goat" delivery clamp has been developed. Technique development followed extensive review and the application of earlier arthroscopic matrix-based meniscal repair techniques, along with cadaveric refinement of the proposed arthroscopic technique. The presented technique includes preparation of the meniscus with initial stabilization of the damaged fragments, preparation of the collagen matrix and placement of this matrix into the open jaws of the goat delivery clamp, introduction of the collagen matrix into the knee and placement of this matrix on the meniscus, suturing of the collagen matrix to the meniscus, and bone marrow blood aspirate injection between the collagen matrix and meniscus.