Induction of tolerance to a murine fibrosarcoma in two zones of dosage--the involvement of suppressor cells.

Small size inocula (10(1)-10(3) cells) of cells from a syngeneic methylcholanthrene-induced fibrosarcoma (FSA) induced tolerance when injected s.c. into C3Hf mice. Mice were unable to respond to subsequent challenge with moderate, immunogenic doses of FSA. Tolerance was demonstrated in an in vivo transfer (Winn) assay and an in vitro tumour-specific TH cell assay. Low zone tolerance was associated with the presence of tumour-specific TS cells in the spleen. Moderate size inocula (10(4)-10(6) FSA cells) were immunogenic but larger cell doses (greater than 10(6)) were again tolerogenic. In the high zone, tolerance was associated with both tumour-specific TS cells and non T suppressor cells that were not tumour-specific. These results support the view that immunogenic tumours, as they grow from small cell numbers, might be able to escape host surveillance by specifically tolerizing the immune system. They also suggest that large tumour burdens can interfere with the host's immune response by inducing suppressor cells

Patient enablement requires physician empathy: a cross-sectional study of general practice consultations in areas of high and low socioeconomic deprivation in Scotland

<b>Background</b> Patient 'enablement' is a term closely aligned with 'empowerment' and its measurement in a general practice consultation has been operationalised in the widely used patient enablement instrument (PEI), a patient-rated measure of consultation outcome. However, there is limited knowledge regarding the factors that influence enablement, particularly the effect of socio-economic deprivation. The aim of the study is to assess the factors influencing patient enablement in GP consultations in areas of high and low deprivation.<p></p> <b>Methods</b> A questionnaire study was carried out on 3,044 patients attending 26 GPs (16 in areas of high socio-economic deprivation and 10 in low deprivation areas, in the west of Scotland). Patient expectation (confidence that the doctor would be able to help) was recorded prior to the consultation. PEI, GP empathy (measured by the CARE Measure), and a range of other measures and variables were recorded after the consultation. Data analysis employed multi-level modelling and multivariate analyses with the PEI as the dependant variable.<p></p> <b>Results</b> Although numerous variables showed a univariate association with patient enablement, only four factors were independently predictive after multilevel multivariate analysis; patients with multimorbidity of 3 or more long-term conditions (reflecting poor chronic general health), and those consulting about a long-standing problem had reduced enablement scores in both affluent and deprived areas. In deprived areas, emotional distress (GHQ-caseness) had an additional negative effect on enablement. Perceived GP empathy had a positive effect on enablement in both affluent and deprived areas. Maximal patient enablement was never found with low empathy.<p></p> <b>Conclusions</b> Although other factors influence patient enablement, the patients' perceptions of the doctors' empathy is of key importance in patient enablement in general practice consultations in both high and low deprivation settings

Long-term follow up to assess criteria for ovarian tissue cryopreservation for fertility preservation in young women and girls with cancer

Funding: K.D. is supported by a CRUK grant (C157/A25193). This work was undertaken in part in the MRC Centre for Reproductive Health, (supported by MRC grant MR/N022556/1). R.A.A. has received consulting fees from Ferring and Roche Diagnostics; payment from Merck and IBSA for educational events; and laboratory materials from Roche Diagnostics.STUDY QUESTION Do the Edinburgh Selection Criteria correctly identify female cancer patients under the age of 18 who are at risk of premature ovarian insufficiency (POI) as candidates for ovarian tissue cryopreservation (OTC)? SUMMARY ANSWER Patient assessment using these criteria accurately identifies those at risk of POI, who can be offered OTC and future transplantation as a means of fertility preservation. WHAT IS KNOWN ALREADY Treatment for childhood cancer can have adverse consequences on future fertility; at the time of diagnosis, fertility risk assessment should be undertaken in order to identify patients to whom fertility preservation should be offered. The Edinburgh selection criteria, based on planned cancer treatment and patient health status, are utilized to identify those at high risk and therefore eligible for OTC. However, this procedure is not without risk and there are few data on the efficacy of the procedure in prepubertal patients. As such, long-term follow-up of reproductive outcomes is necessary, to ensure that OTC is being offered appropriately. STUDY DESIGN, SIZE, DURATION Cohort study encompassing all females diagnosed with cancer under the age of 18 in South East Scotland, from 1 January 1996 to 30 April 2020. Patients were followed up for reproductive outcomes to assess for diagnosis of POI. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 638 eligible patients were identified; patients under the age of 12 or deceased before the age of 12 were excluded from the study, leaving a study population of 431 patients. Electronic records were reviewed for reproductive function, assessed by current menstruation, pregnancy (in the absence of POI diagnosis), reproductive hormone measurements, pubertal progression, or diagnosis of POI. Patients on hormonal contraception (other than for treatment of POI or panhypopituitarism with no history of gonadatoxic treatment) were excluded from analysis (n = 9). Analysis on remaining 422 patients was carried out using the Kaplan–Meier methods, with POI as the defined event, and Cox proportional hazards model. MAIN RESULTS AND THE ROLE OF CHANCE In the study population of 431 patients, median ages at diagnosis and analysis were 9.8 and 22.2 years, respectively. Reproductive outcomes were unavailable in 142 patients; the assumption was made that these patients did not have POI, but a subanalysis excluding these patients was also performed. Of the 422 patients aged >12 at analysis and not taking hormonal contraception, OTC was offered to 37 patients and successfully performed in 25 patients. Of the 37 patients offered OTC (one at time of relapse), nine (24.3%) developed POI. Of the 386 not offered OTC, 11 (2.9%) developed POI. The probability of developing POI was significantly higher in those offered OTC (hazard ratio [HR] 8.7 [95% CI 3.6–21]; P < 0.0001), even when those patients with unknown outcomes were excluded from the analysis (HR 8.1 [95% CI 3.4–20]; P < 0.001). All patients offered OTC who developed POI did so after treatment for primary disease; in those not offered OTC, five patients (45.5%) developed POI after treatment for disease relapse. LIMITATIONS, REASONS FOR CAUTION A significant number of patients had unknown reproductive outcomes; many of these patients were engaged in ongoing follow-up but did not have documented reproductive assessment. This may have introduced bias to the analysis and highlights the need for reproductive follow-up as part of routine cancer aftercare. In addition, the relatively young age of the patient population and short duration of follow-up in some cases demonstrates the need for ongoing follow-up of this cohort. WIDER IMPLICATIONS OF THE FINDINGS The prevalence of POI after childhood cancer is low, but the Edinburgh selection criteria remain a robust tool for selecting those at high risk at the time of diagnosis, to offer OTC appropriately. However, disease relapse necessitating more intensive treatments remains a challenge. This study additionally highlights the importance of routine assessment and documentation of reproductive status in haematology/oncology follow-up.Publisher PDFPeer reviewe

High-pressure behavior of superconducting boron-doped diamond

This work investigates the high-pressure structure of freestanding superconducting ($T_{c}$ = 4.3\,K) boron doped diamond (BDD) and how it affects the electronic and vibrational properties using Raman spectroscopy and x-ray diffraction in the 0-30\,GPa range. High-pressure Raman scattering experiments revealed an abrupt change in the linear pressure coefficients and the grain boundary components undergo an irreversible phase change at 14\,GPa. We show that the blue shift in the pressure-dependent vibrational modes correlates with the negative pressure coefficient of $T_{c}$ in BDD. The analysis of x-ray diffraction data determines the equation of state of the BDD film, revealing a high bulk modulus of $B_{0}$=510$\pm$28\,GPa. The comparative analysis of high-pressure data clarified that the sp$^{2}$ carbons in the grain boundaries transform into hexagonal diamond.Comment: 7 pages, 4 figure

Meaningful values of the EQ-5D-3L in patients undergoing primary knee arthroplasty

AIMS: The aim of this study was to report the meaningful values of the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) and EuroQol visual analogue scale (EQ-VAS) in patients undergoing primary knee arthroplasty (KA). METHODS: This is a retrospective study of patients undergoing primary KA for osteoarthritis in a university teaching hospital (Royal Infirmary of Edinburgh) (1 January 2013 to 31 December 2019). Pre- and postoperative (one-year) data were prospectively collected for 3,181 patients (median age 69.9 years (interquartile range (IQR) 64.2 to 76.1); females, n = 1,745 (54.9%); median BMI 30.1 kg/m(2) (IQR 26.6 to 34.2)). The reliability of the EQ-5D-3L was measured using Cronbach’s alpha. Responsiveness was determined by calculating the anchor-based minimal clinically important difference (MCID), the minimal important change (MIC) (cohort and individual), the patient-acceptable symptom state (PASS) predictive of satisfaction, and the minimal detectable change at 90% confidence intervals (MDC-90). RESULTS: The EQ-5D-3L demonstrated good internal consistency with an overall Cronbach alpha of 0.75 (preoperative) and 0.88 (postoperative), respectively. The MCID for the Index score was 0.085 (95% confidence interval (CI) 0.042 to 0.127) and EQ-VAS was 6.41 (95% CI 3.497 to 9.323). The MIC(COHORT) was 0.289 for the EQ-5D and 5.27 for the EQ-VAS. However, the MIC(INDIVIDUAL) for both the EQ-5D-3L Index (0.105) and EQ-VAS (-1) demonstrated poor-to-acceptable reliability. The MDC-90 was 0.023 for the EQ-5D-3L Index and 1.0 for the EQ-VAS. The PASS for the postoperative EQ-5D-3L Index and EQ-VAS scores predictive of patient satisfaction were 0.708 and 77.0, respectively. CONCLUSION: The meaningful values of the EQ-5D-3L Index and EQ-VAS scores can be used to measure clinically relevant changes in health-related quality of life in patients undergoing primary KA. Cite this article: Bone Joint Res 2022;11(9):619–628

Applications of p-deficiency and p-largeness

We use Schlage-Puchta's concept of p-deficiency and Lackenby's property of p-largeness to show that a group having a finite presentation with p-deficiency greater than 1 is large, which implies that Schlage-Puchta's infinite finitely generated p-groups are not finitely presented. We also show that for all primes p at least 7, any group having a presentation of p-deficiency greater than 1 is Golod-Shafarevich, and has a finite index subgroup which is Golod-Shafarevich for the remaining primes. We also generalise a result of Grigorchuk on Coxeter groups to odd primes.Comment: 23 page

Head-Neck Taper Corrosion in Hip Arthroplasty

Copyright © 2015 S. Hussenbocus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Modularity at the head-neck junction of the femoral component in THA became popular as a design feature with advantages of decreasing implant inventory and allowing adjustment of leg length, offset, and soft tissue balancing through different head options. The introduction of a new modular interface to femoral stems that were previously monoblock, or nonmodular, comes with the potential for corrosion at the taper junction through mechanically assisted crevice corrosion. The incidence of revision hip arthroplasty is on the rise and along with improved wear properties of polyethylene and ceramic, use of larger femoral head sizes is becoming increasingly popular. Taper corrosion appears to be related to all of its geometric parameters, material combinations, and femoral head size. This review article discusses the pathogenesis, risk factors, clinical assessment, and management of taper corrosion at the head-neck junction

Rapid genotype imputation from sequence without reference panels

Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r(2) value of 0.98 in 2,073 outbred laboratory mice (0.15× sequencing coverage). In a sample of 11,670 Han Chinese (1.7× coverage), we achieve accuracy similar to that of alternative approaches that require a reference panel, demonstrating that our approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans

Electron energy loss and induced photon emission in photonic crystals

The interaction of a fast electron with a photonic crystal is investigated by solving the Maxwell equations exactly for the external field provided by the electron in the presence of the crystal. The energy loss is obtained from the retarding force exerted on the electron by the induced electric field. The features of the energy loss spectra are shown to be related to the photonic band structure of the crystal. Two different regimes are discussed: for small lattice constants $a$ relative to the wavelength of the associated electron excitations $\lambda$, an effective medium theory can be used to describe the material; however, for $a\sim\lambda$ the photonic band structure plays an important role. Special attention is paid to the frequency gap regions in the latter case.Comment: 12 pages, 7 figure

Responsiveness and ceiling effects of the Forgotten Joint Score-12 following total hip arthroplasty

ObjectivesTo assess the responsiveness and ceiling/floor effects of the Forgotten Joint Score -12 and to compare these with that of the more widely used Oxford Hip Score (OHS) in patients six and 12 months after primary total hip arthroplasty.MethodsWe prospectively collected data at six and 12 months following total hip arthroplasty from 193 patients undergoing surgery at a single centre. Ceiling effects are outlined with frequencies for patients obtaining the lowest or highest possible score. Change over time from six months to 12 months post-surgery is reported as effect size (Cohen’s d).ResultsThe mean OHS improved from 40.3 (sd 7.9) at six months to 41.9 (sd 7.2) at 12 months. The mean FJS-12 improved from 56.8 (sd 30.1) at six months to 62.1 (sd 29.0) at 12 months. At six months, 15.5% of patients reached the best possible score (48 points) on the OHS and 8.3% obtained the best score (100 points) on the FJS-12. At 12 months, this percentage increased to 20.8% for the OHS and to 10.4% for the FJS-12. In terms of the effect size (Cohen’s d), the change was d = 0.10 for the OHS and d = 0.17 for the FJS-12.ConclusionsThe FJS-12 is more responsive to change between six and 12 months following total hip arthroplasty than is the OHS, with the measured ceiling effect for the OHS twice that of the FJS-12. The difference in effect size of change results in substantial differences in required sample size if aiming to detect change between these two time points. This has important implications for powering clinical trials with patient-reported measures as the primary outcome