Implementing a shared decision-making intervention to support treatment decisions for patients following an anterior cruciate ligament rupture - a protocol for the POP-ACLR feasibility study.

BACKGROUND: Treatment for anterior cruciate ligament (ACL) rupture may follow a surgical or nonsurgical pathway. At present, there is uncertainty around treatment choice. Two shared decision-making tools have been codesigned to support patients to make a decision about treatment following an ACL rupture. The shared decision-making tools include a patient information leaflet and an option grid. We report the protocol for a mixed-methods feasibility study, with nested qualitative interviews, to understand feasibility, acceptability, indicators of effectiveness and implementation factors of these shared decision-making tools (combined to form one shared decision-making intervention). METHODS: A single-centre non-randomised feasibility study will be conducted with 20 patients. Patients diagnosed with an ACL rupture following magnetic resonance imaging will be identified from an orthopaedic clinic. The shared decision-making intervention will be delivered during a clinical consultation with a physiotherapist. The primary feasibility outcomes include the following: recruitment rate, fidelity, acceptability and follow-up questionnaire completion. The secondary outcome is the satisfaction with decision scale. The nested qualitative interview will explore experience of using the shared decision-making intervention to understand acceptability, implementation factors and areas for further refinement. DISCUSSION: This study will determine the feasibility of using a newly developed shared decision-making intervention designed to support patients to make a decision about treatment of their ACL rupture. The acceptability and indicators of effectiveness will also be explored. In the long term, the shared decision-making intervention may improve service and patient outcomes and ensure cost-effectiveness for the NHS; ensuring those most likely to benefit from surgical treatment proceed along this pathway. TRIAL REGISTRATION: Pending registration on ISRCTN.

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.

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.

Circuit mechanisms underlying embryonic retinal waves.

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated stage 1 waves. Using a custom-built macroscope to record spontaneous calcium transients from whole embryonic retinas, we show that stage 1 waves are initiated at several locations across the retina and propagate across a broad range of areas. Blocking gap junctions reduced the frequency and size of stage 1 waves, nearly abolishing them. Global blockade of nAChRs similarly nearly abolished stage 1 waves. Thus, stage 1 waves are mediated by a complex circuitry involving subtypes of nAChRs and gap junctions. Stage 1 waves in mice lacking the ß2 subunit of the nAChRs (ß2-nAChR-KO) persisted with altered propagation properties and were abolished by a gap junction blocker. To assay the impact of stage 1 waves on retinal development, we compared the spatial distribution of a subtype of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), which undergo a significant amount of cell death, in WT and ß2-nAChR-KO mice. We found that the developmental decrease in ipRGC density is preserved between WT and ß2-nAChR-KO mice, indicating that processes regulating ipRGC numbers and distributions are not influenced by spontaneous activity.

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.

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.

Developing Clinical and Research Priorities for Pain and Psychological Features in People With Patellofemoral Pain: An International Consensus Process With Health Care Professionals.

OBJECTIVE: To decide clinical and research priorities on pain features and psychological factors in persons with patellofemoral pain. DESIGN: Consensus development process. METHODS: We undertook a 3-stage process consisting of (1) updating 2 systematic reviews on quantitative sensory testing of pain features and psychological factors in patellofemoral pain, (2) an online survey of health care professionals and persons with patellofemoral pain, and (3) a consensus meeting with expert health care professionals. Participants responded that they agreed, disagreed, or were unsure that a pain feature or psychological factor was important in clinical practice or as a research priority. Greater than 70% participant agreement was required for an item to be considered important in clinical practice or a research priority. RESULTS: Thirty-five health care professionals completed the survey, 20 of whom attended the consensus meeting. Thirty persons with patellofemoral pain also completed the survey. The review identified 5 pain features and 9 psychological factors-none reached 70% agreement in the patient survey, so all were considered at the meeting. After the meeting, pain catastrophizing, fear-avoidance beliefs, and pain self-efficacy were the only factors considered clinically important. All but the thermal pain tests and 3 psychological factors were considered research priorities. CONCLUSION: Pain catastrophizing, pain self-efficacy, and fear-avoidance beliefs were factors considered important in treatment planning, clinical examination, and prognostication. Quantitative sensory tests for pain were not regarded as clinically important but were deemed to be research priorities, as were most psychological factors. J Orthop Sports Phys Ther 2022;52(1):29-39. doi:10.2519/jospt.2022.10647.

Robust T cell activation requires an eIF3-driven burst in T cell receptor translation.

Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here, we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3'-untranslated regions (3'-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3'-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.

Current preoperative physiotherapy management strategies for patients awaiting Anterior Cruciate Ligament Reconstruction (ACLR): A worldwide survey of physiotherapy practice.

BACKGROUND: Anterior cruciate ligament ruptures are the most common ligament injury to the knee with surgical reconstruction considered standard treatment. This study aimed to explore the current physiotherapy management strategies used during the preoperative phase of rehabilitation for patients awaiting anterior cruciate ligament reconstruction (ACLR). METHODS: An anonymous survey was disseminated online via Twitter and the 'interactive Chartered Society of Physiotherapy' message board. Practising physiotherapists who treated at least one patient prior to ACLR in the past year were invited to take part. Responses were collected over a 4-week period in March 2020. Data were analysed using descriptive statistics. RESULTS: In total, 183 respondents replied; 122 completed the full survey. Responses were collected from 20 countries across 3 settings, NHS/public health services, private and sports. Most respondents reported prescribing exercises, advice and education to patients during prehabilitation. Up to 40% also utilised passive treatments including manual therapy, taping/bracing and electrotherapy. The frequency of recommended exercise completion and length of treatment varied. Most respondents (n = 103/84.4%) felt that many patients waiting for ACLR did not receive prehabilitation. Many physiotherapists reported that patients expressed concerns regarding their readiness for surgery (n = 61/50%) and return to preinjury levels of physical activity (n = 112/91.8%). Almost all respondents would discuss non-operative management with patients (n = 112/91.8%) if they had returned to their preinjury level of physical activity before their ACLR. CONCLUSION: Overall, this survey provides some insight as to how physiotherapists manage patients awaiting ACLR. Areas of uncertainty in physiotherapy practice have also been highlighted that require further high-quality research.

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 .

A Decade of Variability on Jakobshavn Isbrae: Ocean Temperatures Pace Speed Through Influence on Mélange Rigidity.

The speed of Greenland's fastest glacier, Jakobshavn Isbrae, has varied substantially since its speedup in the late 1990s. Here we present observations of surface velocity, mélange rigidity, and surface elevation to examine its behaviour over the last decade. Consistent with earlier results, we find a pronounced cycle of summer speedup and thinning followed by winter slowdown and thickening. There were extended periods of rigid mélange in the winters of 2016-17 and 2017-18, concurrent with terminus advances ~6 km farther than in the several winters prior. These terminus advances to shallower depths caused slowdowns, leading to substantial thickening, as has been noted elsewhere. The extended periods of rigid mélange coincide well with a period of cooler waters in Disko Bay. Thus, along with the relative timing of the seasonal slowdown, our results suggest that the ocean's dominant influence on Jakobshavn Isbrae is through its effect on winter mélange rigidity, rather than summer submarine melting. The elevation time series also reveals that in summers when the area upstream of the terminus approaches flotation, large surface depressions can form, which eventually become the detachment points for major calving events. It appears that as elevations near flotation, basal crevasses can form, which initiates a necking process that forms the depressions. The elevation data also show that steep cliffs often evolve into short floating extensions, rather than collapsing catastrophically due to brittle failure. Finally, summer 2019 speeds were slightly faster than the prior two summers, leaving it unclear whether the slowdown is ending.

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.

Are there differences in lifting technique between those with and without low back pain? A systematic review.

Background and aims To systemically review the literature to compare freestyle lifting technique, by muscle activity and kinematics, between people with and without low back pain (LBP). Methods Five databases were searched along with manual searches of retrieved articles by a single reviewer. Studies were included if they compared a freestyle lifting activity between participants with and without LBP. Data were extracted by two reviewers, and studies were appraised using the CASP tool for case-control studies. Results Nine studies were eligible. Heterogeneity did not allow for meta-analysis. Most studies (n = 8 studies) reported that people with LBP lift differently to pain-free controls. Specifically, people with LBP lift more slowly (n = 6 studies), use their legs more than their back especially when initiating lifting (n = 3 studies), and jerk less during lifting (n = 1 studies). Furthermore, the four larger studies involving people with more severe LBP also showed that people with LBP lift with less spinal range of motion and greater trunk muscle activity for a longer period. Conclusions People with LBP move slower, stiffer, and with a deeper knee bend than pain-free people during freestyle lifting tasks. Interestingly, such a lifting style mirrors how people, with and without LBP, are often told how to lift during manual handling training. The cross-sectional nature of the comparisons does not allow for causation to be determined. Implications The changes described may show embodiment of cautious movement, and the drive to protect the back. There may be value in exploring whether adopting a lifting style closer to that of pain-free people could help reduce LBP.

Type IV Pili Can Mediate Bacterial Motility within Epithelial Cells.

