Self-supervised pre-training using so-called "pretext" tasks has recently shown impressive performance across a wide range of modalities. In this work, we advance self-supervised learning from ...permutations, by pre-training a model to reorder shuffled parts of the spectrogram of an audio signal, to improve downstream classification performance. We make two main contributions. First, we overcome the main challenges of integrating permutation inversions into an end-to-end training scheme, using recent advances in differentiable ranking. This was heretofore sidestepped by casting the reordering task as classification, fundamentally reducing the space of permutations that can be exploited. Our experiments validate that learning from all possible permutations improves the quality of the pre-trained representations over using a limited, fixed set. Second, we show that inverting permutations is a meaningful pretext task for learning audio representations in an unsupervised fashion. In particular, we improve instrument classification and pitch estimation of musical notes by reordering spectrogram patches in the time-frequency space.
Exploration for shale gas occurs in onshore basins, with two approaches used to predict the maximum gas in place (GIP) in the absence of production data. The first estimates adsorbed plus free gas ...held within pore space, and the second measures gas yields from laboratory pyrolysis experiments on core samples. Here we show the use of sequential high-pressure water pyrolysis (HPWP) to replicate petroleum generation and expulsion in uplifted onshore basins. Compared to anhydrous pyrolysis where oil expulsion is limited, gas yields are much lower, and the gas at high maturity is dry, consistent with actual shales. Gas yields from HPWP of UK Bowland Shales are comparable with those from degassed cores, with the ca. 1% porosity sufficient to accommodate the gas generated. Extrapolating our findings to the whole Bowland Shale, the maximum GIP equate to potentially economically recoverable reserves of less than 10 years of current UK gas consumption.
The use of patient reported outcome measures might seem to be quite straightforward; however, a number of pitfalls await clinicians with limited expertise. Jill Dawson and colleagues provide a guide ...for individuals keen to use patient reported outcome measures at a local level
To compare arthroscopic hip surgery with physiotherapy and activity modification for improving patient reported outcome measures in patients with symptomatic femoroacetabular impingement (FAI).
Two ...group parallel, assessor blinded, pragmatic randomised controlled trial.
Secondary and tertiary care centres across seven NHS England sites.
222 participants aged 18 to 60 years with symptomatic FAI confirmed clinically and with imaging (radiography or magnetic resonance imaging) were randomised (1:1) to receive arthroscopic hip surgery (n=112) or a programme of physiotherapy and activity modification (n=110). Exclusion criteria included previous surgery, completion of a physiotherapy programme targeting FAI within the preceding 12 months, established osteoarthritis (Kellgren-Lawrence grade ≥2), and hip dysplasia (centre-edge angle <20 degrees).
Participants in the physiotherapy group received a goal based programme tailored to individual patient needs, with emphasis on improving core stability and movement control. A maximum of eight physiotherapy sessions were delivered over five months. Participants in the arthroscopic surgery group received surgery to excise the bone that impinged during hip movements, followed by routine postoperative care.
The primary outcome measure was the hip outcome score activities of daily living subscale (HOS ADL) at eight months post-randomisation, with a minimum clinically important difference between groups of 9 points. Secondary outcome measures included additional patient reported outcome measures and clinical assessment.
At eight months post-randomisation, data were available for 100 patients in the arthroscopic hip surgery group (89%) and 88 patients in the physiotherapy programme group (80%). Mean HOS ADL was 78.4 (95% confidence interval 74.4 to 82.3) for patients randomised to arthroscopic hip surgery and 69.2 (65.2 to 73.3) for patients randomised to the physiotherapy programme. After adjusting for baseline HOS ADL, age, sex, and study site, the mean HOS ADL was 10.0 points higher (6.4 to 13.6) in the arthroscopic hip surgery group compared with the physiotherapy programme group (P<0.001)). No serious adverse events were reported in either group.
Patients with symptomatic FAI referred to secondary or tertiary care achieve superior outcomes with arthroscopic hip surgery than with physiotherapy and activity modification.
ClinicalTrials.gov NCT01893034.
At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum ...response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose - There is a need to understand the reasons why a high proportion of rotator cuff repairs fail to heal. Using data from a large randomized clinical trial, we evaluated age and ...tear size as risk factors for failure of rotator cuff repair.
