An ON-type direction-selective ganglion cell in primate retina.

To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze-stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements1. However, ON-DSGCs have not yet been identified in the retina of primates, raising the possibility that this reflex is mediated by cortical visual areas. Here we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification and morphological analysis to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature and GABA (γ-aminobutyric acid)-dependent mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with those in other mammals. We further identify a candidate ON-DSGC in human retina. The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilization in the developing and mature visual system.

Exotoxin S secreted by internalized Pseudomonas aeruginosa delays lytic host cell death.

The Pseudomonas aeruginosa toxin ExoS, secreted by the type III secretion system (T3SS), supports intracellular persistence via its ADP-ribosyltransferase (ADPr) activity. For epithelial cells, this involves inhibiting vacuole acidification, promoting vacuolar escape, countering autophagy, and niche construction in the cytoplasm and within plasma membrane blebs. Paradoxically, ExoS and other P. aeruginosa T3SS effectors can also have antiphagocytic and cytotoxic activities. Here, we sought to reconcile these apparently contradictory activities of ExoS by studying the relationships between intracellular persistence and host epithelial cell death. Methods involved quantitative imaging and the use of antibiotics that vary in host cell membrane permeability to selectively kill intracellular and extracellular populations after invasion. Results showed that intracellular P. aeruginosa mutants lacking T3SS effector toxins could kill (permeabilize) cells when extracellular bacteria were eliminated. Surprisingly, wild-type strain PAO1 (encoding ExoS, ExoT and ExoY) caused cell death more slowly, the time extended from 5.2 to 9.5 h for corneal epithelial cells and from 10.2 to 13.0 h for HeLa cells. Use of specific mutants/complementation and controls for initial invasion showed that ExoS ADPr activity delayed cell death. Triggering T3SS expression only after bacteria invaded cells using rhamnose-induction in T3SS mutants rescued the ExoS-dependent intracellular phenotype, showing that injected effectors from extracellular bacteria were not required. The ADPr activity of ExoS was further found to support internalization by countering the antiphagocytic activity of both the ExoS and ExoT RhoGAP domains. Together, these results show two additional roles for ExoS ADPr activity in supporting the intracellular lifestyle of P. aeruginosa; suppression of host cell death to preserve a replicative niche and inhibition of T3SS effector antiphagocytic activities to allow invasion. These findings add to the growing body of evidence that ExoS-encoding (invasive) P. aeruginosa strains can be facultative intracellular pathogens, and that intracellularly secreted T3SS effectors contribute to pathogenesis.

Preoperative predictors for return to physical activity following anterior cruciate ligament reconstruction (ACLR): a systematic review.

BACKGROUND: Rates of return to physical activity after anterior cruciate ligament reconstruction surgery are sub-optimal. Optimising presurgical treatment may improve return rates. The purpose of this systematic review was to identify modifiable preoperative predictors for return to physical activity after anterior cruciate ligament reconstruction. METHODS: Seven electronic databases (CINAHL, MEDLINE and SPORTDiscus via EBSCOhost, AMED, PsycINFO and EMBASE via OVID and Web of Science) were searched from inception to 31 March 2023. The population of focus was adults aged 18-65 who had undergone primary anterior cruciate ligament reconstruction. Studies needed to identify at least one potential modifiable preoperative predictor variable and the relationship between the predictor(s) and return to physical activity. All time-points of assessment and study designs were included. Data extraction was completed by one reviewer and verified by a second reviewer. Two reviewers completed the risk of bias assessment using the Quality in Prognostic Studies tool and Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The search identified 2281 studies, eight met the inclusion criteria. Five studies scored 'high', and three studies scored 'moderate' risk-of-bias. All preoperative predictors were of very low-quality evidence. Five different outcome measures were used to assess return to physical activity including Tegner, Marx, Physical Activity Scale, return to play at the elite level and return to preinjury level (undefined). This was measured between 1- and 10-years post-surgery. Nine preoperative physical, six psychosocial and five demographic/clinical factors were assessed and four were found to be predictive. These included quadriceps strength, psychological profile, patient estimated ability to return and graft type (patella tendon, BPTB). CONCLUSION: Very-low level evidence suggests that increasing quadriceps strength, managing patient expectations of their treatment outcomes, improving motivation to resume preinjury activity levels and considering the use of a BPTB graft will support return to physical activity after ACLR. TRIAL REGISTRATION: This study was prospectively registered in PROSPERO: CRD 42020222567.

Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

In Situ Measurement of Thermodynamic Partitioning in Open Hydrogels.

Thermodynamic partitioning dictates solute loading and release from a hydrogel. Design of drug delivery vehicles, cell and tissue matrices, and immunoassay scaffolds that utilize hydrogel materials is informed by an understanding of the thermodynamic partitioning properties of those hydrogels. We develop aberration-compensated laser scanning confocal microscopy (AC-LSCM), a technique that can be applied to all fluorescence microscopy-based equilibrium partition coefficient measurements where the fluorescence is uniformly distributed in the reference material (e.g., many solutes in thermodynamic equilibrium). In this paper, we use AC-LSCM to measure spatially resolved in situ equilibrium partition coefficients of various fluorescently labeled solutes in single-layer and multilayer open hydrogels. In considering a dynamic material, we scrutinize solute interactions with a UV photoactive polyacrylamide gel that incorporates a benzophenone methacrylamide backbone. We observed strong agreement with an adjusted version of Ogston's ideal size-exclusion model for spatially resolved in situ equilibrium partition coefficients across a wide range of polyacrylamide hydrogel densities (R2 = 0.98). Partition coefficients of solutes differing in hydrodynamic radius were consistent with size-based theory in the photoactive hydrogels, but exceed those in unmodified polyacrylamide gels. This observation suggests a deviation from the size-exclusion model and a shift in the thermodynamic equilibrium state of the solutes toward the gel phase. AC-LSCM also resolves differential partitioning behavior of the model solute in two-layer gels, providing insight into the transport phenomena governing the partitioning in multilaminate gel structures. Furthermore, AC-LSCM identifies and quantifies depth-dependent axial aberrations that could confound quantitation, highlighting the need for the "aberration compensated" aspect of AC-LSCM.

The effectiveness of preoperative rehabilitation programmes on postoperative outcomes following anterior cruciate ligament (ACL) reconstruction: a systematic review.

BACKGROUND: To explore the effectiveness of preoperative rehabilitation programmes (PreHab) on postoperative physical and psychological outcomes following anterior cruciate ligament reconstruction (ACLR). METHOD: A systematic search was conducted from inception to November 2019. Randomised controlled trials (RCTs) published in English were included. Risk of bias was assessed using Version 2 of the Cochrane risk-of-bias tool, and the Grading of Recommendations Assessment system was used to evaluate the quality of evidence. RESULTS: The search identified 739 potentially eligible studies, three met the inclusion criteria. All included RCTs scored 'high' risk of bias. PreHab in all three RCTs was an exercise programme, each varied in content (strength, control, balance and perturbation training), frequency (10 to 24 sessions) and length (3.1- to 6-weeks). Statistically significant differences (p < 0.05) were reported for quadriceps strength (one RCT) and single leg hop scores (two RCTs) in favour of PreHab three months after ACLR, compared to no PreHab. One RCT reported no statistically significant between-group difference for pain and function. No RCT evaluated post-operative psychological outcomes. CONCLUSION: Very low quality evidence suggests that PreHab that includes muscular strength, balance and perturbation training offers a small benefit to quadriceps strength and single leg hop scores three months after ACLR compared with no PreHab. There is no consensus on the optimum PreHab programme content, frequency and length. Further research is needed to develop PreHab programmes that consider psychosocial factors and the measurement of relevant post-operative outcomes such as psychological readiness and return to sport. TRIAL REGISTRATION: PROSPERO trial registration number. CRD42020162754 .

Cellular distribution of secretory pathway markers in the haploid synergid cells of Arabidopsis thaliana.

