The light-sense in strabismus : especially in the amblyopia of strabismus : examined by means of a new photometer

One is now in a position to draw conclusions. I have put together all the cases of convergent strabismus with amblyopia, examined as to the light -sense either with or without glasses, which show a marked difference in their light-sense (groups 1 and 9).That is, of 15 cased (Divisions 1 and 2), in which the L.M. is affected markedly, 9 have it increased, and 6 have it diminished.On the other hand, of 20 cases (divisions 1 and 3), in which the L.D. is similarly affected, 15 have it increased, and 5 have it diminished.In like manner I put together those cases of convergent strabismus, without amblyopia, in which there was a marked difference in the light -sense of the two eyes. (Tables 14 and 37).Here then, of 7, which have a variation in the L.M., in 3 the L.M. is greater, and in 4 less. Of 6 which vary as to the L.D., in all the L.D. is increased.In the next place, I have made a similar summary of the cases of divergent strabismus, with amblyopia, which, with or without glasses, show a marked difference in the light-sense of the two eyes (Tables 21 and 42).That is, where the L. M. is affected- markedly, in 3 out of 4 it is increased, and in 1 diminished.Where the L.D. is markedly affected, out of 5 cases it is increased in 3, and diminished in 2.So far as it goes, this table points to defect in the L.T.C., and also, though in less degree, to defect in the L.P., but the number of cases is too small to permit of useful generalisation.Also, the number of cases of divergent strabismus without amblyopia (Group. 7.) is too small to be worth considering.Lastly, I may recall the fact (p.48) that, in amblyopic eyes without strabismus, there is no overwhelming evidence pointing either to the L.M. or the L.D., though either may be affected.This inquiry then has a negative result, for no abso- lute rule as to the light -sense in squinting or amblyó_ is eyes, as compared with the et in their normal fellows, has been revealed. In all the groups, a large proportion of the cases present equal or nearly equal light -sense in the two eyes. Of the remainder, some have defective L.7., and some defective L.D., some have more acute L.M. and some more acute L.D. And neither acutt: of vision, age, nor refractive error, seems to assist in determining any classification of each kind. Of those cases of Convergent Strabismus however, either with or without amblyopia, in which the light- sense is markedly different in the squint- ing eye from that in the normal eye, the majority show a defective L.D. In other words, these cases seem to have some affection of the optic nerve or nervous elements of the retina.One is forced to the conclusion, therefore, that probably the light -sense is not primarily responsibe for the squint or for the amblyopia. The explanation of squint is still hidden.PHOTOMETRY OF NORMAL EYES:- In order that I might report on the cases cf toxic amblyopia, which I have examined the light -sense of, it is necessary to determine the average of the normal eyes, as to their L.M. and L.D.In doing this, I have included all the eyes of the preceding study, which did not squint, and a few extra ones which were seen during the same time.All were perfectly healthy, as evidenced by the ophthalmoscope and the visual acuity. I have accordingly made tables of 73 eyes,whose light -sense was examined while they wore the correcting glasses necessary, and of 29 eyes which were examined naked. I have tabulated each lot in accordance with their decades of life, having sub- tables of the different acuities of vision under each decade.The figure in the third column is the area of the circular ring formed by the partly opened diaphragm and the central cylinder of wood. That in the fourth column is the proportion expressed as a decimal fraction, of the extra area, needed to enable the observer to note a difference in the brilliancy of the discs, to the L.M. The figure in the fifth column is the diameter of the diaphragmatic aperture at the first reading, and that in the sixth column is the diameter at the second reading (p.16)The form-sense is that obtained by correcting the refractive error with glasses, which were removed before introduction to the photometer.These two tables collected into one, ,under the decades of age, give a result as follows:These, again collected together under the decades, give the following figures as the averages for the five decades named, and they are seen to be all similar;We can now reckon the cases of Tobacco amblyopia, of which I have 12 eyes to report on.3 of these eyes have distinct increase in the L M. one of 6 them seeing Ja, and two 6/36.3 have markedly increased L.D. one seeing 6/6-0, one of them seeing 6/36, and one 6/24.In most of these eyes, therefore, there is no affection of the L.M. or the L, D., so that neither the retina nor the optic nerve, so far as its connection with the light-sense centre is concerned, need be affected. The cases are too few, however, to permit of dogmatism. So far as the observation goes, it is in accord with Henry's (op.cit.), who also found with his photometer that the L.M. was not affected in toxic-amblyopia

Specialist Clinicians' Management of Dependence on Non-Prescription Medicines and Barriers to Treatment Provision : An Exploratory Mixed Methods Study Using Behavioural Theory

This research was funded by THE SOCIETY FOR THE STUDY OF ADDICTION in the form a PhD studentship awarded to Niamh Fingleton. Supplementary Materials: The following are available online at http://www.mdpi.com/2226-4787/7/1/25/s1, Table S1: Summary of belief statements and illustrative quotes assigned to the theoretical domainsPeer reviewedPublisher PD