Patients and methods - Between 2007 and 2014, 65 surgeons from 47 hospitals in the National Health Service (NHS) recruited 447 patients with atraumatic rotator cuff tendon tears to the United Kingdom Rotator Cuff Trial (UKUFF) and 256 underwent rotator cuff repair. Cuff integrity was assessed by imaging in 217 patients, at 12 months post-operation. Logistic regression analysis was used to determine the influence of age and intra-operative tear size on healing. Hand dominance, sex, and previous steroid injections were controlled for.
Results - The overall healing rate was 122/217 (56%) at 12 months. Healing rate decreased with increasing tear size (small tears 66%, medium tears 68%, large tears 47%, and massive tears 27% healed). The mean age of patients with a healed repair was 61 years compared with 64 years for those with a non-healed repair. Mean age increased with larger tear sizes (small tears 59 years, medium tears 62 years, large tears 64 years, and massive tears 66 years). Increasing age was an independent factor that negatively influenced healing, even after controlling for tear size. Only massive tears were an independent predictor of non-healing, after controlling for age.
Interpretation - Although increasing age and larger tear size are both risks for failure of rotator cuff repair healing, age is the dominant risk factor.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
ObjectivesTo define the population prevalence of rotator cuff tears and test their association with pain and function loss; determine if severity symptom correlates with tear stage severity, and ...quantify the impact of symptomatic rotator cuff tears on primary healthcare services in a general population cohort of women.DesignCross-sectional observational study.ParticipantsIndividuals were part of the Chingford 1000 Women cohort, a 20-year-old longitudinal population study comprising 1003 women aged between 64 and 87, and representative of the population of the UK.Main outcome measuresRotator cuff pathology prevalence on ultrasound, shoulder symptoms using the Oxford Shoulder Score and resultant number of general practitioner (GP) consultations.ResultsThe population prevalence of full-thickness tears was 22.2%, which increased with age (p=0.004) and whether it was the dominant arm (Relative Risk 1.64, OR 1.58, 95% CI 1.07 to 2.33, p=0.021).Although 48.4% of full-thickness tears were asymptomatic, there was an association between rotator cuff tears and patient-reported symptoms. Individuals with at least one full-thickness tear were 1.97 times more likely than those with bilateral normal tendons (OR 3.53, 95% CI 2.00 to 5.61, p<0.001) to have symptoms. Severity of symptoms was not related to the severity of the pathology until tears are >2.5 cm (p=0.009).In the cohort, 8.9% had seen their GP with shoulder pain and a full-thickness rotator cuff tear, 18.8% with shoulder pain and an abnormality and 29.3% with shoulder pain.ConclusionRotator cuff tears are common, and primary care services are heavily impacted. As 50% of tears remain asymptomatic, future research may investigate the cause of pain and whether different treatment modalities, aside from addressing the pathology, need further investigation.
Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before ...and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, and inflammation was characterized through activation of pathways mediated by interferon (IFN), nuclear factor κB (NF-κB), glucocorticoid receptor, and signal transducer and activator of transcription 6 (STAT-6). Inflammation signatures revealed expression of genes and proteins induced by IFN and NF-κB in early-stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced-stage disease. The proresolving proteins FPR2/ALX and ChemR23 were increased in early-stage disease compared to intermediate- to advanced-stage disease. Patients who were pain-free after treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain after treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and IFN target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi lipoxin A4, a stable lipoxin isoform derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation.
Rotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, ...only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing. We investigated the tissue response to a multifilament electrospun polydioxanone (PDO) suture in a sheep tendon injury model characterised by a natural history of failure of healing.
Eight skeletally mature English Mule sheep underwent repair with electrospun sutures. Monofilament sutures were used as a control. Three months after surgery, all tendon repairs healed, without systemic features of inflammation, signs of tumour or infection at necropsy. A mild local inflammatory reaction was seen. On histology the electrospun sutures were densely infiltrated with predominantly tendon fibroblast-like cells. In comparison, no cellular infiltration was observed in the control suture. Neovascularisation was observed within the electrospun suture, whilst none was seen in the control. Foreign body giant cells were rarely seen with either sutures.
This study demonstrates that a tissue response can be induced in tendon with a multifilament electrospun suture with no safety concerns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK