Purpose
The purpose of this study was to investigate the acute effect of head impacts, sustained over the course of three rounds of amateur boxing, on indices of cerebrovascular function.
Methods
...Eighteen university amateur boxers (six female) completed three experimental trials in a randomised order; (1) three rounds of boxing (BOX), (2) an equivalent bout of pad boxing (where no blows to the head were sustained; PAD), and (3) a time-matched seated control trial (CON). Indices of cerebrovascular function were determined immediately before and 45 min after each trial. Specifically, dynamic cerebral autoregulation (dCA) was determined by considering the relationship between changes in cerebral blood velocity and mean arterial pressure during 5 min of squat-stand manoeuvres at 0.05 and 0.10 Hz. Cerebrovascular reactivity was determined using serial breath holding and hyperventilation attempts.
Results
Participants received an average of 40 ± 16 punches to the head during the BOX trial. Diastolic, mean and systolic dCA phase during squat stand manoeuvres at 0.05 Hz was lower after BOX compared to pre BOX (
P
≤ 0.02, effect size (
d
) ≥ 0.74). No other alterations in dCA outcomes were observed at 0.05 or 0.10 Hz. The number of head impacts received during the BOX trial was associated with the change in systolic phase (
r =
0.50,
P
= 0.03). No differences in cerebrovascular reactivity to breath holding or hyperventilation were observed.
Conclusions
A typical bout of amateur boxing (i.e., three rounds) can subtly alter cerebral pressure-flow dynamics, and the magnitude of this change may be related to head impact exposure.
Summary
Reasons for performing study: There are no published results of subchondral cystic lesions (SCLs) in the medial femoral condyle (MFC) treated with arthroscopic injection of corticosteroids ...into the lining of the cyst.
Objectives: 1) To determine the success rate for treatment of SCLs in the MFC with arthroscopic injection of the fibrous tissue of the cyst with corticosteroids. 2) To identify any factors that may predict outcome.
Hypotheses: Injection of the fibrous tissue of SCLs of the MFC with corticosteroids utilising arthroscopic guidance yields a similar or higher chance for intended performance than does arthroscopic debridement as previously reported; this technique will be effective for treating SCLs in older horses.
Methods: Horses with clinical and radiographic evidence of a SCL in the MFC were injected with corticosteroids under arthroscopic guidance, and case records and radiographs were reviewed retrospectively. A telephone survey of referring veterinarians, owners and trainers was conducted.
Results: Thirty‐five of 52 (67%) cases were classified as successful involving 73 SCLs of which 56 (77%) were classified as successful. There was no significant association between age group (age ≤3 years vs. >3 years) and outcome, or cyst configuration and outcome. Significantly more unilateral SCLs (28/31 90% SCLs) were classified as successful than bilateral (28/42: 67%). There were significant differences in outcome based on the surgeon operating the case and an association between pre‐existing radiographic findings of osteophytes and negative outcome.
Conclusions: Injection of SCLs utilising arthroscopic guidance is an effective alternative method of surgical treatment of SCL.
Potential relevance: This technique offers a similar chance of success as has been reported with debridement and may allow for a shorter period of convalescence. If unsuccessful, the option remains to debride the cyst in a second surgery.
Abstract
Background
The long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal ...change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19.
Methods
We conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0–4 per lung (Nil = 0, < 25% = 1, 25–50% = 2, 51–75% = 3, > 75% = 4).
Results
101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45–63) years and length of stay 9 (5–17.5) days. The median CXR follow-up interval was 82 (77–86) days with median baseline and follow-up CXR scores of 4.0 (3–5) and 0.0 (0–1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS ≥ 15 days, Level 2/3 admission, LDH > 750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81).
Conclusion
Persistent CXR abnormality 12-weeks post COVID-19 was common in this cohort. LOS, obesity, increased serum LDH, and smoking-status were risk factors for radiograph abnormality. These findings require further prospective validation.
We report a method of growing a diamond layer via chemical vapour deposition (CVD) utilizing a mixture of microdiamond and nanodiamond seeding to give a low effective thermal boundary resistance ...(TBReff) for heat-spreading applications in high-frequency, high-power electronic devices. CVD diamond was deposited onto thin layers of both GaN and AlN on Si substrates, comparing conventional nanodiamond seeding with a two-step process involving sequential seeding with microdiamond then nanodiamond. Thermal properties were determined using transient thermoreflectance (TTR), and the samples were also analysed with SEM and X-ray tomography. While diamond growth directly onto GaN proved to be unsuccessful due to poor adhesion, films grown on AlN were adherent and robust. The two-step mixed-seeding method gave TBReff values < 6 m2 K GW−1 that were 30 times smaller than for films grown under identical conditions but using nanodiamond seeding alone. Such remarkably low thermal barriers obtained with the mixed-seeding process offer a promising route for fabrication of high-power GaN HEMTs using diamond as a heat spreader with an AlN interlayer.
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Given that cardiovascular safety liabilities remain a major cause of drug attrition during preclinical and clinical development, adverse drug reactions, and post‐approval withdrawal of medicines, the ...Medical Research Council Centre for Drug Safety Science hosted a workshop to discuss current challenges in determining, understanding and addressing ‘Cardiovascular Toxicity of Medicines’. This article summarizes the key discussions from the workshop that aimed to address three major questions: (i) what are the key cardiovascular safety liabilities in drug discovery, drug development and clinical practice? (ii) how good are preclinical and clinical strategies for detecting cardiovascular liabilities? and (iii) do we have a mechanistic understanding of these liabilities? It was concluded that in order to understand, address and ultimately reduce cardiovascular safety liabilities of new therapeutic agents there is an urgent need to:
•
Fully characterize the incidence, prevalence and impact of drug‐induced cardiovascular issues at all stages of the drug development process.
•
Ascertain the predictive value of existing non‐clinical models and assays towards the clinical outcome.
•
Understand the mechanistic basis of cardiovascular liabilities; by addressing areas where it is currently not possible to predict clinical outcome based on preclinical safety data.
•
Provide scientists in all disciplines with additional skills to enable them to better integrate preclinical and clinical data and to better understand the biological and clinical significance of observed changes.
•
Develop more appropriate, highly relevant and predictive tools and assays to identify and wherever feasible to eliminate cardiovascular safety liabilities from molecules and wherever appropriate to develop clinically relevant and reliable safety biomarkers.
We analysed 10-year survival data in 19,411 women aged 50-64 years diagnosed with invasive breast cancer in the West Midlands region of the United Kingdom. The aim was to estimate the survival ...advantage seen in cases that were screen detected compared with those diagnosed symptomatically and attribute this to shifts in prognostic variables or survival differences specific to prognostic categories.
We studied tumour size, histological grade and the Nottingham Prognostic Index in very narrow categories and investigated the distribution of these prognostic factors within screen-detected and symptomatic tumours. We also adjusted for lead time bias.
The unadjusted 10-year breast cancer survival in screen-detected cases was 85.5% and in symptomatic cases 62.8%; after adjustment for lead time bias, survival in the screen-detected cases was 79.3%. Within narrow categories of prognostic variables, survival differences were small, indicating that the majority of the survival advantage of screen detection is due to differences in the distributions of size and node status.
Our results suggested that a combination of lead time with size and node status in 10 categories explained almost all (97%) of the survival advantage. Only a small proportion remained to be explained by biological differences, manifested as length bias or overdiagnosis.
This paper describes the CryoSat satellite mission, due for launch in 2005, whose aim is to accurately determine the trends in Earth’s continental and marine ice fields. The paper’s purpose is to ...provide scientific users of the CryoSat data with a description of the design and operation of the SIRAL radar and the CryoSat platform, the data products, and the expected error budget. The ‘low-resolution mode’ (LRM), ‘synthetic aperture mode’ (SARM) and “synthetic aperture interferometric mode’ (SARInM) of the SIRAL radar are described, together with its system parameters, its antenna gain pattern and interferometer phase difference pattern, and its calibration modes. The orbit is described, together with the platform attitude and altitude control law and control systems, and the expected pointing and altitude knowledge. The geographical masks that are used to determine acquisitions in the three SIRAL modes are described. The SIRAL data products, and the processing applied to produce them, are described.
Level 1b,
level 2 and
higher-level products are described in turn, with a particular emphasis on the new procedures applied to the SARInM and SARM processing over ice surfaces. The beam forming and multi-looking is summarised, and a description is given of the behaviour of the SARM and SARInM echoes over idealised surfaces. These inform descriptions of the elevation retrievals of the
level 2 processing, including the SARInM retrieval of interferometric phase. The combination of these data, through cross-over analysis over continental ice sheets, and through averaging over sea-ice, to determine areal averages of ice sheet elevation change or sea-ice thickness, is described. The error budget in these higher-level products is described, together with its breakdown into errors arising from the instrument and errors arising from the retrievals. The importance of the co-variance of these errors in determining the final error is stressed. The description of the errors also includes a summary of the experiments required following the launch to validate the CryoSat mission data. An estimate of the mission performance over ice surfaces is made at various spatial scales, and it is concluded that even the relatively short, three-year duration of the CryoSat mission will allow it to make an important scientific contribution, particularly when combined with results from earlier satellite missions.
Management of screen-detected ductal carcinoma in situ (DCIS) remains controversial.
A prospective cohort of patients with DCIS diagnosed through the UK National Health Service Breast Screening ...Programme (1st April 2003 to 31st March 2012) was linked to national databases and case note review to analyse patterns of care, recurrence and mortality.
Screen-detected DCIS in 9938 women, with mean age of 60 years (range 46–87), was treated by mastectomy (2931) or breast conserving surgery (BCS) (7007; 70%). At 64 months median follow-up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or mastectomy (4.5%) (p < 0.001). Breast radiotherapy (RT) after BCS (4363/7007; 62.3%) was associated with a 3.1% absolute reduction in ipsilateral recurrent DCIS or invasive breast cancer (no RT: 7.2% versus RT: 4.1% p < 0.001) and a 1.9% absolute reduction for ipsilateral invasive breast recurrence (no RT: 3.8% versus RT: 1.9% p < 0.001), independent of the excision margin width or size of DCIS. Women without RT after BCS had more ipsilateral breast recurrences (p < 0.001) when the radial excision margin was <2 mm. Adjuvant endocrine therapy (1208/9938; 12%) was associated with a reduction in any ipsilateral recurrence, whether RT was received (hazard ratio HR 0.57; 95% confidence interval CI 0.41–0.80) or not (HR 0.68; 95% CI 0.51–0.91) after BCS. Women who developed invasive breast recurrence had a worse survival than those with recurrent DCIS (p < 0.001). Among 321 (3.2%) who died, only 46 deaths were attributed to invasive breast cancer.
Recurrent DCIS or invasive cancer is uncommon after screen-detected DCIS. Both RT and endocrine therapy were associated with a reduction in further events but not with breast cancer mortality within 5 years of diagnosis. Further research to identify biomarkers of recurrence risk, particularly as invasive disease, is indicated.
•Adjuvant radiotherapy (RT) after wide excision is associated with a reduced risk of ipsilateral recurrence but not mortality•Survival after treatment of DCIS is excellent, with few subsequent deaths from breast cancer.•Further DCIS or invasive breast cancer is not uncommon (6.8% at 5 years)•5-year mortality was not impacted by the use of RT or endocrine therapy.
Oxidative stress is proposed as an important factor in osteoarthritis (OA).
To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA.
SOD expression was ...determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin-Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression.
All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin-Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression.
This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function.
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