In flowering plants, cell-cell communication plays a key role in reproductive success, as both pollination and fertilization require pathways that regulate interactions between many different cell types. Some of the most critical of these interactions are those between the pollen tube (PT) and the embryo sac, which ensure the delivery of sperm cells required for double fertilization. Synergid cells function to attract the PT through secretion of small peptides and in PT reception via membrane-bound proteins associated with the endomembrane system and the cell surface. While many synergid-expressed components regulating PT attraction and reception have been identified, few tools exist to study the localization of membrane-bound proteins and the components of the endomembrane system in this cell type. In this study, we describe the localization and distribution of seven fluorescent markers that labelled components of the secretory pathway in synergid cells of Arabidopsis thaliana. These markers were used in co-localization experiments to investigate the subcellular distribution of the two PT reception components LORELEI, a GPI-anchored surface protein, and NORTIA, a MILDEW RESISTANCE LOCUS O protein, both found within the endomembrane system of the synergid cell. These secretory markers are useful tools for both reproductive and cell biologists, enabling the analysis of membrane-associated trafficking within a haploid cell actively involved in polar transport.

Correction: Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa.

[This corrects the article DOI: 10.1371/journal.ppat.1006392.].

Regularized Coulomb Friction Laws for Ice Sheet Sliding: Application to Pine Island Glacier, Antarctica.

The choice of the best basal friction law to use in ice-sheet models remains a source of uncertainty in projections of sea level. The parameters in commonly used friction laws can produce a broad range of behavior and are poorly constrained. Here we use a time series of elevation and speed data to examine the simulated transient response of Pine Island Glacier, Antarctica, to a loss of basal traction as its grounding line retreats. We evaluate a variety of friction laws, which produces a diversity of responses, to determine which best reproduces the observed speedup when forced with the observed thinning. Forms of the commonly used power law friction provide much larger model-data disagreement than less commonly used regularized Coulomb friction in which cavitation effects yield an upper bound on basal friction. Thus, adoption of such friction laws could substantially improve the fidelity of large-scale simulations to determine future sea level.

A loaded self-managed exercise programme for patellofemoral pain: a mixed methods feasibility study.

BACKGROUND: A novel loaded self-managed exercise programme that includes pain education and self-management strategies may result in better outcomes for people with patellofemoral pain (PFP). However, establishing program feasibility is an essential first step before testing efficacy. The purpose of this study was to evaluate the feasibility and acceptability of conducting a definitive RCT which will evaluate the clinical and cost-effectiveness of a loaded self-managed exercise programme for people with PFP compared with usual physiotherapy. METHODS: In a mixed methods, pragmatic, randomised controlled feasibility study, 60 participants with PFP (57% female; mean age 29 years) were recruited from a physiotherapy clinic within a large UK teaching hospital. They were randomly allocated to receive either a loaded self-managed exercise programme (n = 30) or usual physiotherapy (n = 30). Feasibility indicators of process, resources, and management were collected through follow-up of standardised questionnaires six months after recruitment and semi-structured interviews with 20 participants and physiotherapists. RESULTS: Recruitment rate was 5 participants per month; consent rate was 99%; adherence to intervention appointments was 87%; completeness of questionnaire data was 100%; and adherence to intervention delivery was 95%. Three exercise diaries were returned at six months (5%). At six months, 25 questionnaire booklets were returned (9 in the loaded self-managed group, 16 in the usual physiotherapy group), with a total retention rate of 42%. At six months, 56% (5/9) of respondents in the loaded self-managed group and 56% (9/16) in the usual physiotherapy group were classified as 'recovered'. Both groups demonstrated improvements in average pain (VAS), kinesiophobia, pain catastrophizing, general self-efficacy and EQ-5D-5 L from baseline to six months. CONCLUSION: The results of this feasibility study confirm that it is feasible and acceptable to deliver a loaded self-managed exercise programme to adults with PFP in an NHS physiotherapy outpatient setting. However, between group differences in lost to follow up and poor exercise diary completion mean we are uncertain on some feasibility aspects. These methodological issues need addressing prior to conducting a definitive RCT. TRIAL REGISTRATION: ISRCTN 35272486 . Registered 19th December 2016.

MILDEW RESISTANCE LOCUS O Function in Pollen Tube Reception Is Linked to Its Oligomerization and Subcellular Distribution.

Sexual reproduction in flowering plants requires communication between synergid cells and a tip-elongating pollen tube (PT) for the successful delivery of sperm cells to the embryo sac. The reception of the PT relies on signaling within the synergid cell that ultimately leads to the degeneration of the receptive synergid and PT rupture, releasing the sperm cells for double fertilization. In Arabidopsis (Arabidopsis thaliana), NORTIA, a member of the MILDEW RESISTANCE LOCUS O (MLO) family of proteins, plays a critical role in the communication processes regulating PT reception. In this study, we determined that MLO function in PT reception is dependent on MLO protein localization into a Golgi-associated compartment before PT arrival, indicating that PT-triggered regulation of the synergid secretory system is important for synergid function during pollination. Additionally, a structure-function analysis revealed that MLO homooligomerization, mediated by the amino-terminal region of the protein, and carboxyl-terminal tail identity both contribute to MLO activity during PT reception.

Current management strategies for patellofemoral pain: an online survey of 99 practising UK physiotherapists.

BACKGROUND: Patellofemoral pain (PFP) is considered one of the commonest forms of knee pain. This study aimed to identify how physiotherapists in the United Kingdom (UK) currently manage patellofemoral pain (PFP), particularly in relation to exercise prescription, and response to pain. METHODS: An anonymous survey was designed with reference to previous surveys and recent systematic reviews. Practising UK physiotherapists who treat patients with PFP were invited to take part via an invitation email sent through professional networks, the 'interactive Chartered Society of Physiotherapy (iCSP)' message board, and social media (Twitter). Descriptive statistics were used to analyse the data. RESULTS: A total of 99 surveys were completed. Responders reported a wide range of management strategies, including a broad selection of type and dose of exercise prescription. The five most common management strategies chosen were: closed chain strengthening exercises (98%); education and advice (96%); open chain strengthening exercises (76%); taping (70%) and stretches (65%). Physiotherapists with a special interest in treating PFP were statistically more likely to manage patients with orthotics (P = 0.02) and bracing (P = 0.01) compared to physiotherapists without a special interest. Approximately 55% would not prescribe an exercise if it was painful. Thirty-one percent of physiotherapists would advise patients not to continue with leisure and/or sporting activity if they experienced any pain. CONCLUSION: Current UK practice in the management strategies of PFP is variable. Further high quality research on which to inform physiotherapy practice is warranted for this troublesome musculoskeletal condition.

Should exercises be painful in the management of chronic musculoskeletal pain? A systematic review and meta-analysis.

BACKGROUND: Chronic musculoskeletal disorders are a prevalent and costly global health issue. A new form of exercise therapy focused on loading and resistance programmes that temporarily aggravates a patient's pain has been proposed. The object of this review was to compare the effect of exercises where pain is allowed/encouraged compared with non-painful exercises on pain, function or disability in patients with chronic musculoskeletal pain within randomised controlled trials. METHODS: Two authors independently selected studies and appraised risk of bias. Methodological quality was evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment system was used to evaluate the quality of evidence. RESULTS: The literature search identified 9081 potentially eligible studies. Nine papers (from seven trials) with 385 participants met the inclusion criteria. There was short- term significant difference in pain, with moderate quality evidence for a small effect size of -0.27 (-0.54 to -0.05) in favour of painful exercises. For pain in the medium and long term, and function and disability in the short, medium and long term, there was no significant difference. CONCLUSION: Protocols using painful exercises offer a small but significant benefit over pain-free exercises in the short term, with moderate quality of evidence. In the medium and long term there is no clear superiority of one treatment over another. Pain during therapeutic exercise for chronic musculoskeletal pain need not be a barrier to successful outcomes. Further research is warranted to fully evaluate the effectiveness of loading and resistance programmes into pain for chronic musculoskeletal disorders. PROSPERO REGISTRATION: CRD42016038882.

A highly polarized excitable cell separates sodium channels from sodium-activated potassium channels by more than a millimeter.