Non-prescription medicine misuse, abuse and dependence : a cross-sectional survey of the UK general population

BACKGROUND: Non-prescription medicines (NPMs) can be misused, abused or lead to dependence, but the prevalence of these problems within the UK general population was unknown. The aim of this study was to estimate the prevalence of self-reported misuse, abuse and dependence to NPMs.METHODS: A cross-sectional postal survey was sent to 1000 individuals aged ≥18 randomly drawn from the UK Edited Electoral Register.RESULTS: A response rate of 43.4% was achieved. The lifetime prevalence of NPM misuse was 19.3%. Lifetime prevalence of abuse was 4.1%. Younger age, having a long-standing illness requiring regular NPM use and ever having used illicit drugs or legal highs were predictive of misuse/abuse of NPMs. In terms of dependence, lifetime prevalence was 2% with 0.8% currently dependent and 1.3% dependent in the past. Dependence was reported with analgesics (with and without codeine), sleep aids and nicotine products.CONCLUSION: Given the increasing emphasis on self-care and empowering the public to manage their health with NPMs, the findings highlight the need for improved pharmacovigilance of these medicines to maximize benefits with minimal risk. Healthcare providers need to be aware of the potential for misuse, abuse and dependence, particularly in patients with long-term illness

Association between benzodiazepine co-prescription and mortality in people on opioid replacement therapy:a population-based cohort study

Objective: To investigate the association between Opioid Replacement Therapy (ORT) and benzodiazepine co-prescription and all-cause mortality compared to the prescription of ORT alone.Design: Population based cohort studySetting: Scotland, UK.Participants: Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.Main outcome measures: all-cause mortality, drug related deaths and non-drug related deaths. Secondary outcome: ORT continuous treatment duration.Analysis: Cox regression with time-varying covariates.Results: During follow up 5776 of 46899 participants died: 1398 while on co-prescription and 4378 while on Opioid Replacement Therapy only. The mortality per 100 person years was 3.11 during co-prescription and 2.34 on ORT only. The adjusted hazard ratio for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted hazard ratio for drug related death was 1.14 (95% CI 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI 1.09 to 1.30).Conclusion: Co-prescription of benzodiazepines in opioid replacement therapy increased risk of all cause mortality, although less than the international literature. Co-prescribing was also associated with longer retention in treatment. Risk from benzodiazepine co-prescription needs to be balanced against the risk from illicit benzodiazepines and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide clear clinical direction.<br/

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy:a population-based cohort study

Objective To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.Design Population-based cohort study.Setting Scotland, UK.Participants Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.Main outcome measures All-cause mortality, drug-related deaths and non-drug related deaths.Secondary outcome ORT continuous treatment duration.Analysis Cox regression with time-varying covariates.Results During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30).Conclusion Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction.Trial registration number NCT04622995.</p

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study

Objective To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone. Design Population-based cohort study. Setting Scotland, UK. Participants Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above. Main outcome measures All-cause mortality, drug-related deaths and non-drug related deaths. Secondary outcome ORT continuous treatment duration. Analysis Cox regression with time-varying covariates. Results During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30). Conclusion Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction. Trial registration number NCT0462299

Magnetic fields in supernova remnants and pulsar-wind nebulae

We review the observations of supernova remnants (SNRs) and pulsar-wind nebulae (PWNe) that give information on the strength and orientation of magnetic fields. Radio polarimetry gives the degree of order of magnetic fields, and the orientation of the ordered component. Many young shell supernova remnants show evidence for synchrotron X-ray emission. The spatial analysis of this emission suggests that magnetic fields are amplified by one to two orders of magnitude in strong shocks. Detection of several remnants in TeV gamma rays implies a lower limit on the magnetic-field strength (or a measurement, if the emission process is inverse-Compton upscattering of cosmic microwave background photons). Upper limits to GeV emission similarly provide lower limits on magnetic-field strengths. In the historical shell remnants, lower limits on B range from 25 to 1000 microGauss. Two remnants show variability of synchrotron X-ray emission with a timescale of years. If this timescale is the electron-acceleration or radiative loss timescale, magnetic fields of order 1 mG are also implied. In pulsar-wind nebulae, equipartition arguments and dynamical modeling can be used to infer magnetic-field strengths anywhere from about 5 microGauss to 1 mG. Polarized fractions are considerably higher than in SNRs, ranging to 50 or 60% in some cases; magnetic-field geometries often suggest a toroidal structure around the pulsar, but this is not universal. Viewing-angle effects undoubtedly play a role. MHD models of radio emission in shell SNRs show that different orientations of upstream magnetic field, and different assumptions about electron acceleration, predict different radio morphology. In the remnant of SN 1006, such comparisons imply a magnetic-field orientation connecting the bright limbs, with a non-negligible gradient of its strength across the remnant.Comment: 20 pages, 24 figures; to be published in SpSciRev. Minor wording change in Abstrac

Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.

Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p &lt; 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p &lt; 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544