Pseudomonas aeruginosa is among bacterial pathogens capable of twitching motility, a form of surface-associated movement dependent on type IV pili (T4P). Previously, we showed that T4P and twitching were required for P. aeruginosa to cause disease in a murine model of corneal infection, to traverse human corneal epithelial multilayers, and to efficiently exit invaded epithelial cells. Here, we used live wide-field fluorescent imaging combined with quantitative image analysis to explore how twitching contributes to epithelial cell egress. Results using time-lapse imaging of cells infected with wild-type PAO1 showed that cytoplasmic bacteria slowly disseminated throughout the cytosol at a median speed of >0.05 µm s-1 while dividing intracellularly. Similar results were obtained with flagellin (fliC) and flagellum assembly (flhA) mutants, thereby excluding swimming, swarming, and sliding as mechanisms. In contrast, pilA mutants (lacking T4P) and pilT mutants (twitching motility defective) appeared stationary and accumulated in expanding aggregates during intracellular division. Transmission electron microscopy confirmed that these mutants were not trapped within membrane-bound cytosolic compartments. For the wild type, dissemination in the cytosol was not prevented by the depolymerization of actin filaments using latrunculin A and/or the disruption of microtubules using nocodazole. Together, these findings illustrate a novel form of intracellular bacterial motility differing from previously described mechanisms in being directly driven by bacterial motility appendages (T4P) and not depending on polymerized host actin or microtubules.IMPORTANCE Host cell invasion can contribute to disease pathogenesis by the opportunistic pathogen Pseudomonas aeruginosa Previously, we showed that the type III secretion system (T3SS) of invasive P. aeruginosa strains modulates cell entry and subsequent escape from vacuolar trafficking to host lysosomes. However, we also showed that mutants lacking either type IV pili (T4P) or T4P-dependent twitching motility (i) were defective in traversing cell multilayers, (ii) caused less pathology in vivo, and (iii) had a reduced capacity to exit invaded cells. Here, we report that after vacuolar escape, intracellular P. aeruginosa can use T4P-dependent twitching motility to disseminate throughout the host cell cytoplasm. We further show that this strategy for intracellular dissemination does not depend on flagellin and resists both host actin and host microtubule disruption. This differs from mechanisms used by previously studied pathogens that utilize either host actin or microtubules for intracellular dissemination independently of microbe motility appendages.

Barriers and facilitators of loaded self-managed exercises and physical activity in people with patellofemoral pain: understanding the feasibility of delivering a multicentred randomised controlled trial, a UK qualitative study.

OBJECTIVES: There is an emergent body of evidence supporting exercise therapy and physical activity in the management of musculoskeletal pain. The purpose of this study was to explore potential barriers and facilitators with patients and physiotherapists with patellofemoral pain involved in a feasibility randomised controlled trial (RCT) study. The trial investigated a loaded self-managed exercise intervention, which included education and advice on physical activity versus usual physiotherapy as the control. DESIGN: Qualitative study, embedded within a mixed-methods design, using semi-structured interviews. SETTING: A UK National Health Service physiotherapy clinic in a large teaching hospital. PARTICIPANTS: Purposively sampled 20 participants within a feasibility RCT study; 10 patients with a diagnosis of patellofemoral pain, aged between 18 and 40 years, and 10 physiotherapists delivering the interventions. RESULTS: In respect to barriers and facilitators, the five overlapping themes that emerged from the data were: (1) locus of control; (2) belief and attitude to pain; (3) treatment expectations and preference; (4) participants' engagement with the loaded self-managed exercises and (5) physiotherapists' clinical development. Locus of control was one overarching theme that was evident throughout. Contrary to popular concerns relating to painful exercises, all participants in the intervention group reported positive engagement. Both physiotherapists and patients, in the intervention group, viewed the single exercise approach in a positive manner. Participants within the intervention group described narratives demonstrating self-efficacy, with greater internal locus of control compared with those who received usual physiotherapy, particularly in relation to physical activity. CONCLUSIONS: Implementation, delivery and evaluation of the intervention in clinical settings may be challenging, but feasible with the appropriate training for physiotherapists. Participants' improvements in pain and function may have been mediated, in some part, by greater self-efficacy and locus of control. TRIAL REGISTRATION NUMBER: ISRCTN35272486; Pre-results.

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.

Light Prior to Eye Opening Promotes Retinal Waves and Eye-Specific Segregation.

Retinal waves are bursts of correlated activity that occur prior to eye opening and provide a critical source of activity that drives the refinement of retinofugal projections. Retinal waves are thought to be initiated spontaneously with their spatiotemporal features dictated by immature neural circuits. Here we demonstrate that, during the second postnatal week in mice, changes in light intensity dictate where and when a subset of retinal waves are triggered via activation of conventional photoreceptors. Propagation properties of triggered waves are indistinguishable from spontaneous waves, indicating that they are activating the same retinal circuits. Using whole-brain imaging techniques, we demonstrate that light deprivation prior to eye opening diminishes eye-specific segregation of the retinal projections to the dorsolateral geniculate nucleus of the thalamus, but not other retinal targets. These data indicate that light that passes through the closed eyelids plays a critical role in the development of the image-forming visual system.