The bioelectrical properties and resulting metabolic demands of electrogenic cells are determined by their morphology and the subcellular localization of ion channels. The electric organ cells (electrocytes) of the electric fish Eigenmannia virescens generate action potentials (APs) with Na(+) currents >10 µA and repolarize the AP with Na(+)-activated K(+) (KNa) channels. To better understand the role of morphology and ion channel localization in determining the metabolic cost of electrocyte APs, we used two-photon three-dimensional imaging to determine the fine cellular morphology and immunohistochemistry to localize the electrocytes' ion channels, ionotropic receptors, and Na(+)-K(+)-ATPases. We found that electrocytes are highly polarized cells ∼ 1.5 mm in anterior-posterior length and ∼ 0.6 mm in diameter, containing ∼ 30,000 nuclei along the cell periphery. The cell's innervated posterior region is deeply invaginated and vascularized with complex ultrastructural features, whereas the anterior region is relatively smooth. Cholinergic receptors and Na(+) channels are restricted to the innervated posterior region, whereas inward rectifier K(+) channels and the KNa channels that terminate the electrocyte AP are localized to the anterior region, separated by >1 mm from the only sources of Na(+) influx. In other systems, submicrometer spatial coupling of Na(+) and KNa channels is necessary for KNa channel activation. However, our computational simulations showed that KNa channels at a great distance from Na(+) influx can still terminate the AP, suggesting that KNa channels can be activated by distant sources of Na(+) influx and overturning a long-standing assumption that AP-generating ion channels are restricted to the electrocyte's posterior face.

Special tests for assessing meniscal tears within the knee: a systematic review and meta-analysis.

BACKGROUND: Musculoskeletal knee pain is a large and costly problem, and meniscal tears make up a large proportion of diagnoses. 'Special tests' to diagnose torn menisci are often used in the physical examination of the knee joint. A large number of publications within the literature have investigated the diagnostic accuracy of these tests, yet despite the wealth of research their diagnostic accuracy remains unclear.Aim To synthesise the most current literature on the diagnostic accuracy of special tests for meniscal tears of the knee in adults. METHOD: An electronic search of MEDLINE, Cumulative Index to Nursing and Allies Health Literature (CINAHL), The Allied and Complementary Medicine Database (AMED) and SPORT Discus databases was carried out from inception to December 2014. Two authors independently selected studies and independently extracted data. Methodological quality was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) 2 tool. RESULTS: Nine studies were included (n=1234) and three special tests were included in the meta-analysis. The methodological quality of the included studies was generally poor. McMurray's had a sensitivity of 61% (95% CI 45% to 74%) and a specificity of 84% (95% CI 69%to 92%). Joint line tenderness had a sensitivity of 83%(95% CI 73% to 90%) and a specificity of 83% (95% CI 61% to 94%). Thessaly 20° had a sensitivity of 75%(95% CI 53% to 89%) and a specificity of 87% (95% CI 65% to 96%). CONCLUSIONS: The accuracy of the special tests to diagnose meniscal tears remains poor. However, these results should be used with caution, due to the poor quality and low numbers of included studies and high levels of heterogeneity.

An update of stabilisation exercises for low back pain: a systematic review with meta-analysis.

BACKGROUND: Non-specific low back pain (NSLBP) is a large and costly problem. It has a lifetime prevalence of 80% and results in high levels of healthcare cost. It is a major cause for long term sickness amongst the workforce and is associated with high levels of fear avoidance and kinesiophobia. Stabilisation (or 'core stability') exercises have been suggested to reduce symptoms of pain and disability and form an effective treatment. Despite it being the most commonly used form of physiotherapy treatment within the UK there is a lack of positive evidence to support its use. The aims of this systematic review update is to investigate the effectiveness of stabilisation exercises for the treatment of NSLBP, and compare any effectiveness to other forms of exercise. METHODS: A systematic review published in 2008 was updated with a search of PubMed, CINAHL, AMED, Pedro and The Cochrane Library, October 2006 to October 2013. Two authors independently selected studies, and two authors independently extracted the data. Methodological quality was evaluated using the PEDro scale. Meta-analysis was carried out when appropriate. RESULTS: 29 studies were included: 22 studies (n = 2,258) provided post treatment effect on pain and 24 studies (n = 2,359) provided post treatment effect on disability. Pain and disability scores were transformed to a 0 to 100 scale. Meta-analysis showed significant benefit for stabilisation exercises versus any alternative treatment or control for long term pain and disability with mean difference of -6.39 (95% CI -10.14 to -2.65) and -3.92 (95% CI -7.25 to -0.59) respectively. The difference between groups was clinically insignificant. When compared with alternative forms of exercise, there was no statistical or clinically significant difference. Mean difference for pain was -3.06 (95% CI -6.74 to 0.63) and disability -1.89 (95% CI -5.10 to 1.33). CONCLUSION: There is strong evidence stabilisation exercises are not more effective than any other form of active exercise in the long term. The low levels of heterogeneity and large number of high methodological quality of available studies, at long term follow-up, strengthen our current findings, and further research is unlikely to considerably alter this conclusion.

Committed sea-level rise for the next century from Greenland ice sheet dynamics during the past decade.

We use a three-dimensional, higher-order ice flow model and a realistic initial condition to simulate dynamic perturbations to the Greenland ice sheet during the last decade and to assess their contribution to sea level by 2100. Starting from our initial condition, we apply a time series of observationally constrained dynamic perturbations at the marine termini of Greenland's three largest outlet glaciers, Jakobshavn Isbræ, Helheim Glacier, and Kangerdlugssuaq Glacier. The initial and long-term diffusive thinning within each glacier catchment is then integrated spatially and temporally to calculate a minimum sea-level contribution of approximately 1 ± 0.4 mm from these three glaciers by 2100. Based on scaling arguments, we extend our modeling to all of Greenland and estimate a minimum dynamic sea-level contribution of approximately 6 ± 2 mm by 2100. This estimate of committed sea-level rise is a minimum because it ignores mass loss due to future changes in ice sheet dynamics or surface mass balance. Importantly, > 75% of this value is from the long-term, diffusive response of the ice sheet, suggesting that the majority of sea-level rise from Greenland dynamics during the past decade is yet to come. Assuming similar and recurring forcing in future decades and a self-similar ice dynamical response, we estimate an upper bound of 45 mm of sea-level rise from Greenland dynamics by 2100. These estimates are constrained by recent observations of dynamic mass loss in Greenland and by realistic model behavior that accounts for both the long-term cumulative mass loss and its decay following episodic boundary forcing.

Development of an intervention for patients following an anterior cruciate ligament rupture: an online nominal group technique consensus study.

OBJECTIVES: (1) To develop an intervention for to support patients diagnosed with an anterior cruciate ligament (ACL) rupture with decision-making regarding treatment. (2) To define evidence-based recommendations for the treatment of patients following an ACL rupture. DESIGN: Nominal group technique consensus study. SETTING: Online meetings with patients and key stakeholders working and receiving treatment in the National Health Service, UK. PARTICIPANTS: Consensus meetings composed of eight voting participants and five non-voting facilitators. Voting participants included five clinicians, one outpatient therapy manager and two patients with experience in an ACL rupture and reconstructive surgery. Non-voting facilitators supported group discussions and/or observed study procedures. This included a clinical academic expert, two methodology experts and two patient representatives. METHOD: Two online meetings were held. Pre-elicitation material was distributed ahead of the first meeting. Premeeting voting was conducted ahead of both meetings. A draft of the shared decision-making intervention and recommendations were shared ahead of the second meeting. Components were discussed and ranked for inclusion based on a 70% agreement threshold. RESULTS: The meetings led to the development of a shared decision-making intervention to support treatment decision-making following an ACL rupture. The intervention includes two components: (1) a patient information leaflet and key questions diagram and (2) option grid. The evidence-based recommendations encompass core components of treatment reaching the 70% threshold agreed by the group. The recommendations cover: (1) advice and education, (2) exercise guidance, (3) intervention delivery, (4) outcome measure use and (5) shared decision-making. CONCLUSION: This study has successfully developed a shared decision-making intervention to support ACL treatment decision-making, ready for testing in a future feasibility study. Evidence-based recommendations for the treatment of patients following ACL injury, ready for testing in a National Health Service (UK) setting, are also presented. TRIAL REGISTRATION NUMBER: NCT05529511.